INDEX A CASE OF POLYARTERITIS NODOSA ASSOCIATED WITH FAMILIAL MEDITERRANEAN FEVER
Autors: M. Harman*,S. Arslan**, H. Arslan*,O. Etlik* and S. Sar**
Departments of Radiology* and Pediatrics**, University Faculty Medicine, VAN, TURKEY
Dr. Mustafa Harman,T‰Ń Fakultesi Hastanesi,Van-Turkey
Telephone: 00 90 432 2164709, Fax: 00 90 432 2167519
We describe an 8 year - old boy which was followed with the diagnosis of familial Mediterranean fever (FMF). The diagnosis was made 6 months before admission to our hospital. He was treated with colchicine. He developed polyarteritis nodosa (PAN) in addition to FMF. He was admitted to our hospital with cutis marmaratus, general weakness, arthritis and hypertension. Renal angiography revealed an aneurysm in both kidneys. PAN was confirmed by renal biopsy. Captopril was added to the treatment of colchicine. The known rare association of FMF and PAN is discussed in this case report.
Familial Mediterranean Fever (FMF) is an autosomal recessive disease which is characterized by recurrent fever with peritonitis, pleuritis and/or bouts of synovitis. It is seen mostly in Sefardik Jewish, Armenian, Arabic and Turkish people (1). Definition of TelhashomerˇÕs FMF criteria is usefull for diagnosis (2).
Polyarteritis nodosa (PAN) is a vasculitis that is characterized with fibrinoid necrosis in small and middle size arteries with involvement of multiorgan systems (3). Incidence of PAN was reported 0.7/100.000 (4). In the study of Saatci et al. (5) nine out of 605 cases (405 cases with FMF and 180 with amyloidosis) were found to have PAN. In another study (6), two cases out of 207 patients with FMF was reported to have PAN.
Table 1 shows the current diagnostic criteria for PAN diagnosis at children (7). Renal angiography should be performed or biopsy from involved organs should be taken for definitive diagnosis of patient with PAN who exhibit at least one major and four minor criteria. Early diagnosis of PAN is important because of aneurysms occuring secondary to vasculitis and life threatening complications such as perirenal hematom. While presenting this case, we aimed to review the current knowledge in the literature on the coexistence of FMF and PAN. CASE REPORT
A 8-year old Turkish boy whose parents are first-degree relatives was diagnosed as having FMF 6 months ago on the basis of recurrent attacks of abdominal, chest pain and fever, the frequency and severity of which subsided with colchicine therapy. His family history was remarkable. One of his two siblings (an 5-year-old girl) and his uncle suffer from
FMF which is treated with colchicine. On the last physical examination, complaints of weightloss, weakness, abnormal prominence of leg vessels and headache were noted. Temperature was 37.3°C, the pulse was 104/min, the respiration was 30/min, the blood pressure was 130/95 mmHg, the body weight was 14 kg, the height was 107 cm. He appeared ill and weak, suffered diffuse tenderness with palpation of extremities. He had cutis marmaratus in lower extremites. Other system findings were normal.
Laboratory investigations revealed a 12.1 gr/dl hemoglobin, 37.1% hematocrit, 7400/mm3 leucocyt, 340.000/mm3 platelet and an erythrocyte sedimentation rate of 45 mm/h. Protein excretion was 2 mg/m2/h in 24 hours urine collections. C-reactive protein 2+, urine and throat cultures were negative. Blood urea nitrogen, creatinine and liver enzymes were normal. Serum IgA was 3.12 g/l (normal 1.9-4.5 g/l), IgM 3.47 g/l (normal 0.6-2.8g/l), IgG 23.1 g/l (normal 3-18 g/l). Renal function tests, electrolytes, chest roentgenogram, abdominal ultrasonography, C-reactive protein, Compleman 3, Compleman 4 levels were in normal range. Hepatitis B surface antigen was negative. Serological tests for rheumatoid factor, antinuclear antibody, anti-double-stranded DNA, anticardiolipin antibodies were all negative. Renal Doppler investigation revealed aneurysm in the central pole of left kidney. Thereafter renal angiography revealed aneurysms in both kidneys (Picture 1A,1B). Renal biopsy confirmed PAN diagnosis. Histologically; Fibrinoid necrosis and leukocystic infiltrate were seen in small and medium sized arterial wall of the kidney.
The patient was diagnosed with FMF and was treated with colchicine. As PAN was diagnosed in this FMF patient, Captopril (3X25 mg) was added to the current Colchicine treatment.
FMF is characterized by recurrent and self limited episodes of polyserositis and fever (1). Since its first description in 1945, a few cases with vasculitides have been reported (8).
The prevelance of PAN in the general population of the United Kingdom is 4.6 per 1.000.000 and 9.0 per 1.000.000 in the United States (9). It has been suggested that the coexistence of these two diseases seems to be more frequent than explained by Chance (8). Since both disease are characterized by fever and abdominal pain , the diagnosis of PAN in patients with FMF may be difficult. Severe myalgia without arthritis is relatively rare in FMF. The appearence of rush, nodule lesions, myalgia, hypertension,weight loss and nephritis should anse a suspicion of PAN (5). Perirenal hematoma is a well-known but rare complication of isolated PAN (5), but occured in more than half of the patients with FMF who developed PAN (8). The reason for the high occurence of this complication is unclear.
The pathogenesis of PAN in patients with FMF is unknown. Hypersensitivity, genetic and/or autoimmune mechanisms have been suggested. The findings of immune complexes in 50% of patients with FMF, complement consumption during attacks, increase of urinary fibrin degration products, and the return of this test to normal at the end of the acute attacks suggest that immunological processes may underlie FMF (10). It has been suggested that immune complex diseases are involved in at least some cases of PAN. (11).
Our patient who had applied with recurrent fever, abdominal and chest pain improved with colchisin treatment. According to the Telshashomer FMF criteria, he took the definitive FMF diagnosis.
During the following up period with FMF diagnosis other systemic complaints and symptoms including: myalgia, cutis marmaratus, hypertension, constitutional findings (weight loss, fatique, loss of appetite) and increased sedimentation rate were observed. According to criteria suggested by Özen et al (7), PAN was suspected and was revealed with renal angiography. Renal angiography revealed aneurysms in both kidneys. Diagnosis of PAN was confirmed with renal biopsy because of typical multipl microaneurysms wasnˇÕt seen in renal angiography.
In the series of Saatci et al. (5), and the report of Özdogan et al. (6), the association of FMF and PAN had taken attention and, high prevalance had been given. There are reports on association of FMF and PAN out of Turkey (12). We think that our case with its own clinic and radiologic feature would contribute to the literature about.
1- Glikson M, Galun E, Schlesinger M, et al. Polyarteritis nodosa and familian Mediterranean fever: A report of 2 cases and review of the literature. J Rheumatol 1989; 16:536-9.
2- Sohar E, Gafni J, Pras M. Familiall Mediterranean Fever. London: Freund Publishing House Ltd, London and Telaviv, 1997: 207-208
3- CassidyJT, Petty RE (eds). Vasculitis. In: Textbook of Pediatric Rheumatology (3rd ed). Philadelphia: WB Saunders, 1995: 365-422
4- Michet CJ. Epidemiology of vasculitis. Rheum Dis Clin North Am 1990; 16: 261-268
5- Saatci U, Ozen S, Ozdemir S, Bakkaloglu A, Besbas N, Topaloglu R, Arslan S. Familiall Mediterranean Fever in children: report of a large series and discussion of the risk and prognostic factors of amyloidosis. Eur J Pediatr 1997; 156:619-624
6- Odogan H, Arisoy N, Kasapcopur O, Sever L, Çalskan S, Tuzuner N, Mat C, Yazici H. Vasculitis in Familial Mediterranean Fever. J Rheumatol 1997; 24: 323-327
7- Ozen S , Besbas N, Saatci U, Bakkaloglu A. Diagnostic criteria for PAN in childhood. J Pediatr 1992; 120: 206-209
8- Glikson M, Galun F, Schlesinger M, et al. Polyarteritis nodosa and familial Mediterranean fever a report of 2 cases and review of the literature. J Rheumatol 1989; 16: 536-539
9- Conn DI, Hunder GG, OˇÕDuffy JD. Vasculitis and related disorders. In: Kelly WN, Harris ED, Ruddy S, Sledge CB (eds). Textbook of rheumatology. 4th edn. Saunders, Philadelphia. 1993; pp 1077-1102
10- Said R, Hamzeh Y, Said S, Tarawneh M, Al Khateb M. Spectrum of renal involvement in familial Mediterranean fever. Kidney 1992; Int 41: 414-419
11- Cohen RD, Conn DL, Ilstrup DM. Clinical features, prognosis, and response to treatment in polyarteritis. Mayo Clin Proc 1980; 55: 146-155
12- Sachs D, Langevitz P, Morag B, Pras M. Polyarteritis nodosa and familial Mediterranean fever. Br J Rheumatol 1987;26:139-41
TABLE 1: Diagnostic criteria of PAN
Major findings: Renal involvement
Musculo-skeletal system symptoms
Minor findings: Skin findings
Central nerve system disease
Acute fase reactans
PICTURE 1A,B: Renal arteriogram demonstrating one sacculer aneurysm on left kidney and one aneurysm on right kidney originating from interlober arteries