Familial paroxysmal polyserositis: Analysis of fifty cases

Abstract

The data from fifty personally observed cases of an uncommon disease, the multiple syndrome disorder here designated familial paroxysmal polyserositis (FPP), are presented. Three fatal cases in which autopsy or renal biopsy findings are described in detail, death occurring in renal or cardiac failure. Symptoms and signs of serosal inflammation are characteristic. Elevated temperatures, although often quite brief in duration, may reach 105 °F. Of the four chief syndromes of FPP, paroxysmal peritonitis is the most frequent; either alone or in combination with paroxysmal pleuritis, the second most common syndrome. Intermittent arthralgias, monoarthritis and paroxysmal pyrexia are less frequent. Occasionally, cutaneous eruptions are observed. Thirty-six of these patients are male; fourteen, female. Onset of FPP is chiefly in childhood or in youth. The earliest age at onset was seven months, the latest forty-three years. Attacks, usually of two to three days' duration, often recur every few weeks. Paroxysmal peritonitis closely simulates an acute surgical emergency. Direct and rebound tenderness, at times with involuntary abdominal wall spasm, fever, gastrointestinal upset, constipation and usually leukocytosis, 15,000 to 20,000 cells per cu. mm., complete a picture of “the false acute abdomen.” Paroxysms of pleuritis may recur independently but more often precede or follow the peritonitis. A transient small pleural effusion may be observed on the roentgenogram. Paroxysmal pyrexia was predominant in only one instance. The surgical pathology of paroxysmal peritonitis may be localized or diffuse, with congestion or edema, with or without small amounts of serous fluid, or strands and clumps of fibrin may be present. Microscopically, there is an acute polymorphonuclear exudate with congestion of the peritoneum and omentum. Cultures are sterile. Occasionally during attacks, but invariably during an interval free of attack, laparotomy is unrevealing. Enlargement of the spleen, moderate in degree, was observed in five cases. Accelerated erythrocyte sedimentation rate is frequent, especially during attacks. Moderate anemia, not less than 10 gm. per cent hemoglobin, is occasional. Hepatic disturbance with minor histologic and biochemical abnormalities may accompany paroxysms. Evanescent small bowel changes are frequent during attacks of peritonitis. Cerebral dysrhythmia was observed in the electroencephalogram in two cases in childhood and reported in a single adult case. Progressive renal disease is considered the most significant organ involvement in FPP, but in fifty cases forty-eight were free of nephropathy. Two patients died in uremia; in one chronic glomerulonephritis was found at autopsy, and in the other renal amyloidosis was found on biopsy. In a third case, death was due to rheumatic mitral stenosis. FPP is familial and genetic. It affects especially, but not exclusively, patients of Mediterranean origin, most often Jews (both Ashkenazi and non-Ashkenazi), Armenians and Arabs and, less commonly, Italians, Maltese and Greeks. Of fifty cases, forty-two occurred in Jews; thirty-five are definitely Ashkenazi, three probably Ashkenazi and four Sephardic; seven in Armenians; one in a Maltese. Ten familial cases include two families, Ashkenazi Jewish and Armenian, with five members affected. The role of hypersensitivity in FPP is discussed, with special reference to rheumatic fever. The incidence of atopy is shown to be about twice that in control subjects. Food allergy appeared to be demonstrated in only two of twenty-two cases studied. Endocrine factors involving especially the formation of abnormal pyrogenic steroid metabolites probably derived from adrenal or gonadal hormones may play a significant role in FPP. Pregnancy is often associated with complete inhibition of attacks, and paroxysms may be strikingly associated with the menstrual periods. In some cases emotional factors appear to initiate episodes of FPP. Paroxysmal peritonitis presents the most urgent diagnostic problem, to be differentiated from common acute abdominal infections, acute intermittent porphyria and relapsing pancreatitis. The diagnosis of FPP must be considered with caution in patients with attacks beginning after age forty. Prognosis as to life is generally favorable. Forty-seven of fifty patients are alive despite many years of illness. Five are over age sixty, one being seventy-seven and free of attacks for fourteen years. In two patients progressive nephropathy developed. Most patients remain remarkably well between acute episodes. Rarely, unpredictable remissions occur which may last for years. The prognosis for complete recovery is poor, since FPP usually pursues a lifetime course. Treatment of FPP is generally unsatisfactory. The administration of corticosteroids has been distinctly helpful in aborting attacks in three of fifteen cases. Rarely, exclusion of a specific food, particularly milk and milk products, may produce a prolonged remission. A diet restricted in fat (20 gm./day) is of occasional benefit.