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

M.-G. Rivero, A.-J. Salvatore1, J. A. Gómez-Puerta2, J. M. Mascaró, Jr3, J. D. Cañete2, J. Muñoz-Gómez2 and R. Sanmartí2

Department of Immunology, Hospital Central, 1 Department of Internal Medicine, Hospital Lagomaggiore, Mendoza, Argentina, 2 Department of Rheumatology, 3 Department of Dermatology, Hospital Clínic, Barcelona, Spain.

Correspondence to: R. Sanmartí, Rheumatology Department, Hospital Clínic, Villarroel 170, Barcelona 08036, Catalonia, Spain. E-mail: sanmarti{at}clinic.ub.es

SIR, Accelerated nodulosis (AN) is a well-known complication of methotrexate (MTX) therapy in rheumatoid arthritis (RA) patients [1], characterized by the rapid appearance of small nodules on the hands, elbows and feet [1]. Although subcutaneous nodules have 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 in October 1994 to a rheumatology department due to pain in the wrists, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, and Raynaud's phenomenon of 4 months’ duration. There was no previous history of spontaneous abortions or thrombosis. Physical examination revealed symmetrical polyarthritis affecting the wrists, MCP and PIP, without signs of sclerodactylia. Laboratory findings showed lymphopenia (1100 lymphocytes/mm3), positive antinuclear antibodies [(ANA) 1/640], antiribonucleoprotein (RNP) antibodies, double-stranded DNA antibodies (anti-dsDNA) [15.5 IU/ml (normal <7 IU/ml)] and anticardiolipin (aCL) IgG antibodies (high titres). Rheumatoid factor (RF) and lupus anticoagulant were negative. X-ray of the hands showed no erosive lesions. Low doses of prednisone were started, accompanied by chloroquine 250 mg/day and indometacin (75 mg/day).

In July 1995, the patient presented an episode of polyarthritis, characterized by a bilateral MCP and PIP synovitis, ulnar deviation and swan-neck deformities. New X-rays showed subluxations in MCP and PIP without cortical erosions (Jaccoud's arthropathy). Chloroquine was stopped and oral methotrexate (MTX) therapy was started at 7.5 mg/week with marked improvement in the affected joints. Eleven months later, multiple small (<5 mm) subcutaneous nodules appeared on the elbows, olecranon surface and MCP joints. Subcutaneous nodule biopsy disclosed histopathological findings of a rheumatoid nodule, with areas of fibrinoid necrosis in the deep reticular dermis surrounded by a rim of lymphocytes and histiocytes, without evidence of thrombosis.

In December 1997, MTX was discontinued due to gastrointestinal intolerance and chloroquine (250 mg/day) was restarted. Six months later, subcutaneous nodules had disappeared from some joints, and decreased in number, size and painfulness in others.

During this time, the patient was admitted for a progressive exertional dyspnoea. High-resolution thorax computed tomography and pulmonary scintigraphy were normal. Echocardiography revealed pulmonary artery hypertension (46 mmHg). aCL IgG remained positive in high titres. A diagnosis of secondary pulmonary hypertension related to antiphospholipid syndrome (APS) was made. Oral anticoagulation and nifedipine (10 mg t.i.d.) were started with a periodic echocardiographic follow-up. Currently, the patient's clinical condition remains stable, both with respect to joint involvement and to the pulmonary hypertension.

Rheumatoid nodules (RN) have been associated not only with RA but also, infrequently, in palindromic rheumatism, juvenile chronic arthritis (JCA), SLE [6], primary APS [7] and, occasionally, in healthy people (especially in children) [6]. Wolf et al. [8] reported a high prevalence of aCL antibodies in patients with RA and RN. Although the pathogenic role of aCL in nodule formation is still unknown, a local thrombotic mechanism has been suggested.

There is a clear association between AN and the use of MTX. Patients are generally seropositive for RF and almost 25% have a concurrent vasculitis and develop smaller (less than 5 mm) nodules than patients with RN [1]. Normally, AN appear in atypical sites and their onset is abrupt and painful. However, the histopathology findings are similar to RN. The time elapsed between the beginning of MTX administration and the occurrence of AN is variable (weeks to years) [1].

Subcutaneous nodules are uncommon in patients with SLE [2, 3], and are usually present in the olecranon, MCP and PIP joints. The histopathological characteristics are similar to those found in RA patients. The differential diagnosis in a patient with SLE and a nodular skin lesion must include panniculitis, erythema nodosum, APS, leucocytoclastic vasculitis, tumid lupus and mucinosis, among others.

It has been suggested that only patients with RA are at risk of developing AN when they are treated with MTX. Nonetheless, there are some reports of AN in other seronegative conditions such as systemic onset JCA [9], and in one patient with a non-erosive arthritis and psoriasis [10].

To our knowledge, this is the first reported case of AN induced by MTX in a patient with SLE. Whether a persistent polyarthritis with a deforming Jaccoud's arthropathy may have been a risk factor for MTX-induced nodulosis in our patient is speculative. There are some other reports of Jaccoud's arthropathy and spontaneous subcutaneous nodules with a histology of RN in SLE patients [3]. Although the possibility that AN might be part of the natural history of SLE or be related to aPL antibodies cannot be excluded in our patient, the clinical findings and evolution suggest a close relationship with MTX therapy, supported by the improvement of subcutaneous lesions on discontinuation of the drug. This suggests that MTX-induced AN may be seen not only in RA patients but also in other diseases such as SLE.

The authors have declared no conflicts of interest.

References

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Accepted 4 August 2004





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