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Leflunomide decreases joint erosions and induces reparative changes in a patient with psoriatic arthritis
  1. M Cuchacovich,
  2. L Soto
  1. Rheumatology Section, Department of Medicine, University of Chile Clinical Hospital, Santiago, Chile
  1. Correspondence to:
    Dr M Cuchacovich, Roberto del Rio 978, Providencia, Santiago, Chile;
    mcuchaco{at}ns.hospital.uchile.cl

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We read with great interest the article by Scott and colleagues,1 in which they report radiological improvement or halting of disease progression with leflunomide treatment in a group of patients with rheumatoid arthritis (RA). Leflunomide has also been reported to be effective in some studies including a small group of patients with psoriatic arthritis (PsA), but radiological evolution was not evaluated.2,3 We report the case of a patient with PsA who had clinical remission and radiological amelioration after a year with leflunomide treatment. To our knowledge, this is the first evidence that leflunomide may induce reparative changes such as filling of a bone cyst in a patient with PsA.

CASE REPORT

A 37 year old white man presented in August 1997 with a history of pain in the left wrist, right ankle, and both feet during the previous three months. His past history and physical examination were unremarkable except for synovitis in the painful joints and a single well demarcated erythematous hyperkeratotic plaque on the trunk. A dermatologist was consulted and psoriasis vulgaris was confirmed by biopsy.

No crystals were found in synovial fluid obtained from the right ankle. Hand and foot radiographs did not show osteoarticular damage. His rheumatoid factor was negative, haemoglobin, white cell blood count, and serum uric acid levels were normal; the erythrocyte sedimentation rate was 25 mm/1st h. Meclofenamate 100 mg three times a day was started, with good initial clinical response, and the dose was decreased to 100 mg twice daily.

The patient remained stable until February 1998 when he consulted with recurrent joint symptoms. Marked pain and swelling was found in the previously affected joints. Sulfasalazine at a dose of 2 g/day was added to the meclofenamate, and the arthritis was controlled after two months of treatment. A new set of radiographs of the hands and feet did not show erosive changes.

He continued receiving the same treatment during the next 18 months, experiencing slight pain in both feet after climbing stairs or standing for long periods. In November 1999 he consulted with a new flare in the left wrist, right sacroiliac joint, and right foot. A new set of feet radiographs (fig 1A) was obtained and showed erosions in the right fifth proximal interphalangeal joint and a subchondral cyst in the fifth metatarsal head. The left foot was radiologically normal.

Figure 1

(A) November 1999. Active erosion in the right fifth proximal interphalangeal joint and a subchondral cyst in the fifth metatarsal head (arrow). (B) December 2000. Partial filling of the subchondral cyst, with nearly normal bone structure (arrow), progressive bone absorption of the erosion in the right fifth interphalangeal joint, and no new erosions. The metatarsophalangeal joint surface is regular, and the joint space is conserved.

Methotrexate was added to the treatment, but the patient developed fever and severe diarrhoea after the second dose. Methotrexate was stopped and leflunomide was started in January 2000. He received a three day initial loading dose of 100 mg/day followed by 20 mg daily doses.

With this new schedule the patient had clinical remission of the disease, and meclofenamate was changed to rofecoxib 25 mg/day.

A new set of radiographs (fig 1B) was performed a year later and showed partial filling of the subchondral cyst with bony sclerosis, progressive bone absorption of the erosion in the right fifth interphalangeal joint, and no new erosions.

At the present time the patient's disease remains inactive, but right foot pain appears after excessive mechanical stress.

DISCUSSION

Significant slowing of radiographic disease progression has been described, and reparative changes have been suggested with leflunomide treatment in patients with RA.1 However, up to now no radiological data are available for patients with PsA.

Our report describes a patient with PsA who developed an erosive disease despite being treated with other disease modifying antirheumatic drugs (DMARDs). After the addition of leflunomide to the treatment for more than one year, a bone cyst of a metatarsal head was seen to have filled.

The main objection for accepting the concept of “radiological joint amelioration” is that some authors argue that “filling in” of bone cysts, when presented in association with joint remodelling, may be an expression of disease progression and not a reparative process.4 However, in our patient filling of the bone cyst appeared without any evidence of remodelling in the distal articulating surface of the metatarsal head. The metatarsophalangeal joint surface is regular, and the joint space was conserved. In addition, no new erosions were detected.

There is both experimental and clinical evidence to show that reparative reactions occur in patients with RA treated effectively with DMARDs.5 It has also been reported that functional repairing of articular cartilage can occur if the proper environment is created to promote repair.6 Leflunomide limits T cell proliferation, enzymatic degradation of bone and cartilage by destructive metalloproteinases, and proinflammatory cytokines such as tumour necrosis factor α, interleukin 1, and interleukin 8.7 These mechanisms may explain the prevention of structural damage seen with leflunomide in different studies.

In summary, we present radiological evidence that supports the hypothesis that leflunomide may induce reparative changes such as bone cyst filling in a patient with PsA. To confirm this finding it will be necessary to include radiographic scoring methods in future studies of leflunomide efficacy in PsA.

REFERENCES

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