and pleurisy. The articular disease is the second most common manifestation after abdominal pain. It occurs in 70±75% of the patients and in one-third of.
British Journal of Rheumatology 1997;36:1228±1230 PAEDIATRIC RHEUMATOLOGY SERIES EDITOR: P. WOO
PROTRACTED ARTHRITIS OF FAMILIAL MEDITERRANEAN FEVER (AN UNUSUAL COMPLICATION) F. YALC° INKAYA, M. TEKIN,* N. TUÈMER AND N. OÈZKAYA Departments of Paediatric Nephrology and *Paediatrics, Faculty of Medicine, Ankara University, Ankara, Turkey SUMMARY An unusual case of familial Mediterranean fever and vasculitis in which the patient developed amyloidosis and had protracted arthritis persisting for years is presented. The long-standing arthritis did not respond to corticosteroid and colchicine therapy, but an excellent response to synovectomy was achieved. KEY WORDS: Arthritis, Familial Mediterranean fever, Vasculitis, Amyloidosis.
cousins. From 3 yr of age, she had suered recurrent attacks of abdominal pain and fever. Seven years before admission, she was admitted to another hospital, with hypertension, purpuric rash on her legs and arthritis of the knees, where vasculitis was diagnosed with skin biopsy and steroid therapy was started. Shortly afterwards, she had a pleural eusion accompanied by fever that resolved spontaneously. Laboratory examination revealed elevated erythrocyte sedimentation rate (ESR), anaemia, leucocytosis and intermittent proteinuria. Renal biopsy was normal. She discontinued the drug after a year and because of social problems she was at home without any therapy, during which time her clinical condition deteriorated progressively. She had recurrent arthritic attacks of the knees accompanied by fever during the 5 yr prior to admission. Severe articular pain set in soon after and she experienced diculty in walking. Swelling of the lower extremities and face had developed 6 months ago. On admission, she had the physical features of nephrotic syndrome with oedema and pallor. Blood pressure was normal. Her height and weight values were below the third percentile for age and sex. The height S.D. score was calculated as ±4.8. The knees were swollen with a marked eusion, redness was absent and local warmth was minimal. Muscle atrophy was extreme in the aected limbs (Fig. 1). She could not walk. The joints did not hurt when at rest, but movement of her knees was painful. She had livedo reticularis on her lower extremities. Laboratory values were as follows: haemoglobin 10.4 g/dl; white blood cell counts 15 000/mm3. The ESR was 121 mm/h. Urinalysis was normal, except for massive proteinuria (250 mg/m2/h). Renal function tests, serum electrolytes, liver function tests, creatinine phosphokinase levels and C3, C4 complement components were normal. Total serum protein and albumin levels were 4 and 1.6 g/dl, respectively. Antinuclear antigen and rheumatoid factor (RF) were negative and anti-DNA levels were within the normal range. Renal ultrasound revealed bilateral
FAMILIAL Mediterranean fever (FMF) is an autosomal recessive disease of unknown aetiology with recurrent attacks of fever and in¯ammation of serous membranes involving mainly the peritoneum, synovium and pleura [1±3]. The disease occurs most commonly in individuals of Mediterranean countries and particularly in non-Ashkenazi Jewish, Armenian, Turkish and Middle Eastern Arab populations [1, 4± 8]. FMF is characterized by recurrent acute attacks of fever accompanied by abdominal pain, arthritis and pleurisy. The articular disease is the second most common manifestation after abdominal pain. It occurs in 70±75% of the patients and in one-third of these as the ®rst presenting sign [1, 9]. The arthritis of FMF consists of episodic, recurrent attacks of pain and swelling. Usually, one joint is aected. Short attacks, terminating within 2 or 3 days, are the most common, but protracted articular attacks persisting for months or even years have been described [5, 9±12]. The high prevalence of vasculitis such as Henoch±SchoÈnlein purpura and periarteritis nodosa in combination with FMF has been described [13±16]. It was suggested that the basic pathophysiology of FMF might facilitate the occurrence of vasculitis. The most severe complication of FMF is the development of systemic amyloidosis, ultimately leading to renal failure [1±8]. Here, we describe a patient with vasculitis and FMF who developed amyloidosis and who had protracted arthritis persisting for years. The long-standing arthritis did not respond to corticosteroid and colchicine therapy, but synovectomy controlled her articular disease. CASE REPORT A 12-yr-old girl was hospitalized because of severe pain and swelling of her knees accompanied by generalized oedema. She was the second child of ®rst Submitted 24 March 1997; revised version accepted 7 July 1997. Correspondence to: F. Yalc° |nkaya, C° |nar Sitesi 5. Blok No: 62, UÈmitkoÈy 06530 Ankara, Turkey.
# 1997 British Society for Rheumatology 1228
YALC° INKAYA ET AL.: PROTRACTED ARTHRITIS OF FMF
FIG. 1.Ð The knees of the patient at the time of diagnosis. Note the extreme swelling, deformity and muscle atrophy.
enlarged kidneys with an increase in the thickness of renal parenchyma. Roentgenographic examination of the knees revealed soft-tissue swelling and osteoporosis of the involved joint. Approximately 5 ml of synovial ¯uid were aspirated percutaneously from the synovium in the dorsal region of the right knee. Synovial ¯uid analysis revealed a xanthochromic ¯uid that contained 1000 white blood cells/mm3, mononuclear cells predominated. The synovial ¯uid proteins were elevated and glucose was normal. Bacteriological studies including mycobacteria and RF were negative. Biopsy of the skin taken from the aected area revealed a medium-sized artery with ®brinoid necrosis involving the media in the deep dermis. The periphery of the arterial wall was in®ltrated predominantly by lymphocytes and a number of neutrophils. Renal biopsy revealed amyloid deposits in mesangial areas and in varying amounts in all glomeruli. The patient was diagnosed as having FMF, vasculitis and amyloidosis. Treatment was begun with daily oral prednisone and colchicine. After several weeks, the patient had a little improvement of motion without resolution of swelling. Bilateral synovectomy was performed. A severe chronic in¯ammatory reaction was present in the synovium, amyloid deposition was absent. An excellent response to synovectomy was achieved with
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FIG. 2.Ð The knees appearing entirely normal after synovectomy.
resolution of the swelling and improvement of the movement of the knees (Fig. 2). She continued to take steroid and colchicine therapy. She could walk and since the operation no further in¯ammation of the knees has occurred. DISCUSSION As there is no speci®c test for FMF, the diagnosis is based on the following clinical criteria described by Sohar et al. [1]: (1) short attacks of fever recurring at varying intervals; (2) painful manifestation in the abdomen, chest or joints accompanying the fever; (3) absence of any causative factor or pathologic ®nding capable in itself of explaining the picture; (4) amyloidosis; (5) features of autosomal recessive inheritance; (6) preference for people of Mediterranean ancestry. The patient reported here had associated peritonitis, pleuritis and arthritis, and she was of Turkish ancestry. Arthritis can be seen in vasculitis as well as FMF and the co-existence of FMF and vasculitis has been reported frequently [13±16]. This may be a source of diagnostic confusion if the association of FMF and vasculitis is not recognized. The diagnosis of vasculitis in our patient, which was con®rmed by skin biopsy, delayed the early diagnosis of FMF and initiation of colchicine therapy. Renal involvement with amyloidosis manifests as
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proteinuria, nephrotic syndrome and progresses to uraemia and ®nally to end-stage kidney disease [1±8]. It was clearly demonstrated that colchicine treatment changed the course of the disease, preventing febrile attacks and the development of the fatal complication amyloidosis in most of the patients [8, 17±21]. In 25% of patients, arthritis is the initial symptom. It is important to recognize these children as their condition will not respond to anti-in¯ammatory drugs such as salicylates or steroid therapy [9±11]. Monoarthritis is the most common type, but migratory arthritis is not unusual. The acute attacks of arthritis are typically short. However, long-standing, protracted arthritis that accounts for 5% of cases was reported by Sneh et al. [12]. The attack begins similarly to an acute episode, but there is no resolution. Fever is not present once long-standing arthritis is evident. The eusion is often large and pain is severe, leading to incapacity of the patient, and periarticular muscle atrophy may be extreme. The knee and hips represent 75% of all cases of chronic arthritis. Despite the severity of arthritis, complete functional recovery is the rule, with the exception of hip involvement leading to residual incapacity ranging from limitation of motion to complete ankylosis of the joint [9±12]. It was reported that colchicine is the treatment of choice, but sometimes synovectomy may be necessary for the protracted arthritis [7, 10]. Our patient did not respond to corticosteroids and to the delayed therapy with colchicine, but synovectomy appeared to be eective. We conclude that FMF should be considered in the evaluation of any child with arthritis, particularly if he or she is of Mediterranean ancestry. A conscientious evaluation of arthritis should be performed because early diagnosis is essential for the prevention of protracted complications of FMF. REFERENCES 1. Sohar E, Gafni J, Pras M, Heller H. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 1967;43:227±52. 2. Ehrenfeld EN, Eliakim M, Rachmilewitz M. Recurrent polyserositis (Familial Mediterranean Fever; Periodic Disease). A report of ®fty cases. Am J Med 1961; 31:107±23. 3. Siegal S. Familial paroxysmal polyserositis. Analysis of 55 cases. Am J Med 1964;36:893±918. 4. Schwabe AD, Peters RS. Familial Mediterranean fever in Armenians. Analysis of 100 cases. Medicine 1974; 53:453±62. 5. OÈzdemir AI, SoÈkmen C. Familial Mediterranean fever among Turkish people. Am J Gastroenterol 1969;51:311±6.
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