A retrospective review of 61 patients with antiphospholipid syndrome. Analysis of factors influencing recurrent thrombosis.

BACKGROUND: Antiphospholipid syndrome (APS) is a disorder of recurrent venous or arterial thrombosis, pregnancy losses, and thrombocytopenia. Recurrent thrombosis has particularly adverse effects on patients prognosis. The factors that influence recurrence and management techniques that prevent these events remain controversial. To add further insight regarding predisposing factors and the prevention of thrombotic recurrence, 61 well-characterized patients with APS were followed up for a median time of 77 months. METHODS: A retrospective cohort study was conducted in which the following factors were examined to determine their influence on thrombotic recurrence: primary vs secondary syndrome; the presence of hypertension, hyperlipidemia, diabetes, or smoking; patient age, sex, and race; pregnancy and oral contraceptives use; and treatment with warfarin sodium, warfarin plus aspirin, aspirin alone, prednisone, or no treatment. RESULTS: There was no difference between patients with primary and secondary APS with respect to recurrent arterial (55% vs 38%, respectively) or recurrent venous (47% vs 50%, respectively) thrombotic events. In all patients with APS, white race (P = .02) was associated with recurrent arterial events. Venous thrombosis occurred during pregnancy or in the postpartum period in 16 (30%) of 53 women and in 8 women taking oral contraceptives. Recurrent arterial and venous thromboses were significantly decreased with prophylactic warfarin use when compared with prednisone use or no treatment. Recurrences were infrequent in patients with prothrombin ratios of 1.5 to 2.0. CONCLUSIONS: Treatment with warfarin was most effective in preventing recurrent arterial and venous thrombosis. Pregnancy and the use of oral contraceptives or prednisone may also influence recurrence.

Reflex sympathetic dystrophy associated with antiepileptic drugs.

Reflex sympathetic dystrophy syndrome (RSDS) complicating antiepileptic drug (AED) therapy is not well acknowledged in the neurologic literature. We report 4 patients with reflex sympathetic dystrophy that occurred while they were receiving AEDs. All patients had shoulder and hand involvement, which in 2 was bilateral, and 1 had ipsilateral foot involvement. Two patients did not respond to a change in AEDs, but all improved with a course of prednisone. One patient with phenobarbital (PB)-associated RSDS relapsed on inadvertent rechallenge with secobarbital. A review of the literature showed that several other fibrosing disorders are associated with AED administration, including Dupuytren's contractures, frozen shoulder, plantar and hand nodules, and Peyronie's disease. RSD associated with AEDs is important to recognize because it may result in permanent disability if treatment is delayed.

Evaluation of the mechanisms of antiepileptic drug-related chronic leukopenia.

Antiepileptic drug (AED)-related chronic leukopenia [white blood cell (WBC) count < 4,000/microliters] is a dilemma, especially when the AED is effective in controlling seizures. We evaluated the possible mechanisms of leukopenia in 7 patients. Mean WBC count was 3,000/microliters with a mean of 42% polymorphonuclear leukocytes (PMN). The AEDs were carbamazepine (CBZ) alone in 1 patient or CBZ combined with phenytoin (PHT), primidone (PRM), phenobarbital (PB) and/or valproate (VPA) in 5 patients; one patient was receiving PHT only. Bone marrow (BM) aspirates and PMN antibody studies using chemiluminescence were normal. Two liver-spleen scans showed mild relative splenomegaly. After exercise, WBC count (n = 7) increased by 54% (SEM 12%), while the WBC counts in controls (n = 5) increased by 52 +/- 16%. Antinuclear antibodies (Hep-2) were absent in 6 patients and positive (1:160) in 1. PMN adhesion to nylon wool was decreased (54 +/- 10% in patients vs. 80 +/- 5% in controls: n = 13, p < 0.005). Our data, particularly the appropriate WBC response to the stress of exercise, and normal BM examinations suggest that continuation of AED therapy when leukopenia is stable and the percentage of PMN is normal is probably safe. Caution should be used if the absolute PMN count is consistently < 1,000/microliters. BM examinations need not be performed routinely for every patient with neutropenia due to AEDs, especially if the leukopenia fluctuates in the range of 2,000-4,000 cells/microliters.

Superoxide anion production and phagocytosis of crystals by cultured endothelial cells.

OBJECTIVE: To show that cultured human umbilical vein endothelial cells (HUVEC) are capable of phagocytizing inflammation-causing crystals and of generating superoxide anion (SOA) during phagocytosis. METHODS: The superoxide dismutase-inhibitable reduction of nitroblue tetrazolium (NBT) dye was used as a measure of SOA production. Phagocytosis was quantified by light microscopy and confirmed by transmission electron microscopy. Cytochrome C was also studied but was found to undergo spontaneous reduction by monosodium urate (MSU) without cells. RESULTS: Crystals of MSU, calcium oxalate, hydroxyapatite, and calcium pyrophosphate dihydrate (CPPD) were phagocytized and, except for the CPPD crystals, induced NBT reduction. Cholesterol and cholesterol monohydrate were neither phagocytized nor did they induce NBT reduction. CONCLUSIONS: Endothelial cells may be a significant source of oxygen radicals in crystal-associated and other arthritides.

Supravital staining of synovial fluid with Testsimplets.

We explored the use of Testsimplet (TS) in synovial fluid (SF) analysis. TS is a glass slide coated with a dry mixture of methylene blue and cresyl violet, which in contact with one drop of SF provides a stained fresh preparation. We applied the TS to the study of 159 SFs of patients with different rheumatic diseases. In those SFs of patients with crystal-associated diseases, the crystal search was performed both on unstained preparations and with TS. TS was as good as the Wright's and Papanicolaou stain in characterizing SF cells, lupus erythematosus cells, and detection of occasional bacteria. TS allowed a better visualization of Reiter's cells, cartilage fragments, synovial villi, fat droplets, and fibrin. Crystals were identified in every TS of those patients with crystal-associated diseases. TS is a rapid and reproducible method of SF supravital staining. Crystals are well preserved for simultaneous examination with compensated polarized light.

Clinical and pathologic studies of twenty-six patients with penetrating foreign body injury to the joints, bursae, and tendon sheaths.

Foreign body synovitis has been neglected in the rheumatology literature. We describe 26 patients in whom arthritis, bursitis, or tenosynovitis appeared within 1 day to 7 years after an initial injury by a penetrating foreign body. Twenty-two patients presented with acute synovitis, which was followed by chronic or recurrent inflammation mimicking septic arthritis, osteomyelitis, monarticular juvenile rheumatoid arthritis, bone tumor, or apatite deposition disease. Foreign bodies were not seen in 5 inflammatory synovial fluids studied, but were seen in the synovium or periarticular tissues of 17 patients. Excisional biopsy was required in most patients for precise diagnosis and treatment.

L-tryptophan ingestion associated with eosinophilic fasciitis but not progressive systemic sclerosis.

OBJECTIVE: To assess the use of L-tryptophan by patients with eosinophilic fasciitis and compare this with its use by patients with progressive systemic sclerosis (scleroderma). DESIGN: Retrospective and prospective analysis. Six patients with eosinophilic fasciitis were identified retrospectively and two prospectively. Retrospective identification of patients was done by questioning hospital-affiliated rheumatologists and dermatologists and by searching the hospital dermatopathology database. The patients with scleroderma or morphea were prospectively identified by questioning consecutive office patients with these established diagnoses. SETTING: University of Pennsylvania rheumatology and dermatology practices. PATIENTS: Eight patients with eosinophilic fasciitis; 40 consecutive patients with scleroderma (27 with diffuse cutaneous and 13, limited cutaneous disease); 3 patients with morphea. RESULTS OF DATA ANALYSIS: All eight patients with eosinophilic fasciitis had taken L-tryptophan before the onset of their disease. All had myalgias and high peripheral eosinophil counts (most greater than 5000 cells/mm3). Only 1 of 40 patients with scleroderma (no patients with morphea) had used L-tryptophan preceding illness (P less than 0.001 compared with eosinophilic fasciitis). Six patients with eosinophilic fasciitis had taken L-tryptophan for less than 8 months. One patient had taken it for 9 years before developing skin induration. Two patients were newly identified as having hypothyroidism; two developed neuropathy; and two had severe flexion contractures (several occurring in areas without skin induration). Five patients had low-titer antinuclear antibodies, indicating a possible autoimmune process. Most patients had only a partial response to systemic corticosteroid therapy. One patient has had important disease regression in response to isotretenoin therapy that was evident even while she continued to take L-tryptophan. CONCLUSIONS: L-Tryptophan use can lead to eosinophilic fasciitis whereas it does not appear to cause classic scleroderma. The disease process does not automatically remit after discontinuation of L-tryptophan-containing products.

Foreign body reactions simulating acute septic arthritis.

We describe 2 patients with foreign body synovitis simulating acute septic arthritis. One patient was an 11-year-old boy who developed acute knee swelling due to a penetrating fragment of wood. The other patient was an intravenvous drug abuser in whom silicon was identified in synovial fluid and synovial membrane and whose arthritis improved after complete synovectomy.

Primary (AL) amyloidosis as a cause of breast masses.

Amyloidosis is rarely considered in the differential diagnosis of breast masses. During the past six years, 27 women with primary (24) and multiple myeloma-associated (three) amyloidosis (AL amyloid) were evaluated at our center. In five of these patients, amyloid was demonstrated on microscopic examination of breast tissue. The clinical presentations were similar to fibrocystic breast disease in two cases and malignancy in two others. Amyloidosis of the breast may be more common than previously recognized, especially considering the predilection of amyloid for depositing around fat cells. Therefore, pathologic examination of nonmalignant breast tissue should include Congo red staining and viewing under polarized light.

Familial amyloid polyneuropathy: a new kinship of German ancestry.

Familial amyloid polyneuropathy (FAP) is an autosomal dominant inherited disorder that primarily affects the peripheral and autonomic nervous systems and usually becomes symptomatic in the third or fourth decade. Because of the confusion with other genetically transmitted neurologic conditions, the diagnosis is often delayed until advanced stages. We describe a new German kinship with FAP in which the disorder was detected in two asymptomatic family members who were seeking genetic counseling.