Multicentric reticulohistiocytosis: response to alkylating agents in six patients.

STUDY OBJECTIVE: To determine the efficacy of alkylating agents in multicentric reticulohistiocytosis. DESIGN: Open consecutive case series. SETTING: Tertiary-care referral clinic. PATIENTS: Six patients with skin-biopsy-proven multicentric reticulohistiocytosis. All had skin nodules and polyarthritis. INTERVENTION: Five patients received cyclophosphamide (dose range, 1.25 to 2.2 mg/kg body weight) and one patient received chlorambucil (0.1 mg/kg). Therapy was administered from 6 to 24 months. MEASUREMENTS AND MAIN RESULTS: In five patients treated with cyclophosphamide a response was seen within 4 months. Four patients eventually had a complete remission and one had almost a complete remission. The four patients in complete remission had cyclophosphamide therapy discontinued after 6, 12, 16, and 18 months. Three of the four patients remained in complete remission off therapy at 6, 6, and 22 months, whereas one had a recurrence after 6 months. The one patient given chlorambucil went into a complete remission and stopped treatment after 12 months. He remained in complete remission 32 months after stopping medication. CONCLUSION: Our experience with patients with aggressive multicentric reticulohistiocytosis shows that alkylation therapy is warranted. We conclude that a response to an alkylating agent may be expected. Whether after treatment for 6 to 18 months most patients may be able to discontinue the drug and remain in remission has yet to be shown. The rarity of multicentric reticulohistiocytosis precludes the possibility of a double-blind study.

Relapsing polychondritis with glomerulonephritis. Improvement with prednisone and cyclophosphamide.

A 32-year-old man presented with relapsing polychondritis (RP) and microhematuria. A renal biopsy specimen disclosed focal segmental glomerulonephritis with occasional crescents. Immunofluorescent and electron micrographic studies suggested immune complex--mediated glomerular injury. Initially, life-threatening upper airway obstruction responded to high-dose corticosteroid therapy. Subsequently, progressive renal insufficiency and proteinuria caused by increasingly active glomerulonephritis were treated by adding cyclophosphamide, with sustained improvement. This case supports the concept that RP is an immunologically mediated disease and suggests that a regimen of prednisone and cyclophosphamide warrants consideration for use in cases of RP with glomerulonephritis.

Giant cell (cranial) arteritis: a clinical review.

Giant cell arteritis is a disease of the elderly which is more common than previously recognized. It is important to be aware of this condition because treatment effectively relieves symptoms and prevents serious complications. The disease is suggested when an elderly patient complains of constitutional symptoms, headache, jaw claudication, or the musculoskeletal manifestations of polymyalgia rheumatica. Abnormalities in temporal arteries or other cranial arteries, or evidence of large vessel involvement may be detected by physical examination. A markedly elevated sedimentation rate in association with other clinical features of the disease strongly suggests giant cell arteritis, but a biopsy should be performed to confirm the diagnosis. Corticosteroid therapy should be started promptly in high doses in order to prevent blindness. Prolonged treatment with lower dose corticosteroids is generally necessary for up to 1 to 2 years, and sometimes longer, for continued symptomatic relief. Long-term follow-up of treated patients has demonstrated no detectable effect on survivorship.

Comparison of three immunoassays for immune complexes in rheumatoid arthritis.

Three widely used radioassays that depend on different principles for the measurement of circulating immune complexes (CIC) in biologic fluids are the monoclonal rheumatoid factor (mRF), Raji cell, and C1q binding tests. A comparison of the ability of these methods to measure immune complex-like material in 71 sera and 30 synovial fluids of 91 patients with rheumatoid arthritis (RA) was carried out by a group working in adjacent laboratories in a single institution. The highest number of abnormal levels in the seropositive group was detected by the C1q binding assay (91%). Levels of CIC by the mRF and Raji cell tests were elevated in 81% and 76% of the patients, respectively. The closest correlation was between the Raji and mRF tests (r = 0.44 and P = 0.002) although one depends on complement fixation and one does not. Though significant correlations between the levels of CIC determined by the C1q test and either the mRF (P = 0.2) or Raji cell (P = 0.3) assay were not found in this group, 59% of the samples had elevated levels by all three tests. The frequency of CIC in the sera of patients with seronegative RA was much lower, with the C1q test again giving the highest number of abnormal results (29% versus 16% and 12% for the Raji and mRF tests). In view of the technical problems associated with these tests, particularly lack of a uniform reliable standard, it is likely that all three tests measure the same material in most RA sera and that some of the differences observed are related to inherent variability in the tests themselves rather than intrinsic differences among the CIC detected in these samples.

Left atrial myxoma simulating peripheral vasculitis.

Left atrial myxoma remains a diagnostic challenge clinically. A brief review of previously reported cases and their individualistic clinical and laboratory features are described. The present case report documents an unusual clinical presentation, initially directing attention to the central nervous system as well as to the peripheral arterial system. Histologic evidence of peripheral arterial myxomatous emboli, associated with vasculitis but without other confirmatory immunologic evidence of collagen vascular disease, had predated for 14 months the subsequent echocardiographic diagnosis of left artrial myxoma. These findings further emphasize the importance of recognizing the enigmatic and variable clinical presentation of left atrial myxoma.

Temporal arteritis: a 25-year epidemiologic, clinical, and pathologic study.

Among the population of Olmsted County, Minnesota, 42 patients with temporal arteritis were identified during a 25-year period. The average annual incidence per 100 000 population aged 50 and older rose from 5.1 in 1950-1959 to 17.4 in 1970-1974. The prevalence of patients with a history of the diagnosis of temporal arteritis on 1 January 1975 was 133 per 100 000 population aged 50 and older. All patients received corticosteroid therapy for a range of 1 to 77 months (median, 7 months). Relapses in 10 of 11 patients were associated with corticosteroid reduction. The majority of patients recovered fully and were followed off corticosteroids for 10 months to 19 years (median, 5 years). Temporal arteritis had no significant effect on survival. Vertebral compression fractures and myopathy were the most serious complications of therapy. The presence of giant cells in biopsies was in part related to the number of sections examined, and their presence had no apparent influence on the clinical course.

Circulating immune complexes in systemic lupus erythematosus. Association with other immunologic abnormalities but not with changes in renal function.

In a study of the usefulness of two widely performed tests for immune complexes (IC) in the assessment of disease activity of lupus nephritis the Raji cell assay detected IC in sera of 14 of 32 patients and the monoclonal rheumatoid factor (MRF) test in only five. There was a close correlation of levels of IC with number of organ systems showing disease activity and with serum complement levels and a somewhat less significant correlation with serum levels of anti-DNA. Although in a few patients levels of IC closely paralleled improvement in renal function with treatment, there was no overall correlation of changes of levels of IC with changes in creatinine clearance. Measurement of circulating IC in lupus nephritis cannot at present be justified as a worthwhile clinical measurement in the management of such patients.

Shoulder swelling in rheumatoid arthritis secondary to subacromial bursitis.

A patient with rheumatoid arthritis was seen whose main complaint was marked swelling of the shoulders. Surgical exploration revealed the swelling to be secondary to subacromial bursitis; the glenohumeral joint appeared normal.

Pleural fluid complement, complement conversion, and immune complexes in immunologic and nonimmunologic diseases.

Forty-four pleural fluids and 41 blood specimens from patients with various diseases were examined for concentration of whole complement, C4, C3, conversion products of C3 and C3PA, and immune complexes. C3 conversion was found in all eight pleural fluids from patients with rheumatoid arthritis, five of seven with lupus erythematosus, two of six with congestive heart failure, and nine of 23 with malignant diseases. Conversion of C3PA correlated closely with C3 conversion and both were significantly inversely related to whole complement, C4, and C3. Concentration of immune complexes was highest in patients with rheumatoid arthritis. Pleural fluid immune complex concentrations correlated positively with conversion of C3 and C3PA. These findings suggest that the reduced levels of pleural fluid complement in rheumatoid arthritis and lupus erythematosus may be secondary to complement conversion by immune complexes.

Pulmonary and extrapulmonary sarcoidosis in relation to circulating immune complexes: a quantification of immune complexes by two radioimmunoassays.

Serum specimens from 53 patients with pulmonary sarcoidosis were examined for the presence of immune complexes by 2 methods, the Raji cell and the monoclonal rheumatoid factor radioimmunoassays. We found increased concentrations of immune complexes in the sera of 27 patients by one or both techniques. A significant association was found between increased concentrations of immune complexes and stage III sarcoidosis. Seventeen of 23 patients with stage III sarcoidosis and 10 of 50 with stage I or II disease had increased concentrations of immune complexes. Eight of the 10 patients with stage I or II sarcoidosis and increased concentrations of immune complexes had extrapulmonary sarcoid features, such as erythema nodosum, synovitis, or salivary gland enlargements. The size of the immune complex was 15S in one of the patients examined. Concentrations of C4 were normal. The data suggest a possible role of immune complexes in the pathogenesis of pulmonary and extrapulmonary features of sarcoidosis.