Cavitating pneumonia, a severe complication of leflunomide therapy in chronic polyarthritis.
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Biomedical subjects
Publications and source records attributed to P M Houtman.
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A 52-year-old man presented with polyarthritis and was negative for rheumatoid factor, anti-CCP and ANA. He was treated with low-dose methotrexate, the drug of first choice in rheumatoid arthritis. The arthritis disappeared, but the patient developed fever, progressive dyspnoea, appetite loss and weight loss. Upon hospital admission his medication was stopped and community-acquired pneumonia was diagnosed. The fever persisted despite antibiotic treatment. The tentative diagnosis of rheumatoid arthritis was changed to systemic lupus erythematosus, based on the change in clinical condition that could not be explained by polyarthritis and seroconversion to ANA- and anti-dsDNA-positive. The patient was treated with high-dose steroids and azathioprine and remained in remission for more than 1 year after treatment. The ANA test remained strongly positive, whereas anti-dsDNA was no longer detectable. This case stresses the limited value of classification criteria for the diagnosis of rheumatoid arthritis. To differentiate between rheumatoid arthritis and systemic lupus erythematosus, tests for autoantibodies against citrullinated peptides can be used. To differentiate between systemic lupus erythematosus and infection, tests for anti-dsDNA antibodies, antinuclear antibodies, C-reactive protein and complement can be used.
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This case report describes a 61-year-old rheumatoid arthritis patient with an atypical clinical presentation of a sore throat. Because of rheumatoid arthritis refractory to conventional disease-modifying antirheumatic drug therapy, anti-TNFalpha was felt to be indicated, and a screening for tuberculosis was carried out. As the screening for tuberculosis (PPD) was positive, isoniazid was prescribed prophylactically for six months. After eight months of anti-TNFalpha (adalimumab) treatment, he developed tonsillar enlargement and nodular pulmonary lesions. Histopathological and microbial investigations established the diagnosis of tonsillar tuberculosis.
BACKGROUND: Leflunomide is the prodrug of the disease modifying antirheumatic metabolite A77 1726. More than 50% of patients withdraw from leflunomide treatment within one year, mainly because of adverse drug reactions. Therapeutic drug monitoring of A77 1726 may be useful in predicting the efficacy of leflunomide treatment. OBJECTIVE: To study the relation between A77 1726 steady state serum concentrations and disease activity using the 28 joint (DAS28) response. METHODS: Outpatients with rheumatoid arthritis on a stable leflunomide dose for >4 months were included. DAS28 score and adverse drug reactions were recorded. Blood samples were taken for determination of A77 1726 concentrations. The primary end point was the relation of serum A77 1726 concentrations with DAS28 response category. RESULTS: Serum A77 1726 concentrations were determined in 52 patients. A receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.73 (95% confidence interval, 0.54 to 0.93) (p<0.05). The sensitivity exceeded 99% at concentrations below 16 mg/l. DAS28 values at the point of sampling showed no relation with A77 1726 concentrations (AUC of the ROC curve = 0.50 (0.33 to 0.67) (NS)). CONCLUSIONS: A77 1726 steady state serum concentrations show a relation with DAS28 response. Determination of serum A77 1726 concentrations in patients with insufficient response to treatment may help when decisions have to be made about continuation of treatment or dose adjustment.
A 72-year-old man presented with necrosis of the thumb as a symptom of rheumatoid vasculitis.
AIMS: We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. METHODS: In this prospective case series study, from outpatient medical records a standard dataset was collected including patient and disease characteristics, data on leflunomide use and adverse drug reactions. RESULTS: During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient-years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS(28)) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS(28) response criteria. CONCLUSIONS: In the setting of care-as-usual, rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within a year after start of leflunomide treatment, mainly because of adverse drug reactions.
AIMS: We prospectively studied the efficacy, incidence of adverse drug reactions and withdrawal from leflunomide in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. METHODS: In this prospective case series study, a standard dataset was collected from outpatient medical records, including patient and disease characteristics, data on leflunomide use and adverse drug reactions. RESULTS: During the study period 136 rheumatoid arthritis patients started leflunomide. Median (range) follow-up duration was 317 (11-911) days. Sixty-five percent of patients experienced at least one adverse drug reaction related to leflunomide. During follow-up 76 patients (56%) withdrew from leflunomide treatment, mainly because of adverse drug reactions (29%) or lack of efficacy (13%). The overall incidence density for withdrawal from leflunomide was 56.2 per 100 patient years. Complete data for calculating efficacy using a validated disease activity score on 28 joints (DAS(28)) was available for 48, 36, and 35% of patients at 2, 6, and 12 months follow-up, respectively. Within a 12-month period after start of leflunomide treatment 76% of the evaluable patients were classified as moderate or good responders according to the DAS(28) response criteria. CONCLUSIONS: In the setting of care-as-usual rheumatoid arthritis patients starting leflunomide frequently experienced adverse drug reactions. More than half of the patients withdrew from leflunomide treatment within 1 year of starting leflunomide treatment, mainly because of adverse drug reactions.
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An 80-year-old man using diuretics for chronic cardiac failure was diagnosed with tophaceous gout.
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We report on the radiological abnormalities of bones and joints in Dutch patients suffering from Lyme borreliosis presenting with acrodermatitis chronica atrophicans (A.C.A.). In a highly endemic area of the Netherlands rheumatic complaints were mentioned by 26 out of 60 patients suffering from a late stage of Lyme disease. Radiological findings in our group of patients were subluxation of the toe joint and periostitis of the bones of the lower limb.
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We present a case of synovitis of the wrist due to histoplasmosis, diagnosed only after extensive surgery and culturing. Treatment with amphotericin B in combination with radical surgery was effective in curing the disease. This manifestation was probably an exacerbation of a latent chronic infection with Histoplasma capsulatum, although it was unclear why the exacerbation occurred. Synovitis resistant to treatment should be assessed with great care, especially in view of the growing number of immunocompromised patients. Close collaboration between surgeon, rheumatologist, pathologist and microbiologist is paramount in such cases.