Abraham Menahem Nahir

Rheumatoid lung nodulosis and osteopathy associated with leflunomide therapy

BackgroundLeflunomide (LEF) is indicated in adults for the treatment of active rheumatoid arthritis (RA). LEF inhibits dehydroorotate dehydrogenase, a key enzyme of the pyrimidine synthesis in activated lymphocytes. Among rare adverse effects, fatal interstitial lung disease has been recently reported during treatment of RA with LEF in Japan. Clinical trials outside Japan do not suggest that LEF causes an excess of pulmonary adverse effects. Development and increase of peripheral rheumatoid nodules in typical sites of RA patients following LEF therapy has been recently reported.ObjectivesTwo cases with new and accelerated development of rheumatoid lung nodulosis during LEF therapy were described in this study.MethodsLEF treatment was administered to two male patients (77 and 66 years old) with long-standing active seropositive nodular RA with failure of multiple second line drugs and without lung involvement. Clinical and laboratory assessment using the American College of Rheumatology response criteria, chest computed tomography (CT), quantification of serum rheumatoid factor (RF), and monocyte count of peripheral blood along with routine laboratory follow up were performed on both patients before and during therapy. In case 1, a bone scan was performed due to sustained limbs pain. Open lung biopsy was performed in case 1 and core lung biopsy in case 2.ResultsBoth patients achieved full clinical remission during 2 months of LEF therapy. In case 1, the first complaints were limbs pain after 10 months of treatment associated with intensive bone uptake on a bone scan consistent with hypertrophic pulmonary osteopathy. Productive cough developed after 3 months of the therapy in case 2. Initially, these complaints were not attributed to therapy. New lung disease was present on CT with cherry-like progressive cavitary nodules, predominantly involving the basal segments of the right lung. The first lung lesions were found by CT 13 months (case 1) and 7 months (case 2) after the beginning of therapy and were erroneously related to bronchiectasia in case 2. In both cases, the lung biopsy showed necrosis surrounded by epithelioid mononuclear inflammation with giant cells, consistent with rheumatoid lung node. The time that elapsed between the beginning of the first symptoms to LEF discontinuation was very long: 13 months in case 1 and 24 months in case 2. Discontinuation of LEF therapy was followed by an arrest in growth of lung nodules, resolution of limb pain, and gradual improvement of bone scan. A significant decrease of monocyte count and RF level in peripheral blood was observed during LEF therapy in both cases.ConclusionFor the first time, we described rheumatoid lung nodulosis as complication of successful LEF therapy for RA. Hypertrophic pulmonary osteopathy with severe limbs pain and dry cough were the first manifestations of the lung nodulosis. Monocytopenia during LEF therapy is proposed to be involved in pathogenesis of this rare complication of LEF therapy.

Vitamin D, Parathyroid Hormone, and Acroosteolysis in Systemic Sclerosis

Objective Sclerodactyly with acroosteolysis (AO) and calcinosis are prominent features of systemic sclerosis (SSc), but the pathogenesis of these findings is poorly understood. Vitamin D and parathyroid hormone (PTH) have a crucial role in bone metabolism and resorption and may affect AO and calcinosis. We assessed vitamin D and PTH in patients with SSc. Methods Medical records of 134 consecutive patients with SSc (American College of Rheumatology criteria) followed at the rheumatology department during the years 2003–2006 were reviewed for clinical assessment, laboratory evaluation [including 25(OH) vitamin D, calcium, phosphorus, alkaline phosphatase, PTH, creatinine, and albumin]; imaging data confirming AO and/or calcinosis. Patients followed routinely at least once a year were included (81 patients). Of these, 60 patients’ medical records were found to have complete, relevant clinical, laboratory, and radiographic imaging. Results Thirteen patients had diffuse disease and 47 limited disease — 51 women and 9 men, 44 Jews and 16 Arabs; mean age 55 ± 14 years; disease duration 8 ± 6 years. AO with or without calcinosis was observed in 42 patients (70%). Vitamin D deficiency was found in 46% of patients (16 out of 44 Jewish patients, 10 out of 16 Arab patients). PTH was elevated in 21.7% of patients. Significant correlations were observed between acroosteolysis and PTH (p = 0.015), calcinosis (p = 0.009), and disease duration (p = 0.008), and between PTH and vitamin D levels (p = 0.01). All patients had normal serum concentrations of calcium, phosphorus, magnesium, and albumin, and liver and kidney functions. Conclusion In this group of Mediterranean patients with SSc, the incidence of vitamin D deficiency and secondary hyperparathyroidism was surprisingly high. This finding correlated with the occurrence of AO and calcinosis. Low levels of vitamin D may reflect silent malabsorption and might be a risk factor for secondary hyperparathyroidism and bone resorption. Traditional dress habits and low exposure to sun may contribute to vitamin D deficiency in an Arab population but do not explain all the findings. The pathogenesis of these findings needs to be corroborated in other SSc populations.

Vasculitis in siblings with familial Mediterranean fever: a report of three cases and review of the literature.

Familial Mediterranean Fever (FMF) is characterized by recurrent attacks of self-limited polyserositis and fever. Several types of vasculitis are associated with FMF: polyarteritis nodosa, Henoch–Schonlein purpura (HSP), and protracted febrile myalgia (PFM). We describe three cases of vasculitis in four siblings of a Sephardic Jewish family with FMF and reviewed the literature. One brother and one sister developed severe HSP with intestinal involvement while another brother developed PFM. Genetic tests in three brothers confirmed the M694V mutation on both alleles. Vasculitides may be a clinical feature of FMF with a higher familiar prevalence. MEFV mutations may act as a genetic susceptibility factor for vasculitides in FMF patients.

Is SAPHO syndrome a target for antibiotic therapy

The etiology of the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome remains unclear. Infectious factors are proposed to be relevant in the etiopathogenesis of the disease. To our knowledge, this is the first reported case of a proposed relationship between Staphylococcusaureus cultured from plantar pustule and SAPHO syndrome, which was successfully treated with co-trimoxazole (CTM) (sulfamethoxazole/trimetoprim). CTM might be the drug of choice for therapy for SAPHO syndrome because of combined antibiotic and immunomodulatory properties. Hypersensitivity testing of the medication in vitro was performed to identify, in the preclinical stage, the hypersensitivity reaction to CTM, which may have been severe.

Accelerated pulmonary nodulosis and sterile pleural effusion in a patient with psoriatic arthropathy during methotrexate therapy: a case report.

Pulmonary nodulosis and sterile pleural exudates are well-known extra-articular manifestations in rheumatoid arthritis patients with a positive rheumatoid factor. In some patients, treatment with methotrexate has been postulated as the trigger of these complications. We report a patient with psoriatic arthropathy, negative RF, negative anticyclic citrulinated peptide antibodies but positive antibodies to cardiolipin who developed massive sterile pleural empyema and multiple cavitary pulmonary nodules during methotrexate treatment. We suggest that awareness of methotrexate-induced lung and pleural complications should be extended to other than rheumatoid arthritis diseases, not necessarily accompanied by rheumatoid factor or anticyclic citrulinated peptide antibodies.

Toe necrosis and acute myocardial infarction precipitated by a pheochromocytoma in a patient with systemic sclerosis.

Systemic sclerosis (SSc) patients typically experience Raynaud phenomena that is often complicated by digital ischemic lesions, gangrene, and digital loss. Other causes of peripheral ischemia, such as atherosclerosis, cryoglobulinemia, antiphospholipid syndrome, myeloproliferative disorders, paraneoplastic syndromes, and hyperadrenergic endocrine conditions, may be masked in SSc patients. We present a woman with limited SSc who developed toe necrosis and acute coronary events as a complication of a previously undiagnosed pheochromocytoma.

Successful pamidronate treatment of severe and refractory regional migratory osteoporosis.

We report the case of a middle-aged patient with repeated attacks of regional migratory osteoporosis of the lower limbs, manifesting as severe pain and swelling of both joint and periarticular areas, and marked physical disability during a period of 2 1/2 years. After the therapeutic failure of conservative therapy (physical therapy, rehabilitation therapy, analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs)) and after the correct diagnosis was reached, pamidronate treatment was instituted. The results were a rapid, complete, and long-lasting remission of the symptoms and the renewal of the patients previous activities. Intravenous biphosphates are proposed as a safe and promising therapy for regional migratory osteoporosis. To our knowledge, this is the first report of pamidronate treatment for this condition.

Ticlopidine-induced lupus.

Ticlopidine is a widely used drug for prevention of stroke and other serious vascular events with a multitude of possible side effects. An increasing number of drugs are being recognized as the triggering agents of drug-induced lupus. We describe three patients in whom the etiologic connection between ticlopidine and lupus was supported by the appearance of lupus-like features (fever, rash, arthritis, renal involvement, positive antinuclear and antihistone antibodies), shortly after drug initiation, and their gradual resolution after its discontinuation. If suggested by clinical or/and laboratory findings (fever of unknown cause, musculoskeletal involvement, hematologic abnormalities), the possibility of ticlopidine-induced lupus should be taken into consideration and appropriate investigations should be performed. Patients should resolve slowly but completely after withdrawal of ticlopidine.

Silica-related rheumatoid arthritis without lung involvement

Abstract We report a young male with recent onset of rheumatoid arthritis (RA) in whom the remarkable severity of the disease led to additional investigations. The only significant finding was mediastinal lymphadenopathy, without lung involvement. Biopsy of the mediastinal lymph node revealed pathological findings typical of silicosis. To our knowledge, this is the first report of silicosis apparent solely in the mediastinal lymph node of an RA patient. This suggests that lung involvement is not crucial for the development of silica-related arthritis.