Marcel Eliakim

Recurrent polyserositis (familial mediterranean fever; Periodic disease): A report of fifty-five cases

Abstract The clinical and laboratory features of fifty-five patients with recurrent polyserositis are presented. All patients were Jews, forty-five of Sephardi or Oriental origin, ten of Ashkenazi parentage. A familial incidence was established in 30 per cent of the families. One generation was affected twice as frequently as two generations. The symptoms consisted of attacks of fever (all cases), abdominal pain (98 per cent), chest pain (38 per cent), joint pain (31 per cent), gastrointestinal disturbances, headache, and other less frequent manifestations. The most frequent signs were colloid body-like dots in the eye grounds (50 per cent), palpable spleen (40 per cent), systolic murmur over the apex and parasternally (29 per cent) and palpable (probably enlarged) liver (27 per cent). The main signs during an attack were extreme tenderness and rigidity of the abdominal wall, decreased motility of the diaphragm, and occasional pleural and joint effusion. The attacks lasted from one to four days, and appeared at irregular intervals of two days to several months. The longest remission (still persisting) was five years. Cold seemed to precipitate, and pregnancy to suppress, the appearance of attacks. The chief laboratory findings during an attack were leukocytosis, increased sedimentation rate and increased serum α 2 globulin level. An abnormal serum β globulin appeared during an attack in two cases. Hypersensitivity to old tuberculin was observed in eight of forty-three patients examined. In five of these, attacks could be provoked by the injection of minute quantities of tuberculin. Two of three attempts at desensitization resulted in remissions for as long as eighteen months. Transient electrocardiographic abnormalities were found in four of thirty-one patients examined. In two of these the changes were suggestive of pericarditis, while in the remaining two the changes were non-specific and confined to the T waves. Electroencephalographic abnormalities were observed in seven of sixteen patients examined. In two the changes were present only during an attack. The changes were diffuse and non-specific in five, and of the convulsive type in the remaining two. Amyloidosis developed in four patients (7.2 per cent). Two additional patients had albuminuria without evidence of amyloidosis. Two of the patients with amyloidosis died of renal failure. Autopsy revealed amyloid deposits in the skin, heart, kidneys, skeletal muscle, spleen, ovaries and adrenals. Except for the patients with amyloidosis, the prognosis was good. The average duration of the disease at the time of the study was nine years and one month. One patient survived more than a thousand attacks in the course of thirty-nine years, with no apparent ill effects on his general condition. Numerous kinds of treatment were of no avail. ACTH and corticosteroids suppressed the attacks in eleven of fifteen patients, but could not be given indefinitely because of the relatively large doses required, and because the dangers involved were not justified by the temporary nature of the effects. The pathogenesis of the disease is discussed in the light of present knowledge.

Hospital admissions due to adverse drug reactions.

One hundred three (4.1%) of 2,499 patients hospitalized in a general medical ward were admitted because of an adverse drug reaction (ADR). Of 60 drugs involved, the most common were cardiac, antibiotic, and antineoplastic agents. The main reactions included skin rashes, bone marrow depression, arrhythmia, bleeding, and heart failure. Five (4.9%) of the patients died and 11 (10.7%) had life-threatening reactions. Risk factors predisposing to admissions due to ADR were: female sex, decreased renal function, polypragmasia, and the underlying disease. Twenty-seven percent of the admissions could have been avoided by a more careful choice and dosage of drug.

Fertility and obstetric history in patients with familial Mediterranean fever on long‐term colchicine therapy

Summary. The obstetric histories were examined for 36 women with familial Mediterranean fever (FMF) on long‐term colchicine treatment followed for periods ranging between 3 and 12 years. Seven of 28 pregnancies (25%) associated with colchicine therapy ended in miscarriage. Thirteen women (36%) had periods of infertility; these were due to ovulatory dysfunction in six women, to peritoneal adhesions in four and remained unexplained in three women. The rates for miscarriage and infertility are high but are similar to those reported for women with FMF before colchicine therapy was introduced. All 16 infants born to mothers who had taken colchicine during pregnancy were healthy. Currently, we do not advise discontinuation of colchicine before planned pregnancy but recommend amniocentesis for karyotyping and reassurance.

Gastrointestinal effects of long-term colchicine therapy in patients with recurrent polyserositis (familial mediterranean fever).

Twelve patients with recurrent polyserositis (RP, familial Mediterranean fever) on colchicine prophylaxis (1.0–2.0 mg daily) for three years or more were evaluated for the presence of gastrointestinal effects possibly attributable to the drug. Two patients had bulky stools, two others had transient diarrhea, and one had heartburn. Serum vitamin B12, calcium, and carotene levels were normal in all cases, andd-xylose absorption was normal in 11 of the 12. Three patients had mild steatorrhea (7.5, 7.9, and 9.9 g daily). Jejunal biopsies from these and a fourth patient with bulky stools but normal fecal fat excretion showed no abnormal histological changes. However, (Na+K)-ATPase activity was significantly decreased in all four cases. Colchicine had to be discontinued in only one of the 12 cases. It is concluded that mild steatorrhea and enzyme inhibition may occur in patients on long-term colchicine prophylaxis and that careful periodic observations for this and other adverse effects is imperative in such patients.

Leukocyte chemotaxis in recurrent polyserositis (familial Mediterranean fever)

Polymorphonuclear leukocyte chemotaxis was investigated in 35 patients with recurrent polyserositis during attacks and during spontaneous or colchicine-induced remissions. Chemotaxis was found to be unchanged in the attack-free period in untreated patients, increased by about 50% during attacks, and decreased by about 50% during colchicine treatment.

A cytogenic evaluation of long-term colchicine therapy in the treatment of Familial Mediterranean fever (FMF).

AbstractThirty-eight patients suffering from Familial Mediterranean Fever (FMF) and undergoing colchicine therapy for periods varying from one week to three years were examined cytogenetically. Preparations were derived from short-term lymphocyte cultures; mitotic rate, percent tetraploidy, and chromosome breakage rates were determined. Twenty-one patients were examined prior to treatment, 22 during treatment and 5 both before and during treatment. No statistically significant differences were observed in the parameters studied between ten controls and the patient groups. An in vitro experiment indicated a direct correlation between increased colchicine concentration and mitotic rate. However, tetraploidy or chromosome damage showed no such association with colchicine concentration. Among the patient group, pregnancy occurred in four patients while under treatment; three pregnancies resulted in the birth of normal children while the fourth has not yet been completed. In one pregnancy, cultured fetal amniotic fluid cells demonstrated no effect of colchicine on the cytogenetic parameters investigated. These results indicate no untoward effects on long-term colchicine treatment in FMF with respecttofertility, teratogenicity and chromosomal damage.

Total lymphoid irradiation in refractory systemic lupus erythematosus

In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental.

Clinical, psychological and thallium stress studies in patients with chest pain and normal coronary arteries

The clinical and psychological profiles of 36 consecutive patients with chest pain and normal coronary arteries (study group) were compared to those of 34 patients with chest pain and significant coronary arterial disease (control group). All 70 patients were hospitalized for chest pain at least once prior to coronary angiography. The features of a typical episode of chest pain were similar in the normal coronary arteries and coronary arterial disease groups, but the female patients with normal coronary arteries had a shorter duration of a typical episode of chest pain, and the male patients with normal coronary arteries had a lower frequency of positive effort tests. Psychological testing showed the women with normal coronary arteries to have a tendency to increased somatization, anxiety, and a lower ability to identify origin of difficulties. The patients in the normal coronary and coronary arterial disease groups had psychological profiles typical of patients with chronic somatic disease. A psychiatric interview demonstrated an increased frequency of depressive trait (score 0-2) in the normal women (0.6 +/- 0.8 vs 0, P less than 0.05), and a tendency to increased somatization, anxiety, and sleeping disorders. Increased somatization was found in the normal coronary men (1.1 +/- 0.7 vs 0.5 +/- 0.7, P less than 0.05). Twenty-five patients of the normal coronary group underwent quantitative thallium stress studies, and 13 patients (52%) had evidence of stress-induced myocardial perfusion defect. There were no differences in the clinical and psychological profiles of the patients with normal and those with pathological thallium stress tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Malignant lymphoproliferative disorders in chronic liver disease. Report of four cases and review of the literature.

Four patients who manifested an association between chronic liver disease and lymphoma are reported. Three of them had nonalcoholic cirrhosis and one had chronic cholangitis. Non-Hodgkins lymphoma developed long after the presence of liver disease had been established in three of the patients. The fourth patient died of hepatic coma and Hodgkins disease was discovered incidentally at autopsy. Drugs could not be incriminated in the development of either cirrhosis or lymphoma in any of the patients. A review of the literature is presented, and the view that the association between chronic liver disease and lymphoma is not coincidental is supported.

Coma due to hypercalcemia in a patient with Paget's disease and multiple parathyroid adenomata.

A patient with histologically proven coexistent Pagets disease of the bone and parathyroid adenomatosis is described. She developed coma associated with hypercalcemia and underwent successfully surgical removal of two parathyroid adenomata. The differential diagnosis of hypercalcemia in patients with this rare association is discussed and the importance of early surgical treatment is stressed. A review of similar reported case is presented.