Rheumatoid nodulosis during methotrexate therapy in a patient with rheumatoid arthritis

We report a 62-year-old man with rheumatoid arthritis (RA) who developed nodulosis after methotrexate (MTX) treatment. The epithelioid cells of nodules were positive for matrix metalloproteinases (MMP)-2, MMP-3, MMP-9, and Ki67. The synovial tissues obtained from the same patient were negative for MMP-3, MMP-9, and Ki67. This study demonstrated that MTX-induced nodules are different from synovial tissues in terms of MMP expression, suggesting the presence of different pathologic mechanisms and differential MTX susceptibility.     

Rheumatoid nodulosis during methotrexate therapy in a patient with rheumatoid arthritis

Abstract

We report a 62-year-old man with rheumatoid arthritis (RA) who developed nodulosis after methotrexate (MTX) treatment. The epithelioid cells of nodules were positive for matrix metalloproteinases (MMP)-2, MMP-3, MMP-9, and Ki67. The synovial tissues obtained from the same patient were negative for MMP-3, MMP-9, and Ki67. This study demonstrated that MTX-induced nodules are different from synovial tissues in terms of MMP expression, suggesting the presence of different pathologic mechanisms and differential MTX susceptibility.     

Successful treatment of refractory type 1 autoimmune hepatitis with methotrexate

Background/Aims: Autoimmune hepatitis is a heterogeneous disorder that typically responds to glucocorticoids with or without azathioprine. Treatment options for patients not responding to standard therapy are limited.Methods: We describe a 52-year-old female who presented with jaundice, marked elevation in liver enzymes, positive antinuclear antibody and a liver biopsy consistent with autoimmune hepatitis. Liver enzymes did not normalize with prednisone alone. When azathioprine was added, the disease flared. The patient refused cyclosporine. Methotrexate 7.5 mg po per week resulted in normalization of liver enzymes, improved liver histology, and has maintained remission with a steroid-sparing effect.Results/Conclusion: In this patient methotrexate was used successfully to treat type 1 autoimmune hepatitis. This suggests that methotrexate may have a role in treatment of autoimmune hepatitis refractory to standard therapy.     

Successful salvage treatment of blastic natural killer cell lymphoma with methotrexate

A 69-year-old man with blastic natural killer cell lymphoma (BNKL) was treated mainly with methotrexate (MTX). He presented with skin and bone marrow involvement at onset. Neoplastic cells were blastic in appearance with CD3−, CD4−, CD8−, CD7−, CD16−, CD56+ and HLA-DR+ phenotype. Molecular studies showed germline configuration of both immunoglobulin H and T cell receptor genes, and negative results for Epstein–Barr virus-encoded small RNA (EBER). He was treated with standard acute lymphoblastic leukemia (ALL) induction therapy, followed by 1 cycle of high-dose MTX (HD-MTX) as consolidation therapy. However, BNKL relapsed during standard ALL maintenance therapy. Three cycles of HD-MTX were effective in achieving a second complete remission and then he received low dose MTX as maintenance therapy. BNKL remained well controlled for 4 years. Chemotherapeutic toxicity was mild and manageable. Since BNKL reportedly has a poor prognosis, this encouraging result warrants further investigation of MTX as either a single agent or in a combination regimen as a first-line treatment for patients with BNKL.     

Accelerated nodulosis and vasculitis during methotrexate therapy for rheumatoid arthritis

Three women with classic rheumatoid arthritis, who were receiving weekly doses of methotrexate (MTX), developed accelerated subcutaneous nodulosis, despite good response to the drug. In 2 of the patients, the onset of nodulosis occurred within 3 months and 5 months, respectively, after starting MTX; in the third patient, it was observed only after 4 years of MTX therapy. In all 3 patients, the onset was unusually abrupt, with extensive distribution and remarkable nodule size. Additional manifestations of cutaneous vasculitis in 2 of the patients and Raynaud's phenomenon in the third appeared concomitantly with the nodulosis. Physicians prescribing MTX therapy for patients with rheumatoid arthritis should be aware of these potential complications.     

Accelerated nodulosis during low dose methotrexate therapy for rheumatoid arthritis. An analysis of ten cases.

OBJECTIVE. To obtain information on the occurrence of accelerated nodulosis during methotrexate (MTX) for rheumatoid arthritis (RA), localization, size and presence in heart and lungs of these nodules, predisposing factors, relationship with other extraarticular manifestations (EAM) and their histological features. METHODS. Ten patients with accelerated nodulosis were studied. Four participated in a double blind study of MTX and azathioprine. Patient characteristics, localization, size and histopathology of new nodules were determined. Echocardiography and chest roentgenograms were performed. RESULTS. Accelerated nodulosis occurred exclusively during treatment with MTX in our double blind study. The estimated incidence was 8%. One patient reported was rheumatoid factor negative. Newly developed nodules were small, and located in the fingers in all patients and in additional sites in 7. Pretreatment nodules were not found in the fingers. In one patient nodules on the mitral valve were found, but this was not likely to be associated with the use of MTX. No new pulmonary nodules were found. Other EAM developed concurrently in 4 patients. Histopathology revealed typical rheumatoid nodules. In 3 patients nodulosis regressed after MTX was stopped. In 2 of them they recurred after a rechallenge. CONCLUSIONS. Accelerated nodulosis during MTX for RA is not rare, and occurs despite good clinical response of polyarthritis. Rheumatoid factor positivity is not a prerequisite. New nodules are small and preferentially located in the fingers. Recurrence after rechallenge with MTX suggests causality.     

Accelerated nodulosis during methotrexate therapy in a patient with systemic lupus erythematosus and Jaccoud's arthropathy

SIR, Accelerated nodulosis (AN) is a well-known complicationof methotrexate (MTX) therapy in rheumatoid arthritis (RA) patients[1], characterized by the rapid appearance of small noduleson the hands, elbows and feet [1]. Although subcutaneous noduleshave been described in systemic lupus erythematosus (SLE) [2–5],we are unaware of reports of AN in SLE during MTX treatment. We report the case of a 34-yr-old female who was referred inOctober 1994 to a rheumatology department     

Successful treatment with infliximab and low-dose methotrexate in a Japanese patient with familial Mediterranean fever

We report a Japanese patient with familial Mediterranean fever (FMF) who was successfully treated with the anti-tumor necrosis factor (TNF)-alpha monoclonal antibody, infliximab, and low-dose methotrexate. This patient was diagnosed as having FMF based on periodic fever with polyarthralgia typical of this disease and heterozygous mutations in the MEFV gene. Conventional treatment, such as colchicine and reserpine, failed to sufficiently control the FMF attacks. After starting infliximab (3 mg/kg) and low-dose methotrexate (6 mg/week), the frequency of the FMF attacks dramatically decreased and the clinical effect has remained unchanged for longer than 1 year. Combination therapy with infliximab and low-dose methotrexate may be a potent therapeutic option for FMF patients, particularly when conventional treatment is ineffective or cannot be employed because of adverse events.     

Successful treatment of a patient with Neuro-Behçet’s disease with low-dose weekly methotrexate

A 79-year-old man who had a history of recurrent oral ulcers, arthritis in the left knee joint and ileocecal ulcer was admitted to our hospital because of high fever, dysarthria and progressive dementia. Magnetic resonance imaging (MRI) examinations of the brain disclosed high signal intensity areas in the left pons, left midbrain, bilateral thalamus on T₂-weighted images. These lesions were detected as slightly low signal intensity areas on T₁-weighted images, some of which were ring-enhanced after the administration of gadolinium-DPTA. The cerebrospinal fluid (CSF) interleukin-6 activity was elevated remarkably (0.77 U/ml). A diagnosis of Neuro-Behçet’s disease (NB) was made and methotrexate (MTX) was started at a dose of 2.5 mg per week. After MTX therapy, MRI findings were improved and the IL-6 activity in the CSF was decreased significantly. In addition, the progression of neuropsychiatric symptoms was prevented without any side effects during MTX therapy over 3 years. It is suggested that low-dose MTX therapy might be effective in the treatment of NB.     

D-penicillamine induced suppression of B cell function: in vivo effect of D-penicillamine

We assessed the immunoglobulin secretory capacity of circulating B lymphocytes in 9 patients with classical rheumatoid arthritis (RA) before and after treatment with D-penicillamine. Peripheral blood lymphocytes (PBL) from patients with RA spontaneously synthesized more IgG and IgA than normals. The secretory rate of rheumatoid PBL could not be induced by the polyclonal activator, pokeweed mitogen (PWM). The presence of D-penicillamine in cultures significantly suppressed PWM stimulated immunoglobulin synthesis of control PBL but did not inhibit synthesis of mitogen stimulated RA PBL. After D-penicillamine therapy for 3 months immunoglobulin synthesis by PBL from patients with RA was reduced with or without PWM. The T mu:T gamma ratio was also decreased after therapy. These results support the hypothesis that D-penicillamine selectively impairs helper T cells in vivo, preventing the T dependent expansion and activation of B cells characteristic of RA.     

Successful reintroduction of methotrexate after pneumonitis in two patients with rheumatoid arthritis.

Two patients are described with severe and progressive rheumatoid arthritis in whom methotrexate was reintroduced despite previous methotrexate related pneumonitis. In both patients a marked improvement in disease control occurred without a recurrence of the pneumonitis.     

Palmar rheumatoid nodulosis associated with local pressure.

Rheumatoid nodulosis is a term used to describe adult patients with rheumatoid arthritis with little or no clinical joint inflammation who have numerous subcutaneous nodules indistinguishable from those of patients with active rheumatoid arthritis. This paper reports the case of a woman with quiescent rheumatoid arthritis who developed palmar nodulosis three weeks after the strenuous activity of painting her apartment. This case illustrates the direct association between the appearance of nodulosis and physical pressure despite inactive disease.