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Boston
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RHEUMATOID ARTHRITIS
RHEUMATOID ARTHRITIS
ITS PATHOLOGY, MORBID ANATOMY,
AND
TREATMENT.
GILBERT A. BANNATYNE, M.I). Glas., M.B.C.P. Ed.
Hon. Physician to the Royal United Hospital, and to the. Tioijid Mineral Water Hospital, Hath.
BRISTOL: JOHN WRIGHT & CO. LONDON: SIMPKIN, MARSHALL, HAMILTON, KENT & CO. Ltd.
1896.
nrc : 7 1899
/ _ — <*o— f
•T01IV WKIOIIT AM)
PRINTERS AND PUBLISHERS, BRISTOL
PREFACE.
The writing of a treatise on Rheumatoid Arthritis involves much labour, not only on account of the mass of literature which has to be traced and classified, but, also, and more especially in my case, from the recent discovery of micro-organisms in this disease, implying, in consequence, the revision of all its pathology, morbid anatomy, and treatment. Such an upheaval cannot be accomplished in a day, and this small work is only intended to be an introduction to further and more perfect investigation. Many parts of it will, probably, in the near future require revision, but it has been my ambition to avoid, as far as possible, making any statement unsupported by facts or by logical deductions therefrom. I have here utilized the discovery, of Dr. Wohlmann and myself, of micro-organisms, which we believe to be specific to the disease, and the latter's life history and peculiarities, as worked out and elucidated by Dr. Blaxall. To them both my sincere thanks are due. In
PREFACE.
the lio'lit of our discovery I have been led to enquire into the nature of two complaints which have been hitherto classed as only variations of one and the same disorder. This, for reasons given later on, I do not consider to be correct, and I propose to study and keep distinct Senile Arthritis from the more general- ized and microbic disease Rheumatoid Arthritis.
Bath, 18 96.
CONTENTS
CHAPTER 1.
TAG
INTRODUCTORY AND HISTORICAL - - - 1
Nomenclature — Evidence of its Antiquity — Landre Beau- vais — Heberden — Haygarth — Cruveilhier — Adams — Fuller — Charcot— Devillc— Broca — Key — Senator — Garrod — Virchow — Hutchinson — Spender -Its Individuality— Its Frequency, etc.
CHAPTER II.
.ETIOLOGY AND PATHOLOGY - - 12
Micro-organisms a Cause — Selective Action— Where Found — Heredity — Sex — Age — Catarrh of the Mucous Membranes — Emotional Causes — Atmospheric Conditions — Injury — Rheumatism — Alkalinity of the Blood — Charcot — Pye-Smitb — Hutchinson — Forsbrooke — Dystrophic Theory — Evidence in its Favour — Against it — Ord's Theory — Rerlex Irritation — Functional Depression — Toxic Conditions — Muscular Atrophy — Insufficiency of Theories — Micro-organisms — Effect on Nerve System — Erb — Muscular Atrophy due to Toxic Causes — Multipolar Nerve Cells — Ferrier — Folli — Condition of the Anterior Cornua — Muscular Selection — Vaso-motor System — Pigmentation — Sweating — Tachycardia- Bezanron -Anaemia — Hunter — Summary.
CHAPTER 111
PATHOLOGICAL ANATOMY AND BACTERIOLOGY - 18
Degenerative Character of Changes — Points of Origin — How the Bacteria gain Access— Naked Eye Appearances of Joint — Changes in Synovial Membrane — -Loose Bodies — Liga- ments— Characters of Synovia — Changes in the Cartilages— Cornil and Ranvier — Erosion — Proliferation — Lipping — Changes in the Bones— Rarification — Osteo-sclerosis — Volk- mann — Changes in the Muscles — Central Nerve Changes — Peripheral Nerves — ■ Cardiac Changes — Kidney — Blood — Glands — Fibrous Nodules — Heberden's Nodes — Situation and Mode of Growth — Gout a Cause— Their Nature —Various other Views — Bacteriology, etc.
CONTENTS.
CHAPTER IV
VARIETIES ANT) DIAGNOSIS -
Errors in Diagnosis— Acute Rheumatoid Arthritis— Osteo- Arthritis — Charcot's Classification — Post-Rheumatic, Gonor- rhceal, and Gouty Forms — Acute and Sub-acute Forms — Infantile Arthritis— In Children— In Adults— Differences — Symptoms — Appearance of Joints — Chronic Rheumatoid Arthritis — Age — Appearances — Bony Changes — Diagnosis between it and Nerve Diseases — Charcot's Disease — Gout — Rheumatism, Chronic Rheumatism, etc.
CHAPTER V. SYMPTOMS AND PROGNOSIS - 97
Premonitory Symptoms — Spender — Primary Symptoms due to Micro-organisms — Appearances of Joints — Heat of Skin — Arthrite Seche — Synovial Pouches — Joints first Affected — Symmetry — Ankylosis — Deformities — Dislocations — Osteo- phyte Out-growths — Forms of the Deformities — In Hands and Knees — Its Causes — Difference in Acute and Chronic Cases — Cardiac Symptoms — Endocarditis — Pericarditis — Changes in the Glands — Secondary Symptoms — Muscular Atrophy — Its Characters — Selective Power — Myotatic Irrita- bility— Fever— Pulse Rate — Tachycardia — Tension — Anaemia — Haemorrhages — Purpura — Neuritis — Its Frequency — Tro- phic Phenomena — Skin Changes — Glossy Skin — Loss of Hair — Atrophy— Downy- growth of Hair — Pigmentation — Sweat- ing— Dyspepsia, — Kidney and Cardiac Troubles — Prognosis.
CHAPTER VI.
TREATMENT ------- 126
Preliminary Considerations — Antitoxinc — Causes — Diet — Clothing — Exercise — Drugs — Creasote — Guaiacol — Guaiacol ( larbonate — Benzosol— Phenols — Naphthols — Betol — Salol — Action of Creasote— Hudeod — Douglas Powell — Intestinal Antiseptics — iron — Arsenic — Iodides — Salicylates — Actsea Liacemosa — Ichthyol — Hyoscyamus — Relief of Pain — Dr. Spender's Treatment— Guaiacol Externally — Carbolic Acid Fomentations — Electricity — Thermal Treatment — Alkaline and Sulphurous Waters— Bath — Buxton — Aachen — Action of Bath Waters — Batli Treatment — Hot Air Baths — Sea Voyages — Extension— Excision — Summary.
CONTENTS.
CHAPTER VII.
PAGE
SENILE ARTHRITIS - - - 151
Morbus Coxse Senilis — Senile Arthritis — Monarticular Rheumatoid Arthritis — In whom seen— Symptoms — Morbid Anatomy — Changes in the Bones — Trophic Phenomena — Treatment.
APPENDIX - - - - 156
BIBLIOGRAPHICAL INDEX - - - - - 162
INDEX - - 166
LIST OF ILLUSTRATIONS.
PLATE I, Page 70. Photograph of bones of hand in Rheumatoid Arthritis.
PLATE II, Page 76. Fig. A. — Synovial fluid, stained with gentian violet x 900. Fig. B.— Beef-broth culture, stained with carbolic fuchsine x 900.
PLATE III, Page 89. Fig. A. — Spindle shaped enlargement of joints with atrophy. Fig. B.— Pulpy swelling of joints.
PLATE IV, Page 90.
Photograph showing swellings in joints, etc., and general emaciation.
PLATE V, Page 92.
Another case — the swelling being soft and doughy ; also atrophy of right hand.
PLATE VI, Page 97.
Fig. A. — Enlargements of the heads of bones, synovial swelling
and atrophy. Fig. B.— Ulnar deflection in a chronic case.
PLATE VII, Page 99. Fig. A. — Showing deflection of left hand. Fig. B. — Showing spindle shaped swelling of phalangeal joints.
PLATE VIII, Page 106. Fig. A. — Dislocation backwards of index finger. Fig. B. — Ulnar deflection.
PLATE IX, Page 119. Fig. A. — Fusiform deformity of index finger. Fig. B. — Haemorrhage under nails.
LIST OF ILLUSTRATIONS.
WOOD ENGRAVINGS.
Fig. 1. — Section through phalangeal joint in chronic Rheu- matoid Arthritis- - - - - - 51
Fig. 2. — Osteophytes, eburnated bone, grooves on articu- lating surfaces ------- 52
Fig. 3.— Connective tissue, showing micro-organisms - 55
Fitj. 4. — Sections through diseased cartilage - - - 59
Fig. 5. — Metacarpal bone, showing osteophytes - - 61
Fig. 6. — Osteoclast eating bone ------ 63
Fig. 7. — Multipolar ganglion cells from anterior cornua 64
Fig. 8. —Portion of nerve, showing neuritis 65
Fig. 9. —Head of femur from case of morbus coxas senilis 153
CHAPTEE I. INTRODUCTORY AND HISTORICAL.
Nomenclature — Evidence of its Antiquity — Landre Beauvais — Heberden, — Hogarth — Cruveilhier — Adams — Fuller — Char- cot— Deville — Broca — Key — Senator — G-arrod — Virchow— Hutchinson- —Spender — Its Individuality — Its Frequency, etc.
HITHEKTO, the disease which we call Kheumatoid Arthritis has not only been known by different names, but different diseases have been classed under this heading— the number and diversity of the terms employed corresponding in a certain sense with the number and diversity of the views advanced with re- gard to its aetiology and pathology. It is undoubtedly a disease per se, and has probably existed as such as far back as any other known form of disease, but it was not until the beginning of this century, or the end of the last, that it came to be recognised and differentiated from the allied disorders, gout and rheumatism. Indeed, I am not certain, that in some countries it is even yet recog- nised as a separate form of disease, for in France some still hold it to be only a form of chronic rheumatism. This is curious, as one of the best works ever written on the subject was penned by that great observer, Charcot. Much of the difficulty surrounding the disorder is, I am sure, caused by the ambiguity of the various terms which have, at one time or another, been applied to it, and none of which seem exactly to describe its characteristics, but leave much to the imagination of the individual observer. Of recent years the principal terms employed to desig- nate it have been those of rheumatoid arthritis, and osteo-
1
2 RHEUMATOID ARTHRITIS.
arthritis. Now how much better would it be were we content with one name only, even if that one did not actually describe the condition with perfect accuracy ? What an amount of confusion might have been saved ! This want of exactitude in nomenclature would soon have been compensated for in our increased knowledge, which we would have been enabled to store up and note for comparison about a complaint, the study of which, and the disentanglement of whose literature and prevail- ing impressions, are enough to appal even the boldest. Many and various are the theories which, at one time or another, have been advanced to explain the congeries of symptoms called rheumatoid arthritis ; and many and various are the diseases, which, at one time or another, have come under our notice labelled rheumatoid arthritis, osteo-arthritis, rheumatic gout, etc., these terms being, as a rule, quite indiscriminately apportioned. No wonder confusion has reigned supreme. As far as our still limited knowledge renders possible, I will endeavour to throw a ray of light into the obscurity surrounding the aetiology and pathology of the disease, with the hope that it will, in the near future, enable us to walk with surer footsteps.
Of the many names used to designale the acute or destructive form of the disorder, I have here assumed that that of rheumatoid arthritis is the one best known to the largest number, and, therefore, the one best suited to be used permanently. It, in my opinion, is the one fulfilling to the greatest extent the requirements of science. This term was first applied by Garrod, and although it implies a condition which many deny exists, yet I think, from every point of view, it is the most suit- able. It has been objected that the word Eheumatoid, which means, freely translated, like rheumatism, is mis- leading ; so it is, to a certain extent. Yet no one
INTRODUCTORY AND HISTORICAL. 3
will deny that while quite separate and distinct, it, to a certain extent, in outward appearance at least, does resemble some forms of rheumatism. It is a much more suitable term than any of those which include Eheumatic, as part and parcel of their being. Bheu- matic applies to a totally different condition, and to bring it in leads to endless confusion . Osteo-arthritis is a term implying a condition much more marked in the chronic forms of the disease, and which I would keep for those chronic osteo-sclerotic cases, so often seen in the later stages. Some have objected to the use of arthritis at all, as they hold that the inflammatory changes in the joints are merely secondary to nutritional changes elsewhere ; were it not for this, the term most commonly used in Germany, arthritis deformans, would have become much more popular. This objection to arthritis can hardly be sustained, especially in consequence of our newer light on the origin of the disease.
The following is a list of the terms which have, at one time or another, been applied to the disease : —
1. " Goutte Asthenique Primitif," by Landre Beau- vais, in 1800.1
2. " Digitorum Nodi," by Heberden, in 1804.2
3. " Nodosity of the Joints," byHaygarth, in 1805.3
4. " Chronic Eheumatism of the Joints," by Todd, in 1843.4
5. "Arthrite Seche," by Deville and Broca, in 1848 and 1850.5and6
6. " Eheumatic Gout," by Fuller, in 1852.7
7. " Eheumatisme Chronique Primitif," by Charcot and Vidal, in 1853 and 1855.8
8. " Usure des Cartilages Articulaire," by Cruveilhier, in 1858.9
9. " Chronic Eheumatic Arthritis," by Adams, in 1857.10
4 RHEUMATOID ARTHRITIS.
10. "Kheumatisme Noueux," by Trousseau, in I860.11
11. " Arthritis Deformans," by Virchow, in 1869.12
12. " Eheumatoid Arthritis," by Garrod (Sir A.), in 1876.1::
13. " Osteo-arthritis," by Spender, in 1888. 14
14. " Pernicious Arthritis," by Brabazon, in 1896.66 From this list we see, that even from the beginning,
there has been a difference of opinion as to what is, and what is not rheumatoid arthritis, as well as an uncer- tainty as to the nature of the morbid process ; some ascribing the changes to rheumatism, whereas others have thought they were gouty in nature ; some, in their writings, describing typically rheumatoid cases, and others as typically what are not rheumatoid.
Turning to the history of this complaint, we find its characteristic changes (probably osteophytic) have been found in the bones of its victims in times which, if not quite prehistoric, are practically so. As far as I can learn, the oldest bones showing these changes are those found in lower Egypt by Mr. Petrie,15 who suggests as a probable, date 1300 B.C. Next come those discovered by Mr. Eve,1G also in Eg}rpt, and probably referable to the Ptolemaic period (second century B.C.) ; and following on these are those of a Norse Viking, found in the Christiania Fjord; those found in Pompeii, by Chiaje;17 those in the Convent of Marienthon in Pomerania, by Virchow ;1S those in the Boman Sarcophagus at Smith- field, by Dr. Norman Moore ;19 those in the Catacombs of Paris, found by Leber t ;20 all showing distinct traces of bony rheumatoid, or osteo-arthritic change. Coming down to more recent times, we find the disease was first described by Sydenham,21 from a clinical point of view, in the year 1683, as a modification of rheumatism. In 1703 it is referred to in the writings of Musgrave ;22 in 1764 and 1768 in those of Haller 23 and De Salivates,24
INTRODUCTORY AND HISTORICAL. 5
respectively. In those writings one can trace references to the disease, but it was not actually described as a disease per se until the year 1800, when Landre Beau- vais 25 published his Thesis on " G-outte Asthenique Primitif," which condition we now recognise as one of rheumatoid arthritis. Amongst the other features to which he drew attention was the special liability of women to its attacks, its chronic nature, its destruction of the cartilage, and its enlargement and deformity of the affected joints. He recognised that it could not be due to gout, thus differentiating for the first time between that disease and rheumatoid arthritis. His picture is a typical one. In 1804 Beauvais' opinion received the support of Heberden,26 who, however, went further, and differentiated between it and rheumatism. He men- tioned that there was little or no fever, no redness of the skin, no great pain, but swelling of the affected part; that the disease was not particularly apt to begin in the foot, but if so, it soon ieft it and attacked other parts of the limbs, several of which, one after the other, became the seat of the distemper from the first fit ; that it was very crippling ; and that one attack caused more weakness of the limbs than would have been produced by gout in many years. He mentions that the wrists, and some- times the fingers were specially liable, and that often it remained permanently in these joints. He also described what have ever since been known as Heberden's nodes, as occurring on the terminal phalanges of the fingers.
In 1805 Haygarth 27 published his clinical "History of Diseases," which gives the clinical appearance of rheumatoid arthritis, describing it fully, and also differ- entiating between it and rheumatism. In 1813 Chomel28 alludes to Landre Beauvais' thesis, but believed that the disease referred to by the latter was of a rheumatic type. In 1827 Scudamore20 mentions that he had seldom seen
6 RHEUMATOID ARTHRITIS.
such cases as are described by Haygartli, except second- ary to gout and rheumatism. In 1833 Brodie,30 in his work on " Diseases of the Joints," calls attention to its being quite distinct from both rheumatism and gout ; and during the years 1829 to 1840 Ouveilhier31 wrote mentioning the necessity of observing its clinical charac- teristics, and gave it the name, " Usure des cartilages articulaire." He points out that true bony ankylosis may occur. During this period also it was studied and commented upon by Lobstein s2 (1833), Key33 (1833), Eobert Smith34 (1835), Canton35 (1848), Deville 36 (1848), Broca 37 (1850), and Adams 38 (1857) in this country and France ; whilst in Germany, Meyer 39 (1849\ Weber 40 (1858), and Leis 4] wrote explaining the rationale of the various phenomena observed. These were subsequently confirmed by Cornil 42, Vergely43 (1858), and Banvier 44 (1865). Broca and Deville gave it the name " Arthrite Seche," and Adams that of " Chronic Bheumatic Arthritis." Eobert Smith and Adams both pointed out that many cases of disease of the hip joint, resulting from injury, were of the nature of rheumatoid arthritis, and thereby caused confusion with regard to malum eoxae senile. Adams gives many beautiful illustrations of the morbid anatomy. He says Sandifort,45 of Leyden, was the first to notice the disease, in the hip joint, in the post mortem room. Adams also corroborates Cruveil- hier's observation about the occurrence of true bony ankylosis, and he mentions that the polyarticular cases are usually preceded by acute rheumatism. Moreover, he draws attention to the relationship between the mon- articular cases and injury. Colles, in 1839 — 1857, remarks that two different processes were at work, one absorbing, and one forming fresh bone. In 1843 Todd 4(5 called it " chronic rheumatism of the joints," and con- sidered the changes to be more of an irritative than in-
INTRODUCTORY AND HISTORICAL. 7
flammatory nature. In 1849 Kedfern 47 gives some good illustrations of the disease, and shows the nature of the cartilaginous changes. In 1852 Fuller,48 in his work on " Eheumatism and Allied Disorders," calls it " rheumatic gout." He says that although it is in some respects closely allied to rheumatism, yet he considers it more of the nature of gout ; at the same time he thinks it is not a compound of the two disorders, hut a distinct disease. In 1853 Charcot and Trastour49 pub- lished their thesis. As Charcot's views have been more largely received and criticised than any other, his opinions will come under consideration later on, and as they crop up. In 1855 Vidal 65 followed Charcot with his thesis. They all three give it the name " Kheumatisme Chronique Primitif," and they all held that it was only a form of chronic rheumatism. This view is still held in France by many, as may be seen from Charcot's later writings, and also from those of Besnier,50 Homolle,51 Lacaze-Dori,52 and Mathieu.53 In England, America, and Germany, this is not the view held by most writers on the subject. Most of them have been of the opinion that Heberden and Hay garth were right in regarding it as a disease per se, and that although it presented many outward appearances, resembling both gout and rheuma- tism, yet it differed entirely in essentials, and that it was evidently a distinct disorder. Adams and Fuller, who did much work in the elucidation of the characteristics of the disease, held this view, and coming down to more recent times we find that Sir A. Garrod54 showed unmis- takably that the excess of uric acid, present in gout, was entirely absent in rheumatoid arthritis. It was classed by him under three headings, namely, acute, chronic, and irregular. The chronic form he further subdivided into general and local. Since then many have written on the subject, and their studies have brought about a
8 RHEUMATOID ARTHRITIS.
profound change in the prevailing views as to its nature. Senator 55 describes it under the name of " Arthritis deformans," which had previously been given to it by Virchow,56 and he believed that it was a true constitu- tional disease. Hutchinson 57 looked on it as the result of a rheumatic diathesis, caused by the blending of the elements of gout and rheumatism, now the one and now the other element predominating. In 1884 Sir Dyce Duckworth58 gave it the name of " Chronic rheu- matic arthritis," and thought it was a form of true rheumatism. Lane59 (A.), in 1884, thought that the changes in the joints were caused simply by wear and tear; and Ord,60 in 1885, considered it to be purely of reflex nervous origin. Spender,61 in 1888, pointed out some of the early nerve phenomena under the name of osteo- arthritis. In 1890 Dr. A. E. Garrod62 calling it " Rheumatoid arthritis" wrote a treatise on the subject ; also in that year Lane (H.) and Griffiths 63 pointed out the differences between rheumatoid arthritis, chronic rheumatic arthritis, and osteo-arthritis ; while in 1893 Forsbrooke 64 brought out his dissertation, and advanced the view that it was anaemia to which it and all the vaso-motor and trophic changes were due ; the joint changes he considered being due to trophic mal- nutrition ; and quite recently Dr. Brabazon66 suggested that it might be called "Pernicious anaemia," having reference more especially to the symptoms.
Such are the main points in the history of the disease, and one wonders that with such a mass of literature, having direct bearing on the subject, that we should have been so long in the dark, both with regard to its pathology and its aetiology, and, I am sorry to say, also with regard to its morbid anatomy. Yet such is the case. If it is granted that we are dealing with a disease by itself, one would look for some salient symptom or
INTRODUCTORY AND HISTORICAL. 9
symptoms, without which we would have no rheumatoid arthritis. This we find in the joints and nervous sys- tem. The joint symptoms are always the primary ones, the nerve phenomena being purely secondary, but their presence, in one shape or another, is so persistent that one can only regard them as essential elements of the disorder. The conjunction of symptoms is such as we find in no other morbid process. It is not merely occasional joint troubles, associated with nerve lesions, or vice versa, but it is a constant conjunction of certain symptoms, in a well marked sequence, referable on the one hand to the joints, and on the other to the nervous system.
Turning to the frequency with which it is met, I may say, that it is a common form of disease occurring, as one observer states (Haygarth), as often as 1 in every 310 patients, giving a percentage of 0*32. During the years 1893 and 1894 there were admitted 2,405 patients, of whom 432 suffered from rheumatoid arthritis, 1,558 from rheumatism, and 255 from gout, to the Bath Eoyal Mineral Water Hospital. It is more common in the poor and badly nourished, and is also more common in the cold damp parts of the globe than in either the dry cold or hot damp.
REFERENCES.
1. Landre Beauvais. — " Goutte Asthenique Primitif," 1800.
2. Heberden. — " Commentaries," 18047? —
3. Haygarth. — " Clinical History of Diseases," 1805.
4. Todd. — " On Gout and Rheumatism," 1848.
5. Deville. — " Bull, de la Soc. Anatom.," xxii. and xxiii., 1848.
6. Broca. — " Bull, de la Soc. Anatom.," xxv., 1850. s
7. Fuller. — " Rheumatism, Rheumatic Gout, and Sciatica,"
1852.
8. Charcot.—" These de Paris," 1853.
9. Cruveilhier. — " Anat. Pathologique," Liv. ix.
10. Adams.—" On Rheumatic Gout," 1857, and 3rd edit. 1873.
io RHEUMATOID ARTHRITIS.
11. Trousseau. — " Cliuique Medicale." ^
12. Virchow. — " Virchow's Archiv.," xlvii., 1869. ^
13. Garrod, Sir A. — " Gout and Rheumatic Grout," 1S76.
14. Spender. — "Osteo-arthritis," 1888. v'
15. Petrie. — Museum, Royal College of Surgeons, 1891.
16. Eve.—" Brit. Med. Journal," vol. i., 1890. V
17. Chiaje. — " Arthritis Deformans from Pompeii."
18. Virchow.— Loc. cit., p. 298. V
19. Moore.—1' Path. Soc. Trans.," 1883, xxxiv., p. 226. <
20. Lebert.— " Handbuch der Pract. Med.," 1859, ii., p. 874. ^
21. Sydenham. — " Opera," Sec. vi., cap. v. ^
22. Musgrave. — " De Arthritide Symptomatica," p. 24.
23. Haller. — " Elementa Physiologica," vi., p. 9. "*<'
24. De Sauvages. — " Nosolgia Methodica," class vii., order i. %
25. Landre Beauvais. — Loc. cit.
26. Heberden. — Loc. cit., chap, xxviii. >t
27. Haygarth. — Loc. cit. ?*■»
28. Chomel — " Essai sur le Rheumatisme ; These de Paris, "^
1813.
29. Scudamore— " On Rheumatism," p. 487, 1827.
30. Brodie. — " Diseases of the Joints," 1833. yk
31. Cruveilhier. — Loc. cit. X
32. Lobstein.— " Anat. Pathologique," ii., p. 348, 1833, S
33. Key.—" Med. Chir. Trans.," 1833, xviii., p. 208:
34. Robert Smith. — "Dublin Journal Med. Sciences," 1835, vi., >--
p. 208. V
35. Canton.—'4 London Med. Gazette," N.S., 1848, vi., p. 410. J*
36. Deville.— Loc cit., 1848, xxii., p. 272, xxiii., p. 141.
37. Broca. — Loc. cit., 1850, xxv., p. 435. V
38. Adams. —Loc. cit., 1857. -
39. Meyer.—" Midler's Archiv," 1849.
4.0. Weber. — "Virchow's Archiv.," Jan. 1858, p. 74. X
41. Leis. — Quoted Charcot " Syd. Soc. Trans.," "Maladies des
Viellards," p. 139. X
42. Cornil. — " Niemeyer's Internal Pathologie," vol. ii., p. 556,
(transl.).
43. Vergely.— " These de Paris," 1858.
44. Ranvier.— " These de Paris," 1865.
45. Sandifort. — " Museum Anatomicum," 1793.
46. Todd.— Loc. cit. X
47. Redfern.— " Edin. Monthly Journal," 1849. X
48. Fuller. -Loc. cit. y_
49. Charcot & Trastour. — " These de Paris."
50. Besnier. — "Diet. Enclyclop. des Sciences Med.," 1876, p.
155.
51. Homolle. — " Diet, de Med. et Chir. Prat." : Article, "Rheu-
matisme," 1882.
52. Lacaze-Dori.— " These de Paris," 1882.
53. Mathieu.— " These de Paris," 1884.
54. Garrod, Sir A.— Loc. cit. 1862—1876.
55 Senator. — " Ziemssen's Handbuch," 1875 and 1879. V«f
INTRODUCTORY AND HISTORICAL, n
56. Virchow. — Loc. cit. ^
57. Hutchinson. — " Pedigree of Disease," 1884, p. 126. J 7) *G
58. Duckworth.—" Heath's Diet. Prac. Surg.," 1886, i., p. 293. >
59. Lane, A,—" Path. Soc. Trans.," 18S^and 1886. y-
60. Ord.— " Brit. Med. Journal," 1884, ii., p. 268, and " Trans.
Clin. Soc," 1879. *
61. Spender.—" Osteo-arthritis," 1888.
62. Garrod, A. E. — " Treatise on Rheumatism and Rheumatoid
Arthritis," 1890. *
63. Lane & Griffiths.—" The Rheumatic Diseases " (so-called),
1890. *
64. Forsbrooke. -— " Dissertation on Osteo-arthritis, ;' 1893.
65. VidaL— " These de Paris," 1855.
66. Brabazon.— "Brit. Med. Journal," vol. i., 1896, p. 7237^
12
CHAPTER II. .ETIOLOGY AND PATHOLOGY.
Micro-organisms a Cause— Selective Action—Where Found — Heredity — Sex — Age —Catarrh of Mucous Membranes — Emo- tional Causes —Atmospheric Conditions — Injury — Rheumatism — Alkalinity of the Blood — Charcot — Pye- Smith — Hutchinson — Forsbrooke — Dystrophic Theory — Evidence in its Favour — Against it — Orel's Theory — Reflex Irritation — Functional De- pression— Toxic Conditions — Muscular Atrophy — Insufficiency of Theories — Micro-organisms — Effect on Nervous System — Erb — Muscular xAtrophy elue to Toxic Causes — Multipolar Nerve Cells — Ferrier — Folli — Condition of the Anterior Cornua— Muscular Selection — ♦Vaso-motor System — Pigmentation — Sweating — Tachycardia — Bezancon — Anaemia — Hunter — Sum- mary.
I. — ^Etiology. From the discovery, made by Dr. Wohlmann and my- self, no doubt remains, in my mind, that Rheumatoid Arthritis is caused by micro-organisms, which we have found to exist in the joint fluids and tissues, and which we, as far as our present knowledge extends, look upon as specific. How the micro-organisms gain access to the system is not at present known definitely, but they probably do so through some chronic catarrh of the respiratory, gastro-intestinal or genito-urinary systems. Such catarrhs are not far to seek in this disease. In not a few cases it has been traced, almost with certainty, to an attack of tonsillitis, and we know how common disorders of the intestinal and generative systems are. A catarrh of the mucous membranes acts by producing mucous abrasions, upon which the micro- organisms can settle ; by weakening the epithelial cells in favour of the parasite ; and also by weakening the
AETIOLOGY AND PATHOLOGY. 13
nutrition and vital energy of the body generally. With such conditions it is easy to see there will be little difficulty in the micro-organisms gaining access to the blood, and, having once obtained a footing in the circu- lation, they will pass freely to all the organs of the body. This accounts for the symmetry of the disease, and why one joint after another comes to be involved. The micro- organisms can now proceed to select a suitable nidus in which they may grow and propagate. Like all other pathogenic bacteria they exhibit a selective power, in their choice of a habitat, which never varies. What governs this selective power we know not ; but it appears curious, that out of all the sites to which they obtain access, they should, as far as we at present know, only choose the joints. We know, that in relation to different causes of disease, the various tissues of the body exer- cise the most markedly different influences, even though the cells constituting these various tissues have ori- ginally sprung from the same cell. This difference is not limited to the various tissues of the same species of animal, for, when we compare different species, we find that even the same organ or form of tissue may present the most marked differences in relation to the factors giving rise to disease. For example, we see how in man the liver is an inhospitable host to the bacillus of tubercle. But it is not so with the liver of the ox or the guinea-pig. Of similar import is the fact, that if we examine every one of the pathogenic microbes, we will find different species of animals presenting very varying degrees of susceptibility. Even in the case of such a disorder as anthrax, there are all varieties amongst the various species, from immunity in the frog, to extreme susceptibility, as in the mouse and guinea- pig. This variation in susceptibility applies not only to species, but to varieties and races of animals and men.
i4 RHEUMATOID ARTHRITIS.
It is well known that the white rat presents an almost complete immunity to anthrax, and that the Algerian sheep are much less susceptible than other breeds. A similar fact is observed in man in this respect, that negroes are, as compared with white men, singularly insusceptible to yellow fever.
Turning again to rheumatoid arthritis it may be noted that joints are specially liable to bacterial infection, vide such diseases as pyaemia and gonorrhoea. If, as seems likely, acute rheumatism is due to bacteria, or their products, we have yet further proof of this peculiar liability. In rheumatoid arthritis, as in acute rheu- matism, ulcerative endocarditis, etc., it is possible that the bacteria also grow on the endocardium and peri- cardium, as otherwise it is difficult to account for certain symptoms. This point has not yet been fully eluci- dated. It is probable that they grow freely in the lesions through which they gain entrance, and possibly also in other localities. So far we have no proof one way or another on this point, so must leave it for future consideration. In the joints themselves we have positive proof that the organisms grow and propagate freely, doing so not only in the synovial fluid and mem- brane, but also in the ligamentous, cartilaginous, and, to a less extent, in the bony structures. Their presence gives rise to acute inflammatory changes leading on to ulceration, erosion, and destruction of the hard as well as of the soft tissues. This process varies in intensity and, usually as the disease progresses, is accompanied by a coincident, but varying amount of reparative change which may end in a general hardening and thickening of bones, cartilage and ligaments. This change appears to occur either when the bacteria have exhausted the pabulum on which they exist, or else it is an attempt on the part of nature, to limit and shut off
.ETIOLOGY AND PATHOLOGY. 15
the disease. Possibly the production of toxic products may play some part in this matter. The presence of micro-organisms can be demonstrated in the joint fluids by staining reagents, and also in the tissues on section. The joint and heart symptoms (with possibly the gastro- intestinal and genito-urinary catarrhal symptoms), which are due to the direct action of the micro-organ- isms themselves, may therefore be regarded as primary or essential ; whilst those which are due to their indirect action, by the absorption of their products may be regarded as secondary or symptomatic. Although these latter vary in every case, not only in intensity and in nature, yet they would appear to have a common toxsemic origin ; and some symptom of this toxaemia is invariably present.
Let us now, for a moment, turn to those causes which are likely to bring the body generally into such a con- dition as to be susceptible to the attacks of those parasites, for we know that, in health, the tissues are able to resist all such inroads. As has been stated, the disease may be primary in its onset or else secondary to such diseases as rheumatism, gout, or other arthritic condition. Apart from these, the causes, which predis- pose to it, are all those which have, by some means or other, lowered the constitutional state. Of these causes the principal are : —
1. Heredity. — It is difficult to prove direct inheritance, not only on account of the difficulty in the diagnosis, but also on account of the confusion as to what the name rheumatoid arthritis means. It may happen likewise, even although the proper nomenclature is understood in the individual cases, that the disease may have passed over one or more generations. It may there- fore be described as occurring sporadically; and that, out of a family of brothers and sisters, some are affected, but
1 6 RHEUMATOID ARTHRITIS.
others have escaped. Heredity, therefore, is very hard to trace. It is known besides that an inherited ten- dency to disease does not in all cases manifest itself, in an exact reproduction of the morbid peculiarity of the parent, in the child ; but may tend to give rise to allied conditions. Thus, it may happen, that in those in- heriting an arthritic diathesis, in some rheumatoid arthritis may develop, in others gout, and in others rheumatism. Statistics go to prove that a certain dia- thetic predisposition to arthritic disease does exist. By this we mean a diathesis in general, not in special, and in all cases it is easier to trace and to prove this inheritance of a diathesis than of a disease itself. One member of a family may have gout, one rheumatism, whilst yet another rheumatoid arthritis. In the case of gout and rheumatism heredity has been clearly proved, and this is probably due to the fact that they are both diseases wrell known and have been readily recognised for ages, whereas rheumatoid arthritis has not. By some it has been said also, to be peculiarly liable to occur in those inheriting a tendency to phthisis. This is as one would expect. The rheumatoid micro-organisms would, in such cases, find a system weakened and unprepared to resist their inroads, and which would therefore in all probability fall an easy prey.
As a cause heredity was recognised early in the history of the complaint, for w7e find that Heberden,1 Adams,2 and Fuller,3 amongst the early observers, all mention it. Coming down to more recent times we find a history of heredity was obtained in 11 out of 41 cases by Charcot,4 and in 10 out of 45 by Trastour.5 These statistics are quite unreliable, however, as these ob- servers only regarded rheumatoid arthritis as one of the forms of rheumatism, and as such the family history was taken. GarrodG traced in 84 out of 500 a direct
^ETIOLOGY AND PATHOLOGY. 17
descent, giving a percentage of 16*8. The average per- centage of heredity, in rheumatism (taking the results of Fuller, Syers, Pye- Smith, Garrod, etc.), is 23*9. When we consider the inheritance of other forms of arthritic disease, in rheumatoid arthritis, the percentage is much greater. Garrod 7 gives a percentage of 432. On farther analysis he mentions that there was a history of gout in 20 per cent., whilst only 12*8 gave one of rheumatism. This is very remarkable, and I have quite failed to verify it. Sir A. Garrod and Sir Dyce Duck- worth point out that the disease is most common in female members of gouty families. My statistics do not carry this out, for taking one year at the Bath Koyal Mineral Water Hospital (1894-1895), I had 78 patients suffering from rheumatoid arthritis, and of these only 4 gave a history of direct inheritance. In none could gout be clearly traced. In several there was a history of rheumatism affecting a brother or sister, and in 12 affecting a father or mother ; but never one of gout that could be depended upon. In other years I have obtained such histories, but they are so apparently accidental that I have been quite unable to substantiate this theory. The class of patients, whose statistics I have taken of course may, to a certain extent, account for this, but not entirely. Heredity does not seem to render a patient more liable to be attacked in early life, but it does seem to affect the acuteness of the disorder.
2. Sex. — There can be no doubt that the disease is much more common in women than in men. Out of 78 cases 9 were in men, and the rest in women (11 • 5 and 88*5 per cent.). Gout affects men more commonly, whereas rheumatism does so in nearly equal propor- tions. Hay garth 8 found 1 man to 34 affected, and Garrod9 found that it occurred in 411 females to 89 males (82*2 and 17*8 per cent). As was pointed out by
1 8 RHEUMATOID ARTHRITIS.
Adams, Senator, and others, the joints most affected in men, are the larger ones, such as the hip or shoulder, and in women, the smaller ones. Charcot, Trousseau,10 Duckworth, and others, have also observed it to be more common in women. This frequency in women is almost certainly due to the frequency of some genito-urinary derangement, some abnormal condition of which is pro- bably one of the commonest roads by which the micro- organisms obtain access to the blood, and thence to the joints. In the case of children it is more common in boys than in girls — the younger the child the greater the proportion of males. As puberty is approached this diminishes until the proportion of females equals, and finally greatly exceeds that of males.
3. Age. — Much has been written about the age at which the disease most commonly commences. By most it is held to be essentially a disease of the early degenerative period. Many of the acutest cases occur, however, in young adults, and often even in children. Dr. A. E. Garrocl11 shows that the commencement of the disease steadily increases with each five-yearly period, until that between 45 and 50 is reached, after which the number rapidly falls. In males, on the other hand, the decrease does not occur until 70 has been reached, and in them also there is no steady increase, but two maxima exist, one between 30 and 35, and the other between 50 and 55. The special liability of women, between the ages of 40 and 50, is probably due to the occurrence of the climacteric. In women there are two great periods in life — the period of puberty, and that of the climacteric. The former is a time of great strain, both mentally and physically, not only on account of the new conditions which the reproductive organs have taken on, but also on account of the general bodily conditions induced thereby. It is a period attended by a general
^ETIOLOGY AND PATHOLOGY.
19
aptitude for disease, as there is a special connection between the physiological processes going on, and the general bodily health. At the same time women are liable for less obvious reasons to the attacks of disease of various kinds. The period of the climacteric is at the other end of life, answering in many respects to the period of puberty in being a time in which the whole system is in a state of unrest, unstable and ready to develop unhealthy tendencies. Unfortunately it is a degenerative process, and, from its very nature, we would expect to find it more productive of mischief. The sudden fall in the number of cases occurring after the menopause is probably due to the fact, that all uterine activity having ceased, there are fewer roads by which the micro-organism can gain access — at least its most common road is closed. It is almost certain that a climacteric occurs in men in a similar fashion, but it is not so marked, and probably occurs later in life. The following is an analysis of 78 cases : —
|
AGES OF FIRST OCCURRENCE. |
FEMALES. |
MALES. |
|
Between 10 and 20 „• 20 „ 80 80 „ 40 40 „ 50 50 „ 60 ,, 60 ,, over |
4 16 25 12 H 1 |
1 4 3 1 |
|
Totals |
69 |
9 |
4. Catarrh of the Mueous Membranes. — How far a catarrh of the mucous membranes of the respiratory, gastrointestinal, or genito-urinary systems acts, as a predisposing cause, it is hard to say ; but that it is through its agency that the micro-organisms finally
20 RHE UMA TOW AR THRIT1S.
gain a footing is almost undoubted. I have traced the onset of the disease in several cases, almost with absolute certainty, to chronic catarrhal tonsillitis ; several to the onset of dyspeptic conditions ; and a still larger number to the onset of genito-urinary troubles. It is a frequent follower of confinements, and, more rarely, begins during pregnancy. Uterine derangements are responsible for the onset of many disorders, but none more markedly so than rheu- matoid disease ; and how can we wonder at it, when we find, as a consequence of some local irregu- larity, women in a state of mental worry, anxiety, sleeplessness, pain, and nervous exhaustion, both their mental and physical powers being at their lowest ebb ? I)r. Ord laid special stress upon this fact, and I think it is well merited, though for different reasons. He noticed that, in certain instances, the disease in the joints was limited to one side ; and in these cases there was ovarian pain, and tenderness on the same side as the joint lesions. He also noticed paroxysms of pain occurred with the monthly periods. He considers these uterine and ovarian derangements to be the cause of the disease, through reflex action. To my mind, it is more probable that they only act as affording a lesion through which they may reach the circulation ; and, by the induced irritation and debility, render the system so lowered and impaired as readily to fall a victim.
In 78 cases, 1 was due to tonsillitis ; 4 occurred after confinements ; 1 during pregnancy ; and 1 after a mis- carriage.
In a large number there was irregularity in the monthly functions, but I rarely could trace a case directly to these disorders. Garrod says that 105 out of 176 were normal in their menstruation. Five occurred
.-ETIOLOGY AND PATHOLOGY. 21
soon after a confinement, 3 after miscarriages and 8 during pregnancy.
5, Emotional Causes. — The influence of these is not confined to the period immediately preceding the onset of the disease, but it also to a certain extent influences the progress of the disorder. Over and over again do we find patients who say they are worse after any anxiety or worry. The disease has been known even to arise after prolonged worry ; but in such cases worry probably only acts by lowering the tone of the constitution. Other mental causes assigned have been sudden shock and fright. Both Kohts12 and Leyden13 mention cases in which it occurred after severe shock, caused by the bursting of shells in time of war.
6. Atmospheric Conditions. — Eheumatoid arthritis is most commonly met with under those influences most favourable to the prevalence of catarrhal and inflam- matory affections of the air and digestive tracts, that is, on cold and damp soils with a variable temperature, and as we know at those seasons of the year, the spring and autumn, when these conditions are most likely to prevail. Professor Charcot regarded a combination of damp and cold as the most potent cause. He was of the opinion that the exposure, to such influences, must be prolonged, and that articular lesions did not necessarily arise until some time had elapsed. Many sufferers ascribe the onset of their complaint to dampness, and there can be no doubt that cold and damp often markedly increase the misery of the wretched patients. The disease is more common in Ireland than in Eng- land, and this is accounted for by the prevalence of damp in the former country. Adams14 has pointed out that it is specially common in Holland. Although a dry climate is least favourable to its development, it is not unknown in any locality. In this respect we are apt
22 RHEUMATOID ARTHRITIS.
to confound, and it is difficult to avoid confounding, its indirect effects as predisposing agents with its direct effects as exciting cause. Further, when we would test the relative influences of atmospheric conditions, our endeavours to arrive at a just conclusion are seriously hampered by the co- existence with them (but partly no doubt arising out of them) of peculiarities of habit, and modes of life, and other special conditions of unhealthi- ness. Out of 78 cases, 2 developed after getting wet, and 1 after a chill.
7. Injury. — Injury, as injury pure and simple, has not a marked effect on the occurrence of acute rheumatoid arthritis. In only a few cases have I been able to trace a direct history of its onset to traumatic injury, but if we look at it in its wider sense it comes to have a much more important bearing. In the joints an injury, in its immediate consequences, may appear so trifling as to merit little or no attention, yet it may, in its ultimate results, end in the crippling and loss of the use of an important member of the body. Occasionally, but more rarely, it appears to follow on some injury which has set up some acute inflammatory condition. In one case I found it occur subsequent to fracture of a patella, and whilst the patient was in the recumbent position in con- sequence of this fracture. A history of such direct injury, and its consequences, is rare. One more often hears of injury after a joint is diseased, and then the question of effect and cause comes to be a difficult one. If we regard injury as having a broader meaning, and look on it as any lesion of the joint structures may-hap caused by traumatism, may-hap by disease, then our idea of the importance of injury as a cause alters. In 78 cases 20 occurred after acute or chronic rheumatism. I here regard the injury caused to a joint, more or less of the nature of a direct injury, when caused
^ETIOLOGY AND PATHOLOGY. 23
by rheumatism, gout, gonorrhoea, or any other form of arthritis which may so frequently precede a rheumatoid onset. That rheumatoid disease frequently follows such attacks is not to be wondered at, when we remember the injury done to a joint by such an attack, and when we consider that rheumatism, and most other forms of acute arthritis, are probably caused by micro- organisms— at least, at present there seems to be good ground for believing that such is the case (15 and 36). Arguing then on analogy, we may assume that one form of organism may predispose to the attacks of another. What the exact mode of action in these cases is we know not ; whether they act by reducing the resistent power which normally exists in all tissues — but in this case more especially in the joints, or else of the blood, which, as is stated by, amongst others, Ewing17 and Foder,ls occurs from anything which reduces its alkalinity and thereby its germicidal power, we at present know not. Ewing found that normal blood serum is a powerful protective agent against the inroads of bacterial infection, and that toxines act harmfully, not merely by their direct effect, but also by lowering the resistant power of the blood against secondary infections. He found that snake poison, which in its nature belongs to the same class of poisons as those formed by bacteria, greatly lowers the blood's germicidal power. Dr. Fodor records a number of experiments showing the influence of the alkalinity of the blood on diseases produced by micro-organisms. Four series of experiments on ani- mals are first reported which show clearly that, by the administration of alkalies (sodium bicarbonate by the mouth or by subcutaneous injection), the power of resistance against infection with cultures of anthrax bacilli is greatly increased. The normal alkalinity of the blood was determined bv the examination of seven tv-
24 RHEUMATOID ARTHRITIS.
six healthy rabbits, and four experiments are reported
showing the increase in the alkalinity of the blood which
occurs after the administration of sodium bicarbonate.
He then records the results of a large number of
observations on the alkalinity of the blood in rabbits
after infection with the bacilli of anthrax, cholera,
typhoid fever, tuberculosis, and erysipelas. These
observations show that in the living organism, after
infection with certain bacilli, there is first an increase
of the alkalinity of the blood and then a diminution of
the same, more or less. If the infection is fatal, the
diminution of the alkalinity is marked and progressive ;
if not fatal, the diminution is slight, and is followed by
an increase of the same, in consequence of which the
alkalinity of the blood becomes permanently higher than
before the infection. Thus there exists a connection
between the pathological action of certain bacteria and
the alkalinity of the blood. Those rabbits having the
greater alkalinity of the blood, as well as those in which
the alkalinity of the blood is increased to a greater
extent alter infection, have greater power of resistance
against certain infectious organisms (anthrax bacilli)
than the rabbits in which the alkalinity of the blood
is less. It appears, therefore, that the degree of
alkalinity of the blood, as well as the power of the
organism to increase this alkalinity with corresponding
intensity after infection, is of essential influence upon
immunity.
I herewith append a list of the causes assigned in 38
cases out of 78 : —
After confinement ... ... ... ... ... 4
,, miscarriage ... ... ... ... ... 1
During pregnancy ... ... ... ... .. 1
Alter acute rheumatism ... ... ... ... 20
,, chronic rheumatism ... ... .. ... 1
,, getting wet ... ... ... ... ... 2
hard work ... ... ... ... ... 3
sETIOLOGY AND PATHOLOGY. 25
After, diphtheria ,, tonsillitis ... ,, influenza ... ,, fractured patella ... ,, concussion of spine „ necrosis of the jaw from caries of teeth
Total 38
In the other 40 instances the causes given were either too unreliable or could not be traced.
II. — Pathology.
Turning to the views which have, from time to time, been advanced as to its pathology, we find a variety of theories which I will shortly state and criticise.
i.— According to Charcot, and most French observers, it is only a secondary form of rheumatism, but as, in the majority of cases the disease arises as a primary one, we have no ground of this belief. It, undoubtedly, may arise as a sequela of acute rheumatism, or in fact of any acute arthritis; but to say it is only a form of rheumatism is, I think, grossly misrepresenting the disease, and its characteristics. One has only to look at its clinical characters, quite apart from its morbid anatomy, to perceive the difference. In this country it has always been regarded as a disease yer se, at least ever since its peculiarities were thoroughly appreciated, and, I think, it is hardly neccessary, for me here, to point out each individual difference, but will take it for granted that in this country this individuality is admitted.
ii.— Dr. Pye Smith i9 holds that the disease is often of a senile character. This is not often the case in true Eheumatoid, and something more than senility must exist, in the acute cases, as they mostly arise in the young or comparatively young.
iii. — Hutchinson 20 looks upon it as simply a result of the combined action of the rheumatic and gouty processes,
2 6 RHE UMA TOW A R THRU IS. '
now the one and now the other element predominating. He believes in a basic Rheumatic diathesis, capable of subdivision into off-shoots. In many ways such a theory is supported by facts ; but we must regard this basic diathesis as only a diathesis. The poison of gout is as different from that of rheumatism as they are both from that of rheumatoid arthritis. We are positive, however, that a certain form of diathesis does predispose to arthritic changes, but what these changes may be will depend on local conditions.
iv.— Forsbrooke 21 holds that the anaemia, which is present in this disease, is responsible for the joint and other changes. He states that at first, owing to the deficiency of oxygen in the blood, the vaso-motor centre in the medulla is stimulated, and by consequent con- strictions of the minute vessels supplying the joints and smaller nerves, the nutrition of these parts is interfered with. This deprivation of blood, which although at first functional in nature, may give rise to organic change. The stimulation of the vaso-motor centre, if prolonged, ends in exhaustion, followed by dilatation of the joint vessels and inflammation. Ingenious as this theory is, it rests on the assumption that anaemia is present before any of the joint or nerve troubles. This has not been found to be the case, so how can it be the cause ? Personally, although I have noticed anaemia in a large proportion of cases, it has not been invariably present, and it has certainly not been the first symptom. It is more likely that the anaemia is caused by the poison generating the disease ; and is therefore only a sequela, not a cause. The anaemia of rheumatoid arthritis has all the characteristics of a toxaemic anaemia, and is more fully considered elsewhere (p. 41).
v.— Remak, 22 Senator,23 Ord,24 Sir Dyee Duckworth,25 and many others, have all been of the opinion that
sETIOLOGY AND PATHOLOGY. 27
the disease is due to some abnormal trophic condi- tion, although they differ as to the cause being due to a primary lesion of the nervous system or only secondary to a lesion elsewhere. Most of them hold that the joint changes originate in a similar manner to those occurring in Tabes Dorsalis. But tabetic changes are due to a degeneration of the intermedio-lateral tract, with a corresponding degeneration of the peripheral nerves, and, as no such degeneration has yet been found in rheumatoid arthritis, we may probably safely assume that this argument is erroneous. This is what is called the Dystrophic theory. If due to trophic changes one would look for some gross organic lesion either in the central nervous system (a), or in the peripheral nerves (b) ; or else some reflex (c), nutritional (d) or toxic (<?) condi- tion might exist which could give rise to the necessary abnormal impulses.
(a,) If clue to a gross change in the central nervous system the lesion will, of necessity, be so extensive that we can think of no condition, which could possibly give rise to it, unless it be a blood one. A poison circulating in the blood is the most likely agent to affect the exten- sive area necessarily involved : for we must remember that the trophic influences which govern the nutrition of the joints, bones, and skin are under the control of the cord, the centre being probably situated in the inter- mediate grey matter, whilst that of the muscles is con- trolled by the anterior grey matter (probably the motor nerve cells). As the nerve endings have a structural continuity with the tissues, the nutrition of the tissue molecules depends on the nutritional condition of the nerve and nerve centres. So far no gross organic change has been detected in the central nervous system, except in three cases in which Folli 45 discovered an atrophic condition in the cells of the anterior cornua. Klippel, 36
28 RHEUMATOID ARTHRITIS.
according to Massolongo, observed somewhat similar changes, and in one case I have also observed alterations in the conditions of the ganglion cells. These conditions are, however, so altogether inextensive, and have been entirely confined to the motor ganglion cells, that one must reject the idea that they can originate such a wide- spread disorder.
Quite apart from the question of finding gross lesions the question is, can trophic abnormal impulses produce such lesions as we find in the deseased joints ? I hold that they cannot. They can, and undoubtedly do, pro- duce muscle, integumentary, and other nutritional changes. But can they bring about such joint alterations? In tabes the joint changes are altogether different in nature and appearance, and depend on a definite lesion. In syringo-myelia they are also different. In ataxic paraplegia, and many other forms of nerve disease, we also see arthritic changes, but, on the one hand, they are all accompanied by definite nerve lesions, and on the other they seldom present more than swelling, and effusion into the joint. A wasting, with some slight re- parative change, one might possibly get ; but it appears to me inconceivable that such extensive inflammatory lesions could arise without some sure and certain guide to a lesion, easily recognisable on both macro- and microscopic examination. Marie,52 and 53 one of our most accurate observers, on this subject says that the patho- logical anatomy of tabes and rheumatoid arthritis is quite distinct, and that although points of difference might be mentioned, in his eyes, this is not necessary.
(b, ) If due to a gross lesion in the nerves themselves we would expect to find symptoms of nerve degeneration, in all and every case of rheumatoid disease — but this is not the case. In only a certain number is an unmis- takable neuritis present, and this so often markedly
^ETIOLOGY AND PATHOLOGY. 29
follows the arthritis that there can be no doubt it is secondary in its nature. This neuritis may be caused by the existing joint inflammatory process, or else it may be due to the action of toxines circulating in the blood. It is undoubted that toxines may thus give rise to such a condition, thereby showing not only a -selective action in the parts acted on, but also a peculiarity in the acting virus. MM. Pitres and Yaillard 26 have found well- marked neuritis in several cases, and they believe that there is a distinct relationship between the presence of this neuritis and the development of the trophic changes. It must be noted that although finding marked changes in the nerves supplying the wasted muscles yet they found none in those supplying the articulations. On the other hand Duplay and Cazin 27 found an inflammatory condition of the nerves supplying the affected joints. As will be seen, the results of such examinations have hitherto been so uncertain and contradictory that one must assume there is no constant occurrence of neuritis. This agrees well with all clinical experience, and with what one would expect from the nature of the disease.
(c,) Dr. Orel's 2S view of the disease is that it is entirely caused by reflex action set up by some uterine or other visceral derangement. Although admitting that the reflex influences, from the joints, may cause trophic changes in the skin and muscles, and apart from the fact that the disease occurs in men free from genital irritation in a proportion of one to eight women, one can- not believe that acute organic changes in the joints can be set up by such reflex action. Trophic lesions have been traced to injuries of the nerve centres, and of the nerves leading to the part, but not to reflex irritation, and there is no evidence that reflex irritation can give rise to such lesions of the nerves or nerve centres. Dr.
30 RHEUMATOID ARTHRITIS.
Orel believes that the irritation engendered in the uterus causes impulses to be conveyed to the central nervous system, which in turn give rise to other morbid impulses which are conveyed, by the peripheral nerves, to the joints, etc., and there cause the changes which we know by the name of rheumatoid arthritis. Although denying that they can cause organic mischief, yet I admit, that by causing debility and anaemia, they may so lessen the natural defences of the joints that these may readily become the prey of the poison, which causes rheumatoid disease. They must therefore be borne in mind as potent predisposing causes.
(d,) Is this disease then, as we cannot explain it other- wise, due to a functional depression of certain areas of the cord or of some of the peripheral nerves ? It is pos- sible to conceive that deficient nutrition of certain areas might set up trophic changes, and as this condition is likely to occur in all debilitating states we would look for it as a sequela of acute illness, or else in those who are congenitally weak. Dr. Garrod 29 states that out of 500 cases of rheumatoid arthritis he traced a family history of arthritic trouble in 216. Eheumatoid disease prac- tically only occurs in debilitated people, and is often a sequela of some acute condition which has left impair- ment or enfeeblement of the nutritional state, both of the body generally and of the nervous system locally. This, however, may be said of any disease, and is only therefore of negative value ; what is of more importance is the fact that it would be against all experience to find permanent symptoms, such as are seen in this disease, arise without some slight change in the ultimate nerve elements, which might be recognisable on microscopic examination. If due to nutritional changes we would look for some alteration in the medulla as being that portion of the motor path winch has the least nutritional
AETIOLOGY AND PATHOLOGY. 31
stability. Could we explain the joint symptoms by other means, we might readily conceive how nutritional changes might be set up which would account for the trophic and vaso-motor symptoms. In this probably lies the truth.
(e,) With regard to the toxic action of bacterial poisons on the nervous system it is of importance to note that nutritional, as well as actual organic changes, may result. The nerves under these circumstances are usually more liable to be affected than the spinal cord. Toxic agents, however, often exhibit a remarkable selective action, and as yet we do not know what are the influences which de- termine such susceptibility. For example, take the case of alcohol, which being itself the result of the growth of organisms, and being almost as low in the scale as the bacterial toxic agents, gives rise to many and diverse nerve conditions. To admit the action of toxic poisons on the nerve system and exclude that of their originators on the local joint structures would be illogical.
Having thus disposed of the more common views, let us now consider some other arguments which have, from time to time, been advanced to prove that the disease is due to a nerve disorder. Thus we find Dr. Garrod 30 quoting several cases where it developed after a shock to the nerve system. Again, Dr. Spender 31 mentions various nerve phenomena which he has noticed occurring at the same time, if not previous to the joint lesions. He mentions such symptoms as pigmentation of the skin, local sweatings, neuralgia, tachycardia, etc. He also mentions cases where " bulbar warnings " were noticed quite early in the disease, 3l and 32 and which progressed to only terminate with the death of the patient. He maintains that the arthritis does not cause the atrophy, and that what is called " arthritic muscular atrophy," has nothing to do with that of rheumatoid arthritis. He
32 RHEUMATOID ARTHRITIS.
says the muscular atrophy of rheumatic arthritis is a reflex tropho-neurosis, a pure irritation of the articular nerves, causing atrophy through the anterior cornua of the cord. The most difficult point to explain in rheuma- toid arthritis is this muscular atrophy. It is one of the most important and earliest symptoms, and is usually, from the very first well marked. It extends to the whole of a muscle, and not only to that part which is in contact with the joint, or distal to it ; and it follows so closely on the first appearance of the joint- trouble as to preclude the possibility of extension of inflammation to the nerves. It is found that the extensors are principally affected, but not exclusively so. The selective character of the atrophy is a sufficient proof that the changes in the muscles cannot be set down to mere disease. It has usually been attributed to some reflex nerve influence having its origin in the peripheral nerves of the affected joints. This has been suggested by Paget, Vulpian, 33 Charcot, and others. They argue that, assuming a derangement of the nutrition of the motor cells of the cord determined by the morbid impulses from the joint- nerves, the influences from the motor cells will, in all probability, determine the alterations in the muscle nutrition. This theory, they hold, is supported by the fact that by the previous division of the posterior spinal roots, 34 and 35 wasting of the muscles can be prevented in arthritis of the knee-joint artificially produced. Such an argument cannot be admitted to apply to the atrophy of rheumatoid arthritis, as this is a bacterial disease and the experimental arthritis was not. It is known that disease in a joint may set up spinal trouble,36 e.g., primary spastic paraplegia, and from this we gather that the influences from the joint nerves act on the controlling structure of the muscle reflex centre. The muscle reflex centres seem also to be under the influence of other
ETIOLOGY AND PATHOLOGY. 33
centres, because if there be disease higher up they also pass into a condition of increased activity. The path which determines their activity is the pyramidal tract. Other theories are that the atrophy is caused by reflex vaso-motor spasm : this view was advanced by Brown- Sequard; whilst Striimpell37 suggested that this inflam- mation might have spread from the joints to the muscles, setting up a myositis ; and in one class of cases it has been noted by Sabourin 3S that inflammation does spread from a joint and, affecting the nerves as well as the muscles, gives rise to an ascending neuritis. If neuritis has occurred the muscle fibres will be found to be narrowed, and the shorter muscles to have undergone proliferation.39 Vallat 40 noticed such a change in the muscle fibres, but he found that the motor nerves were normal. These changes were all microscopical.
We are now face to face with a difficulty. We must either admit that the disease is one depending entirely on an abnormal nerve condition, or else we must formu- late a new theory as to its causation. The nerve theory is quite unsatisfactory and unsatisfying. It explains in a sort of way many of the symptoms, more especially the skin changes, and muscular atrophy ; but it leaves alone, except for a half-hearted sort of attempt, the joint condition. Owing to our want of knowledge, as to the morbid processes which govern the vaso-motor, and trophic impulses, we have been unable hitherto to closely criticise any theory advanced with regard to their method arid mode of action, especially in cases where only some abnormal disturbance of their functional activity exists. Without the joint lesions we should have no rheumatoid arthritis, and therefore unless a theory can explain this fact we have no right to consider it perfect. It has been mentioned already that many observers hold the changes to be similar to those which occur in tabes ; but are they?
3
34 RHEUMATOID ARTHRITIS.
To me they appear not to be so — they differ in appearance, in minute anatomy, and also in clinical history. In tabes the joint changes are due to a descending degeneration of the nerves, a change always found when looked for, and therefore they differ in origin essentially from those of rheumatoid disease. To my mind this fact invalidates the whole argument.
*Turning then to the Pathology of the disease, as I un- derstand it, and have already stated, we have a disease due to the presence of micro-organisms found in the joint fluids and tissues, and which must, until disproved, be regarded as specific. How these micro-organisms gain access to the blood is not definitely known, but they probably do so through some chronic catarrh of the gastro-intestinal or genito- urinary systems, and such catarrhs are usually close at hand. In not a few cases, as I have already mentioned, it has been traced, with almost absolute certainty, to the tonsils. Having gained a footing in the circulation, the micro-organisms pass freely to all the organs of the body — thus explaining the symmetry of the disorder, and why one joint after another should be involved. They now proceed to select a suitable nidus for their growth, and, like all other pathogenic bacteria, they exercise a selective power in their choice which never varies. What governs this selective action is not known, but it appears curious that out of all the sites to which they gain access they should, as far as we at present know, only choose the joints for their habitat. I may again note that joint tissues seem specially liable to bacterial infection, vide such diseases as pyaemia and gonorrhoea. It is possible that the endo- cardium and pericardium are also liable to their attacks, as otherwise it is difficult to account for the symptoms referable to those tissues. Probably also the micro-
* This portion appeared in the Lancet, April 25th, 1896.
^ETIOLOGY AND PATHOLOGY. 35
organisms grow, and propagate, in the lesions through which they gain access to the circulation, giving rise to those local catarrhs so common during the course of the disease. Owing to the want of post-mortem material, these points must be left for future consideration. In the joints, Dr. Wohlmann and I found positive proof that the micro- organisms grow, and propagate, doing so not only in the synovial membranes, ligaments, etc., but also in the bone- marrow, and cartilaginous structures. Their presence gives rise to acute inflammatory changes leading to ulcerations, erosion, and destruction of the hard, as well as of soft joint tissues. This process varies in intensity, and usually as the disease progresses a co-incident, but varying amount of reparative change is seen, which ends in general hardening and thickening of both bones and ligaments. The presence of micro-organisms can be demonstrated in the joint fluids by staining, and in the tissues on section. The joint and heart symptoms are those only which would appear to be due to the direct action of the micro-organisms, and may therefore be regarded as primary or essential ; whilst those which are due to their indirect action through their products, (definite chemical substances produced by all bacteria), may be regarded as secondary or symptomatic. These latter may vary in every case not only in intensity, but in nature; yet they would all appear to have a common origin in toxic action. During their life cycle these, like all other bacteria, give rise to poisonous products which being absorbed pass to the body generally, and what is of more im- portance, to the nervous system locally. Here again we see either a peculiar selective action on the part of the products acting on, or else a peculiar susceptibility of the parts acted on. In this, as in other bacterial diseases, we have no definite proof that it is not the micro- roganisms themselves which cause the changes in the
36 RHEUMATOID ARTHRITIS.
nerve system, but all argument, analogy, and proof are against their doing so ; and, therefore, I may assume that such is the case in this disease. As evidence, we have the experiments of MM. Vidal and Bezanc^on 41 which show that several micro-organisms have the power of producing central nerve degeneration, and although they have been isolated from the blood, yet they have not been found in the central nerve tissues. They therefore appear to act by the elaboration of a soluble poison. Such would appear to be the case in rheumatoid disease. With regard to the toxic action of bacterial poisons on the nervous system, it is of importance to note that nutritional as well as actual organic changes may result. Although these nutritional changes are more common in the peripheral nerves, yet toxic agents exhibit such a re- markable selective action, and as we do not, as yet, know what are the influences which determine such susceptibility, it would not be surprising to find similar changes in the central nerve system. From every side evidence is gathering that what may at first be only a depression of the function of a certain centre or group of centres may end, if the irritation be severe, whether it be applied locally in the shape of a toxine or reflexly, in becoming an organic degeneration, not only of that centre or group of centres, but also of the nerve path or paths descending from them. Erb 4'2 speaking of pro- gressive muscular dystrophy, says there is a possibility that the disease starting in a functional disturbance might in the long run become associated with a coarse lesion of the spinal centres. He says there are many things about such a condition which agree well with this supposition. From this we may conclude that bacterial poisons act on either the peripheral or central nerve system, producing, in the one case, an organic lesion, and in another, only a functional depression.
.■ETIOLOGY AND PATHOLOGY. 37
Having accounted for the joint- symptoms by the action of the micro-organisms, let us look at the rheumatoid symptoms due to absorption of their products and action on the nerve tissues. The principal, and most difficult symptom to explain, is undoubtedly the muscular atrophy which occurs not only early in the disease, but is one of the most constant symptoms. The atrophy extends to the whole of a muscle, and not only to the part which is in contact with the joint or distal to it, and it follows so closely on the first appearance of the joint troubles as to preclude the possibility of an extension of the inflamma- tion from the joint to the nerves or muscles. Apart from true rheumatoidal atrophy we have atrophy occurring as a consequence of a neuritis distinctly secondary in character, and only seen in the later stages. Such a condition has been described by Sabourin, 38 Vallat, 40 Striimpell, 37 Duplay and Cazin,27 and is of less interest than the true rheumatoidal atrophy, and can be easily distinguished from it as it presents all the characters of ordinary muscular atrophy in the re-action of degenera- tion and alteration in the muscle structure, etc. This is absent in the true form in which the extensors are prin- cipally, but not exclusively affected. The selective character of the atrophy is sufficient proof that the changes cannot be set down to mere disease. How then do we account for it ? I think that it is due to an abnormal condition of the multipolar nerve cells in the anterior cornua.* It is reasonable to suppose that given a soluble
* The path of motor innervation is composed of two portions, (a) the pyramidal cell with its dendritic processes, and centri- fugal or axis cylinder process which courses along the pyramidal tract, and ( bj the spinal multipolar cell with its processes, and axis cylinder process ending in the muscle fibre. It has been shown by Golgi's43 method of staining that the pyramidal axis cylinder ends in an arborescence which merely comes into contact with the spinal cell or interlaces with its dendritic processes, and there is no actual continuity.
38 RHEUMATOID ARTHRITIS.
poison circulating in the blood, some areas in the central nerve system should be affected, and these all the more especially as they are in all probablity predisposed to it by reflex irritation from the joints. That such an irrita- tion does occur has been stated by many observers, and has been even said to be sufficient to cause the atrophy itself (Paget, Vulpian, 33 Charcot, and others). It has been argued that, assuming a derangement of the motor cells of the cord determined by the morbid impulses from the joint nerves, the influences from the motor cells will, in all probability, determine the alterations in the muscle nutrition. In the light of the discovery of the micro- organisms, and of recent observations with regard to the action of toxines on the nerve system, we may disregard this reflex irritation except in so far as only to regard it as a predisposing cause. On turning again to the cells themselves, we find according to Ferrier 44 that the cell body with its nucleus is primarily concerned in the nutrition of the motor nerve, and its correlated muscular fibre, while the dendritic processes serve to convey incitations to functional activity. He also states that lesions of these processes may cause paralysis with all the symptoms of a spinal paralysis, but with no muscular degeneration. If such a condition can exist, might we not consider it possible that by the action of a toxic body, the cell's action might by itself be so lowered or held in abeyance that nutritional changes in the muscles would ensue without much disturbance of the conductive faculty of the processes, and also without any degeneration of the muscle beyond wasting. In progressive muscular atrophy we have a slowly progressive lesion of the ganglion cells, and their prolongation in the axis cylin- ders of the nerve fibres. Might we not have on a modified scale such symptoms if, instead of a complete destruction of these cells, we had only a depression of their function?
ETIOLOGY AND PATHOLOGY. 39
In fact such a condition must exist, as we cannot other- wise account for the atrophy either by reflex or direct toxic action. The cell's vitality must be lowered. In one class of cases, of which those mentioned by Dr. Spender 46 may be taken as typical examples, we must assume that the action on the cells has been so great as actually to give rise to a distinct lesion, and this spread- ing upwards in the pyramidal tract, has finally come to affect the bulbar neuclei. Folli's 45 discovery of atrophy of the motor cells, goes a long way to confirm this theory. What was probably only at first a depression of function due to the vascular changes set up by the rheumatoid toxine had apparently, in the long run, become actual organic change.
With regard to the selective site of the muscular atrophy, we find Dr. Ferrier 47 saying, "It is not unreason- able to suppose that the degree of representation, and therefore the trophic strength, of the extensors in the anterior cornua is less than that of the flexors, while such extensors as have the most numerous connections with the spinal segments would have a greater vital resistance than those whose segments are fewest." From this we may deduct that those muscles with the lowest trophic representation will be those which are first, and most affected, in any disease which lowers the vitality of the nerves and nerve centres. Duplay and Cazin 4S have suggested that it is due to the anatomical rela- tionship between the nerves which supply the joint corpuscles, and those which supply the affected muscles. This does not explain it all however, and Dr. Ferrier's explanation seems the more probable, and the more easily understood, especially if we add that reflex im- pulses may possibly help in the selection.
It has been proved that certain toxines have the power of producing changes in the vaso-motor system, and also
40 RHEUMATOID ARTHRITIS.
in the trophic condition of the skin. It is thus that we account for the local sweatings and pigmentation. We know that normal pigment is formed from a particular product of metabolism of the cutis, being formed both in the ordinary epithelial cells and in the connective tissue cells. These connective tissue pigment cells are the regulators of the metabolic process, as they consume the surplus pigment-forming substance. The abnormal pig- mentation of rheumatoid arthritis is probably due to a local increase in the formation of the normal pigment, consequent upon some abnormal trophic innervation, and to a deficient consumption of the surplus by the connective tissue cells. The vaso-motor changes are in all probability due to the centre situated in the cells, in the intermedio-lateral tract, being affected in a similar fashion to those in the anterior cornua. One of the greatest points of interest is the tachycardia. Bezanc;on 49 states that tachycardia may in some cases be due to pressure on the vagus, but he suggests that more often it is due to the absorption of certain toxines. He cites the case of the bacillus tuberculosis, and also of certain staphylococci, streptococci, etc., of the secondary purulent infection so common in phthisis. Bouchard obtained from tuberculin a substance to which he gave the name eetasine, which had the property of producing dilatation of the vessels. Toxines, with similar powers, have been obtained from the product of the bacillus pyocyaneus by Charrin and Gley ; and from those of the staphylococcus aureus by Arloing. By acting as vaso-dilators these substances would tend to produce tachycardia, since the heart tends to act more rapidly as the peripheral friction diminishes. In other cases the toxines, by giving rise to a neuritis of the vagus may cause it. Vierordt in a case of Phthisis found such a neuritis, as evidenced by a great number of vagus fibres having undergone degeneration
AETIOLOGY AND PATHOLOGY. 41
and atrophy. With regard to the local sweating, it is probably due to paresis, caused by the toxine acting on the sudoriferous, and vaso-motor centre of the bulb. Similar action is seen in influenza (Semmola 51).
It has been found by Hunter 50 that, in all probability, pernicious anaemia is caused by the presence of bacterial poisons, just as it has been found to occur from the presence of cadaveric poisons, and analogous ferments. Such being the case it requires little imagination to conceive that a similar process may occur in rheumatoid arthritis. These bacterial poisons would seem to act by a hemolytic process which is specially limited in its action to the portal blood.
With regard to this anaemia there are some points of interest. These are the diminution of the haemoglobin value of the red cells and the increase of the white. Forsbrooke also notes this diminution of the haemoglobin. According to Ostler we have three classes of anaemia : —
(1,) Those in which the percentage of haemoglobin in each corpuscle remains the same, and the percentage of colouring matter corresponds to the percentage of the corpuscles. This is usually seen in anaemia due to haemorrhage, or arising from some organic disease. It may be noted that Laker 54 and Mackenzie 55 both point out that in malignant disease the haemoglobin value is decreased. The former states that from this fact alone one can diagnose the nature of the tumour, at least in so far as to say it is malignant or benign.
(2,) Those in which the haemoglobin is reduced out of all proportion to the reduction of the corpuscles, so that the individual value of each red cell in colouring matter may be greatly lowered. Chlorosis is the typical example of this class.
(3,) Those in which the percentage of haemoglobin is increased, and in which, therefore, the anaemia is not so
42 RHEUMATOID ARTHRITIS.
great as the reduction would appear to indicate. This is seen most markedly in pernicious anaemia.
In rheumatoid arthritis, then, we have to do with an anaemia belonging to the second class — in fact an oligochroniaemia.
We have now to ask ourselves why, in one form of anaemia, the haemoglobin value should be lessened, and in another increased ? Where it remains constant it is probably due to a loss of blood as a whole, whereas, in the other cases, it must be due to some abnormal con- dition having a direct influence on the blood cells or their contents. We know that anaemia implies a want in the adjustment between the gains and the losses of' the blood — defective haemogenesis or excessive haemolysis, the former depending upon deficiencies in quantity or quality of the food, insanitary surroundings or mode of life, inherited or aquired defect in the haemo- poietic viscera etc., and the latter on the processes of fever and inflammation, or to the presence of deleterious substances in the blood. With the former condition we have nothing to do. It would appear as if most forms of anaemia in which destruction of the red cells and their contents is the typical feature, must depend, for their occurrence, on some substance, harmful to their existence, circulating throughout the system. Dr. Hunter 56 says that blood destruction is of two kinds — (a) passive, which is the ultimate destiny of the red corpuscles, and which being a process of natural decay is evidenced by the presence of pigment in the spleen, liver and bone- marrow ; and (b) active, in which the haemoglobin escapes from the corpuscles into the plasma, and is in great part excreted by the liver as bile pigment. In health no trace of this breaking up and excretion of free haemoglobin is found, but in such a disease as pernicious anaemia there is abundant evidence in the liver cells.
ETIOLOGY AND PATHOLOGY. 43
This has been found not only in pernicious anaemia but also in malaria, and as the result of certain poisons which destroy the blood. Now, this destruction of the blood would not appear to take place so much in the liver as one would expect, as in the spleen and to a less extent in the gastro-intestinal capillaries. This Hunter has demon- strated by many beautiful experiments. He found that almost all haemolytic process was stopped by removal of the spleen, whilst experimenting with toluylenediamin. The chief function of the liver would, therefore, appear to be the disposal of the products of haemolysis. He goes on further to show that certain substances, such as toluylenediamin, act on the blood indirectly and depend for their effect on the action of certain cells and especially of those of the spleen ; whereas such substances as pyro- galic acid, glycerine, distilled water, etc., act directly, and depend on the quantity injected for their effect.
This, however, does not help us much in solving the question as to why, in one case, the same class of poison should produce an increase in the haemoglobin value, whilst in another it diminishes it. Are we to suppose that each individual poison possesses a selective action, and that it has the power of picking out one constituent only, of the blood, for special attention ? This is possible from what we know of the action of bacterial poisons, but it is hardly probable. It appears to me more likely that the different classes of bacterial poisons will have different effects — thus the toxic albumens may have the power of dissolving out the haemoglobin without destroy- ing the cell (see the action of snake poison and that of malaria) and the ptomaines may be more destructive to the life of a corpuscle than to its contents.
In rheumatism we have an acute disease which is most probably due to an infective organism (Newsholme) 57 and, in which, Dr. Garrod 5S finds a loss of the red
44 RHEUMATOID ARTHRITIS.
corpuscles with a corresponding loss of haemoglobin — the corpuscular value remaining constant. In some cases, daring the course of the disease, there is, however, a tendency to a decrease in the corpuscle value of a tran- sitory nature, but which may become more permanent during convalescence, producing a more or less chronic anaemia. In malaria, a disease due to an infective protozoa in all respects resembling a bacterial infection,60 we have, according to many observers (see Mannaberg,61 Evans,59 etc.), a reduction in the haemoglobin value, especially after the paroxysms. Mannaberg says that " for several days after the last paroxysm of fever the proportion of haemoglobin still fell." He gives as explan- ation of this the supposition that the haemoglobin is dissolved out by the parasitic poison, dissolved in the liquor sanguinis. Surgeon Evans 59 notes a reduction in the number of the red corpuscles, and also of the haemo- globin— the loss of the latter exceeding that of the former. He found no change in the number of the white corpuscles. Finally, in pernicious anaemia, Dr. Hunter maintains that the anaemia is due to the presence of bacterial poisons acting on the blood in the portal capil- laries, thus causing an anaemia in which there is an increase in the haemoglobin value of the individual cells. I take it that in the first disease, as there is no increase in the number of the white corpuscles, we are dealing with a pure toxaemia — the bacteria themselves not entering into the blood. And in the second we have a mixed cause — the parasite not only destroying the cells and their contents by their presence, but their toxines, by dissolving out the haemoglobin, produce a diminished haemoglobin value. And in the last case we are probably dealing with an alkaloidal poison absorbed from the intestinal canal. According to Cohnheim 62 certain sub- stances, of which snake poison is one, has the effect of
vETIOLOGY AND PATHOLOGY. 45
dissolving the blood corpuscles, and Meragliano 63 states that there are certain pathological conditions in which the blood serum exercises a destructive influence upon the red cells, which causes them to give up their hemo- globin to the menstruum, and that it then disappears from the blood. In the present state of our knowledge one does not like to dogmatise, but it would appear to me as if the two classes of bacterial poisons (ptomaines and albumoses) had each distinctive actions. In rheuma- toid arthritis we are dealing with a disease in which the micro-organisms exist in the blood, but they, as far as I know, do not live on it as do the malarial parasites, and that probably, therefore, the anemia is to a great extent due to their toxic products, dissolved and circu- lating in the blood.
The increase in the number of white corpuscles is of interest, as it is found in most infective conditions, and according to Hunter 64 the increase is roughly propor- tional to the severity of the disease. Habershon 65 says he has noticed an increase, not only after the introduc- tion of alkaline carbonates, but also from the presence of toxines in the blood. Should bacteria themselves be present, the destruction of the red cells will probably be greater and occur sooner than where their products only exist.
REFERENCES.
1. Heberden. — " Commentaries," Appendix, p. 417.
2. Adams. — ■" On Rheumatic Gout."
3. Fuller. — "Rheumatic Gout and Sciatica," note, p. 335.
4. Charcot.— " Maladies des Vieillards," 2nd Ed. p. 223.YL
5. . Trastour. — "Du Rheumatisme," 1853.
5. Garrod.— " Rheumatism and Rheumatoid Arthritis," p. 238.
7. Garrod. — Loc. cit., p. 239.
8. Haygarth. — " Clin. History of Diseases," 1805.
9. Garrod. — Loc. cit., p. 240.
46 RHEUMATOID ARTHRITIS.
10. Trousseau. —" Clin. Med.," 1865. (Syd. Soc. transl.).
11. Garrod. — Loc. cit., p. 241.
12. Kohts.— " Berlin klin. Wochenschr.," 1873, p. 304.
13. Leyden. — " Klinik der Riickenniarks-krankheiten,'' 1874.
14. Adams. — Loc. cit., p. 15.
15. Sahli. — " Deutclies Arch, fiir Innere Medicin," 1893.
16. Nevvsholme. — " Lancet," vol. i., 1895, p. 661.
17. E wing.— "Lancet," vol. L, 1894, p. 1&36.
18. Fodor.— " Centralb. f. Bakt. u. Parasitenk," Feb. 28, 1895.
19. Pye Smith. — " Guy's Hospital Reports," 1874, xix
20. Hutchinson.—" Pedigree of Diseases."
21. Forsbrooke. — " Dissertation on Osteo-Arthritis."
22. Remak.— " Deutsche Klin." 1863.—" Med. Centralzt.," 1861.
23. Senator. — " Ziemssen's Handbuch," 1875 and 1879.
24. Ord.— "Brit. Med. Journal," vol. ii., 1884, p. 268.
25. Duckworth.—" Brit. Med. Journal," vol. ii., 1884, p. 263.
26. Pitres and Vaillard.— " Rev. de. Medicin," No. 6, 1887. *
27. Duplay and Cazin. — "Arch. Generales," January, 1891.
28. Ord.— Loc. cit.
29. Garrod. — " Treatise on Rheumatism, etc." p. 239.
30. Garrod.— Loc. cit., p. 287.
31. Spender. — " Early symptoms of Osteo-Arthritis."
32. Spender.—" Brit. Med. Journal," vol. i., 1894.
33. Vulpian. — " Lecons sur 'lAppareil Vaso-moteur," 1875.
34. Raymond—" Rev. de Medicin," 1890, p. 374. V
35. Hoffa.— " Volkmann Klin. Vortrage," 1892.
36. Gowers. — " Diseases of the Nervous System," p. 443.-'<» 36a. Massolongo. — "Riforma Medica," vol. ii., 1893, p. 159.
37. Strumpell.— " Munchener Med. Wochensch.," 1888.
38. Sabourin. — " These de Paris," 1873.
39. Darkschewitsch.— " Neur. Cent," 1891, p. 353.
40. Vallat.— " Arch. Generales," 1877.
41. Vidal and Bezaneon. — " Annales de l'lnstitut Pasteur,"
February, 1895.
42. Erb. — "Progressive Muscular Dystrophy."
43. Schafer. — " Brain," vol. xvi., p. 147.
44. Ferrier.— " Brit. Med. Journal," 1893, vol. ii.
45. Folli.— "II Policlinico," December, 1894.
46. Spender.—" Brit. Med. Journal," 1893.
47. Ferrier. — Loc. cit.
48. Duplay and Cazin. — Loc. cit.
49. Bezaneon.--" Revue de Medicin," January, 1894.
50. Hunter.— " Practitioner," 1890 and '89, and "Brit. Med.
Journal," vol. ii., 1892.
51. Semmola. — " Transl. of the Academie de Medicin," 1891 —
1892.
52. Marie P. — " Lectures on Diseases of the Spinal Cord " (Syd.
Soc), p. 236.
53. Marie P. — Quoted Souza Leite in thesis on " Acromegaly,"
(Syd. Soc.) p. 77.
54. Laker.—" Centralb. f. d. Med. Woch.," 1S87, p. 405.
oo
JETIOLOGY AND PATHOLOGY. 47
Mackenzie. — "Brit. Med. Journal," 1891, vol. i.
56. Hunter.—" Brit. Med. Journal," 1889, vol. ii.
57. Newsholme. — Loc. cit.
58. Garrod.— " Brit. Med. Journal," 1892, vol. i., p. 335 and 1139.
59. Evans.—" Brit. Med. Journal," 1891, vol. i., p. 759.
60. Mannaberg. — " Malarial Parasites," (Syd. Soc.,transl.) p. 389.
61. Mannaberg. — Loc. cit., p. 385.
62. Cohnlieim. — " Lect. on General Pathology," (Syd. Soc.
transl.) vol. i., p. 474.
63. Meragliano. — " Berlin Idin. Woch.," 1892, August 1.
64. Hunter.— Loc. cit., 1892, vol. i., p. 1139.
65. Habershon.— " Brit. Med. Journal," 1892, vol. i„ p. 1139.
48
CHAPTER. III.
PATHOLOGICAL ANATOMY AND BACTERIOLOGY.
Degenerative Character of Changes-Point of Origin — How the Bacteria gain Access — Naked Eye Appearances — Changes in Synovial Membrane— Loose Bodies — Ligaments — Characters of Synovia — Changes in the Cartilages — Cornil and Ranvier's Views — Erosion — Proliferation — Lipping — Changes in Bones — Rarefication — Osteo- sclerosis — Volkmann — Changes in the Muscles — Central Nerve Changes — Peripheral Nerves — Cardiac Changes — Kidney — Blood — Glands — Fibrous Nodules — Heberden's Nodes— Situation and Mode of Growth — Gout as a Cause — Their Nature — Various Observers' Views — Bacteri- ology— Dr. Blaxall's Report, etc.
On examining the changes after death in Rheumatoid Arthritis, we are at once struck by the extensive and degenerative character of the lesions. Much has been written and said on the subject, but owing to the scarcity of post-mortem material, until the acute stages at least are past, few observers agree. Colles l and Todd2 held that the disease was not inflammatory in nature, whilst Adams,3 Brodie,4 and Cruveilhier 5 did; Fuller0 looked upon it as a disorder of nutrition, rather than the result of inflammation ; and Senator 7 regarded the changes as partly inflammatory, and partly degenerative, whilst Garrod8 also takes this view. Bindfleisch9 held that the disease was essentially one of those lingering inflam- matory conditions, which accompany the decay of the organism, like atheromatous disease of the internal coat of the arteries. He says that the inflammation, not being powerful enough to cause suppuration, sets up a hyperplastic over-growth. Trousseau,10 in his clinical
PATHOLOGICAL ANATOMY. 49
lectures, says the synovial membrane demonstrates its inflammatory origin. From what we know of the disease its changes must be inflammatory in origin, and probably begin in the synovial membrane, and spread from thence to the cartilage and deeper structures. In acute rheumatoid arthritis the changes are, of course, principally degenerative or destructive in character; but, as the disease progresses and becomes more chronic, there comes to be more and more reparative change leading to cartilaginous, osteophytic and ligamentous hardening and overgrowth. As I have said, in the acute cases, the inflammatory and destructive element is in excess, whilst in the chronic or osteo-arthritic, the fibroid or sslerotic is.
Brodie, Adams and others, thought that the disease eommeneed in the synovial membrane, whilst Yolkmann, Billroth ll and Garrod consider it starts in the cartilages. Given a micro-organism circulating in the blood, I think it probable that the synovial membrane will be the first to suffer. As the micro-organism is of fairly rapid growth, especially after gaining access to the joint fluid, one would expect it to spread rapidly and affect almost simultaneously, by dissemination, the whole of the internal surface of the synovial cavity. The question is, How do the micro-organisms gain access to the joint cavity in the first instance? The probability is that they set up an endarteritis in one of the small vessels on the surface of the synovial membrane, with a diffuse cell exudation, and this, by extension and rupture, breaks into the joint cavity, and thus liberates them for further mischief. As regards this point the experiments by Chvostek12 are of interest as they show: (1,) That the walls of blood-vessels, not evidently altered anatomically, are permeable to bacteria ; (2,) That the anatomical structure of the synovia and its vessels is an obstacle,
4
5o RHEUMATOID ARTHRITIS.
and bacteria enter the joints considerably later than they do the kidneys through the renal vessels ; (3,) That the exit of bacteria depends on (a,) their kind — - thus a staphylococcus passes most readily, then a streptococcus, and lastly the bacterium coli. This is probably due to the virulence of the micro-organism for the animal, and also to certain tissues being more liable to certain bacilli than others ; (b,) their virulence — in tjais .cojinection the action of toxines must be con#gmi^&-? (fc^ijtet factors, chiefly nervous — thus c\iui£^ the nerves haQpjs the exit of bacteria. If this itheor^Ua^orr^atQit- of^Aourse, makes the synovial memWine far more wily to be primarily affected than the c^tyage^^^gojvvever,3^/ do not think one can lay much str^^^if^^i^Jjmion is primarily affected, nor is it of vital importance.
1. General naked eye appearance of the joint. — We find an affected joint presents the following general characteristics : It is swollen and increased in size, usually, in the acute stages, in a characteristic ovoid manner ; but which, in the more chronic stages, becomes less marked and more irregular. In the chronic forms there is often deformity produced, partly by out-growth from the cartilages or bones, and partly by twisting or distortion of the joint ; the deformity may be due to both or either of these causes. On opening the joint we probably find some fluid, certainly in the earlier, and acuter cases almost always. Trousseau remarks that the joint is often distended by hydrarthrosis. This presence of synovial fluid during life is often deceptive, and the doughy or pulpy synovial membrane produces a feeling difficult to differentiate from that of fluid. The synovial membrane we notice is thickened — in acute cases this thickening being soft and pulpy, whilst in the chronic stages it is hard and dense. The ligaments
PA THOL OGICAL ANA TOM Y. 5 1
are affected in a similar way, and, in very chronic cases, may present cartilaginous or even bony deposits. The inner surface of the synovial membrane is injected, often intensely so, and is granular in appearance. Here and there small abrasions may be noticed, but they are seldom of any depth. The villi are thickened, and more prominent than usual ; this is easily demonstrable by placing a piece in water, when the villi float up, showing their character beautifully. The peri-articular cellular tissue is affected in a similar fashion to its neighbours. All the soft tissues undergo great develop- ment of new formed tissue, and the subsequent contraction and adhesion of which, with the surrounding parts, give rise to stiffness and limitation of the joint movements, and finally to fibrous ankylosis. These adhesions and contractions play a great part in the development of deformities. On turning to the articular surfaces we find, if the cartilage be not completely worn away, as it may be in the chronic ^"~ ~\
cases, that they present a velvety appearance quite characteristic. In places will be seen small or large erosions of the bone, accord- E' ing to the severity of the case. D This, in the acute cases, is red, rarefied, vascular and soft, but later on becomes sclerosed, hard,
, , , . „ . Fig. 1.— Section thrcmgh pha-
dense and almOSt OI an lVOry COn- laugeal joint in chronic Kheu-
n mi i •-! i matoid Arthritis: A, erosion of
SIStency ; there Will alSO pOSSlbly cartilage; B, thickened mem-
. brane with cartilaginous depo-
be SOme lipping 01* growth Of new sits ;C,eburnatedsiirface of bone
from rubbing of cartilaginoiis
cartilage round the edges of the body ; r>, eburnated articulating
surface; E, thickened soft
articulating surfaces. Beneath tissues. the cartilage the bone presents, as a rule, a normal appearance showing that where protected it does not undergo change. This, however, is not invariably the
52
RHE UMA TOW A R THRITIS.
case, as we now and then see changes going on in bone protected by cartilage. Such are the appearances en masse, so now let us study the individual elements separately.
2. Changes in the synovial mem- brane and surrounding" parts. — The synovial membrane, as we have already mentioned, presents at first a bright red appearance from the injection of its vessels, but in the later stages it becomes duller, granular and hypertro- phied ; and, as a whole, much thickened. Lebert13 mentions a varicose condition of the vessels of the synovial membrane, but
, osteophytes; B, *
eburnated bone; C, Grooves on probably he refei'S to a Congested articulating surfaces (after Bill- r J r>
roth)- condition. The villi become
prominent and hypertrophied ; they may undergo fatty or cartilaginous degeneration, so that the appear- ance may be that of a number of pedunculated fatty polypi, or else of a quantity of dendritic vegetations, villi, or fingers, some fatty, .and some cartilaginous. The polypi arise from the budding, and growth of the normal villi. In the normal state we know that the synovial membrane is edged by fringes and villi, and that these have appendages ; and it is from these fringes that the polypi and other vegetations arise. These fringes look highly vascular, and have a soft velvet-like feel. Under the microscope we see that the synovial cells have undergone proliferation, and that large numbers of new formed blood-vessels exist, some full of blood, but all with thickened walls. Scattered throughout are numbers of small round cells. M.M. Cornil and Eanvier u state that the cartilage may
PA THOL OGICAL ANA TOM Y. 5 3
be formed in the synovial fringes as follows: "The normal fat cells in the fringes or villi, undergo degener- ation, and are replaced by embryonic cells, and whilst those in centre form cartilage, those at the periphery, form fibrous tissue." According to Kolliker,15 in the normal state, cartilage cells exist in the synovial fringes, and it is more reasonable to suppose that the cartilage is developed from them, than in the method suggested by M.M. Cornil and Eanvier. Kindfleisch corrobor- ates the evidence with regard to the presence of pedunculated polypi, vegetations, villi, and fringes. As a rule these only become prominent in the chronic stages, and this specially refers to the cases where cartilaginous degeneration has occurred. The pedicles which fasten those nodules of cartilage to the synovial membrane, are apt to become stretched, and may in the end break off, giving rise to loose bodies which lie free in the cavity of the joint. In very chronic cases, these cartilaginous bodies may still farther undergo change, and become ossified. It has also been stated that loose cartilaginous bodies are found in various bursas. Personally, I have failed to verify this.
The loose bodies found in Eheumatoid Arthritis may be classified into: (a,) Melon- seed-like bodies, and masses of coagulated fibrin, derived from the synovial surfaces ; (b,) Loose bodies derived from the synovial membrane, consisting of fully formed tissues, such as cartilage and bone ; and (c,) Loose bodies derived from the articular end of the bones, being detached ecchondroses and osteophytes.
(a,) -seed-like bodies. — Kokitansky 15a refers to
bodies of this kind, and mentions cases in which he has seen fibrous or fibroid small bodies, varying in size and shape, projecting from the surface of the synovial membrane, and which he says can quite conceivably
54 RHEUMATOID ARTHRITIS.
become detached. Again, it is stated that fibrinous exudation gives rise to both melon-seed bodies, and to fibrinous masses. A case of the latter is mentioned by Dr. Logan Turner.45 On microscopical examination the fibrinous mass was found to consist of fibrin with a large number of cells, resembling leucocytes, entangled in its meshes.
(b,) Loose bodies derived from the synovial membrane, consisting of fully formed bone or cartilage. — Most of the loose bodies found in rheumatoid joints undoubtedly arise from abnormal development of the fringes, which normally exist at the margins of the articular cartilages. These increase in size and vascularity, giving rise to sessile and pedunculated bodies, varying in number and size. During this process the membrane itself undergoes change, and the connective tissue cells develop into fibrous tissue, fibro-cartilage, cartilage, and bone. As time goes on, the connecting pedicle of the peduncu- lated bodies grows thinner, and finally the body may drop off, in some cases after a slight sprain or wrench, but in others during some natural movement of the joint. These bodies, examined microscopically, present the character of hyaline cartilage, with here and there cells undergoing proliferation.
(c,) Loose bodies derived from the articular ends of the bones, being detached eeehondroses and osteophytes.— In rheumatoid joints formative changes are constantly taking place at the periphery, giving rise to nodular outgrowths of cartilage, and finally by deposition of lime salts or ossification they become bony. These nodules may become detached possibly by injury, and thus lead to such a body existing loose in the joint. In one such case the body was found to consist of hyaline cartilage irregularly arranged. In some places it was proliferating, and in others ossification had begun.
PATHOLOGICAL ANATOMY. 55
The ligaments which form part of the affected joints become swollen and inflamed, and finally undergo absorption, or are so replaced by new formed connective tissue, that it is impossible to trace them on the most careful dissection. Owing to the cellular tissue under- going great development, and from the formation of new connective tissue, adhesions are formed with the surrounding parts which lead to stiffness and difficulty in moving the joint, and finally even to fibrous ankylosis.
Under the microscope the synovial membrane is seen to be infiltrated with newly formed connective tissue cells, the blood-vessels are dilated, and their walls thickened, and here and there are small collections of leucocytes surrounding them. On proper staining micro-organisms are discovered scattered throughout the mem- brane,but more especially wherever there are any collections of round cells.
Similar changes are
1 j ■ i-i ar.ff -,-v^v; Fig. 3.— Diagrammatic sketch of connective
llOieu. m ine SOIL peri- tissue, showing micro-organisms (much en-
articular connective tis- larged)-
sue. In the ligamentous structures, during the acute stages, the intercellular spaces seem to be increased in size and number, and a few round cells present them- selves ; whereas, in the chronic stage, they are replaced and converted into a mass of dense connective tissue, in which little or no structure can be traced.
It has often been stated that in Eheumatoid Arthritis there is no effusion. This however, is quite incorrect, as again and again have I definitely proved its presence by tapping a joint. It certainly is present in the most acute cases, and often in considerable quantities. It is most often noticed in the knees, wrists, and phalangeal
56 RHEUMATOID ARTHRITIS.
joints. In these latter joints it often forms small, tense, synovial protrusions, which give the impression of small elastic bags full of fluid. Broclie, Adams, Fuller, Garrod, Trousseau and others, have recognised the presence of fluid, whilst Besnier,10 Senator, and Homolle,17 deny it. On examining the fluid, Hoppe Sejder ls found that it contained the following ingredients : —
|
Mucin |
. |
18-19 |
per |
thousand, |
|
Albuminous Substances |
- |
20-92 |
35 |
|
|
Etherial Extracts |
- |
•93 |
||
|
Alcoholic ,, |
- |
1-30 |
11 |
|
|
Watery ,, |
- |
•65 |
H |
|
|
Acetic ,, |
- |
1-53 |
11 |
|
|
Inorganic Substances - |
- |
8-79 |
?' |
|
|
Total 1 |
Solids |
52-31 |
11 |
|
|
Water |
947-69 |
11 |
The etherial extracts were cholesterin, lecithin, and traces of fat. I have found the fluid to be a straw coloured viscid fluid, with a dash of reddish colouration (trace of blood), moderately alkaline.
Under the microscope (on cold stage) large numbers of multinuclear granular corpuscles are seen, very little, if any, larger than red-blood discs. Most of the round cells are quiescent, but a considerable number of irregular ones showed active amoeboid movements. There were a few rouleaux of red corpuscles, and a few scattered individual red discs. Also indistinctly seen are numerous small round bodies, some highly retractile, and with them a few bodies (very faint), apparently micro-organisms. On staining, these latter proved to be so in enormous numbers.
Normal synovial fluid is found to contain in addition to fat molecules, a few amoeboid corpuscles, as well as cells similar to those which occur on the projections of the membrane.19 We thus see that, beyond the micro- organisms, this fluid differs also in the number of cells
PATHOLOGICAL ANATOMY. 57
present, both amoeboid and granular. The presence of blood was probably accidental. Dr. Goodhart, as men- tioned by Dr. Fagge, on one occasion found blood effused into a rheumatoid joint.
It is very rare to have suppuration, and, in fact, I know of no case in which it has occurred. Dr. Mansel Moullin,20 however, reports three such cases. He believes that the bacteria which caused it reached the joint by the blood. The disease in all cases began in the soft parts, and spread from thence to the bones, cartilages, and ligaments. Dr. J. K. Lunn, also reports one such case.46
3. Changes in the cartilages. — Many believe that the first changes begin in the cartilages, but I am not inclined to agree with them. I think, however, that the cartilage must be involved at a very early stage. Post- mortem, we usually find that the whole surface of the cartilage has suffered, but, if seen early, it is also not uncommon to find the disease limited to one or more small patches, from whence it spreads to the surround- ing areas. Kindfleisch says the cartilage undergoes a perfectly homologous proliferation, beginning in the outermost or superficial layers, and gradually extending to the deeper ; that the cells divide, and group them- selves into rows of eight to twenty, and go on growing until the matrix has disappeared, and a tissue made up of cells or large vesicles results. Billroth says the intercellular substance does not soften as in inflamma- tion generally, but that it breaks up into filaments. He says the changes commence in the cartilage, and spread from thence to the synovial membrane, and then to the bone and periosteum.
To the naked eye the first change is a loss of natural polish, and it comes to present an appearance which has been likened to velvet. As the disease spreads and
58 RHEUMATOID ARTHRITIS.
becomes more developed, the central parts of the affected areas break down, and erosions occur which, gradually extending and deepening, cause the whole of the cartilage to be absorbed, and the heads of the bones exposed. As the erosion goes on a new formation of cartilage may take place round the edge, giving rise to the lipping or heaping up so often seen in the advanced cases. A. sort of pseudo-lipping may be observed when the central portions are erosed down to the bone, whilst the marginal portions are nearly, if not quite, unaffected. Close investigation is necessary to distinguish this alteration. When true lipping does occur, it does not do so in very regular sequence, but rather does so in nodules, and it is from this circumstance that the name " Rheumatisme Noueux," by which it was long known, was derived. Under the microscope, we find that the process of disease consists in a proliferation of the cartilage cells, beginning in the outermost or superficial layers, and gradually extending to the deeper. The process was first described by M.M. Cornil and Ranvier. They show how the cells undergo multiplication, and form groups of from eight to twenty cells sur- rounded by capsules, and that in some cases there are large mother cells, and capsules inside which the daughter cells develop. Of these some will have their own capsule, whilst others will be without. They show how it can be demonstrated, by staining with iodine, that these cells are not true cartilage cells, as their capsules only stain very faintly, if at all. According to them the superficial layer of capsules swells, and becoming globular bursts, and discharges their contents into the joint cavity. The capsules in the next and succeeding rows, being only able to grow perpendicularly, open into the more superficial rows forming parallel tubules, and, as time goes on, these
PATHOLOGICAL ANATOMY. 59
burst in turn into the joint leaving the tubules empty (Eindfleisch and Weber21), whilst the ground substance or matrix lying between them, becomes separated into filaments, giving rise to its fibrillated and velvety appearance. According to Eindfleisch, mucous degener- ation of the fibrils occurs, causing them to disappear the more easily, and thus also explaining the presence of mucin in the joint fluid. I have never been able to verify this description.
In sections one sees proliferation of the cartilage cells, but I have never been able to detect any arrangement into tubules as described by Cornil and Eanvier. Did it occur, one would expect to find cartilage cells in the joint fluids. I have never done so with certainty, and I have examined many cases in the hope of finding them. Of course, the cells may have undergone so much degen- eration, and alteration, that they would be unrecognis- able. What I have seen under the microscope is, round an erosion, a large number of round cells which penetrate for some distance into the substance of the cartilage. In this area the cartilage cells are seen to be proliferat- ing freely, and the matrix to be disappearing, being
Fig. 4.— Sections through diseased cartilage; A, proliferating cartilage cells; B, round celled tissue ; C, periarticular loose connective tissue.
eaten away, partly by the round cells, and partly replaced by the new formed cartilage cells. Deeper down the proliferation still continues, but in a less marked way. With regard to the fibrillation of the
60 RHEUMATOID ARTHRITIS.
matrix, the use of staining reagents rather interferes with one's results, so on that point I can make no definite statement, but I can emphatically state that I have never seen anything at all approaching the drawings which illustrate most of our text books. The process is one resembling, I take it, all other erosions, and inflammatory conditions of cartilage. A few micro-organisms I have always found in the superficial layers, mixed up with the round celled tissue.
The cells, at the edges of the cartilage, proliferate in a similar manner. Cornil and Eanvier ascribe the mar- ginal overgrowth to the fact that the cartilages, at their margin, are overlapped by a layer of synovial membrane which prevents the escape of the cellular contents into the cavity of the joint. The cartilaginous overgrowth may become converted into osseous tissue, the change beginning as shown by Volkmann in the layer nearest the original bone. As a rule, even when seen in the late stages of the disease, these osteophytes have still a covering of cartilage. The lipping which is seen in gout differs from that just described. According to Dr. Wynne the overgrowths in the latter disease are a sprouting of the cancellous tissue of the epiphysis, carrying with it the cartilage, which, however, only covers it as far as its summit — the rest being covered by fibrous tissue continuous with that of the periosteum, and synovial membrane.
4, Changes in the bones. — As the cartilage erodes, and leaves bare the bone underneath, we have certain changes occurring. In the acute stages, we find the disease in the cartilage extends and involves the bone, which presents a red and vascular appearance. It is soft, and readily breaks down as the bony constituents are absorbed. These are replaced by a red, semi-fluid material differing greatly from the normal marrow. This substance, under
PATHOLOGICAL ANATOMY. 61
the microscope, is found to consist largely of giant cells, with many nuclei (osteoclasts), in a mass of round cells. As the disease becomes more chronic we find the bone comes to present a hard, white, polished, ivory-like sur- face, to which the term "eburnation" has been applied. This hard dense layer is thin, and erosions through it showing the cancellous tissue beneath, presenting features as above, are not uncommon.
On the surface of the exposed bone, as it hardens, we see grooves and striae, which are found to correspond with the eminences, and protuberances, on the opposing articulating surface (see Fig. 2). As the result of the processes of destruction and new growth, the bones often present a mushroom-like appearance.
Volkmann22 described such a condition, saying that they looked as if they had been moulded whilst in a softened con- dition.
True bony ankylosis rarely occurs, except in the spinal column (Bowlby). fig. 5.— Metacarpal
.-, j«-i • ™ . bone, showing osteo-
Aclams noticed occasionally hypertrophy phytes (after Billroth), of the shafts, whilst Broca23 described this as being chiefly confined to the epiphysis.
Various theories have been advanced to explain the eburnation. It is, probably, one of Nature's safeguards to prevent the further inroads of the disease. Zeigler 24 states that, whilst the superficial layers of the cartilage are proliferating, and becoming fibrillated, a softening process is going on, in the deeper layers, which leads to the formation of cavities ; and these becoming filled, later on, with the vascular medullary substance, which grows into them from the bone, give rise to ossification. Cornil and Banvier believe the eburnation to be due to the discharge into the adjacent medullary spaces of the
62 RHEUMATOID ARTHRITIS.
contents of the most deeply seated cartilage capsules, which as they enlarge, cause the bone to be absorbed ; and these cells from the capsules, by a process of osteo- sclerosis, give rise to the hardened surface. In some cases they attribute it to the extension of inflammatory processes to the most superficial layers of the bone. Some think local osteitis is the principal cause, and others that it is due entirely to mechanical means, i.e., the rubbing of the bones one upon another. The bony structure of the epiphysis may also be altered.
Volkmann, whose theory is probably correct, has pointed out that the changes are caused, to his mind, by a rarefying osteitis followed by an osteosclerosis. That the wTasting of the bone is not purely mechanical is proved by the fact that the change sometimes goes on in parts protected by cartilage.
On examining sections of bone, and also of the medul- lary tissue, I was struck by the appearance of some of the cells in the latter. They were large granular cells with many nuclei, and, in a few instances, I found places where they occurred in depressions of the bone. From this circumstance there could be no doubt as to their nature. They were osteoclasts, and it is evident that the nature of the process is a rarefying osteitis ; but at the same time a process of sclerosis, due to osteoblasts, must either be going on, or else will follow, as the more acute stage passes off.
I have failed to find micro-organisms in the soft medullary tissue, but I have no doubt they exist. I find Gwilt25 mentions that, in this disease, he noticed the medullary tissue was a great deal more vascular with proliferation of corpuscles than in the normal. This has also been noticed by Husse, 26 and Kussmaul.27 If we compare the medullary substance with that found in morbus coxae, senilis, wre see that, in the latter disease,
£iiii£
PATHOLOGICAL ANATOMY. 63
which is due almost entirely to a process of absorption, the bony interstices are filled with a yellow fatty sub- stance, quite different from the red vascular substance of rheumatoid disease.
To recapitulate, I would say, we have an acute inflammatory disease set up by micro-organisms starting in the synovial membrane, spreading
thence tO the Cartilage, Fig. 6. -Osteoclast eating bone.
bones, and ligaments, causing in the cartilage and bones, at first an ulcerative or eroding process followed, as the disease becomes less acute, by hardening and thickening. This is following all other types of disease, and explains, perfectly, all the post-mortem appearances as well as all the symptoms.
Before leaving this division of the subject, let us con- sider some other points of interest.
5, Changes in the muscles. — The principal change is a well marked atrophy of the muscle substance which affects the whole of the muscle, and not only a part of it. There is no diminution in the number of the fibres, but each fibre is found to be lessened in size. As a whole the muscle presents, what Debove 2S calls, the colour of dead leaves. In a few cases degeneration of the muscles has been found, showing itself by longitudinal striation with proliferation of the sheath nuclei, and increase of the interstitial tissue (Vallat).29 This change, probably, only occurs in those cases in which inflammatory changes have spread from the joint to the muscles, nerves, or central nerve system.
6, Changes in the central nerve system. — The only changes, hitherto noticed, have been an atrophy of the motor cells in the anterior cornua in several cases, seen
64
RHE UMA TOW A R THR1TIS.
by Folli.30 specimens this one,
I have only been successful in obtaining from the nerve system in one case. In on examining the spinal cord, I found degeneration, and vacuola- tion 31 and 32 of the ganglion cells of the anterior cornua. The vacuolation of nerve cells consists in the appear- ance, within the nerve cell, of oval or perfectly spheroidal bodies of high refractile power quite unaffected by any staining reagent, colour- less, but lustrous. In many cases this quality is wanting, and it is then evident that the spheroidal outline is of a genuine cavity or vacuole from which the former con- tents have escaped by rupture. The removal of the contents of such vacuoles may be effected during life by the lymph connective system. The protoplasm surrounding t.-multipolar gaxgliox Cells the vacuoles is, more or less,
in a state of granular degen- eration. The degeneration, and the feeble staining, indi- cate a fatty change in the cell protoplasm. The sig- nificance of this is understood when we realize that fatty degeneration and vacuolation indicate a change in the blood corpuscles, leading to defective oxygenation. We see examples of this in chronic pul-
FlG.
X 350-
FROM AnTKRIOR CORNUA.
/ 1 Cell swollen with bright trail s- ' lucent contents. 2 a, Vacuoles with degenerated cell ; b, Granular degeneration.
'3 and 4 show vacuolation, seen
also in 5 and 6, in degenerated cells, and t 7 swollen degenerated cell.
PA THOL OGICA L A NA TOM Y.
65
monary affections, alcoholic states, and from the effect of certain poisons (arsenic, phosphorus, etc.), or any of the many circumstances which restrict the supply of oxygen to the tissues. Those elements naturally suffer earliest, and most, whose nutrition is carried on at the greatest disadvantage. The exact importance of this occurrence cannot at present be accurately estimated, but shortly I hope to obtain farther and certain evidence.
Massolongo 32a refers to changes in the anterior cornua observed by Klippel, but does not particularise them.
7. Changes in the nerves. — In a certain number of cases peripheral neuritis has been noticed, but in so few as to negative any idea that this is the cause of the disease. It is almost certain that it is set up by an extension of the inflammation from the joint lesions. Pitres and Vaillard 33 report some cases where they found such a condition of the nerves, and they express the opinion that these changes cannot be the cause of the joint lesions. In other cases again we find that the spinal cord and nerve roots have been affected by a spinal arthritis, probably by com- pression and narrowing of the foramina. In these cases we may have a descending neuritis. I have been fortunate enough to obtain sections from the nerves, in a case of rheumatoid disease which had undoubtably given rise to a secondary neuritis. There could be no doubt that it was secondary. Under the microscope there was an infiltration of small round
Fig. 8. — Portion of nerve in which there was neuritis : A, thickened con- nective tissue, nucleated ; B, nerve bundles greatly diminished in size; C, blood-vessels with thickened walls.
66 RHE UMA TOW A R THRITIS.
cells in the nerve sheath, around the vessels, and amongst the nerve fibres themselves, especially in the neighbourhood of the sheath. Thickening of the endo- neural septa, and of the interfibrillary substance, was also seen ; and there was a thickening of the intima of the blood-vessels, which encroached upon the lumen of the vessel.
8. Changes in the heart. — Lesions of the endocardium and pericardium are comparatively rare, but not so rare as is thought. MM. Charcot and Cornil mention numerous cases in which changes were present, and with no rheumatic history, and in which the lesions developed after rheumatoid joint troubles. Any valve may be affected, but my experience has been that the disease is almost entirely confined to the mitral valves. I find out of 78 cases, of which I give an analysis, 14 had cardiac troubles. I have had no opportunity of examining such cases post-mortem, but other writers state that the affected areas present a hardening, and thickening, with vascularity, and present small vegeta- tions upon their surfaces. Pericarditis has occurred in several instances.
9. Changes in the kidneys. — Charcot and Trousseau lay special stress on the occurrence of chronic albuminous nephritis, but I think it is a much rarer complication than they would lead one to suppose, at least in this country.
10. Changes in the blood. — In almost 95 per cent, we find anaemia exists in a greater or lesser degree. The blood, under these circumstances, presents the following characters. There is a slight, but well marked diminu- tion in the number of red blood corpuscles, a marked diminution in the haemoglobin, and a slight increase in the number of the white corpuscles. The percentage of the diminution of the red corpuscles ranges from 85 per
PATHOLOGICAL AAA TOM Y. 67
cent, to 56 per cent.; whereas that of the hemoglobin does so from 80 per cent, to 45 per cent. It is thus evident that the haemoglobin value of each corpuscle is lessened. The percentage increase of the white corpuscles is small. The blood showed red corpuscles of varying size and varying shapes, but did not present any microcytes nor yet any nucleated corpuscles. The haemoglobin appears to be less in quantity in each cell, as well as in a less stable union with the cell stroma. It crystallizes out more readily and is more easily acted upon by such substances as common salt, acetic acid and sulphate of soda in solution. There is a difficulty sometimes in distinguishing between a swollen red cell with its haemoglobin dissolved out and a white cell. This might account for the variability in the estimation of the number of the latter.
11. Changes in the glands. — As one would expect, we find in the glands of the arm pit and groin, some enlargement, but there is none in the spleen. This enlargement is such as is found in other bacterial diseases, and consists of a chronic hyperplasia.
12. Fibrous nodules, although more common in acute or chronic rheumatism, are not unknown. They consist of round celled tissue which, probably, originates in an endarteritis. Dr. Pitt 34 describes such a condition, and mentions that this endarteritis may account for the cold extremities so often seen in this disease. Nepven35 describes a nodule formed round a vessel with small dis- integrating clots. Cavafy 36 mentions that the nodules are vascular in origin. A subject now crops up of much interest, namely, the relationship between chronic rheu- matoid arthritis, and what are known as Heberden's nodes. These are small enlargements or osteophytic outgrowths from the normal nodules, present round the articular surfaces of the bones of the hand. They were first described by Heberden 3T who gave it as his opinion
68 RHEUMATOID ARTHRITIS.
that they had nothing whatever to do with gout. This has been, and still is, a much vexed question. As these nodes may occur in the more chronic forms of polyar- ticular rheumatoid arthritis we have to ask ourselves what their relationship to this disease may be.
They occur, as I have said, as small rounded nodular growths, usually arising from the third phalanges, but sometimes from the second. They are painless, and have no tendency to ulcerate, and though they some- what interfere with the movements of the fingers, yet they are more disfiguring than painful. The nodes may be the only symptom of disease present, but they are more usually associated with a generalised disease. They may precede or follow such a disease. On examina- tion they are found to consist of an outgrowth from the bony tissue, and are covered by a hernial process or projection of the synovial membrane, forming a pouch or bag, which, as a rule, contains fluid, and acts much as a bursa. On microscopical examination, they are found to be formed of true bone. It is found that these nodes, usually, as Heberden says, present themselves in elderly people of the female sex, above 60 years of age ; but I have seen them well developed in patients of 40. At first, we find that the third joint is enlarged, and as a whole, and not only on one aspect. On the dorsum of the finger the furrows which mark the normal joint are seen to have disappeared, and are replaced by an elevation — the whole joint forming a distinct thickening. This can be detected on the palmar aspect as well. The enlargement of the bones is not confined always to one phalanx, but both of the opposing phalanges may be affected. This enlargement goes on until we have a small tumour, obviously growing from the bone, about the size of a pea, over which glides, possibly, a burse or synovial pouch. The development of these nodes is accompanied
PATHOLOGICAL ANATOMY. 69
by peculiar sensations in the fingers, such as numbness, and they are often accompanied by pain on pressure, or on movement. They may, however, be quite painless, and even if not so, the pain is never severe. When they become quiescent the pain goes completely. If the disease is not arrested, the movements of the joints become much interfered with, and ankylosis may finally result. When nodes are present in rheumatoid arthritis we find that deformities seem to develop specially early, and to be more persistent. The usual deformity is de- flection of the terminal phalanges towards the radial side, and this is rendered more conspicuous by the deflection of the finger, as a whole, to the ulnar side. Are these growths then the ordinary osteophytic out- growths, so common in rheumatoid arthritis, or are they something different ? Some assert that they are true gouty formations, and others that they have nothing- whatever to do with gout, but are by nature a form of rheumatoid arthritis. Heberden, as I have said, main- tained that they were not gouty, as he had seen them in people who had never been affected with gout. Begbie38 differed from him entirely, and says they are intimately connected with gout. He stated that he had watched their development from the first, being sometimes the result of an inflammatory affection, more or less acute, and attended with the constitutional disturbance which marks the fit of gout ; but more commonly they were the consequence of a slow, and chronic gouty disorder. He also says he had never seen them except in those suffering from gout or from the gouty diathesis. Charcot,39 on the other hand, agreed with Heberden, and denied that they had any connection whatever with gout. He stated that it was a form of rheumatoid arthritis, and that the ana- tomical changes were those of this disease. Sir A. B. Garrod 40 stated that he had seldom seen them in patients
70 RHEUMATOID ARTHRITIS.
suffering from true gout, and agreed with Heberden's view, with regard to them. Dr. A. E. Garrod 41 is of the same opinion, but says he has seen them in cases with clear his- tories of gout, and no other arthritic affection. Duck- worth 42 believes that they are of a true gouty nature, and says that the changes, found by Charcot, were frequently of an undoubted gouty nature. In gout he has seen true ankylosis result from the deposit of urates, and exostoses may also be caused thereby. Lecorche 43 also takes this view. Pfeiffer44 maintains that it is a symptom of true gout, as he has seen them arise in cases of gout, and in cases where uratic deposits existed, but he admits that he has also found them in people in whom there was no gout. Personally, I have seen these nodes most frequently in chronic rheumatoid arthritis, never in the acute forms; but I have also seen them in true gout. Is it not possible that they may be common to both diseases. They are unquestionably the result of some irritation giving rise to an increased, and morbid growth in the normal nodules ; so why should not this irritation have its origin as much in the poison of one disease as in the other ? I have seen a considerable number of such cases, and I have in no instance found any deposit of gouty material in the nodules. They have always been of pure bony substance, but this, of course, does not invalidate the argument that the gouty poison may have originally started the morbid process.
The accompanying photograph {Plate I) was taken by J. W. Gifford, Esq., of Chard, the patient being an inmate of the Bath Eoyal Mineral Waters Hospital, and through whose kindness I am permitted to publish it.
The patient, a lad of 20, was the subject of acute rheu- matoid arthritis — the synovial swellings being marked. A small sesamoid bone can be distinguished on the inner side of the first metacarpophalangeal joint.
PLATE I.
Photograph of the Bones of the hand in a case of Rheumatoid Arthritis.
BACTERIOLOGY 71
What is of special interest, however, is the fact, that in the acute stages no bony outgrowth occurs. Indeed, as this photograph shows, there is, if anything, a diminution in the size of the bone, as may be seen in the heads of the metacarpals — which have a rounded off appearance not seen in the normal bone. This is specially noticeable in the second metacarpal at its ulnar side, the disease in this joint being specially acute. The deformity of the little finger was due to contraction of the flexor tendons, with atony of the extensors.
Bacteeiology. For some time before the actual discovery of the micro- organisms, Dr. Wohlmann and I, looking at the clinical nature of the disease, and at the course of the symptoms, had practically made up our minds that the disease was microbic in character. The absence of iiost-mortem material complicated the case, but in the absence of this material, we decided to obtain what specimens we could from the living subjects. In this way we were led to aspirate affected joints, and examine the fluids so obtained microscopically and by cultivation. On stain- ing we were readily successful in determining a micro- organism was present, but at the same time were troubled with the difficulty in staining it properly, and getting it free from precipitate. However, we, to a certain extent, overcame these difficulties, and got fairly good results with carbo-fuchsine and methyl-blue, sufficiently so to satisfy ourselves that it was a micro-organism we were dealing with. Our first culture attempts utterly failed, but by degrees we got fair results. Our apparatus was deficient, and this led in most instances to the growths dying out in the course of from three to four weeks' time. We obtained growths on blood-serum, agar- agar, and on beef bouillon. The bacillus, for to us it
72 RHEUMATOID ARTHRITIS.
appeared to be a dumb-bell shaped bacillus, is about 2//, long, the ends staining deeply, the connecting portion not at all. In fact in many cases it resembles a diplo- coccus. It appears to grow more freely when it has a plentiful supply of air, possibly pointing to a greater need of oxygen. In all, we found it in 24 cases out of 25 examined. We also found it in several pieces of synovial membrane obtained during aspiration and in the car- tilages, synovial membrane, and periarticular tissues in the few sections we were fortunate enough in obtaining. On Dr. Blaxall's suggestion we examined the blood in some of the acute cases, and in several were successful in finding it by microscopic examination, but never so characteristically as to warrant one in diagnosing the disease from that alone.
Having arrived at this stage, and feeling the utter inadequacy of our apparatus, I felt compelled to call to our assistance more skilled aid, and Dr. Blaxall of the British Institute of Preventive Medicine, kindly under- took the duty. For the last eighteen months he has been working hard at the elucidation of its life-history, and the result we see in the following report* : —
" This investigation was undertaken at the request of Dr. Bannatyne, of Bath, who stated, that he, with Dr. Wohlmann, had arrived at the conclusion from the clinical aspect of cases suffering from rheumatoid arthritis, that the disease was due to a micro-organism, and further that by microscopic examina- tion of the synovial fluid from affected joints, they had found an organism, constant and distinct, and this mirco-organism they considered to be specific.
" Synovial fluid from affected joints, was sent me from Bath; the fluid was aspirated with antiseptic and aseptic precautions, with such success that out of eighteen cases which have been submitted to me, only twice have I found it contaminated.
* This report appeared in the "Lancet," April 25th, 1896.
BACTERIOLOGY. 73
" My first attempts to obtain organisms in the synovia and to obtain cultivations from it, resulted in failure. I adopted the ordinary methods of bacteriological procedure, staining films of the synovial fluid for a few minutes with aniline dyes, and inoculating serum tubes and all ordinary culture media, as well as making plate cultivations of nutrient agar-agar and gelatine after Koch's method. But I was unable to observe any organisms in the microscopic specimens, or to recognize any appearance of growth upon any of the culture media.
" I then varied the staining methods, leaving the specimens in the dyes for a prolonged time in the cold, applying heat, and using concentrated solutions. By these means organisms could be perceived in the specimens corresponding exactly to those described by Drs. Bannatyne and Wohlmann, and morphologically identical with those seen in their microscopic specimens. But their recognition was unsatisfactory, owing to several causes. In the first place, it was evident that the organisms took up the stains with great difficulty, and only by their prolonged action, or by the application of heat; but these means resulted in a very dense colouration of the synovial film. Secondly, they were decolourized with great ease, for attempts to decolourize the substratum left the organisms unstained.
" Again, the microbe being very minute, it was exceedingly difficult in heavily stained specimens to discriminate it from cUlris or from precipitate of the dye used. It was necessary then to find a method, by which the organism should be well stained, should retain the stain, and yet allow the synovial film to be sufficiently decolourized, and one that should obviate all precipitate of the dye. I cannot claim to have attained this result, but after many trials I have adopted the following procedure as being most satisfactory.
"A thin film of synovial fluid, draAvn out between two cover- glasses, is dried over the flame and fixed in the usual way, by passing through the flame five or six times, as otherwise the organisms are apt to be washed out. The cover-glass is then immersed in dilute acetic acid for about two minutes, well washed with water and dried again, this second drying being
74 RHEUMATOID ARTHRITIS.
to prevent the cover-glass sinking in the staining fluid. The stain which I have found most useful is aniline methylene blue. The cover-glass is placed, specimen side down, on a watch-glassful of the stain, and the whole placed in a moist chamber, in the dark, for three to five days. It is then washed in gently running water for some hours, rinsed in distilled water, dried and mounted in the usual way. More expeditious, though not giving such clear and well defined specimens are aniline gentian violet and carbolic fuchsine. This latter stain I have found it advantageous to dilute one-third with distilled water. Twelve to thirty-six hours are sufficient for these, in a moist chamber. The cover-glasses are washed in running water in the same way, then well rinsed with thirty per cent, alcohol, washed in distilled water, dried and mounted. The acetic acid clears the synovial film and allows the dye to penetrate more readily. The prolonged staining deeply colours the organisms, so that the washing process leaves them well stained, though the film is decolourized ; and the moist chamber, by preventing the evaporation of the dye, obviates the precipitate.
"Microscopic examination of the specimens reveals an or ganism possessing peculiar characteristics. At first-sight it appears to be a diplococcus, the two cocci being distinctly stained, but separated by a clear unstained interval — about equal in length to the diameter of either stained end. This interval I have never succeeded in staining. But careful observation will show, especially where the substratum is faintly coloured, that the intervening portion is nearly as broad as the diameter of either stained extremity, and that it has parallel contours. I therefore consider the organism to be a bacillus, which exhibits very marked polar staining. The average length is 2/x and the average breadth "6^, but this latter measurement varies greatly with the intensity of the staining. But the organism, as seen under the microscope, appears much smaller than the measurements would indicate, owing to the limited portions stained.
"The number of organisms met with in a cover-glass specimen
BACTERIOLOGY. 75
of synovial fluid from a joint, affected with rheumatoid ar- thritis, varies greatly. Sometimes the field is crowded with them; at other times they are scattered and hard to find. These differences appear to follow very closely the acuteness or chronicity of the disease.
" The organisms are generally evenly distributed through the film, showing, however, a tendency to congregate around the leucocytes. Their arrangement is always discrete; I have never seen chains or masses formed.
" Though the staining methods mentioned above have given me the most satisfactory specimens, yet the organisms can be seen when stained for a much shorter time, especially with gentian violet, methyl-violet, or carbolic fuchsine. But it is found that these stains if allowed to evaporate, deposit upon the cover-glass a precipitate of dye, which so closely resembles the organism, that it is by no means easy to recognize them when but few are present in a preparation so observed — be- cause after such a brief staining, attempts to remove the pre- cipitate by washing and the use of re-agents, bring about more or less completely the clecolourization of the organism; whereas after a longer contact with the stain, the microbes are coloured more firmly, and are less easily decolourized. But there is one exception to this statement, in a method which I have devised and found useful.
" Impressed with the small size of the organism and the minute portion stained, it occurred to me that the protoplasm might take up dyes more readily if it came into contact with them while moist. With this in view, I mixed a drop of synovial fluid with a few drops of the stain (aniline methylene blue being best) on a cover-glass, and rubbed out with a platinum needle. The cover-glass, with the stain and synovial fluid together, was then dried slowly over a burner, and when quite dry, fixed by passing several times through the flame, then freely washed with water, dried and mounted. In this way I obtained very fair results, the greater part of the stain being washed off, leaving the organism well coloured. For rapid diagnosis, this method is very useful.
y6 RHEUMATOID ARTHRITIS.
" Treated by Gram's method, the organism is almost com- pletely decolourized.
" I have been able also to detect the organism in the synovial fluid in the hanging drop specimen, but this is far from easy, unless they were present in larger numbers.
" I have now stained and examined the synovial fluid from various joints from eighteen cases affected with rheumatoid arthritis, and in every case have observed the organism which I have described above (see Plate II, Fig. A) ; but in fluids from distended joints, due to other causes, as chronic synovitis, gonorrhceal and tubercular affections, I have entirely failed to find them.
Cultivation.
"At first all attempts at cultivation, both aerobic and an- aerobic, yielded apparently no result. But I imagined that this might be due in part to the small size of the organism, so that if it formed colonies they might be scarcely per- ceptible, and judging from the scattered distribution in synovia that the tendency to a free growth might be small, and in part to a slow development. Keeping these points in view I resolved to try it upon a large scale, and in such a manner, that any change in the medium might be easily detected. Into litre and half-litre flasks were put 250 ccs. of peptone beef-broth, filtered repeatedly until it presented a perfectly clear and bright appearance. Great care was taken over this to avoid the slightest obscuration. The flasks were sterilized and placed in an incubator kept at blood heat for several days to prove their sterility, and also to be sure that the fluid remained perfectly clear. If these conditions were fulfilled, the flasks were carefully opened, and a drop or two of synovial fluid from an affected joint allowed to enter. The flasks were then incubated at blood heat. Similar flasks, but uninoculated were also incubated at the same time to serve as controls.
" I was fortunate enough to attain success with the first experiment. The first point noticed was that for three days
PLATE II.
Fir/. ..{.-Synovial fluid, stained with gentian violet, x 900.
Fig. 5.— Beef- broth culture, stained with carbolic fuchsine, x 900.
BACTERIOLOGY. 77
the beef-broth remained perfectly clear, pointing strongly to the conclusion that the synovial fluid contained no ordinary organism. But, from the fourth day and onwards, there could be seen floating in the clear fluid very minute particles, and these increasing gave rise to an appearance resembling " gold dust." This effect was enhanced by lightly shaking the flask. Sometimes the growth seems to stop at this "gold dust"' stage, but at other times it may become slightly flocculent, recalling to mind the appearance of a commencing growth of tubercle bacilli in glycerine beef-broth. The beef-broth never becomes turbid, but always retains its bright appearance.
" The control flasks showed no such development. Micro- scopic examination of such a culture, stained as before, displays the organisms in considerable numbers, but it can be readily understood from the delicate nature of the cultures and the imperfections of staining methods, that a too great reliance on stained specimens was not advisable, and that additional evidence would be helpful.
" Verification was obtained by making hanging drop speci- mens, and this is the easiest method of demonstrating the presence of the organism.
" In the hanging drop, the microbe appears, precisely as in the stained specimens, with two bright refractile ends, and an intermediate part much less obvious. They may occur in zoogloea masses, or as discrete individuals hugging the edge of the drop. They are non-motile, but have a marked oscil- latory movement. I have been fortunate enough to see them undergo division in the hanging drop specimen.
"The intervening portion lengthens out, the ends appearing to pull against one another energetically, and the whole organism oscillating the while uneasily. The middle part lengthens out more and more, so that the organism appears to be about twice its ordinary length ; then suddenly the link snaps, and freed ends fly off in contrary directions, and are lost amidst their fellows.
" This phenomenon helps, I think, to explain some variations in length frequently noticed in stained specimens from culture.
78 RHEUMATOID ARTHRITIS.
In these some bacilli will be seen very short, the stained ends quite close together, with a minute unstained connecting link, very suggestive of a diplococcus.
" These I take to be quite young organisms. Some, however, are much longer, attaining a length of 3/x, or possibly 4//, the stained edges widely separated, and a clear unstained sheath faintly visible with the highest powers. These I imagine to be the older forms, soon about to divide. In these older forms too, the staining is sometimes somewhat different. Instead of the staining portion being more or less spherical at the ends of the organism, the coloured part is in the form of a conical cap, the base towards the centre of the bacillus, and spreading faintly down the edges of the sheath. These forms show best the claim of the organism to be considered a bacillus. It will be obvious, however, that it is very difficult to bring out these subtle differences in a photograph — and indeed the limited staining of the organism and its minuteness, render the production of good photographs by no means easy (see Plate II, Fig. B).
"The organism also grows upon nutrient agar-agar. If beef- broth cultures are inoculated on tubes of sloping nutrient agar -agar, and incubated at blood heat, growth takes place in about three days, and in a very characteristic manner. This growth is exceedingly delicate. It appears no more than as a fine transparent film, which under a lens can be seen to consist of minute colonies no larger than a pin point, and perfectly transparent. To the naked eye it bears a very close resem- blance to condensation water, though control tubes and the obvious tests show that this is not the case.
" It grows also in Loffler's serum, but here the growth is even more difficult to recognize owing perhaps to the opalescence of the medium. It occurs as minute points, less difficult to observe at the lower part of the tube, where the condensation water has washed off the cholesterin. Stained cover-glass speci- mens, and hanging drop specimens made from such cultures, reveal an organism identical morphologically with that des- cribed as present in the beef-broth cultures and synovial fluid.
BA CTERIOLOG Y. 79
" I have also grown the organism in milk, where it appears to nourish, but without causing curdling, or precipitation of the casein. On nutrient gelatine, however, at 22° a, I have never succeeded in getting a growth, and in liquid gelatine incubated at 37° C. there is no visible growth.
" Examination of the blood in cases affected with rheumatoid arthritis has also afforded me positive results of the presence of the organism.
" I have examined the blood taken near to an affected joint, and also that from a distance, and in both have been able to detect the organism in microscopic specimens. Out of five specimens of blood submitted to me, I have been successful in three, and these were the most severe cases. But further proof of the presence of the organism in the blood is the fact that twice I have been able to obtain cultures from it. The method was the same as previously described. The blood was inoculated into flasks of clear sterilized beef-broth and inoculated at blood heat temperature. Subcultures were also made from these flasks on to agar-agar and blood-serum. The organism found was identical in every respect with that which grew from the synovial fluid, and with that which was observed in the stained specimens.
" Some animal experiments have been made, for which I am indebted to the Council of the Royal College of Surgeons, and to Dr. J. Sims Woodhead. Two ccms. were injected subcu- taneously into mice, guinea-pigs, and rabbits, but without a fatal result. There is some reason to think, however, that the cultures set up a disease in rabbits, which affected the joints; but further experiments are necessary to arrive at the truth with regard to this matter.
"As far as I am aware only one organism has been previously associated with rheumatoid arthritis, which it is necessary to discuss. This was described by Schuller.* He writes of a bacillus 2-6yu long and '75— '995/x broad, which exhibits polar staining. It is easily coloured by ordinary stains, especially
* Max Schiiller : "Berliner Klinisch. Wochenschrif t, " Septem- ber 4th, 1393.
8o RHEUMATOID ARTHRITIS.
carbolic fuchsine, but very easily decolourized. It is noteworthy that Schiiller thinks it incumbent on him to point out the distinction between his organism and tubercle bacilli.
" It grows readily upon gelatine at 25° c. In two, three, or six days, small white grains or knobs appear. The gelatine is liquified, and eventually the organism grows to such an extent, that tho whole mass becomes opaque white. On agar-agar ic grows as greyish white flecks or films.
" It is obvious that the organism described by Schiiller differs markedly from the one under discussion. In fact the only points of resemblance are the polar staining and the easy dis- colorization. It therefore appears to me to be indisputable that this organism of Schiiller's is not that which was dis- covered by Drs. Bannatyne and Wohlmann.
" To sum up : —
"(1,) In the synovial fluid in eighteen cases of rheumatoid arthritis an organism has been demonstrated, which is constant in its characteristics.
" (2,) The organism is a minute bacillus, exhibiting marked polar staining. It is difficult to stain and easily decolourized.
" (3,) The organism can be grown in culture media, and pre- sents striking characteristics. In beef-broth it gives the appearance of gold dust ; and on agar-agar and serum its growth is almost invisible.
" It does not grow on nutrient gelatine at ordinary tem- perature.
" (4,) It is present in the blood of severe cases.
" (5,) It has not been found in the synovial fluid from distended joints due to other causes.
" It should be added, that it has been impossible to examine sections of the synovial membrane, owing to the want of pathological specimens.
" In conclusion I should like to record my thanks to Mr. Barnard, for the care and skill he has expended on the photographs."
BACTERIOLOGY. 8;
This report not only corroborates what Dr. Wohlmann and I had previously determined, but it carries us much further. The staining methods, as described, and cul- ture experiments, are the labour of months, and may be safely recommended to all those who would pursue the subject further.
To summarise, I may say, we have found a constant microbe presenting marked peculiarities in all but one of the cases examined, this one failure being easily explainable on account of our deficient methods and knowledge. We have not succeeded by re-inoculation as yet in producing the original disease in animals, but the experiments have been so few as to be of little or no value (what results have been obtained are on our side). As far as I know the disease is practically unknown amongst them, and, in fact, they may be naturally immune. The subject is one of great interest, but, as will be gathered from the foregoing, of considerable difficulty.
REFERENCES.
1. Colles. — Quoted Garrod, "Rheumatism and Rheumatoid
Arthritis," p. 274.
2. Todd.—" On Gout and Rheumatism," 1843.
3. Adams.—" On Rheumatic Gout," 1873.
4. Brodie.— " Diseases of the Joints," 1833.
5. Cruveilheir. — "Anat. Pathologique," Lee. ix.
6. Fuller. — "Rheumatism, Rheumatic Gout and Sciatica," 1852.
7. Senator. — " Ziemsson's Handbuch."
8. Garrod. — "Treatise on Rheumatism and Rheumatoid
Arthritis"
9. Rindfleisch. — " Pathological Histology."
10. Trousseau. — " Lect. on Clinical Medicine," (Syd. Soc.transl.)
11. Billroth. — "Gen. Surgical Pathology and Therapeutics,"
(transl).
12. Chvostek.— " Wien. klin. Wochenschrift," June 27, 1895.
13. Lcbert.— " Handbuch der Pract. Med." 1859, ii.
14. Cornil and Ranvier. — " Manual of Pathological Histology,"
vol. i., 1892.
15. Kolliker. — " Elements of Human Histology."
82 RHEUMATOID ARTHRITIS.
15a. Rokitansky. — " Path. Anatomy," Sydeuham Society, vol. iii., p. 289.
16. Besnier. — " Diet. Encylop. des Sciences Med." 1876, p. 155.
17. Homolle--" Diet, de Med. and Chir. Prat." 1882.
18. Hoppe Seyler.— " Virchow's Arch." 1872.
19. " Qnain's Anatomy," 9th edit., p. 219.
20. Monllin, M.— " Lancet," 1891, vol. ii., p. 125.
21. Weber. — " Journal of Nervous and Mental Dis." New York,
1884.
22. Volkmann. — " Handbuch der Chirurgie," Band ii., p. 555.
23. Broca.--" Bull, de la Soc. Anatom." xxv., 1850.
24. Ziegler.— " Virchow's Archiv." 1877, lxx., p. 592.
25. Gwilt. -" Handbuch der Path. Anat." p. 1,000.
26. Husse.— " Zeitschrift flir Rat. Med." vol. v., p. 192.
27. Kussmaul. — " Arch, ftir Physiolog. Heilkunde," vol. xi., 1852.
28. Debove.— " Prog. Med." 1880, p. 1011.
29. Vallat— " Arch. Generates de Med." 1877.
30. Folli.— " II Policlimco," December, 1894.
31. Voit and Bauer. — " Zeitschrift fiir Biologie," vii.
32. Trzebinski. — " Arch, fiir Path. Anat. u. Phvsiolog. u. fiir Klin.
Med." Bd. cvii., Heft 1. 32a. Massolongo.— " Riforma Medica," 1893, vol. ii., p. 159.
33. Pitres and Vaillard.— " Revue de Med.," 1887, No. 6.
34. Pitt.—" Clin. Soc. Trans.," vol. xxvii., 1894, p. 54.
35. Nepven. — " Comptes rendus de Soc. de biologie," Paris,
1890, vol. ii., p. 328.
36. Cavafy.— " Path. Trans.," 1883, p. 41.
37. Heberden. — " Commentaries," 1804.
38. Begbie.— Contrib. to " Practical Medicine," 1862, p. 28.
39. Charcot. — " (Euvres Completes," tome, vii., 1889, p. 217.
40. Garrod, Sir A. B.— " Gout and Rheumatic Gout," 1876, p. 503.
41. Garrod, Dr. A. E. — "Rheumatism and Rheumatoid
Arthritis," 1890, 266.
42. Duckworth, Sir Dyce.— " Treatise on Gout," 1889, p. 71.
43. Lecorche.— " Traite de la Goutte," 1884, p. 122.
44. Pfeiffer.— " Lancet," vol. i., 1891, p. 819.
45. Turner. — " Edin. Hosp. Re£)orts," vol. iii., p. 627.
46. Lunn.— " Lancet," vol. i., 1896, p. 294.
S3
CHAPTEE IV. VARIETIES AND DIAGNOSIS.
Errors in Diagnosis — Acute Rheumatoid Arthritis — Osteo- Arthritis — Charcot's Classification — Post-Rheumatic, Gonor- rheal and Gouty Forms— Acute and Sub-acute Rheumatoid Arthritis — Infantile Arthritis — In Children— In Adults — Differences — Symptoms — Appearances of Joints — Chronic Rheumatoid Arthritis — Age — -Appearances— Bony Changes — Diagnosis between it and Nerve Diseases — Charcot's Disease — Rheumatism — Gout — Chronic Rheumatism, etc.
l.-VARIETIES.
Peobably Eheumatoicl Arthritis is responsible for more errors in diagnosis than almost any other form of known disease. This not only arises from the difficulty in recognising the disease from certain forms of rheu- matism and gout, but also because under the name rheumatoid arthritis several forms of disease have been, and still are classified. A further differentiation is greatly to be desired, not only on account of the treatment, but likewise for prognostic purposes. It has been my lot to see annually a large number of cases sent to Bath for treatment, and to which, in the greater proportion of cases, the wrong name is given. Most confusion arises apparently between what is, and what is not chronic rheumatism, the larger proportion of cases, thus designated, being cases of rheumatoid disease; and, again, there often is confusion between rheumatoid arthritis, and some forms of chronic gout. With care one can usually differentiate between these conditions, but it is not always easy to do so straight off.
84 RHEUMATOID ARTHRITIS.
It is my intention to divide the disease into two sections. In one : (a,) I will class all those acute and sub-acute cases characterised by inflammatory changes in the joints — ulceration and erosion of the cartilages and bones, muscular atrophy, and by other nerve and trophic phenomena ; and, in the other (b,) all those chronic cases characterised by a slowly progressive thickening and hardening of all the joint structures, by the development of deformities, by the formation of osteophytes, and by the lipping of cartilage, etc. Owing to the bony changes and to the general thickened character of the joints, it is to this form of the disease, rather than to the acuter, that I would more especially confine the term osteoarthritis.
My plan of sub-division then is as follows : —
I. Acute Rheumatoid Arthritis, divided into the (a,) Acute, and (b,) Sub-acute forms, and
II. Chronic Rheumatoid Arthritis or Osteo-Arthritis. Now, for a moment, let us glance at the other forms
of classification hitherto adopted — most of them being- based on that of Charcot.1 His method was as follows: —
1. Rheumatisme Artieulaire Chronique primitif general- ise ou progressif (the Rheumatisme Noueux of others). — This group is distinguished by the disease having a tendency to become general, by the small joints of the extremities, such as those of the hand, and, especi- ally of the metacarpo-phalangeal, being symmetrically affected, and, by the fact, that during the progress of the disease, most of the other joints are successively attacked in a definite order, and for the most part the mischief is irreparable.
2. Rheumatisme Artieulaire Chronique primitif fixe on partial. — In this group the disease is usually localised to one or two of the larger joints, producing deep seated mischief. It is sometimes called arthrite seehe or morbus eoxse senilis.
VARIETIES. 85
3. Nodosites d' Heberden.- — This group contains those cases usually classed amongst gouty affections, and confined either to the extreme joints of the fingers, or else to the next row, leaving, as a rule, the metacarpo- phalangeal joints free.
More latterly, Dr. Garrod2 has qualified this classi- fication by adding a fourth group of cases which occur subsequent to attacks of acute rheumatism, gout, or gonorrheal arthritis. These two classifications form the basis of all subsequent ones, and for all practical purposes are efficient. On one point I dissent from both writers, and in fact from all English authors, and this is with regard to Morbus Coxae Senilis. This form of disease I hold, is not true rheumatoidal, and, therefore, I have omitted it from my classification.
Before proceeding further, allow me to refer briefly, to those forms of rheumatoid arthritis which occur secondary, to some acute arthritic attack. In spite of being secondary in nature, they present all the charac- teristics of the primary forms, and, after a few remarks, will be classed, and considered, with them.
(«,) Post Rheumatic Form. — As has been already stated, rheumatoid disease is a frequent sequela of acute attacks of rheumatism. Some observers hold that the rheumatoidal attack is merely the continuation of the rheumatic changes ; but, of recent years, other views have been advanced and accepted. We have come to understand how any acute arthritic attack lays the joint tissues open to a subsequent attack of the same disease, and also to one of some other disease. What is curious is, that a disease originally limited to one joint should render the patient liable to a generalised disease — yet such is the case. This rather points to some blood condition, than to one entirely dependent on a local joint state. McArdle3 points this out, and I have often
86 RHEUMATOID ARTHRITIS.
proved the truth of his observation. If Ave believe, as I do, that both rheumatism and rheumatoid arthritis are caused by infective organisms, or by their elaborated poisons, we can more readily understand, and appre- ciate, the significance of this rather remarkable fact. Schuller 4 goes the length of proving that the rheumatic poison renders the joints and constitution more liable to be affected by rheumatoid arthritis. This probably also applies to as great an extent in the case of gout, gonorrhoea, or indeed, to any infective form of arthritis. In post-rheumatic forms, we find an increased tendency to the occurrence of visceral lesions.
(b,) Post Gouty Forms. — Hutchinson 5 mentions such cases as proof of his theory, as to the nature and origin of the disease. Garrod supports the view that it is a common sequela, but Sir Dyce Duckworth disagrees with it entirely. The latter holds that all deformities and distortions, met with in uratic arthritis, are due entirely to gout. With regard to their clinical features, he says, they in many ways resemble those of rheuma- toid arthritis.
(c,) Post Gonorrheal Form. — The occurrence of rheu- matoid changes, after a gonorrheal arthritis, is naturally much rarer than that following a rheumatic attack. It, however, does occur, and has been mentioned in the writings of Charcot, Lorain,6 who gave it the name Rheumatisme blenorrhagique a forme noueux, Sir Alfred Garrod, Dr. A. E. Garrod, and others.
Just as one form of bacteria, by being antagonistic to another, prevents the development of the latter, in the presence of the former, so we would expect to find the converse ; and not only during the period of their activity, but after their attack has passed, they may either have so exhausted the body's natural protective powers, or else, by the presence of a toxine or
VARIETIES. 87
ferment, so have paralysed this power, as to. render the system an easy prey to an otherwise innocuous attack. We might expect that one micro-organism, if it did not afford immunity, would render the joints doubly liable to the attacks of another organism, having a somewhat similar nature, and a somewhat similar action. As yet we are only on the borderland of know- ledge of such subjects, and one's remarks must perforce contain a large amount of what is, as yet, pure supposition. We know nothing for certain.
While on this subject, I may mention again Drs. Ewing's7 and Foclor's8 experiments, showing that anything which reduces the alkalinity of the blood, reduces its germicidal power. Now we have in this a clue to the action of bacteria in this disease when it follows on rheumatism and gout. In both these latter, the blood's alkalinity is notoriously decreased. What with the reduced alkalinity, and the destructive action of the primary poison, we can understand how easily the tissues may come under the influence of secondary infections.
I. — Acute Eheumatoid Arthritis. In this division come all cases, acute and sub-acute, seen alike in the young, and in the grown up ; occurring either as a primary disease, or secondary to some other form of arthritis, or to injury. In these forms it is always poly-articular. Although occurring at any period of life, the acuteness of the disorder varies largely with the age of the individual attacked. In children it rarely is chronic, but tends to assume a rapidly pro- gressive character, only differing from the acute form seen in adults, by its more frequent fatal termination. In young adults it also is usually acute or sub- acute. In elderly people acuteness is rarely seen, but, in this respect, it makes up by its intractableness.
88 RHEUMATOID ARTHRITIS.
(a,) Acute Rheumatoid Arthritis. — Fuller 9 was the first to point out the characteristics of this form, and subsequently Garrod drew attention to it, pointing out various things to be noted in the differential diagnosis between it and acute rheumatism. Both he and Fuller draw attention to its obstinacy, to the character of its articular swellings, and to the liability of certain joints to be involved. Some deny that this form exists, holding that it is only a modification of acute rheumatism, but, although, if care be not ex- ercised it lends itself to much confusion, yet, to one who has studied the two diseases, no confusion is possible. In rheumatoid arthritis the disease involves the bones, cartilages, synovial membrane, and ligaments, and is accompanied by well marked atrophy, trophic, vaso-motor, and other nerve phenomena, which render it quite distinctive and characteristic. In children, we must carefully distinguish it from those cases of multiple nerve arthrites — a few of which have been recorded. These are so similar to what one would expect in rheumatoid disease, that I am almost tempted to believe, that they are cases of this disorder, only, occurring in a somewhat unusual manner. Pasteur10 mentions such a case, in which there was no enlarge- ment of the ends of the bones, but there was arthritis, accompanied by a hide-bound condition of the skin. Barlow n reports another such case, in which there were subcutaneous nodules. One must remember that arthritis has been known to arise in scleroderma, and scleroderma in rheumatoid arthritis. Jaccoud12 mentions a class of cases somewhat similar, under the name of Rheumatisme fibreux. Wagner13 also has described similar cases. From examinations, these joints show little change in the cartilages, but fibrous bands develop across the joints, and greatly restrict their movements,
Er-
VARIETIES. 89
as well as lead, by slow contraction to great deformity. There is always great doubt as to what we are dealing with in such cases, but one must always bear in mind that arthritic changes are fairly common, as the result of spinal degenerative changes. Such being the case, great care is not only necessary in the diagnosis, but in the treatment.
Acute rheumatoid al disease is undoubtedly more important from the clinical standpoint, than the average chronic case. What makes these cases so interesting is the age at which they occur, children and young adults, being for the most part affected. We find it usually com- mences in one joint, probably one of the metacarpo- phalangeal ones. It does not remain long confined to this one joint, but spreads like wild-fire, to most of the other joints of the body. It shows a wonderful symmetry not only in the joints affected, but, to a less extent in the degree. Symmetry is also seen in the other phenomena present. The joints are swollen, presenting a characteristic, ovoid or spindle shaped enlargement, painful and tender to the touch, and hot. On palpation, they either feel resistent and elastic (Plate III, Fig. A), with distinct fluctuation, or else they feel as if they had undergone maceration. The ligaments and other joint structures being soft, and doughy, and admitting of a finger tip being sunk into the joints, between the heads of the bones ; they at times feel as if they would drop apart (Plate III, Fig. B). The second condition is in all probability secondary to the first — the cartilages, and other joint structures being destroyed, whilst the acute inflammatory condition still exists. Later on it will become harder again as cicatrisation occurs. This feeling, and that of tense resistance, are quite characteristic. Along with this the extremities feel cold, and look blue, being bathed in a cold clammy
90 RHE UMA TOW A R THRIT1S.
perspiration, although the body temperature is raised generally. Eecent pigmentations, and other integu- mentary abnormalities, develop on the face, body, and forearms, etc., whilst all the time a progressive muscular atrophy is occurring. The affected muscles are not merely those in the immediate neighbourhood of the diseased joints, or even distal to them, but may be situated on the proximal side as well. A characteristic selection of the muscles is observed, the atrophy is accompanied by cramps, and fibrillary twitchings, with, sometimes, increase of the reflexes, but, unless peripheral neuritis has been set up, no reaction of degeneration. As the case progresses the pain becomes greater, worse probably at night, and on movement of the joint ; the movement also gradually becomes more and more limited. No sleep may be obtainable, except by the use of powerful hyp- notics, and the disease becomes more and more distressing to watch and to treat. Cardiac abnormalities are fairly common, and we have other visceral derangements.
The question of its occurrence in children is of interest. The disease as seen in them is usually very acute, and pre- sents all the symptoms as seen in adults. The youngest child I have seen affected was a boy, aged four, the next, also a boy, aged seven (Plate F), and the next a girl, aged eight (Plate IV). Undoubted cases have been recorded by Sir Alfred Garrod,14 Lecaze Dori,15 Monocoro,16 Dr. A. E. Garrod, Lloyd Davies,17 etc. In his diseases of children, Dr. Money 18 mentions that rheumatoid arthritis is seen in children, and that it may follow on an acute attack of rheumatism : that it may affect both the feet and hands, and resemble the multiple joint affection of middle aged women, rather than the arthritis sicca of the old. The propensit}^, he says, to deformities and ankylosis in awkward positions is rather great. Henoch, in his book on diseases of chil-
VARIETIES. 91
dren, also mentions certain cases of apparently rheuma- toid disease, but he, like many foreign observers, does not differentiate between it and chronic rheumatic arthritis.
(&,) Sub-aeute Rheumatoid Arthritis. — This also is most common in children, and young adults, and is seen more rarely in elderly people. As a rule, it occurs only as a stage of a more acute attack, but, of course, it may from the first be sub-acute in nature. It is marked by all the symptoms of the acuter form in a milder degree, with super-added greater liability to deformities and distortions. The muscular wasting is as marked, but there is greater cicatricial thickening of the synovial membrane and ligaments, leading to adhesions and deformities (Plate VII, Fig. A). There is increased osteophytic formation, the heads of the bones enlarging until they assume the mushroom-like appear- ance of the typically chronic case. There is less synovial fluid present, and we now get crepitation and grating on movement, most often of the coarser variety. It is rarely fatal, but tends to gradually become more and more chronic, assuming all the characteristics of the latter form.
II. — Cheonic Rheumatoid Akthritis or Osteo-Arthritis. In this form it may arise per se, and be always chronic ; or it may be only the later stages of an acute attack ; or it may follow on some other form of arthri- tis ; or as the result of injury. It may affect many joints, or it may be confined to only one or two. As a primary disease it is most often seen in middle aged, and elderly women. It is characterised by great hardening and thickening of the joint tissues, both soft and hard ; by eburnation of bone ; by erosion of the cartilages ; by osteophytic deposits ; by cartilaginous
92 RHEUMATOID ARTHRITIS.
overgrowths and new deposits ; by lipping, etc. There is consequently much deformity, distortion, and stiffness. This latter varies, as in one case it may be of the slightest, whilst in another, it may resist all treatment, and end in ankylosis. Pain as a rule is not acute, being more of a constant, gnawing, or wearying charac- ter. One joint only may be affected, and in which it may remain, or it may advance steadily from joint to joint, causing great crippling, not only from deformity, but from fixing and ankylosis. One marked feature is the absence of fever, of almost all heat in the joints, and by the absence of the trophic and nerve changes. It looks as if the sclerosis or condensation of the bones and tissues, so peculiar to this condition, had given them power to resist not only the inroads of the micro- organisms, but the absorption of their toxines. We must in these cases discount all the trophic and nerve abnormalities of the acuter stages and those arising from disuse. In many respects in Eheumatoid Arthritis one sees resemblances to phthisis, but in none more so than between the acute and chronic forms, for, have we not an almost analogous condition between phthisis and fibroid phthisis ?
2.-DIAGN0SIS.
From Charcot's Joint Disease it may be distinguished clinically, by the absence of the nerve symptoms so well marked in that disease, especially the muscular inco- ordination, etc., and by the fact that the joint changes in tabes are marked by the suddenness of the onset ; by the absence of pain ; by the large quantity of fluid in the joint ; by the fact that the joint changes at first are always atrophic, although they may later on become hypertrophic, and by the increased mobility.
From other nerve arthropathies by the absence in
>
-3
Cxi
DIAGNOSIS. 93
them of pain, and by the presence of well marked nerve symptoms.
From Syringomyelia, by the formation of new bone in rheumatoid arthritis being confined to the interior of the joint capsule, while in syringomyelia and other spinal arthropathies there may be extreme ossification of the periarticular soft parts (Volkmann). This cannot be relied upon, however, as in the chronic cases of rheumatoid arthritis there may be considerable formation of bone in the adjacent tendons, ligaments, bursse, etc.
From Pulmonary Hypertrophic Osteo-arthropathy, by the presence of pulmonary troubles in that disease, and by the changes being almost entirely confined to the bones. Until more is known of this disease we are not in a favourable position to lay down strict laws with regard to its differential diagnosis.
From Acute Rheumatism there is little difficulty in making a diagnosis, except in those rare cases of Eheu- matoid Arthritis, where several joints become acutely inflamed at one time. The whole history of the case is otherwise different. Its preponderating frequency in women is a point of importance. Apart from this, the general clinical features of the arthritis are quite different ; while acute rheumatism begins in the medium sized joints and spreads to the smaller, rheumatoid arthritis begins in the smaller and spreads to the larger. The former too is migratory and uncertain in its extension ; the latter is slowly progressive, with a greater tendency to symmetry. The pyrexia of acute rheumatism, the perspiration, the greater liability to cardiac complications, are all characteristic. The real difficulties arise in sub-acute, and chronic cases, when the joint must be minutely examined so as to make out that the stiffness, swelling, and deformity, depend upon
94 RHEUMATOID ARTHRITIS.
a general thickening of the textures about the joints, and not on destructive changes in the joint.
From Chronic Gout the distinction is made by noting the previous history, and by careful examination of the joints. Besides the fact of its greater frequency in men in middle life, whose habits and mode of life contribute to bring it on, there is usually an account of previous acute attacks in the joints, mostly the great toe, and, while in the course of time other joints are affected, the disease cannot be said to have the same progressive character and symmetrical spread. The joint changes too are different. Urate of soda deposits may be noticed in, or about the joint, as well as elsewhere, as in the ears, etc. What is quite certain is that the destruction of inter- articular cartilage, and alterations in the ends of the bones in rheumatoid disease, are not due to previous gouty deposits.
A point to be noted in diagnosis is the muscular atrophy, which presents the following peculiar and typical features : —
1. It is most marked in the muscles in the immediate neighbourhood of the joints (interossei, etc.).
2. It is not infrequently found to have affected muscles beyond this region (trapezius, deltoid pec- torals, etc.).
3. It improves, and tends to disappear if the joint trouble ceases, although it would seem to persist at times long afterwards.
4. It is sometimes accompanied by changes in the electrical excitability of the muscles.
DIAGNOSIS.
95
|
o is |
Inflammatory thicken - ing of the joint tissues, with deposits of Urate of Sodium, but does not tend to destroy tissues. |
Most common in men. |
CO ■+= O CO a II o CO |
Uric acid always pres- ent, either in blood or deposited in tissues. |
Chiefly affects great toe. |
||||||||
|
CO «! a B tf o d K b O |
Has little tendency to the destruction of the joint tissues, and no ten- dency to the formation of bony and cartilaginous deposits. |
1 1 1 |
1 1 i 1 |
CD -4-3 O CO -t-3 O CO l—i |
1 i ! 1 |
1 i 1 |
1 |
c3 CO c3 u -4-3 CD a a >> CO O |
|||||
|
s CO s a B O |
Affects only the fibrous tissues, and is marked by great synovial disten- sion, pain, and heat. |
° q CD O S3 .a o -4-= >VcO 'eg co CO ^ L) co ^ co |
1 1 1 |
CD CD O CO co" CD |
I ra I .2 5 3 f c6 ft t a.= o - CO P |
3 ■i ^4 Q -1 i 1 3 2 "I l-H j .2 2 -+3 |
u CD > CO q .2 'co CD O nd O ^ c q a o o |
1 1 1 ! i |
1 1 1 |
Does not affect neck and jaw as a rule, and symmetry not so marked. |
|||
|
co CO co CD 1-1 3 |
CO ?■ M C C |
||||||||||||
|
co 3 a a p s D S 3 |
Inflammation quickly involves cartilages and bones, and, in chronic cases, is characterised by great new formation of tissue. |
co o CD CO i-H +3 CD S o q q co ° a co CD o g ^ CD |
CD .a q o a 1 o o -4-3 ^ IS a |
CD q o c6 CO -4J O q °3 CD £ S Q q o o |
'q o CO .2 "02 q CP o a .5 o CO j^ CO |
Acute form accompan- ied by muscular atrophy, and many trophic phe- nomena. |
1 1 1 1 |
Is specially liable to to affect small joints, neck and jaw symmetrically. |
|||||
|
i—i |
CM |
CO |
^ |
iO |
8D |
C~ |
CO |
Oi |
96 RHEUMATOID ARTHRITIS.
REFERENCES.
1. Charcot. — " Maladies des Vieillards."
2. Garrod. — "Rheumatism and Rheumatoid Arthritis," p. 236.
3. McArdle.—" Dublin Med. Journal," 1885, lxix., p. 490,
and lxx., p. 398.
4. Schiiller.— " Med. Record," Sept. 23rd, 1893.
5. Hutchinson. — "Med. Times and Gazette," 1881, vol. i.
6. Lorain.— "Union Medicale," 1866, xxxii., p. 617.
7. Ewing.— "Lancet," vol. i., 1894, p. 1336.
8. Fodor. — "Centralb. f. Bakt. u. Parasitenk.," Feb. 28th,
1995.
9. Fuller. — "Rheumatism, Rheumatic Gout and Sciatica,"
1852.
10. Pasteur. — " Clin. Soc. Trans," vol. xxii.
11. Barlow. — Quoted Garrod, loc. cit. p. 247.
12. Jaccoud. — " Le9ons de Clin. Med.," 1867, le<;on, xxiii., p.
598.
13. Wagner.—" Mlinchener Med. Wochenschr.," 1888.
14. Garrod, Sir A. — " Rheumatism and Rheumatic Gout."
15. Lecaze Dori. — " These de Paris," 1882.
16. Monocoro — " Rheumatisme Chronique Noueux des
Enfants," 1880.
17. Lloyd Davies.— " Lancet," vol. ii., 1893 p. 928.
18. Money. — "Diseases of Children," p. 130.
PLATE VI,
Fig. A. Shows cartilaginous and bony enlargements of the heads of the bones, with considerable synovial swelling and thickening. Atrophy is marked . K — Shows thickening of wrist joint.
Fig. B. — Ulnar deflection in a chronic case.
CHAPTER V. SYMPTOMS AND PROGNOSIS.
Premonitory Symptoms — Spender — Primary Symptoms due to Micro-organisms — Appearance of Joints — Heat of Skin — Ar- thrite Seche — Synovial Pouches — Joints first Affected — Sym- metry — Ankylosis — ■ Deformities — Dislocations — Osteophytic Oat -growths — Forms of the Deformities — In the Hands and Knees — Its Causes — Difference in Acute and Chronic Cases — Cardiac Symptoms — Endocarditis — Pericarditis— Changes in the Glands — Secondary Symptoms — Muscular Atrophy — Its Characters — Selective Power — Myotatic Irritability — Fever — Pulse Rate — Tachycardia — Tension — Anaemia — Haemorrhages — Purpura — Neuritis — Its Frequency — Trophic Phenomena — Skin Changes — Glossy Skin — Loss of Hair — Atrophy — Downy- growth of Hair — Pigmentation — Sweating — Dyspepsia — Kid- ney— Cardiac troubles — Prognosis.
1. — Symptoms.
As a rule, in every disease we find some salient and constant symptoms which may be taken to represent individual disorders — for without them we would have no characteristic abnormalities. It is so in Rheumatoid Arthritis. In this disease the joint symptoms are charac- teristic and constant ; but besides, and as will be seen later, the character and number of them, and the number of the structures attacked, all suggest a systemic disease of some blood poison.
The symptoms may be divided into
A. -Premonitory Symptoms ;
B.— Primary Symptoms, due to the direct effect of the micro-organisms themselves, and
C— Secondary Symptoms, due to the absorption of toxines elaborated by the micro-organisms.
7
98 RHEUMATOID ARTHRITIS.
A.— The Premonitory Symptoms.
The disease, in many cases, has no premonitory symptoms, the first indication of anything being wrong in the joint being slight pain, with some swelling, and tenderness on pressure, or on movement. Should, how- ever, premonitory symptoms be present, they usually present themselves in the form of numbness, tingling, or other abnormal sensation of the extremities. Howard,1 Homolle,2 and Garrod,3 all mention such cases. Howard compares them with the abnormal sensations noticed in spinal disease. Garrod quotes cases in which there was a history of sensations of pins and needles in the arms and hands, and growing pains in the bones. In my ex- perience I have never been able to get a really reliable history of any premonitory symptom. I have had patients say they felt abnormal sensations, but on further investigation I have found that there has almost invari- ably been some antecedent trouble which has caused such confusion as to make their evidence quite unreliable. Patients naturally pay more attention to such sensations than they do to a trivial pain or swelling of a finger joint or knuckle. I think, therefore, we may dismiss from our minds, as not of much importance, the premonitory symptoms. Before leaving the subject, however, I must mention the symptoms described by Dr. Spender,4 which according to him, if not actually pre- monitory, occur very early after the onset of the disease. The symptoms referred to are various vaso-motor and trophic disturbances, which will be discussed more fully later on, and pain. The pain on which he lays such stress is one occurring in the ball of the thumb, and on the inner side of the wrist. He considers it to be of great importance, and almost pathognomonic, and it may be accompanied by a feeling, described by patients, as of being ''parboiled, scalded, stung all over with nettles,"
PLATE VII.
Fig. A. Shows deflection of left hand. There is complete dislocation of 1st phalanx of index finger on to palmar surface of metacarpal, and partial of '2nd phalanx on to palmar surface of 1st ring finger.
Fig. B. Showing spindle shaped swelling of phalangeal joints.
SYMPTOMS. 99
etc. The pains themselves are various in character, but those of a neuralgic character are common and characteristic. They are more often referred to the bones than to the joints themselves.
Given then a disease ushered in by the foregoing pre- monitory sensations, or by neuralgic pains, it is not long before we find evidence of the disease in the joints themselves ; and, following on the joint symptoms, come atrophy of the muscles with, at shorter or longer intervals, certain other symptoms due, for the most part, to derangement of the nervous and vaso-motor systems. The occurrence of certain changes in the joints, with or without these other symptoms, then, constitutes the disease called rheumatoid arthritis. Of the local symptoms, of course, the most important are those referable to the joints.
B.— Primary or essential Symptoms.
1. Symptoms due to the presence of the micro-organisms in the joints. — To the eye the earliest symptom is some enlargement of one or more joints. This may vary in degree from the most trivial swelling to an enormous distension. It assumes all sorts of shapes, and charac- teristics, and the skin covering the joints may be subject to many, and various trophic changes. Apart from the trophic changes it may be reddened, but more often pre- sents a bluish, asphyxiated look quite characteristic. As a rule, the shape is more or less characteristic in so far as the joint alone is affected, but should the tendons or their sheaths have undergone rheumatoid changes one can never say what the alteration may be. In an ordinary case then the joint will be more or less spindle- shaped, merging gradually into the tissue above and below {Plate VII, Fig. B, and Plate III, Fig. A).
In acute cases, we may have such an enlargement, due either to the presence of fluid, or else to pulpy swell-
ioo RHEUMATOID ARTHRITIS.
ing of the synovial membrane ; or again, we may find that the swelling is not symmetrically spindle-shaped, and there are what seem to be pseudo-depressions between the heads of the bones, due to these latter being pushed apart by the swollen joint tissue, and to the general softening of the ligaments and tendons (Plate III, Fig. B) . In chronic cases the enlargement is usually more irregular, and may, from the enlargement of the heads of the bones, and from the presence of nodules of osteophyte growth, as well as from the swelling of the synovial membrane and presence of fluid, present an enormous and irregular enlargement. As the disease commences in the synovial membrane it is not until the later stages, of the acute, or in the chronic form that we see much bony enlargement (Plate VI, Fig. A).
Owing to cystic enlargements, or bursse, certain aspects of the joint may be increased in size out of all proportion to the rest. In many cases the mapping out of the syn- ovial sacs is very perfect, from the swelling being almost entirely confined to them, and, in such cases, the enlarge- ment is sharply demarcated from the surrounding tissues.
While the acute stage is still in progress, to the touch the joints feel hot — the temperature often being raised l°-2° Fahr. above that of the surround- ing surfaces.
As to the eye, so to the touch, we find three con- ditions : —
(a,) A tense, elastic, and resistant swelling with distinct fluctuation, often with secondary sac-like protrusions of synovial membrane — best seen in the joints of the fingers, and evidently caused by the presence of a considerable quantity of fluid under some tension.
(b,) A soft flabby doughy feeling, as if joints, ligaments, and all the surrounding tissue had undergone maceration.
SYMPTOMS. 101
Over the joint cavity there is a sort of depression in the middle of the otherwise generalised swelling, and every- thing feels doughy or pulpy. There is seldom much fluid present in such cases, but they are most acutely progressive. It is usually a secondary stage of the acute form, and shows that much dis-organisation of the joint has taken place.
(c,) The third condition is that described by the French under the name, " Arthrite Seche." In these cases the joints are enlarged and nodular, and one feels that the heads of the bones have undergone enlargement ; the synovial membrane is doughy; there is much crepitation on movement ; joints can with difficulty be moved, and this even, if passive, causes much pain; and there may be ankylosis. It is usually a sequel of the more acute stages.
At first, on passive movement, there may be little or no pain, and there may be no tenderness ; but pain in the acute forms soon becomes marked, and persistent both on movement, and at rest, especially at night. On move- ment in the drier, and more chronic forms, we get grating on moving the heads of the bones one over another. This may become quite a marked feature. At first it resembles fine crepitation, but soon passes into the coarser varieties which only cease from total inability to move the joint.
During the first stages the skin over the joints may be reddened, and dusky in hue, along with the other symp- toms of acute trouble, and in the later we see various trophic changes, such as " glossy " skin, increase of pigment, etc.
With regard to the pouches or cysts seen either in connection with, or in proximity to, a joint, Mr. Morant Baker5 says that they arise from the synovial cavities by a process of distention. The synovial fluid
102 RHEUMATOID ARTHRITIS.
on reaching a certain degree of tension finds its way out into the tissues in the direction of least resistance. It does so either through some normal channel, such as that by which a bursa communicates with a joint, or else by the formation of a hernial projection of synovial membrane. Finally it pushes its way into, and between, the tissues until its boundaries come to be formed by the muscles and other surrounding tissues. I have often seen such pouches gradually being pushed through the tissues surrounding the joints, and one can readily understand how they might have their communication with the joint cut off either by pressure, from the quickly enlarging joint, or else by a twist, or by some inflammatory process. I do not think that these synovial pouches ever actually burst. On puncturing them I have, more than once, seen the escape of all the fluid from a joint ; and, on pressure, one can make them disappear with a temporary increase of the fluid in the joint.
With regard to the presence of fluid in the joints : in almost all the acute cases it is present, often in large amount. However, with the synovial membrane and ligaments in a state of softening and degeneration, it is not always easy to differentiate between the two condi- tions. Haemorrhages into the joints are rare, but not altogether unknown. Suppuration is even rarer, and I have never seen it (see p. 57).
In the acute forms of rheumatoid arthritis the small joints of the hand are those most liable to be affected by the rheumatoid changes. They are usually the joints first affected, and often form the starting point from which it spreads all over the body. It not infrequently happens, however, that the disease is not only confined to the fingers, but to the terminal interphalangeal, or even one terminal interphalangeal joint.
SYMPTOMS. 103
Charcot gives the following statistics from 45 cases, as to its origin 6 : —
25, or 55*5 per cent., started in the small joints of the hands,
and feet first. 4, or 8*8 ,, started in the great toe first.
7, or 17*7 ,, started in the hands and feet at the same
time as in a larger joint. 9, or 20*0 ,, started in the larger joints first.
He says the arthritis, as a rule, spreads from the periphery to the centre; the fingers first being affected, then the elbows, and then the shoulders. In young patients he says it is usually general from the first, and that it is only in the elderly or chronic cases that its progressive character is so well seen. Haygarth 7 men- tions that 20 out of 34 cases had the hands affected first, and Ord8 24 out of 38. Garrod out of 500 found that 252 commenced in the hands, 64 in the knees, and 28 in the feet ; whilst in 430, or 86 per cent., the hands were affected at the same period of the disease.
In the 78 cases I take for comparison, I could only get a reliable history in 50 with regard to the joint first affected. Out of these 50, 34 or 68 per cent, began in the hands ; 8 or 16 per cent, in the ankles ; 5 or 10 per cent, in the knees ; 2 or 4 per cent, in the shoulders, and neck ; and 1 or 2 per cent, in the elbows and hips.
The disease rarely, or never, travels down a limb, although it may occasionally do so from a knee or elbow to the fingers or toes. It is noticed that the joints most liable to other conditions, are those most liable to be affected also in this complaint, with one exception. This is the temporo-maxillary joint, which is rarely affected in other disorders, but shows a peculiar liability, almost pathognomonic, to be affected in rheumatoid disease. It may happen that the disease in the jaws is so extreme that all movement is prevented, and feeding has to be effected through the vacant space left by the
|
Garrod' s |
||
|
Percentage. |
Percentage |
|
|
hands affected.. |
97*4 . |
.. 86-0 |
|
elbows ,, |
84-6 |
.. 25-0 |
|
neck ,, |
82-0 |
. — |
|
knees ,, |
73-0 |
60-6 |
|
ankles ,, |
67-9 . |
.. 34-4 |
|
jaws ,, |
67-9 . |
.. 25-0 |
|
shoulders ,, |
61-9 |
.. 25-0 |
|
hips ,, |
12-5 . |
.. 14-6 |
|
sterno-claviculai |
2-5 |
— |
104 RHEUMATOID ARTHRITIS.
removal of a tooth. The inability to open the jaw may only be from stiffness and cicatricial contraction, but it may also happen from true ankylosis.
Garrod gives a table of the joints most frequently affected. For comparison, I also give my results : —
66 64 56 53 53 48 10 2
The centripetal order is broken at the neck, and knees, but as these joints are specially liable to arthritic trouble we would almost expect them to be so also in this disease. In acute rheumatism, the knees are the joints most frequently affected. One of the most marked features of the disorder is its symmetry. This is not only seen with regard to the joints affected, but also to the time of the invasion, and, to a less extent, to the degree of severity with which individual joints are affected. It is usual to find one limb more affected than the other, and the peri- pheral joints more than the more central ones. This is often beautifully demonstrated. Garrod says this sym- metry is carried so far that corresponding portions of the cartilages are destroyed. This I cannot confirm.
When ankylosis occurs it may be from true, or fibrous ankylosis, or more rarely from interlockings of the osteophytic out-growths. This latter is most common in the case of the jaws. Fibrous ankylosis may usually be diagnosed from true or bony ankylosis, by some slight movement detected on careful examination, or the attempt to obtain movement may cause a contraction of the muscles which oppose it, or else pain may be induced.
SYMPTOMS. 105
Spondylitis, or disease of the vertebrae, is not uncommon, but it is confined almost entirely to the acute form.
In all cases, at one time or another, there is pain. The pain is varied, and arises from many different causes. That arising in the joints is, as a rule, of a gnawing character, is made worse by movement, and often by the warmth of the bed. It differs in intensity, in different cases, and from time to time. Although there may be no actual pain in the joints, patients often complain of a pain as if the joints were being stretched, in the liga- ments, and tendons. Pain is usually less in the joints distended with fluid, but in acute cases with comparatively no effusion, and where the cartilages rub one on another, it is most marked. Besides this we may have pain from cramp or spasms of the muscles, or there may be pain referable to the bones. Again, we have neuralgic pains ; and pain along the course of a nerve, due to neuritis. In some cases there may be radiating pains which, if there be spondylitis, is probably due to irritation or compression of the nerve roots.
We must now consider the deformities and dislocations which ensue. In every joint affection there is a certain amount of deformity or distortion due to the thickening and swelling of the joint tissues. Possibly in rheumatoid arthritis it may stop at this stage, but, on the other hand, as it progresses, and as the tissues become contracted, destroyed, or greatly weakened, there may arise those great alterations from the normal which cause so much crippling and distortion. The disease, as it advances, may cause an increased tonicity on the part of certain muscles, and a weakness, or atony, on the part of others, the result being a deformity which, although at first readily reducible, soon becomes irreducible and permanent. Along with the development of such deformities we find marked wasting, and shortening of
106 RHEUMATOID ARTHRITIS.
certain muscles which may occur to such an extent that joints quite free from disease may actually become partially or completely dislocated, as has also been known to occur in such diseases as paralysis agitans, congenital brain atrophy, etc. (Plate VIII, Fig. A).
This process is of course very slow, and chronic in its course. A somewhat similar condition has been described by Jaccoud,9 as occurring in his " Kheumatisine fibreux." Such deformities also occur in certain conditions of the nervous system, and in all chronic forms of arthritis.
In rheumatoid arthritis the principal deformities are seen in the hands and knees. The deformities of the hand occur in two ways. There may be deflection to the ulnar or radial side, or there may be extension or flexion. A combination of these two types is what we most commonly see. Let us first study the deflection type.
The disease having commenced in the fingers, spreads in course of time to the knuckles and wrists. These be- come large, and nodular, and, probably, at the same time some deflection of the fingers occurs. This may either be ulnar, when the whole of the finger is involved, or else radial, when only the terminal phalangeal joint is affected. This radial deflection of the terminal joint has been explained, by some, as being due to osteophytic outgrowths on the ulnar side. The ulnar deflection only takes place from the knuckle joints, and, except for radial deflection of the terminal joints, the deformity of the phalangeal joints is usually confined to a fusiform enlargement due to synovial thickening (see Plate VIII, Fig. B, and Plate IX, Fig. A).
When, however, the knuckles have become affected the fingers may begin to deflect from that joint, but always to the ulnar side. At first easily reducible, it rapidly becomes irreducible. These deformities are brought about prin-
PLATE VIII.
Fig. ..4.— Dislocation backwards of index finger through relaxation of ligaments and erosion of the cartilages and head of the bones ; also partial dislocation of ring finger.
Fig. B. Shows ulnar deflection
SYMPTOMS. 107
cipally and primarily by relaxation of the ligaments and tendons. Herringham suggests that it may be caused by atrophy of the abductor indicis, and by the then unsup- ported ringer pushing the others to the ulnar side. Duckworth11 points out that such atrophy is not a constant feature, and this therefore has to be discounted. Pure atrophy alone will not cause it.
As a rule the thumb escapes, if the terminal joints alone are affected, but it suffers if the disease becomes more general. As the wrist enlarges the natural shape of the arm and forearm is lost, and it comes to appear as if the limb from the elbow to the wrist were of the same thickness. One often notices that the bursae in the neigh- bourhood of the olecranon are enlarged, and it is fairly common to find that cartilaginous bodies have developed in these bursae. In the larger joints it is usually impossible to find any deflection. The deformities arise in a similar manner in the feet, but are less common.
Under the second type we find those deformities due to flexion or extension. They were first described and classified by Charcot,12 who divided them into two main types, with several sub- varieties :—
I. — The first form is that most often met with. It is marked by
(a,) Flexion of the terminal phalanges on the second at an obtuse, right, or even an acute angle.
(b,) Extension of the second phalanges on the first.
(c,) Flexion of the first phalanges on the metacarpals.
(d,) Flexion to a less obtuse angle, of the metacarpa