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.

Phrenic nerve function in patients with diaphragmatic weakness and systemic lupus erythematosus.

Diaphragmatic weakness has been identified as one of the pulmonary manifestations of systemic lupus erythematosus. Whether this weakness results from a neuropathic or myopathic process has not been established. Thirty patients with SLE were screened for the presence of inspiratory muscle (IM) weakness. Detailed studies were performed in nine with IM weakness. All nine were found to have diaphragmatic weakness (mean +/- SD, maximal transdiaphragmatic pressure 50 +/- 12 cmH2O). Phrenic nerve latencies, evaluated using transcutaneous stimulation, were normal in all individuals excluding a demyelinating neuropathy. Compound diaphragm action potential (CDAP) with phrenic nerve stimulation was normal in six of these nine patients. Reduced CDAP in three of nine patients was consistent either with axonal degeneration of the phrenic nerve or diaphragm myopathy. Nerve conduction and electromyographic studies on peripheral nerves and muscles respectively failed to demonstrate an associated generalized neuropathy or myopathy. We conclude that diaphragmatic weakness in patients with SLE is both common and is very unlikely to be caused by a phrenic neuropathy.

The risk of iridocyclitis in juvenile rheumatoid arthritis.

A retrospective study comparing 14 patients with juvenile rheumatoid arthritis (JRA) complicated by chronic iridocyclitis (Group I) with an equal number of JRA patients without this complication (Group II) was conducted to determine which factors might aid in the earlier diagnosis of chronic iridocyclitis. Eleven patients in Group I had oligoarticular disease compared to 5 in Group II. Antinuclear antibody was found in 13 patients in Group I compared to only 2 in Group II. Only one of nine patients tested in Group I for the histocompatibility antigen W-27 was positive. The patient with oligoarticular disease and a positive ANA test should be followed closely by the ophthalmologist for the development of chronic iridocyclitis.

Interpreting blood tests in rheumatology.

The diagnosis of most rheumatic conditions is based on clinical findings. Blood tests help to narrow down the differential diagnosis in a problem rheumatologic case, and may help determine the activity and severity of the disease being followed, but should not be relied upon in isolation.

Gold-induced enterocolitis. Case report and literature review.

A case of gold-induced enterocolitis and a review of the literature are reported. Gold-induced enterocolitis appears to be an uncommon reaction, occurring in middle-aged females who have received low doses of gold preparations. Symptoms may include fever, nausea, vomiting, abdominal cramps, and diarrhea with or without blood. The whole of the gastrointestinal tract may be involved and fatal cases occur. The diagnosis of a primary enteropathic arthropathy may be suggested. Cessation of gold, glucocorticoids and supportive therapy are indicated. The mechanism of the reaction is still unknown.

Procainamide-induced lupus erythematosus: report of a case with a large pericardial effusion and fluid analysis.

A patient with procainamide lupus erythematosus had a large pericardial effusion. As in other reported cases histology revealed a fibrinous mononuclear pericarditis and the pericardial fluid was a serosanguinous inflammatory exudate with a high LDH level and normal glucose concentration. The ANF and LE cell preparation were positive in the fluid but the C3 complement was normal. The frequency of pericarditis is similar in systemic and drug-induced lupus erythematosus yet low complement levels need not occur. Complement activation may therefore be unnecessary for the development of either type of lupus pericarditis.

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.

Persistent synovial lymphocyte responses to mumps and adenovirus antigens.

A man in his 50s with rheumatoid arthritis showed maximal synovial lymphocyte reactivity to mumps antigen on 9 of 10 testings over a period of 6 years; peripheral blood lymphocytes showed no significant responses to mumps antigen in 5 testings over 5 years. A boy of 15 with recurrent arthritis of the right knee showed maximal synovial lymphocyte reactivity to adenovirus antigen. This reactivity was again present during a subsequent episode more than 3 years later; peripheral blood lymphocytes showed no such response to adenovirus antigen.

Ascorbic acid-induced uricosuria. A consequency of megavitamin therapy.

The effect of ascorbic acid on the serum and urinary uric acid was studied in 14 subjects. Two to 6 h after the ingestion of 4.0 g of ascorbic acid, the fractional clearance of uric acid increased to 202% +/- 41% of the control value. This uricosuria was inhibited by pyrazinamide and by low-dose acetylsalicylic acid, but was not accompanied by an increase of the creatinine clearnace. Ascorbic acid did not diminish protein-bound uric acid. In 3 subjects who ingested 8.0 g of ascorbic acid for 3 to 7 days the serum uric acid decreased by 1.2 to 3.1 mg/dl as a result of a sustained uricosuria. These results suggest that ascorbic acid could invalidate studies involving the measurement of uric acid and obscure the diagnosis of gout in some cases. Theoretically it could precipitate attacks of gouty arthritis or renal calculi in predisposed persons. These observations show a pharmacologic effect of megadoses of a simple vitamin.

Hyposplenia in a patient with systemic lupus erythematosus.

During the course of systemic lupus erythematosus in a young female patient the peripheral blood smear incidentally showed the features of hyposplenism. Silent lupus vasculitis with splenic infarction was suspected as the cause of this.

Herpes simplex hepatitis in a patient with psoriatic arthritis taking prednisone and methotrexate. Report and review of the literature.

Herpes simplex hepatitis is a rare disease in adults and with high mortality (81%). Most cases are seen in immunocompromised hosts or in the third trimester of pregnancy. A 43-year-old woman with psoriatic arthritis, treated with prednisone and methotrexate (MTX), presented with an acute abdomen and elevated liver enzymes. The diagnosis was made by liver biopsy. MTX was stopped and acyclovir was started. The patient survived. The diagnosis of Herpes simplex should be suspected in immunocompromised hosts and established by liver biopsy and viral cultures. Treatment includes parenteral acyclovir and discontinuation or reduction of immunosuppressive therapy.

Penicillamine induced pemphigus.

Three cases of penicillamine induced pemphigus are described and compared to 35 previously reported cases with typical direct immunofluorescence. The incidence in our clinic was 0.57%. The penicillamine dose ranged from 250 to 1500 mg/day and the mean duration of treatment was 11 months at the onset of pemphigus in the 38 cases. Morphology and immunopathology was indistinguishable from spontaneously occurring pemphigus. The majority of cases resolved within 4 months after stopping, penicillamine; however, 8 cases, including 2 in this report, have persistent pemphigus.

Penicillamine compared to previous chrysotherapy in rheumatoid arthritis.

Of 331 patients in our 3 penicillamine clinics, 312 had been taking chrysotherapy previously. In 232 patients, responses to both drugs could be determined: there was no difference in the response rate to penicillamine when patients in the largest clinic with good and those with poor responses to gold were compared. Adverse reactions to penicillamine were more frequent in patients who had reacted adversely to gold in 2 of the 3 clinics. Proteinuria tended to occur more frequently in patients who had had proteinuria when taking gold than in patients who had not had gold-induced proteinuria.

Yersinia-related arthritis in the Pacific Northwest.

Serologic evidence of Yersinia enterocolitica infection was sought by agglutination testing in serum samples from several populations, including Haida Indians, Red Cross blood donors, and Caucasian patients with rheumatoid arthritis, ankylosing spondylitis, and Reiter's syndrome. No evidence was found to indicate that yersinial infection was etiologically related to Haida spondylitis or Reiter's syndrome. Four of 28 patients with acute arthritis were diagnosed from serologic evidence as having Yersinia-related arthritis.

Felty's syndrome. Clinical and serological analysis of 34 cases.

Review of 34 cases of Felty's syndrome showed this to be a form of 'super' rheumatoid disease because of the severity of joint disease, the prominence of extra-articular features and the remarkable incidence of infection. The response to splenectomy in these 34 patients was shown by a return towards normal of peripheral blood abnormalities and a decrease in bone marrow granulopoiesis. Although some patients remained free of infection after splenectomy, others have continued to have infections despite the return of white blood cell counts to normal levels. Although splenectomy and subsequent increase in white blood cell levels may be beneficial, our experience suggests that other factors are important in the susceptibility to infection of Felty's syndrome patients. Moreover, we think that splenectomy may have been instrumental in the fatal infection of one of our patients.

The intestinal bypass: arthritis-dermatitis syndrome.

Of the 31 patients who developed polyarthritis following jejunoileal bypass for obesity, 24 had cutaneous vasculitis (urticarial, pustular, and nodular), 11 paresthesias, 10 Raynaud's phenomenon, and 1 pericarditis. Blind loop symptoms (14 of 26 patients), cryoglobulinemia (10 of 28), and immune deposits in biopsied skin lesions (5 of 7) support the theory of a relationship between bowel bacteria and immune complexes. Treating the blind loop with antibiotics and sphincteroplasty to prevent bacterial reflux into the blind loop helped 5 of 10 and 6 of 9 patients, respectively. A comparison is made to other bowel associated arthritides.

Clinical and roentgenographic aspects of pseudogout: a study of 50 cases and a review.

Pseudogout, defined as recurrent acute arthritis due to intrasynovial deposition of calcium pyrophosphate dihydrate crystals, is a relatively common arthritic disorder of the elderly. The clinical and roentgenographic aspects of 50 cases of pseudogout in hospitalized patients are reviewed in this paper. Oligoarticular and polyarticular episodes were observed in half of these patients. Antecedent problems included infection, trauma, surgery and vascular events. Consistent with previous reports, most patients had roentgenographic evidence of chondrocalcinosis. A third had asymptomatic capsular or periarticular calcific deposits or both, and a third had pyrophosphate arthropathy, a progressive, destructive, accelerated form of osteoarthritis. An attack of pseudogout may offer a clue to the presence of an unsuspected metabolic disease, such as primary hyperparathyroidism or idiopathic hemochromatosis.

Hemorrhagic complications of long-term anticoagulant therapy in 7 patients with systemic lupus erythematosus and antiphospholipid syndrome.

OBJECTIVE: To describe the presentation, course, and management of serious hemorrhagic complications of anticoagulant therapy for patients with antiphospholipid syndrome (APS). METHODS: Charts of patients identified with serious bleeding complications from anticoagulation for APS were reviewed. RESULTS: Patients included 6 women and one man with systemic lupus erythematosus (SLE) and one woman with primary APS. One patient had 3 separate hemorrhagic events. There were 6 episodes of subdural hematoma in 5 patients, one episode of pericarditis with tamponade, one episode of hemoptysis, and one episode of ovarian hemorrhage. In 2 patients, symptoms related to hemorrhage were initially attributed to active SLE. Duration of anticoagulation was between one month and 10 years at the time of bleed. International normalized ratio (INR) and prothrombin time were above the intended range in 6/9 episodes. There were no deaths and no permanent sequelae due to bleeding. Anticoagulant therapy was resumed in 6/7 patients. CONCLUSION: The management of APS must include vigilance, patient education, and anticoagulation to maintain the INR between 3 and 3.5. To prevent hemorrhagic complications, low molecular weight heparin is an option that deserves further study.

Longterm therapy of psoriatic arthritis: intramuscular gold or methotrexate?

OBJECTIVE: To compare the efficacy and toxicity of methotrexate (MTX) and intramuscular (im) gold in the treatment of psoriatic arthritis (PsA). METHODS: Medical records from all patients with PsA attending the gold and MTX clinics at the Vancouver Mary Pack Arthritis Centre between 1971 and 1995 were reviewed. The odds of a clinical response (defined as at least a 50% reduction in active joint count from initial to last visit or for at least 6 months) and the relative risk of discontinuing therapy associated with treatment (MTX or im gold) were calculated after controlling for significant baseline covariates, using logistic regression and Cox regression analyses, respectively. The frequency of side effects and the reasons for treatment cessation were also compared between treatment groups. RESULTS: Eighty-seven patients received 111 treatment courses: 43 of MTX and 68 of im gold. The likelihood of a clinical response was 8.9 times greater (95% CI 1.8; 44.0) with MTX than im gold. Patients were 5 times more likely (95% CI 2.4; 10.4) to discontinue therapy with im gold than with MTX. No major toxicity occurred and frequency of side effects was similar for both treatments. Patients with a longer duration of PsA prior to initiation of study treatment were less likely to achieve a clinical response. CONCLUSION: MTX and im gold are safe and well tolerated in the treatment of PsA. In our experience. MTX was superior to im gold in the likelihood of achieving a clinical response and in permitting an individual to continue longterm treatment. Our data suggest that earlier treatment may be associated with a better response.