Howard B. Stein

Adverse Effects of D-Penicillamine in Rheumatoid Arthritis

Adverse effects to D-penicillamine were studied prospectively over 3 years in 259 patients with rheumatoid arthritis. Ninety-five percent had had gold therapy previously, yet 70% benefited from D-penicillamine therapy. Of the 275 courses given, 160 (58%) were complicated by at least one reaction, including rashes (44%), dysgeusia (20%), gastrointestinal upset (18%), stomatitis (10%), proteinuria (7%), thrombocytopenia (3%), and leukopenia (2%). Their occurrences peaked in the first 6 months of treatment, except for proteinuria and thrombocytopenia, which peaked in the second 6 months. Reactions were commoner at daily doses above 250 mg; mean daily doses for proteinuria, thrombocytopenia, and leukopenia were higher (approximately 600 mg/d) than for the others (approximately 500 mg/d). Of 114 discontinued courses, 73 (27%) were due to adverse reactions. The remaining reactions were controlled by altering dosages and symptomatic treatment. Only obliterative bronchiolitis (two cases) was irreversible; it resulted in the only death in our series, possibly attributable to penicillamine.

Splenic atrophy in systemic lupus erythematosus.

Five of 70 patients with systemic lupus erythematosus seen over a 5-year period had peripheral blood films suggestive of hyposplenism. Technetium-99m-sulfur colloid scans showed no splenic activity in three patients. One of these three patients, who had a spontaneous remission of persistent thrombocytopenia concurrent with the appearance of functional asplenia, had splenic atrophy shown by computed tomography; a second patient, who died of pneumococcal septicemia, was shown to have splenic atrophy with lymphocyte depletion at autopsy. The development of functional asplenia in the third patient has now, to date, had any obvious effect on her disease. In the two patients with normal scans, blood film findings returned to normal with treatment of the underlying disease. Polyvalent pneumococcal vaccine is recommended for patients with lupus erythematosus who have splenic atrophy.

Clavicular Hyperostosis with Enthesopathy, Hypergammaglobulinemia, and Thoracic Outlet Syndrome

Abstract The syndrome of sternocostoclavicular hyperostosis with painful bilateral clavicular enlargement and subclavian vein obstruction has been recently described in older adults. We report a si...

Penicillamine-induced proteinuria: Risk factors

Twenty-six of 300 patients (9%) with rheumatoid arthritis (RA) developed penicillamine-induced proteinuria. The mean daily dose and duration of therapy at onset of proteinuria were 591 mg and 9 months, respectively, while the mean duration of proteinuria was 5.5 months. However, six patients developed proteinuria at 250 mg/d and six after 9 months of therapy. Twelve patients were successfully either restarted (five) or maintained (seven) on penicillamine with resolution of proteinuria. No permanent renal impairment occurred. Positive risk factors included the presence of HLA-B8 and DR3 and prior gold-induced proteinuria. Patients with prior gold-induced proteinuria should be observed more carefully, but tissue typing is not recommended as proteinuria is reversible. Furthermore, penicillamine can be restarted or maintained in these patients if the RA has responded favorably to the drug.