3 The term ‘rheumatic disorders’ covers a number of diseases that cause chronic pain, stiffness and swelling around joints and tendons. Many common conditions, such as influenza, are associated with painful muscles and joints, but the rheumatic disorders are guished by (1) their chronicity and (2) the appearance of local and systemic features of inflammation, Many ~ perhaps all ~ result from a faulty immune reaction to an antigenic stimulus, against a background of genetic predisposition, RHEUMATOID ARTHRITIS: Rheumatoid arthritis (RA) is the commonest cause of chronic inflammatory joint disease. The most typical features are a symmetrical polyarthritis and tenosyn- ovitis, morning stiffness, elevation of the erythrocyte sedimentation rate (ESR) and the appearance of anti-IgG lobulins (rheumatoid factors) in the serum. However, changes can be widespread in the tissues of the body and the condition should really be called rheumatoid disease. The reported prevalence of RA is 1-34, with a peak incidence in the fourth or fifth decade. Women are affected 3 or 4 times as commonly as men. Both the prevalence and the clinical expression vary between Populations; the disease is more common (and gener- ally more severe) in the urban. communities of Europe and North America than in the rural populations of Africa (Solomon et al, 1975). Cause The cause of RA is still incompletely worked out. However, a great deal is mow known about the circum stances in which it develops and hypotheses about its etiology and pathogenesis have been narrowed down to manageable lines of discussion. The following is a very simplified account; for more detailed information the reader is referred to one of the larger reference works (Kelley et a, 1997). Important factors in the evolution of RA are (1) genetic susceptibility; (2) an immunological reaction, possibly involving a foreign antigen, preferentially focused on synovial tissue; (3) an inflammatory reac- tion in joints and tendon sheaths; (4) the appearance of anti-IgG antibodies (‘cheumatoid factors’) in the Rheumatic disorders blood and synovium; (5) perpetuation of the inflam- matory process; and (6) articular cartilage destruction. Genetic susceptibility A genetic association is suggested by the fact that RA is more common in first-degree relatives of patients than in the population at large; furthermore twin studies have revealed a concordance rate of around 30% if one of the pair is affected. Immunological processes The human leukocyte anti- gen (HLA) DR4 occurs in about 70% of people with RA, compared to a frequency of less than 30% in normal controls, HLA-DR4 is encoded in the major histocompatibility complex (MHC) region on chro- mosome 6. In common with other HLA Class II mole- ccules, it appears as a surface antigen on cells of the immune system (B lymphocytes, macrophages, dendritic cells) which can act as antigen-presenting cells (APCs). In some T-cell immune reactions, the process is initiated only when the antigenic peptide is presented in association with a specific HLA allele. It has been suggested that this is the case in people ‘who develop RA; the idea is even more attractive if one posits that the putative antigen has a special affinity for synovial tissue. So far no such antigen has been discovered, but the conditions surrounding the early development of RA suggest that it might be an arthrotropic virus or retrovirus. The inflarmotory reaction Once the APC/T-cell interac tion is initiated, various local factors come into play and lead to a progressive enhancement of the immune response. There is a marked proliferation of cel in the synovium, with the appearance of cytokines, which are important in mediating intercellular communication and activating macrophages and B-cells. Local factors also have a role in stimulating vascular proliferation. The resulting synovitis, both in joints and in tendon sheath linings, is the hallmark of early RA. Rheumatoid factor B cell activation leads to the produc tion of anti-IgG auto-antibodies, which are detected in the blood as ‘rheumato‘d factor (RF). Tis finding isso characteristic that it was once regarded as diagnostic {even pathognomonic) of RA. It is now known not to be so, but patients with a positive RF test tend to be more severely affected than those with a negative test. ‘A current theory is that the RF antiglobulins play an important role in perpetuating the chronic inflamma- tory process. soipapdoyug [p13u2y 81Chronic synovitisand join destruction Chronic rheumatoid synovitis is associated with the production of proteolytic enzymes, tissue factors such as prostaglandins and inter- Jeukin-1 (IL-1), and possibly also anti-colagen antibod ies. Immune complexes are deposited in the synovium and on the articular cartilage, where they appear to augment the inflammatory process. This combination of factors leads to depletion of the cartilage matrix and, eventually, damage to the chondrocytes, Vascular prolif= ration and osteoclastic activity, most marked at the edges of the articular surface, may contribute further to cartilage destruction and periarticular bone erosion. Pathology ‘The condition is widespread, but the brunt of the attack falls on synovium. The constant and characteristic feature is a chronic inflammation; an inconstant but pathognomonic lesion is the rheumatoid nodule. JOINTS AND TENDONS ‘The pathological changes, if unchecked, proceed in three stages. Stage 1 synovitis Early changes are vascular congestion, proliferation of synoviocytes and infiltration of the subsynovial layers by polymorphs, lymphocytes and plasma cells. There is thickening of the capsular struc- tures, villous formation of the synovium and a cell-rich effusion into the joints and tendon sheaths. Though painful, swollen and tender, these structures are still ntact and mobile, and the disorder is potentially reversible. Stage2- destruction Persistent synovitis causes joint and tendon destruction, Articular cartilage is eroded, partly by proteolytic enzymes, partly by vascular tissue in the folds of the synovial reflections and parlly due to direct Invasion of the cartilage by a pannus of granulation tissue ereeping over the articular surface. At the margins ofthe joint, bone is eroded by granulation tissue inva- sion and osteoclastic resorption. Recent evidence suggests that bone erosions are the result of synovial hyperplasia rather than inflammation (Kirwan, 1997). me a / \I G thf is) F lien | he 3.1 Pathology of rheumatoid arthritis (a) The normal joint (0) Stage | ~synovkis and joine swelling (c) age 2~ erly struction with perartiuar erosions.) Stage 3~ advanced fein dstrvcton and deform. Similar changes oceur in tendon sheaths, causing tenosynovitis, invasion of the collagen bundles and, eventually, partial or complete rupture of tendons. A synovial effusion, often containing copious amounts of fibrinoid material, produces swelling of the Joints, tendons and bursae. Stage 3 - deformity The combination of articular destruction, capsular stretching and tendon rupture leads to progressive instability and deformity of the joints. By this time the inflammatory process may have subsided; the emphasis is now on the mechanical and functional effects of joint and tendon disruption. EXTRA-ARTICULAR TISSUES The rheumatoid nodule is a small granulomatous lesion consisting of a central necrotic zone surrounded by a radially disposed palisade of local histiocytes, and beyond that by inflammatory granulation tissue. Nodules occur under the skin (especially over bony prominences), in the synovium, on tendons, in the sclera and in many of the viscera, Lymphadenopathy can affect not only the nodes draining inflamed joints, but also those at a distance such as the mediastinal nodes. This, as well as a mild splenomegaly, is due to hyperactivity of the reticu- Ioendothelial system. Vasculitis, more usually asso- ciated with disseminated lupus, may be fairly widespread. Muscle weakness is common. It may be due toa generalized myopathy or neuropathy, but it is impor- tant to exclude spinal cord disease or cord compression due to vertebral displacement. Sensory changes may be part of a neuropathy, but localized sensory and motor symptoms can also result from nerve compression by thickened synovium. Visceral disease can occur in the lungs, heart, Kidneys, gastrointestinal tract and brain. Clinical Features The onset of RA is usually insidious, with symptoms ‘emerging over a period of months. Occasionally the disease starts quite suddenly. In the early stages the picture is mainly that of a polysynovitis, with soft-tissue swelling and stiffness. Typically, a woman of 30-40 years complains of pain, swelling and loss of mobility in the proximal joints of the Fingers. There may be a previous history of “muscle pain’, tiredness, loss of weight and a general lack of well-being. As time passes the symptoms ‘spread’ to other joints ~ the wrists, feet, knees and shoulders in order of frequency. Another classic feature is generalized stiffness after periods o tivity, and especially after rising from bed in the early morning3.2 Rheumatoid synoviels (a) The macroscopic appearance af rheumatoid syrovis with Rbrinoid material oozing through a rene in le (b) Histology shows prolferating sovium with round-el ration and brincid pares inthe oie cavity (120). 2.3 Rheumatoid arthritis ~ clinial features (a) Ear ~spnding of the fryers and synovtsofhe wrists. (B) The cass hand dfor- sis of exabsed RA (c) Occasional RA stare with synovitis of ingle rg one (in this cae the right ke). sical signs may be slight, but usually there is Joint movements are restricted and often very painful trically distributed swelling and tenderness of About a third ofall patients develop pain and stiffness geal joints, the proximal inter- _ in the cervical spine. Function is increasingly disturbed joints and the wrists. Tenosynovitis is and patients may need help with grooming, dressing in the extensor compartments of the wrist and eating. «flexor sheaths of the fingers; itis diagnosed nickening, tenderness and crepitation over EXTRA-ARTICULAR FEATURES are often seen in patients with + back of the wrist or the palm while passively severe disease, The most characteristic is the appearance ne fingers. Ifthe larger joints are involved, of nodules. They are usually found as small sub- rmth, synovial hypertrophy and intra-articu- cutaneous lumps, rubbery in consistency, atthe back of sion may be more obvious. Movements are the elbows, but they also develop in tendons (where imited but the joints are still stable and defor- they may cause ‘triggering’ or rupture), in the viscera 5s unusual, and the eye. They are pathognomonic of RA, but occur in only 25% of patients, Joint deformity becomes increasingly Less specific features include muscle wasting, Iymph- int and the acute pain of synovitis is replaced by adenopathy, scleritis, nerve entrapment syndromes, skin re constant ache of progressive joint destruction. atrophy or ulceration and peripheral sensory neuropa- vination of joint instability and tendon rupture thy. Marked visceral disease, such as pulmonary fibro- s the typical ‘rheumatoid’ deformities: ulnar sis, is rare. Vasculitis of some degree is almost of the fingers, radial and volar displacement ubiquitous and may account for many of the features sts, valgus knees, valgus feet and clawed toes. listed here metacarpoph (soipondoyuug joxauay :1 uous) S4ap1oSip INDUNIYY Lo3.4 Extravarticular features (ab) Subcutaneous nodules accurepicalyon the extensor aspects ofthe elbow and che hand.T are pathognomonic of RA. (c) Tendon rupture is conion the rap fingers in this pacent ae due 0 rupture ofthe excensor te 2.5 Rheumatoid arthritis = sequence of changes The progres of disease i well show In chi paians xrays. (a) Fist there was only sofe-ussve swe and per later jean appeared (¢) ual the jo became unstable and deformed, with four of the metcarpophi Tange! joins dslocated ar osteoporosis) 26 Rheumatoid arthritis -atermath The sce phat is ovr bu the pint let with secondary oneoarids of (a,b) he Nps and ae) knees.ys show only the features of synovitis: sue swelling and periarticular osteoporosis. The ges are marked by the appearance of marginal rosions and narrowing of the articular space, in the proximal joints of the hands and feet. vanced disease, articular destruction and joint sity are obvious. Flexion and extension views of al spine often show subluxation at the atlanto- smid-cervical levels; surprisingly, this causes few in the majority of cases. tigations mocytic, hypochromic anaemia is common and is, 1 of abnormal erythropoiesis due to disease may be aggravated by chronic gastroin- joss caused by anti-inflammatory drugs. ases the ESR is raised, C-reactive protein it and mucoprotein levels are high. Serological tests for RF are positive in about 80% of id antinuclear factors are present in 30%. hese tests Is specific and neither is required gnosis of RA. vial biopsy issue may be obtained by neeiile biopsy, via scope, oF by open operation. Unfortunately, « histological features of RA are non-specific port is more likely to read ‘consistent with’ nostic of, sual criteria for diagnosing rheumatoid disease presence of a bilateral, symmetrical rthritis Involving the proximal joints of the hands or feet, and persisting for at least 6 weeks. If there-are subcutaneous nodules or x-ray signs of periarticular erosions, the diagnosis is certain. A posi- tive test for RF in the absence of the above features is not sufficient evidence of RA, nor does a negative test exclude the diagnosis if the other features are all present. The chief value of the RF tests Is in the assessment of prognosis: persistently high titres herald more serious disease. Atypical forms of presentation are not uncommon. ‘The early stages may he punctuated by long spells of guiescence, during which the diagnosis is doubted, but sooner or later the more characteristic features appear. Occasionally, in older people, the onset is explosive, with the rapid appearance of severe joint pain and stiff ness; paradoxically these patients have a relatively good prognosis. Now and then (more so in young, women) the disease starts with chronic pain and swelling of a single large joint and it may take months ‘or years before other joints are involved, In the differential diagnosis of polyarthritis several disorders must be considered, ‘SERONEGATIVE INFLAMMATORY POLYARTHAMS Polyarthritis is a feature of a number of conditions vaguely related to RA: psoriatic arthritis, juvenile chronic arthritis (JCA; Still's disease), systemic lupus erythematosus (SLE) and “other connective-tissue diseases. These are considered in later sections, ANKYLOSING SPONDYLITIS This is primarily a disease of the sacroiliac and intervertebral joints, causing back pain and progressive stiffness; however, it may also involve the peripheral joints. REITER'S DISEASE The larger joints and the lumbosacral spine are the main targets. There is usually a history of urethritis or colitis and often also conjunctivitis. POLYARTICULAR GOUT Tophaceous gout affecting multiple joints can, at first sight, be mistaken for RA. On x-ray the erosions are quite different from those 27 Rheumatoid arthritis = diflerential diagnosis These tree gaint all presenced with pan welen figor oie. (a) The proximal re elarged and detormed (heumatidardis)(b) ee dal jas are the worst (Heberdensontsoarthr:() the apmmetrical fs are actualy gouty ph56 of RA; the diagnosis is clinched by identifying the typical birefringent crystals in the joint fluid or a nodular tophus. It is a curious fact that, although both gout and RA are fairly common, the two conditions are rarely seen in the same patient. The reason for this is unknown. ‘CALCIUM PYROPHOSPHATE DEPOSITION DISEASE This condition is usually seen in older people. Typically it affects large joints, but it may occur in the wrist and metacar- pophalangeal joints as well. X-ray signs are fairly characteristic and crystals may be identified in synovial fluid or synovium, OSTEOARTHRITIS Polyarticular osteoarthritis (QA), which typically involves the finger joints is often mistaken for RA.A moment's reflection will usualy dispel any doubt: (A always involves th distal interphalangeal joints and causes @ nodular arthritis with radiologically obvious osteophytes, whereas RA affects the prarimal joints of the hand and causes predominantly erosive features Some confusion may arise from the fact that RA, in its later stages, is associated with loss of articular carti- lage and secondary OA. Enquiry into the early history will usually untangle the diagnosis. Sometimes, however, RA atypically affects only a few of the langer Joints and itis then very difficult to distinguish from (A; x-ray features such as loss of articular cartilage throughout the entire joint and lack of hypertrophic hone changes (sclerosis and osteophytes) should suggest an inflammatory arthritis SARCOIDOSIS Sarcoid disease sometimes presents with a symmetrical small-joint polyarthritis and no bone involvement; erythema nodosum and hilar lymphadenopathy are clues to the diagnosis. The condition usually subsides spontaneously within 6 months. Another form of the disease, with chronic granulomatous infiltration of bone, synovium and other organs, Is more common in black Africans and descendants. In addition to polyarthritis and tenosynovitis, x-rays show punched-out ‘cysts’ and cortical erosions in the bones ofthe hands and feet. The ESR is raised and the Kveim test may be positive. ‘Treatment with non-steroidal anti-inflamumatory drugs (NSAIDs) may be adequate but in more intractable cases, corticosteroids are necessary POLYMYALGUA AHEUMATICA This condition, which is seen mainly in middle-aged or elderly women, is characterized by aching discomfort around the pectoral and pelvic girdles, post-inactivit stiffness and muscular weakness. The joints are not tender but the muscles are. The ESR is almost always remarkably high. This is @ form of sant-cell arteritis and carries the risk of temporal arteritis resulting in blindness. Corticosteroids (as litle as 10mg a day) provide rapid and dramatic relief of all symptoms, ‘and this response is often used as a diagnostic test ‘Treatment ‘There is no cure for RA. This must be explained to the patient, who also needs to be reassured that it is not necessarily a crippling disease, that much can be done 10 alleviate symptoms and delay progression and that there is every chance of a useful and active life despite ‘some functional limitations. ‘Management is guided by five injunctions: (1) stop the synovitis; (2) keep the joints moving; (3) prevent deformity; (4) reconstruct; (5) rehabilitate. ‘A multidisciplinary approach is needed from the beginning: ideally the therapeutic team should include a rheumatologist, orthopaedic surgeon, physiotherapist, ‘occupational therapist, orthotist and social worker ‘Their deployment and priorities will vary according to the stage of the discase. The following scheme should met the needs of the ‘average’ patient. At te onset of the discose both the patient and the doctor will be uncertain about the likely rate of progress Treatment is mainly palliative and supportive: the control of pain and stifiness with NSAIDs, maintaining muscle tone and joint mobility by a balanced programme of exercise and general advice on coping with the activities of daily living During the early phase of established RA (the first 6-12 ‘months) the main problem is the control of synovi- tis, NSAIDs may have to be stepped up and, if the pain, swelling, stiffness and joint tenderness are not alleviated, may need to be supplemented by the intro- duction of love-dosage corticosteroids (5~7.5mg pred nisolone daily) and ‘second-Hine’ diugs such as gold or penicillamine. Systemic corticosteroids, once feared because of their side-effects, have been shown to be effective at ow dosage in delaying the onset of articular erosion and slowing disease progression (Kirwan et al, 1995; Kirwin, 1997), cis recommended that they be used in the early active phase of RA for up to 2 years. During that time, the ‘second-line’ drugs, which take a long time 10 start acting, can be introduced and then continued (if necessary} when corticosteroid treatment is talled off, Additional measures include the injection of long- acting corticosteroid preparations into inflamed Joints and tendon sheaths. It fs sometimes feared that such Injections may themselves cause damage to articular cartilage or tendons. However, there fs litle evidence that they are harmful, provided they are used sparingly and with full precautions against infection. Physiotherapy is still important. But so is rest ~ one of the oldest methods of treating inflammation. During an acute flare-up, the patient may benefit from a few weeks’ rest in bed gentle aetive and passive exercises are kept up and care should be taken 10 prevent2s Treatment of heumatold arthritis side-effects ofsys- ceric cortconteroids Ansofanatory drugs are nacessary pecan bahar (a,b) This yung woman on corticosteroid ne severly eshingoi(e) Th plane had mulpe ech cee whic combined with essue-paper skin add ta the risks fib srzer, rmities. Sometimes a week or two of 2s splintage (e.g. for the knees or wrists) is 3 splints can be used intermittently at any ze of the disease, ase of progressive erosive arthritis (1-8 years) mbination of muscle weakness, joint instability rupture may lead to progressive deformity. the patient will probably be on long-term ith one of the ‘second-line’ drugs such as old, penicillamine or methotrexate. However, these drugs cannot restore what has already been destroyed, and local counteractive measures become increasingly important, Preventive splintage and orthotic devi may delay the march of events. If these fail to restore and maintain function, operative treatment is indi cated. At first this consists mainly of soft-tissue proce- dures (synovectomy, tendon repair or replacement and joint stabilization); in some cases osteotomy may be ‘more appropriate. In late rheumatoid disease (5-20 yeors), severe joint destruction, fixed deformity and loss of function are clear indications for reconstructive surgery. Arthrodesis, osteotomy and arthroplasty all have their place and are considered in the appropriate chapters. However, it should be recosinized that patients who are no longer suffering the pain of active synovitis and who are content with a limited pattern of life may not want or need heroic surgery merely to improve their anatomy. Careful assessment for occu~ pational therapy, the provision of mechanical aids and adjustments to their home environment may be ‘much more useful NOTE: The various drugs employed in the treatment of RA, and the indications for using them, are reviewed in a “guidelines’ paper published by the American College of Rheumatology (1996). Complications FIXED DEFORMITIES The perils of RA are often the ‘commonplace ones resulting from ignorance and neglect. Early assessment and planning should prevent postural deformities, which will result in joint contractures MUSCLE WEAKNESS Even mild degrees of myopathy or neuropathy, when combined with prolonged inactivity, may lead to profound muscle wasting and weakness. This 43.9 Treatment of rheumatotd arthritis ~ prevent defor- ‘ity (a) Spineage to ree inlames joints may. started early hale the progress of deformity. (b) An early fees deformity of ‘the knee ean be corrected by gentle manipulation and tempo- rary plaster eplintge58 Shoulder (are) I Metatarsal a Head ot radius eas 3.10 Surgical treatment of rheumatoid arthritis Stes where reconstruccve operation: maybe wel should be prevented by physiotherapy and pain control, if possible; if not, the surgeon must be forewamed of the difficulty of postoperative rehabilitation. JOINT RUPTURE Occasionally the joint lining ruptures and synovial contents spill into the soft tissues. Treatment is directed at the underlying synovitis ~ ic. splintage and injection of the joint, with synovectomy as a second resort. INFECTION Patients with RA - and even more so those on corticosteroid therapy ~ are susceptible to infection. Sudden clinical deterioration, or increased pain in a single joint, should alert one to the possibility of septic arthritis and the need for joint aspiration. SPINAL CORD COMPRESSION This is a rare complication of cervical spine instability. The onset of weakness and upper motor neuron signs in the lower limbs is suspicious. If they occur, immobilization of the neck is essential and spinal fusion should be carried out as soon as possible. SYSTEMIC VASCULITIS Vasculitis is a rare but potentially serious complication. High doses of corticosteroids: and intravenous plasma volume expanders may be called for. AMYLOIDOSIS This is another rare but potenttally lethal complication of long-standing rheumatoid disease. The patient presents with proteinuria and progressive renal failure. The diagnosis is made by finding amyloid in a rectal or renal biopsy. There is no specific treatment. Prognosis RA runs a variable course. When the patient is first seen itis difficult to predict the outcome, but high titres of RE, periarticular erosions, rhcumatoid nodules, severe muscle ‘wasting, joint contractures and evidence of vasculitis are poor prognostic signs. Women, on the whole, fare some- ‘what worse than men. About 10% of patients improve steadily after the fist attack of active synovitis; 60% have intermittent phases of disease activity and remission, but ‘with a slow downhill course over many years; 20% have severe joint erosion, which is usually evident within the first 5 years; and 10% end up completely disabled. ANKYLOSING SPONDYLITIS Like RA, ankylosing spondylitis (AS) Is a generalized chronic inflammatory disease - but its effects are seen mainly in the spine and sacrotiac joins. It fs charac- terized by pain and stiffness of the back, with variable involvement of the hips and shoulders and (more rarely) the peripheral joints. Its reported prevalence is 0.0%-0.29 in western Europe and North America, but s much lower in Japanese and black African peoples. Males are affected more frequently than females (esti- ‘mates vary from 2:1 to 10:1) and the usual age at onset Js between 15 and 25 years. There is a strong tendency to familial aggregation and association with the genet rmarker HLA-B27AS is similar to that of RA. There is evidence for regarding it as a geneti- ned immunopathological disorder. The ‘s much more common in family members .¢ general population; HLA-B27 is present of Caucasian patients and in half of ee relatives (as compared with 89 of eneral population); and racial groups with an ow prevalence of AS also show a very low HLA-B27 (eg. 14% in ople). There are various theories about fering factor’ that initiates the abnormal response. It may be a bacterial antigen sely resembles HLA-B27 that induces an response which targets also the HLA-B27 s; or, aS in the case of RA, the HLA-B27 may be involved in the presentation of a nntigen to the T-cells which then react with gen-presenting cells. Since classic AS is es associated with genitourinary or bowel 1, and disorders such as Reiter's disease and ative colitis cause vertebral and sacroiliac ges indistinguishable from those of AS, it is ht that the putative organism may be carried by local lymphatic drainage, nce of less than © two basic lesions: synovitis of diarthrodial iflammation at the fibro-osseous junc syndesmotic joints and tendons. The prefer~ vement of the insertion of tendons and c entheses} has spawned the unwieldy is of the sacroiliac and vertebral facet ses destruction of articular cartilage and rricular bone. The costovertebral joints also are tly involved, leading to diminished respira- xcursion. When peripheral joints are affected ime changes occur. mmation of the fibro-osseous junctions i¢ intervertebral discs, sacroiliac ligaments, sis pubis, manubrium sterni and the bony rtions of large tendons. Pathological changes three stages: (1) an inflammatory reaction und-cell infiltration, granulation tissue forma- and erosion of adjacent bone; (2) replacement of ation tissue by fibrous tissue; and (3) ossi- of the fibrous tissue, leading to ankylosis of cation across the surface of the dise gives rise bony bridges or syndesmophytes linking ad bodies. If many vertebrae are involved may become absolutely rigid. 3.11 Ankylosing spondylitis early The ery features are (a) suff spine, (6) ‘squaring’ of che lumbar vertebrae and (@ blaterlsarolac erosion. Clinical features The disease starts insidiously: a teenager or young adult complains of backache and stiffness recurring at inter vals over a number of years. This is often diagnosed as back strain’, but (unlike back strain) the symptoms are worse in the early morning and after inactivity. Referred pain in the buttocks and thighs may appear as ‘sciatica’ and some patients are mistakenly treated for interver tebral disc prolapse. Gradually pain and stiffness become continuous and other symptoms begin to appear: general fatigue, pain and swelling of joints, tenderness at the insertion of the tendo Ackillis, ‘foot strain’, or intercostal pain and tenderness. Occasionally the disease starts with pain and slight swelling in a peripheral joint such as the ankle, or pain and stiffness of the hip. Sooner of later, though, back- ache will come to the fore. Early on there is little to see apart from slight flat- tening of the lower back and limitation of extension in the lumbar spine. There may be diffuse tendemess over the spine and sacroiliac joints, or (occasionally) swelling and tenderness of a single large joint. In established cases the posture is typical: loss of the normal lumbar lordosis, increased thoracic kyphosis and a forward thrust of the neck; upright posture and balance are maintained by standing with the hips and knees slightly flexed, and in late cases these may become fixed _(2ypendowuug roi2u29 :1 woHS) S49PLOS1P JUDUNIYY60 ‘deformities. Spinal movements are diminished in all direc- tions, but loss of extension is always the earliest and the most severe disability. It is revealed dramatically by the wall test’: the patient is asked to stand with his or her back to the wall; heels, buttocks, scapulae and occiput should all be able to touch the wall simultaneously. IF extension is seriously diminished the patient will find this Impossible. In the most advanced stage the spine may be ‘completely ankylosed from occiput to sacrum, sometimes in positions of grotesque deformity. Marked loss of cervi- cal extension may restrict the line of vision 10a few paces Chest expansion, which should be at least 7em in young men, is often markedly decreased. In old people, who may have pulmonary disease, this testis unreliable. Peripheral joints (usually shoulders, hips and knees) are involved in over a third of the patients; they show the features of inflammatory arthritis — swelling, tenderness, effusion and loss of mobility. There may also be tenderness of the ligament and tendon inser- tions close to a large joint or under the heel PXTRASKELETAL MANIFESTATIONS General fatigue and loss of weight are common. Acute anterior uveitis occurs in about 25% of patients; it usually responds well to treatment but, if neglected, may lead to glaucoma. Other extraskeletal disorders, such as aortic valve disease, carditis and pulmonary fibrosis, are rare and occur very late in the disease. Xerays The cardinal sign ~ and often the earliest ~ is erosion and fuzziness of the sacroiliac joints. Later there may be periarticular sclerosis, especially on the iliac side of the joint, and finally bony ankylosis, The earliest vertebral change is flattening of the normal anterior concavity of the vertebral body (‘squar- ing’). Later, ossification of the ligaments around the Intervertebral discs produces delicate bridges (syndesmo- phytes) between adjacent vertebrae. Bridging at several levels gives the appearance of a bamboo spine: Osteoporosis is common in long-standing cases and there may be hyperkyphosis of the thoracic spine due to wedging of the vertebral bodies. Peripheral joints may show erosive arthritis or progressive bony ankylosis. Special investigations The ESR is usually elevated during active phases of the disease. HLA-B27 is present in 90% of cases. Serological tests for RF are negative. Diagnosis Diagnosis is easy in patients with spinal rigidity and typical deformities, but it is often missed in those with early disease or unusual forms of presentation. In over 10% of cases the disease starts with an asym: metrical inflammatory arthritis ~ usually of the hip, knee or ankle ~ and it may be several years before back pain appears. Atypical onset is more common in women, who may show less obvious changes in the sacroiliac joints. A history of AS in a close rela~ tive is strongly suggestive. [MECHANICAL DISORDERS Low back pain ih young adults is usually attributed to one of the more common disorders such as muscular strain, facet joint dysfunction or 3.12 Ankelosing spondylitis late (a.b) Bony bridges (eyndesmapyes) between the vertebral bodies convert the spin nto clurn (bamboo spine): ote thatthe roi oints we fused Spinal esteorory may bene ‘essary at ths stage: (€) before operation this man could see only 3 few pes ahead () ater osteotomy his back sel gl but hs posture, faneton and outlook are vase improvedspondylolsthesi. These conditions differ from AS in several ways: the onset of pain is related to specific physical activities, sifiness is ess pronounced and symptoms are cased rather than aggravated. by inactivity, Tendemess is also more localized and the peripheral joints are normal. ANKYLOSING HYPEROSTOSIS (FORESTIE'S DISEASE] This is a fairly common disorder, predominantly of older men, characterized by widespread ossification of ligaments ‘and tendon insertions. X-rays show pronounced but asymmetrical intervertebral spur formation and bridging throughout the dorsolumbar spine. Although it bears a superficial resemblance to AS, it is not an inflammatory disease, spinal pain and stiffness are seldom severe, the sacroiliac joints are not eroded and, the ESR is normal THE SERONEGATWESPONDARTHRITIDES A number of disorders are associated with vertebral and sacroiliac lesions indistinguishable from those of AS. They are Reiter's disease, psoriatic arthritis, ulcerative colitis, Crokn's disease, Whipple's disease and Behget’s syndrome. In cach there are certain characteristic features: the rash. or nail changes of psoriasis, intestinal ulceration in enterocolitis, genitourinary and ocular inflammation in Reiter's disease, buccal and genital ulceration in Behget's syndrome. Yet there is considerable overlap between them; all show some familial aggregation and all are associated with the histocompati HLA-B27. Patients with one of these (including AS) often have close relatives with another, cor with a positive HLA-B27. ‘Treatment ‘The disease is not nearly as damaging as RA and most patients continue to lead an active life. In the absence of a specific agent, treatment consists of (1) general -meastres to maintain satisfactory posture and preserve ‘movement, (2) anti-inflammatory drugs to counteract pain and stiffness and (3} operations to correct defor- imity of restore mobility GENERAL MEASURES Patients are encouraged to remain active and follow their normal pursuits as far as possible. They should be tauight how to maintain satisfactory posture and ued to perform spinal ‘extension exercises every day. Swimming, dancing and ymnasties are ideal forms of recreation. Rest and immobilization, effective in other inflammatory j diseases, are contraindicated because they tend to increase the general feeling of stiffness. NON-STEROIDAL ANTLINFLAMMATORY DRUGS It is doubtful ‘whether these drugs prevent or retard the progress to ankylosis, but they do control pain and counteract, soft-tissue stiffness, thus making it possible to benefit from exercise and activity. Indomethacin is often used. Dut other, less powerful, drugs may be adequate; they usually have to be continued for many years. OPERATION Stiffness of the hips can be treated by joint replacement, though this seldom provides more than ‘moderate mobility. Moreover, the incidence of infection is higher than usual and patients may need prolonged rehabilitation, Deformity of the spine may be severe enough to ‘warrant lumbar or cervical osteotomy. These are diffi- cult and potentially hazardous procedures; fortunately, with improved activity and exercise programmes, they are seldom needed, If spinal deformity is combined with hip stiffness, hip replacements (permitting full exten- sion) often suffice. Complications SPINAL FRACTURES The spine is often both rigid and ‘osteoporotic; fractures may be caused by comparatively mild injuries. The commonest site is C5-7, but it is prudent to x-ray the entire spine in ac ‘who have AS. Treatment in these cases is directed at preventing further deformity. HYPERKYPHOSIS In long-standing cases the spine may become severely kyphotic, so much so that the patient has difficulty lifting his head to see in front of his feet. SPINAL CORD COMPRESSION This is uncommon, but it should be thought of in patients who develop long-tract symptoms and signs. It may be caused by atlanto-axial subluxation or by ossification of the posterior longitudinal ligament. LUMBOSACRAL NERVE ROOT COMPRESSION Patients may ‘occasionally develop root symptoms, including lower limb weakness and paraesthesia, in addition to their “usual' pelvic girdle symptoms. REITER'S SYNDROME AND REACTIVE ARTHRITIS ‘The syndrome described by Hans Reiter in 1916 (and 100 years before that by Benjamin Brodie) fs a clinical triad of urethritis, arthritis and conjunctivitis occur- ring some weeks after either dysentery or venereal infection. It is now recognized that this Is one of the classic forms of reactive arthritis, Le, an aseptic inflam matory arthritis associated with non-specific uroger tal or bowel infection.62 Its prevalence is difficult to assess, but itis proba- bly the commonest type of large-joint polyarthritis in ‘young men. Itis thought to occur in 1-3% of all people ‘who develop either non-specific urogenital infection or Shigella dysentery, but its incidence may be as high as 250 in those who are HLA-B27 positive. Men are affected more often than women (the ratio is about 10:1), but this may simply reflect the difielty of diag nosing the venereal infection in women. The usual age at onset is between 20 and 40 years, but children are affected too ~ perhaps after an episode of diarrhoea, Cause Familial aggregation, overlap with other forms of seroneg- ative spondarthrtis in first-degree relatives and a close association with HLA-B27 point to a genetic predisposi- tion, the bowel or urogenital infection acting as a trigger. Dysenteric organisms include Shigella flexneri, Salmonella, Campylobacter species and Yersinia entero- colitica. Lymphogranuloma venereum and Chlamydia trachomatis have been implicated as sexually transmitted infections. All these bacteria can survive in human cells; assuming that either the bacterium or a peptide bacterial fragment acts as the antigen, the pathogenesis could be the same as that suggested for AS. Pathology The pathological changes are essentially the same as those in AS, with the emphasis first on subacute large- joint synovitis and later tending towards sacrolitis and spondylitis, Clinical features Theacute phase of the disease is marked by an asymmet- rical inflammatory arthritis of the lower limb joints ~ usually the knee and ankle but often the tarsal and toe Joints as wel. The joint may be acutely painful, hot and ‘swollen with a tense effusion, suggesting gout or infec- tion. Tendo Achillis tendemess and plantar fas. (evidence of enthnesopathy) are common, and the patient may complain of backache even in the early stage. Conjunctivitis, urethritis and bowel infections are often mild and easily missed; the patient should be carefully questioned about symptoms during the previous few weeks. Cystitis and cervicitis may occur in women. Less frequent, but equally characteristic, features are a vesicular or pustular dermatitis ofthe feet (keratoderma blennorrhagicum), balanitis and mild buccal ulceration. The acute disorder usually lasts for a few weeks or months and then subsides, but most patients have either recurrent attacks of arthritis or other features of chronic disease. The chronic phase is more characteristic of a spon- arthropathy. Over half of the patients with Reiter's disease complain of mild, recurrent episodes of polyarthritis (including upper limb joints). About half of those again develop sacroilitis and spondylitis with features resembling those of AS. Uveitis is also fairly ‘common and may give rise to posterior synechiae and glaucoma. X-RAYS Sacroiliac and vertebral changes are similar to those of AS. If peripheral joints are involved, they may show features of erosive arthritis. ‘SPECIAL INVESTIGATIONS ‘Tests for HLA-B27 are positive in 7596 of patients with sacroilitis. The ESR may be high In the active phase of the disease. The causative organism can sometimes be isolated from urethral fluids or faeces, and tests for antibodies may be positive. gnosis The diagnosis should be considered in any young adult ‘who presents with an acute or subacute arthritis in the lower limbs. It is more likely to be missed in women, in 3:13 Reiter's syndrome - the classic triad The csi tra of Retr syncrome - conned. urethees (Gometmes cole) and arth Tendernas of the tendo chilis and the plantar fei i ako commen,23.14 Reiter's disease ~ other features The charscterttie esl derma of he fet — laratoderma Blenorrhagcum snd in those with very mild (and often forgotten} episodes of urogenital or bowel infection. Some patients sever develop the full syndrome and one should be alert 1 forme fruste with large-joint arthritis alone. TIVE ARTHRITIS Reiter's disease, gout and ction should all be considered in the differential gnosis of inflammation in a large peripheral joint. xamination of synovial fluid for organisms and crystals may provide important clues. OCCAL ARTHRITIS Gonococcal arthritis takes two ‘ms: (1) bacterial infection of the joint, and (2) a ive arthritis with sterile joint fluid. A history of wenereal infection further complicates the distinction rom Reiter's disease, and diagnosis may depend on fying the organism or gonococcal antibodies. HAMS Ulcerative colitis and Crohn's disease be associated with subacute synovitis, causing pain 2nd swelling of one or more ofthe peripheral joints. These subside when the intestinal disease is controlled, Treatment here is no specific treatment for Reiter's disease; even if he triggering infection is identified, treating it will have no effec on the reactive arthritis. However, there is some evidence that treatment of Chlamydia infection with