602

RECENT ADVANCES IN THE PATHOLOGYOF CHRONIC ARTHRITIS AND

RHEUMATIC DISORDERSBy DOUGLAS H. COLLINS, O.B.E., M.D., M.R.C.P.

Joseph Hunter Professor of Pathology in the University of Sheffield

The word rheumatism, except in its limitedsense of acute rheumatism or rheumatic fever,has no meaning in pathology. The rheumaticdiseases are a heterogeneous group of morbidstates, mainly affecting the locomotor system andmost of them painful, chronic and of low mortality.To this major group, certain minor groups of ail-ments are from time to time added, or subtracted,according to the bias of current medical thoughtand the expediences of current medical practice.The last large subtractions have been most of thepainful peripheral neurological disorders, and thelatest additions are certain dermatological diseaseswith systemic effects which are supposed toresemble rheumatoid arthritis in their basicpathology.The fact remains, however, that most of the

rheumatic disorders have nothing in commonpathologically except that they affect the more orless specialized mesenchymal tissues of the jointsand other parts of the locomotor apparatus, andthat the cause of each, if not completely unknown,is imperfectly understood. The chronicity of thediseases, their dependence upon largely subjectivemanifestations for their detection in the earlystages, the limited reaction patterns of connectivetissues and the impossibility of reproducing inanimals the identifiable counterparts of thehuman ailments, all hinder the pathologist insearching for the causes and origins of rheumaticdisease. Nevertheless, his studies have materiallyhelped in separating the different forms of diseaseand in explaining some of their clinical charac-teristics.Much the most important of the chronic rheu-

matic disorders are the two contrasting forms ofchronic arthritis, osteoarthritis and rheumatoiparthritis. Each disease has pathological featuresof great interest, which have formed the field ofmany recent researches, and they alone will bediscussed in detail in what follows.

OsteoarthritisA lesion of articular cartilage is now generally

held to be the initial lesion of osteoarthritis. In

most cases, this is a gradual and progressive lossof depth resulting from attrition of cartilage,which through ageing or other causes has becomeless resilient and less resistant to mechanicalinfluences. Occasionally, direct injury, fractureinvolving the joint surfaces, hard loose bodies, orprevious inflammatory joint disease may damagepreviously healthy articular cartilages and initiatea rapidly developing osteoarthritis, just as Ax-hausen (1925), 30 years ago, observed the develop-ment of marginal osteophytes and 'arthritisdeformans' in the joints of the rabbit and thedog after cauterizing or otherwise injuring thecartilaginous surfaces.

Articular cartilage comprises a tracery ofcollagen fibres springing from the underlyingbone and set in a matrix of which the chief com-ponent is the mucopolysaccharide, chondroitinsulphate A (Meyer, 1954). The cartilage cellsapparently play little or no active part in itspathological changes which are essentially de-generative. Cartilage has only a feeble capacityfor repair, and it seems that the existence of asuitable matrix is necessary before any multi-plication of cartilage cells can take place (SubbaRao, 1954). It is this virtual irreversibility ofdegeneration and destruction of cartilage, oncebegun, that allows the development of the fullcycle of osteoarthritic changes in a joint. Traumacan initiate the process, but in general the diseaseis so closely linked with age that we must supposethat involutional changes in cartilage structurepermit its wearing down by the ordinary use ofthe joint. Although fissuring of cartilage has beenobserved in certain areas of the hip joint notexposed to pressure or friction (Harrison et al.,1953), the cartilage lesions really associated withosteoarthritis are always first seen on areas of thejoint surface exposed to friction, weight-bearingor great movement. The collagen fibres in carti-lage form an arcade towards the surface, and theearliest changes take the form of a tangentialflaking off of the surface zone (Fig. x). Laterthe cartilage cracks along the perpendicularcollagen-fibre lines, a process known as fibrilla-

by copyright. on M

ay 28, 2020 by guest. Protected

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.31.362.602 on 1 D

ecember 1955. D

ownloaded from

December 1955 COLLINS: Recent Advances in the Pathology of Chronic Arthritis 603

..

F.B. -.·.%, X.pj;ii

k

. *f '.**

..s* 1r ·B, . .cr-lf. i ..,. ";. *. LSZ · ;* 'I·)E·. . .I "O "·· r

...f-+ * IEI. It k 1·. ra! .. .AA ·g I

FIG. i.-Osteoarthritis. Early cartilage lesion. Tan-gential flaking of surface layers. Doubling of thedeep calcified line, as here, is not a constantfeature. Haematoxylin and eosin x 20.

tion, which in time extends to the underlyingbone and is accompanied by the death of thecartilage cells (Fig. 2). Both histological appear-ances and chemical analyses (Matthews, I953)indicate a degradation and loss of chondroitinsulphate matrix in advance of actual mechanicalattrition. It is this that justifies the American useof the term ' degenerative arthritis' for osteo-arthritis. But almost everything else that followsis regenerative or formative on the part of thebony and fibrous tissues of the joint.

Cartilage degeneration and destruction mustboth operate together in leading to an alterationof contour of the articular surfaces. This is metby an adaptation of form on the part of the boneand synovial and capsular tissues of the joint,which, unlike cartilage, retain the power ofregeneration, repair and remodelling. The evolu-tion of osteoarthritis follows its own course in anyparticular joint, the structural adaptations therebeing dependent upon the changing mechanicalconditions. As cartilage degenerates, the normalstability of the chondro-osseous junction is lost,and ossification advances into the proper territoryof cartilage. Some marginal osteophytes areformed this way; others result from intramem-branous ossification at the points of periostealattachment of the vascular synovial membrane.Sclerosis of the subchondral osseous plate and are-alignment of the trabeculae of the cancellummay also occur. The capsule usually becomesfibrotic, and inflammatory changes in the synovial

*;~ ...,

FIG. 2.-Osteoarthritis. Later cartilage lesion. Fibrilla-tion extends down the vertical fibres and variousdegenerative changes in the cartilage cells are alsoseen. H. and E. x 20.

membrane are minimal and generally confined toa mild reaction around engulfed particles of deadbone or cartilage. The extent of the synovitis isof the same order as that seen after simple trau-matic injury to the joint, and when there is aneffusion it is viscous and clear with a totalnucleated-cell count usually well below 5,000per c.mm. and polymorphonuclear leucocytesrarely more numerous than 20 per cent.Over the age of 50, cartilage changes are seen

on naked-eye examination in about 90 per cent.of knee joints and of acromio-clavicular joints, inthe majority of hallux, elbow and hip joints, andin a lesser proportion of sterno-clavicular andshoulder joints (Heine, I926). Advanced changesin cartilage with some remodelling of the boneends and osteophytic outgrowths are to be foundat necropsy on persons over 50 in about 25 percent. of knee joints, rather less frequently in thehallux and acromio-clavicular joints, in aboutio per cent. of hip and elbow joints, less com-monly in the shoulder and very rarely in thesterno-clavicular joint. These figures are strongarguments for the view that osteoarthritis is theprojection to a pathological degree of the agechanges which develop in functioning joints andthat local mechanical conditions in each jointdetermine its development. Local mechanicalconditions also certainly determine its degree and

cl

by copyright. on M

ay 28, 2020 by guest. Protected

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.31.362.602 on 1 D

ecember 1955. D

ownloaded from

POSTGRADUATE MEDICAL JOURNAL

probably its age of onset, for local conditionswhich expose a particular joint to undue mechani-cal stress lead to an early and quickly evolvingosteoarthritis. Examples of such conditions areold rickety deformity, genu valgum, coxa vara,Paget's disease, paralysis of the opposite limb,old fracture and old rheumatoid or infectivearthritis.Viewed from the standpoint of pathogenesis, it

seems evident that the principle therapeutic aim,apart from symptomatic relief, must be so tostabilize the mechanical conditions operating atthe affected joint that no further deformation ofthe joint results.Up to now I have stressed the local nature of

osteoarthritis. In discussing the possible systemicbackgrounds of osteoarthritis we are on moredebatable ground. Senile involution of connectivetissues must play a part. Obesity is an aggra-vating factor. Osteoarthritis may clinically affectmany joints simultaneously, a fact which is notsurprising, since at necropsy of any old personone may find the disease in various subclinicalforms in most joints.The radiographic features of osteoarthritis can

be closely correlated with what has been found byanatomical dissection and histology. What isusually called ' loss of joint space ' is, in fact, lossof cartilage depth. Marginal osteophytes resultfrom advancing ossification at disturbed chondro-osseous junctions or from periosteal new boneformation. Moulding of the bone ends is due toremodelling of the plastic living bone, by resorp-tion and regeneration, under the stimulus ofchanging mechanical forces, and may be inter-preted as an attempt to maintain congruity of thearticular surface. Cysts often seen in the boneends in osteoarthritis have been shown histo-logically to communicate with the joint cavity andmay arise from the propulsion of synovial fluidinto the cancellous bone (Landells, I953).By definition, osteoarthritis is a disease of

synovial joints. The mere demonstration of osteo-phytic spurs which may arise by ossification intotendinous or fascial attachments, or in areas ofperiosteal elevation, does not constitute the diag-

I nosis of osteoarthritis. There is still some doubti whether all forms of Heberden's nodes (Stecher,i955) really represent osteoarthritis. The well-known condition of osteophytosis of the vertebralbodies, or spondylosis deformans, is not a trueosteoarthritis, since diarthrodial joints are notaffected. It arises from changes in the inter-vertebral discs in a manner which has been fullydescribed elsewhere (Collins, I949, p. 305).Rheumatoid ArthritisThe pathological features of rheumatoid ar-

thritis are often more distinctive than the clinical.As opposed to osteoarthritis the disease seems tobe one of systemic distribution in which theaffection of the joints constitutes the major butnot the whole part, and the tissue changes arethose of subacute and chronic inflammation.These are accompanied in some situations, butnot everywhere, by focal degeneration of fibroustissue, a relatively minor feature in the morpho-logical pathology of the disease which has led toits inclusion within that nosological chimera, theso-called collagen diseases.

Joints. Rheumatoid arthritis starts in thejoints as an inflammatory synovitis characterizedby hyperaemia, exudation and leucocytic reaction,shown, respectively, by the increased heat of thejoint, by oedema of the synovial tissues and jointeffusion, and by the presence of polymorpho-nuclear leucocytes in the joint fluid and lympho-cytes and plasma cells in the synovial membrane.An inflammatory effusion is always present in theearly and active stages of the disease in bothsmall and large joints. It contains sufficient cells,on the average 20,000 per c.mm., to make itslightly turbid, and most of these cells, often upto 90 per cent., are neutrophil polymorphs. Yetthe inflammation does not proceed to suppuration,unless, as occasionally happens, the joint becomessecondarily invaded by pyogenic organisms. Nordoes the inflammation readily resolve. It per-sists in a subacute phase, and proliferation of thesynovial connective tissue produces hyperplasticsynovial granulation tissue and a form of diffusegranuloma within the joint. The synovial mem-brane becomes thickened by new fibroblasts,fibrocytes and histiocytes, more richly vascular,and thrown into folds. Enlarged or newly formedvilli, covered by a greatly increased number ofmore or less well differentiated synovial liningcells, crowd into the joint cavity. At the sametime, the hyperplastic synovial tissues start tocreep across and attach themselves to the articularsurfaces, clothing them in a pannus (Fig. 3).The infiltrating leucocytes, as is the rule in non-suppurative but persistent inflammations, aremainly lymphocytes, but sometimes more promi-nently plasma cells, congregating first around thevessels whence they have come, and whennumerous forming follicular aggregates in thesubsynovial layer and villi (Fig. 4).

Kulka et al. (I955) have recently studied thehistological character of the synovial lesions in theearly course of rheumatoid arthritis. The domi-nant feature was always a diffuse proliferativesynovitis. Lymphocytic infiltration was oftenlight and follicles seldom prominent. A fibrinoidtype of exudate was particularly noticed in theseearly lesions, but histochemical tests were not

604 December 1955

by copyright. on M

ay 28, 2020 by guest. Protected

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.31.362.602 on 1 D

ecember 1955. D

ownloaded from

December 1955 COLLINS: Recent Advances in the Pathology of Chronic Arthritis 605

·.:~

t.j* l

:.w

FIG. 3.-Rheumatoid arthritis. Chronically affectedknee-joint, opened with patella reflected upwards.Note the hyperplastic granulomatous synovialtissues with great numbers of villi. The pannuslying over the tibial condyles also adhered to thefemoral cartilage which shows erosion just abovethe intercondylar notch.

:as.JS`r

ftai a iQc

Ij:iB.;'...RXS·.*;.I.c.:l;r,.rB.I. .rL.s.IIZ.E.PdtB.H.L4.Jt..Ls.ji.:...i"?i:::!.*

.·ii·i f"· ';% .i* i

I· ·.,;::.·; ··::: .··e.·;1.* *j

FIG. 4.-Rheumatoid arthritis. Characteristic syno-vitis. Proliferation of all synovial connectivetissues with dense lymphocytic or plasma-cell in-filtration often forming compact aggregates in thebulbous and enlarged villi. H. and E. x 20.

;t": *'' M E j

K:' i": " '~It.e;*'...?ri-·. 4

·*'*-~L~I

FIG. 5.-Rheumatoid arthritis. Advanced disease of aproximal interphalangeal joint. Granulation tissuehas grown into the joint, spreading as a pannus overboth cartilages, and eroding much of the head of theproximal phalanx (right). Only a small island ofarticular cartilage remains, at the top of the cavityand on the right (proximal) side. The bone isatrophied. The joint was fixed by capsular andintracapsular fibrosis. H. and E. x 3.5.

specific, and rather similar appearances are seenin other forms of arthritis and in fibrinous inflam-mations generally. In my own experience, anyexpansion of a synovial or bursal cavity takesplace by a process resembling fibrinoid degenera-tion, and this appearance has little of rheumaticspecificity about it except when it forms part ofthe whole characteristic picture of the rheu-matic or rheumatoid granuloma.The granulomatous reaction, starting in the

synovial membrane, progressively involves thejoint more and more extensively. The articularcartilages become eroded by adherent pannus,an effect which may result from histolytic activity,perhaps enzymic, on the part of the cells in thegranulation tissue or from intrinsic degenerationof matrix. The bone-ends also become invadedby granulation tissue arising in the periostealreflection of the synovial membrane, and thisaccounts for the small nibbled-out rarefactions sooften seen radiographically in the bones forminga severely affected rheumatoid joint. It is thisrelentless progression of erosion of previouslynormal structures by granulation tissue that leadsto the ultimate gross deformities of the joints withdestruction of bone and cartilage, subluxation,intra-articular adhesions and capsular fibrosis(Fig. 5).A severe degree of bone atrophy is usual in the

region of an affected joint. Much, but perhaps notall, of this can be explained on a basis of disuseatrophy, for local atrophy of bone can proceedvery rapidly from disuse and becomzs especially

by copyright. on M

ay 28, 2020 by guest. Protected

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.31.362.602 on 1 D

ecember 1955. D

ownloaded from

606 POSTGRADUATE MEDICAL JOURNAL December i955'*.

n*' ass.sl8.ri.%..'cu

ri.+. ·-*'.iie:.I;···: X·- jlB1 .rl·.'.\I* .*.*;t·· ::;i.

,*."'' :!ij.·

·;.?p. ''1··:·.i .- I·".e. .g ·,.·.*II

.u.:.*-.-J.I..·r.sg.i.;k.EB.E8.3Zs..;.;-.i. ':5:

:P.Y 1'*" r.l'·'

;iji ..

...s,.;.l.aRll.as:.-.ussl·.-.*.sr.m*l.-. -1

.:,··

!·.i.LI.Ei.S. ;;.'·:-·* r·.nc.c.:

..·· .-- -.rr-· -;.i.wprur.l.nrrr·.a.-.i.-IRF.-.L... ;.:

FIG. 6.-Rheumatoid arthritis. Tenosynovitis. Thestratum synoviale near the cavity of the tendonsheath is infiltrated by lymphocytes. All tissues areproliferated and the sheath is itself greatly thickened.Two necrotic foci with marginal palisading of cells,resembling the structure in Fig. 8, are seen, onejust below the synovial surface and the other muchmore deeply placed. Trichrome x 20.

obvious where the bones are mainly cancellous, asin most epiphysial areas. In addition, there areexcavations of bone by invading inflammatorytissue, and perhaps by independent deeplysituated foci of inflammatory osteitis.

Tendons and tendon-sheaths. Tenosynovitis isnot uncommon in rheumatoid arthritis and takesthe same form as articular synovitis, except thatfor some reason centres of fibrinoid necrosis aremore often encountered in the granulomatoussynovium of tendon-sheaths than of the joints(Fig. 6). Buried in the deeper parts of the synovialtissues they histologically resemble small sub-cutaneous nodules. Near the cavity of thetendon-sheath they may discharge their fibrinoidnecrotic centres, which if inspissated and notbroken up may form melon-seed bodies just likethose produced by the analogous process ofcaseation in tuberculous tenosynovitis. Rheu-matoid nodules sometimes develop within thecollagenous substance of the tendons themselvesand may cause great thickening and nodularity(Kellgren and Ball, 1950) and sometimes theirspontaneous rupture (Harris, I95i).

Disseminated lesions. Until fairly recently thesubcutaneous nodules were the only extra-

·'·'.**..." -· , '.PL*lf.'·...**..

L·.·*.i...Ll.i 1.rr

·" .t-.t

1 *'-s.e. IF.iirc"'* ?1* ·r···.·,'' .. ,_z

:·7* .1 ·. "rj; L;r.e.*·

'''.iB 1IiJ6.+.;·'L'·: /V ..· .f.'t*; "-.·1.f

.*:·

FIG. 7.-Rheumatoid arthritis. Disseminated lymphoidfoci in bone marrow (acromial process) and ininvesting fascia and muscle. H. and E. x 20.

articular lesions recognized as part of the rheu-matoid arthritis picture, but pathological lesions,as a rule clinically silent, are present in manysituations, especially in the more severe andchronic case. These are of two kinds: (a) micro-scopical inflammatory foci or lymphorrhages, and(b) nodules, often visible to the naked eye, whichinclude one or more centres of collagen degenera-tion. In addition to these two kinds of discretelesions there are often certain generalized systemicdisturbances-lymphoid hyperplasia of a reactivelymphadenopathy type (Motulsky et al., 1952),splenomegaly, neutropenia, anaemia, hyperglo-bulinaemia and amyloidosis.

Disseminated inflammatory or lymphoid foci.These consist mostly of lymphocytes, but maycontain also a few histiocytes, fibroblasts orplasma cells. They have been found in theinterstices of voluntary muscles, not necessarilywasted or related to affected joints, and in thesheaths of peripheral nerves (Cruickshank, 1952).They may be found also in the bone marrow,periosteum and fascia generally (Fig. 7). Some-times the lymphorrhages are related to bloodvessels. Distinctly inflammatory focal arteritis ofthe necrotizing angiitis type (Zeek, 1952) has alsobeen found in rheumatoid arthritis (Cruickshank,1954). These small lesions can seldom be relatedto clinical features; they are the fruit of patho-logical searching. The very fact that lesions ofthis type are not specific to the disease carriessome significance, for they may be found also inrheumatic fever, dermatomyositis, lupus ery-thematosus and in hypersensitivity animal experi-ments. They may be the index, not of thewidespread action of virus or toxin, but of anacquired hypersensitivity of the tissues in rheu-matoid arthritis.

by copyright. on M

ay 28, 2020 by guest. Protected

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.31.362.602 on 1 D

ecember 1955. D

ownloaded from

December 1955 COLLINS: Recent Advances in the Pathology of Chronic Arthritis 607U~·~C YL· * * ~,9

vii!"-9~tii

)·;;M4· ,fv ~'E·~:·.

··

FIG. 8.-Rheumatoid arthritis. Subcutaneous nodule.Characteristic necrotic centres with palisade offibroblasts and histiocytes. H. and E. x 30.

Nodules. The subcutaneous nodules of rheu-matoid arthritis have been studied for many years(Collins, 1937) and their structure is now wellknown. The central area of necrosis, I believe,develops within a new formation of connectivetissue which has arisen as a granuloma at a siteof mild repeated trauma. The expanding necroticcentre is surrounded by a palisade of fibroblastsand histiocytes (Fig. 8), and outside this is acellular fibrous tissue rich in small blood vesselsand diffusely infiltrated by lymphocytes andplasma cells. Bennett (I953) has remarked thatthe overall histological picture is not unlike asyphilitic gumma, although not implying therebyany common pathogenesis. There is some truthin the simile, for both are formative granulo-matous lesions in which centres of necrosisappear, but the relative parts played by histolyticagents and by ischaemia in the production ofnecrosis in the rheumatoid nodule are unknown.A most interesting recent development has been

the discovery of morphologically typical rheu-matoid nodules in other connective tissues,especially those where compact hyalinized collagenalready exists. Nodules in the substance oftendons have already been mentioned. Noduleshave been seen occasionally in scarred heartvalves and annulus fibrosus (Baggenstoss andRosenberg, 1944), in cranial dura mater, sclera ofthe eye, hyalinized splenic capsule and peri-

cardium (Ellman et al., I954; Maher, I954), andrecently Gough et al. (I955) have illustrated arheumatoid nodular reaction around collagenousfoci in the lungs of coal miners with rheumatoidarthritis.

Rheumatoid arthritis and the ' collagen diseases.'There is today a widespread belief in the existenceof a pathological monster called ' collagendisease,' like the chimera an apparently integratedbeing, although composed of incongruous parts.This popular term was introduced by Klempererand his colleagues largely in consequence of theirstudy of the lesions in systemic lupus erythema-tosus. It is too seldom remembered that inlinking together clinically distinct diseases suchas rheumatic fever, rheumatoid arthritis, dis-seminated lupus erythematosus and generalizedscleroderma there was no intention of attributinga common aetiology to them (Klemperer, I947).The idea was proposed in order ' to call attentionto the significance of the connective tissue as thesite of morbid changes and to invite investigationsof the reasons for its alteration ' (Klemperer, I954).If it is indeed helpful to seek pathological simi-larities rather than dissimilarities amongst thesediseases, then it is better to speak of ' collagendiseases,' to avoid the implication that there is anall-embracing pathogenic state of ' collagendisease.' A realistic attitude to what is impliedmay be engendered by speculating on whetherthe necrobiotic lesions of tuberculosis andsyphilis or the dermal and vascular lesions ofdiabetes would have been designated collagendisease had the responsible aetiological agents notalready been known.The concept of collagen diseases originated not

only as an extension of, but as a corrective to,Klinge's (i933) assertion that fibrinoid swellingof connective tissue was the common basis of thelesions in rheumatic fever, rheumatoid arthritisand certain other diseases, indicating that they allhad an allergic background and were based uponhypersensitivity reactions in the tissues. Klem-perer, it appears, introduced a new term in orderto avoid the implication that those diseases withdisseminated focal lesions of collagenous connec-tive tissues were necessarily dependent uponhypersensitivity or allergy. Some of this groupcertainly are so dependent. Rheumatic fever is amanifestation of a special form of acquiredsensitivity to group A Str. pyogenes, and there isvery strong evidence that polyarteritis nodosa andsome other forms of necrotizing angiitis arehypersensitivity reactions. But the evidence isless convincing in the case of disseminated lupuserythematosus and very difficult to assess in thecase of rheumatoid arthritis.

It is best to admit that no explanation yet

by copyright. on M

ay 28, 2020 by guest. Protected

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.31.362.602 on 1 D

ecember 1955. D

ownloaded from

608 POSTGRADUATE MEDICAL JOURNAL December 1955

advanced of the pathogenesis of rheumatoidarthritis tallies with all the evidence we haveabout its course and its pathological features. Inshort, the major lesions, those within the joints,are inflammatory and granulomatous. In theearly stages fibrinous exudation is prominentlyassociated with diffuse proliferative synovitis.That the initial lesions of the disease are of thecollagen-degeneration type is a hypothesis opento question, and the view that disintegrationproducts of collagen may account for the varioustoxic and inflammatory features of rheumatoiddisease (Kellgren, I952) still awaits proof. Thedisseminated nodular lesions showing well-definedfocal necrosis of connective tissue are usuallylater manifestations and might be a measure ofhypersensitivity acquired during the progress ofthe disease. It is disappointing that the introduc-tion of adrenocortical hormones has done so littleto elucidate the pathogenesis of rheumatoidarthritis, although it has led to many importantdiscoveries about tissue reactions in general.SummaryWhat are now called the rheumatic disorders

are a group of pathologically diverse diseases,unified only by their mode of clinical presentation,and by the facts that they affect the locomotorsystem and that they are painful, chronic andmostly of unknown aetiology.

Recent advances in our pathological knowledgeof the two major forms of chronic arthritis, osteo-arthritis and rheumatoid arthritis, serve stillfurther to distinguish between them.

In osteoarthritis, we do not yet know theprecise conditions under which the initial changesoccur in articular cartilage, but the ensuing changescan be explained by a mechanistic concept, havingregard to the powers of repair and reconstructionwith which the various connective-tissue struc-tures are endowed.

In rheumatoid arthritis, the major lesions in

the joints are inflammatory and granulomatous.Disseminated lesions in many other parts of thebody are of two main kinds: (a) microscopicinflammatory foci or lymphorrhages, (b) nodularlesions, often visible to the naked eye, whichinclude one or more centres of connective-tissuedegeneration or necrosis. In addition, there areoften generalized systemic disturbances, such aslymphoid hyperplasia, hyperglobulinaemia andamyloidosis. The position of rheumatoid arthritisin relation to the hypothesis of' collagen diseases 'has been briefly discussed in view of the mis-interpretations which the free use of such aphrase is likely to engender.Acknowledgments

I am very grateful to many colleagues invarious parts of the country for sending mematerial, and to my chief technician, Mr. A. W.Collins, for the photographs.

BIBLIOGRAPHYAXHAUSEN, G. (1925), Virchows Arch., 255, I44.BAGGENSTOSS, A. H., and ROSENBERG, E. F. (I944), Arch.

Path., 37, 54.BENNETT, G. A. (1953), in ' Pathology,' ed. W. A. D. ANDER-

SON, 2nd edition, London, p. 1257.COLLINS, D. H. (I937), J. Path. Bact., 45, 97.COLLINS, D. H. (I949), ' The pathology of articular and spinal

diseases,' London.CRUICKSHANK, B. (I952), J. Path. Bact., 64, 2I.CRUICKSHANK, B. (I954), Ann. Rheum. Dis., 13, I36.ELLMAN, P., CUDKOWICZ, L., and ELWOOD, J. S. (I954),

J. Clin. Path., 7, 239.GOUGH, J., RIVERS, D., and SEAL, R. M. E. (I955), Thorax,

I0, 9.HARRIS, R. (I95I), Ann. Rheum. Dis., 10, 298.HARRISON, M. H. M., SCHAJOWICZ, F., and TRUETA, J.

(I953), J. Bone t Surg., 35B, 598.HEINE, J. (1926), Virchows Arch., 260, 521.KELLGREN, J. H. (1952), Brit. med. J., i, 1152.KELLGREN, J. H., and BALL, J. (I950), Ann. Rheum. Dis., 9, 48.KLEMPERER, P. (I947), Bull. N.Y. Acad. Med., 23, 59I.KLEMPERER, P. (I954), in 'Connective tissue in health and

disease,' ed. G. ASBOE-HANSEN, Copenhagen, p. 25I.KLINGE, F. (1933), Ergebn. allg. Path. u. path. Anat., 27, 1.KULKA, J. P., BOCKING, D., ROPES, MARIAN W., and

BAUER, W. (1955), Arch. Path., 59, 129.LANDELLS, J. W. (I953), J. Bone Jt Surg., 35B, 643.MAHER, J. A. (1954), Arch. Path., 58, 354.MATTHEWS, B. F. (1953), Brit. med. J., ii, 660.MEYER, K. (I954), in 'Connective tissue in health and disease,'

ed. G. ASBOE-HANSEN, Copenhagen, p. 54.MOTULSKY, A. G., WEINBERG, S., SAPHIR, 0., and ROSEN-

BERG, E. (1952), Arch. int. Med., 90, 660.STECHER, R. M. (1955), Ann. Rheum. Dis., I4, I.SUBBA RAO, K. V. (I954), J. Path. Bact., 67, 455.ZEEK, PEARL M. (I952), Amer. J. Clin. Path., 22, 777.

HOWVV TO GET THEREAn Address Book for the Medical profession, showing how to reach thevarious Colleges, Societies, Institutes and Hospitals in or near London

New (Fourth) Edition: 1954 Price 2s. 6d. (2s. 9d., post free)Published by the

FELLOWSHIP OF POSTGRADUATE MEDICINE60 Portland Place, London, W.I

by copyright. on M

ay 28, 2020 by guest. Protected

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.31.362.602 on 1 D

ecember 1955. D

ownloaded from