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.

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.

Soft tissue tuberculosis: a series of 11 cases.

OBJECTIVE: To describe the clinical characteristics of soft tissue tuberculosis (TB). METHODS: Retrospective review of all cases of soft tissue TB seen by the authors. RESULTS: Eleven cases were seen between 1988 and 1994. All patients but one were foreign born. Six patients had collagen vascular disorders and another had a kidney transplant. Five were taking immunosuppressive therapy and/or prednisone. Three had preceding trauma to the affected area. Five had evidence of previous TB by history or chest radiograph. Symptoms (mean duration 4.4 months) included swelling and pain and often mimicked the underlying disease. Six patients had definite or suspected active TB at other sites. Good initial responses were seen with debridement or drainage and multiple drugs for 6 to 12 months. Two patients have had possible relapses at other sites. Medication intolerance was frequent. CONCLUSION: TB should be considered in patients who present with unexplained soft tissue swelling and pain, particularly if they are immunosuppressed, were foreign born in an endemic area, have an abnormal chest radiograph, or have had trauma to the affected area.

Lymphocytes from the site of disease suggest adenovirus is one cause of persistent or recurrent inflammatory arthritis.

The assessment of synovial lymphocyte reactivity to adenovirus antigen stimulation was undertaken in patients with persistent or recurrent inflammatory arthritis. The 3H-thymidine uptake procedure was employed, incorporating multiple microbiological antigens. Five patients were found with repeated maximal responses to adenovirus antigen; in one of these adenovirus nucleotide sequences were present in a synovial biopsy specimen. It is concluded that adenovirus may be one cause of persistent or recurrent inflammatory arthritis.

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.

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.

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.

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.

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.

Lymphomatoid granulomatosis presenting as polyarthritis.

Polyarthritis in lymphomatoid granulomatosis is rare. We report a patient with lymphomatoid granulomatosis who presented with polyarthritis and nodular cutaneous lesions.

Lichenoid lesions of the oral mucosa in rheumatoid arthritis patients treated with penicillamine.

Seven of 56 consecutive patients taking penicillamine for rheumatoid arthritis developed oral lesions that clinically and histologically resembled lichen planus. All 7 patients had rashes with prior gold therapy and 4 had rashes with penicillamine therapy. Lesions appeared between 3 and 12 months of therapy at an average dose of 400 mg/day and disappeared within 3 months of stopping the medication. Discontinuation of the drug for oral lichenoid lesions is not necessary. Topical steroids can be used for symptomatic relief.

Penicillamine and other remittive agents in rheumatoid arthritis: comparisons and interaction.

Penicillamine treatment of rheumatoid arthritis was compared with gold and other remittive agents by reviewing the literature and studying the patients in our penicillamine clinic with respect to their previous responses to chrysotherapy. Penicillamine compares well with other remittive agents with respect to efficacy and toxicity. Prior chrysotherapy does not determine or predict the subsequent efficacy of penicillamine . Patients who reacted adversely to gold tended to react adversely to penicillamine; proteinuria and rash tended to recur.

Selected adverse reactions of D-penicillamine.

Selected adverse reactions of penicillamine encountered in our clinic since 1975 are described. They include: proteinuria (26 cases), lupus erythematosus (six cases), myasthenia gravis (two cases), pemphigus (three cases), obliterative bronchiolitis (two cases) and obstructive jaundice (one case).

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.

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.

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.