Correspondence

Fludarabine and Psoriasis

N Engl J Med 1994; 330:1540-1541May 26, 1994

Article

To the Editor:

Fludarabine monophosphate is a synthetic purine antimetabolite that has been used almost exclusively in the treatment of chronic lymphoid cancers1. The medication may cause dose-related myelosuppression. Recently, CD4+ T-lymphocytopenia with associated opportunistic infections has been observed in a small number of patients treated with this agent2. CD4+ T lymphocytes are believed to have a pivotal role in the pathogenesis of psoriasis3. We describe a patient with B-cell chronic lymphocytic leukemia and chronic plaque psoriasis whose skin condition remitted during fludarabine monophosphate therapy.

A 67-year-old man with a 10-year history of B-cell chronic lymphocytic leukemia received fludarabine monophosphate (20 mg per square meter of body-surface area as an intravenous bolus for five days) in two monthly cycles after his disease had become refractory to standard combination chemotherapy. Psoriasis had been diagnosed in 1952. The patient had been free of psoriasis only for a three-month period after inpatient treatment with anthralin. Previous ultraviolet-B irradiation was unsuccessful. When treatment with fludarabine monophosphate was begun, the patient had marked pustular psoriasis involving the hands and feet, widespread plaques on the limbs and trunk, and marked psoriatic nail changes. One week after the completion of the first course of therapy, the patient's skin was entirely clear of psoriatic changes. Treatment was discontinued after two cycles because the leukemia was not responding to the therapy. The patient's skin remained clear of psoriasis for nine more weeks. Psoriatic changes then reappeared, and the patient was treated with topical therapy, with little response.

Although the molecular defect causing psoriasis is unknown, there is strong evidence that aberrations in the immune and inflammatory processes have key roles3. Psoriasis is characterized by the infiltration of T lymphocytes and macrophages into the dermis. The ratio of CD4+ cells to CD8+ cells is higher in the dermal infiltrate than in the blood, suggesting selective recruitment of CD4+ cells into the skin lesion4. Favorable clinical responses in patients with psoriasis who are treated with cyclosporine have been accompanied by reductions in CD4+ and CD8+ populations in the dermis and epidermis4.

Fludarabine monophosphate is the 2-fluoro-5'-monophosphate derivative of vidarabine (adenosine arabinoside). Unlike vidarabine, it resists deamination by adenosine deaminase, a key enzyme involved in the normal growth, development, and differentiation of lymphocytes5. The cytotoxic action appears to involve the metabolic conversion of the parent compound to its active 5'-triphosphate5. The mechanism responsible for the clinical response in our patient remains to be elucidated.

More than 40 years ago, psoriasis in a patient with both rheumatoid arthritis and psoriasis was reported to respond to aminopterin,6 the predecessor of methotrexate. Methotrexate is now the favored agent among several antimitotic and immunosuppressive agents used for severe psoriasis. Our serendipitous therapeutic observation deserves further investigation. In view of the toxicity of fludarabine, further studies should be confined to patients with severe psoriasis and conducted as clinical trials with careful monitoring of patients.

Owen P. Smith, M.R.C.P.
Alan V. Hoffbrand, F.R.C.P.
Colin Buckley, D.M., M.R.C.P.
Royal Free Hospital School of Medicine, London WC1N 3JH, United Kingdom

6 References

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Citing Articles (3)

Citing Articles

1. 1

   Hidehisa SAEKI, Shusaku HOSONO, Yuichiro TSUNEMI, Kiyo SASAKI, Takafumi KADONO, Hironobu IHN, Mayumi KOMINE, Akihiko ASAHINA, Kanako KIKUCHI, Kunihiko TAMAKI. (2007) Psoriasis vulgaris associated with superior vena cava syndrome due to lung cancer metastasis. The Journal of Dermatology 34:5, 356-359
   CrossRef

2. 2

   B. J. Kennedy, Jane L. Torkelson, Emina Torlakovic. (1999) Uracil mustard revisited. Cancer 85:10, 2265-2272
   CrossRef

3. 3

   Barry Eibschutz, Stephen M. Baird, Michael H. Weisman, Diane G. Amox, Mary Spellman, Daniel Piacquadio, Carlos J. Carrera, Dennis A. Carson. (1995) Oral 2-chlorodeoxyadenosine in psoriatic. Arthritis & Rheumatism 38:11, 1604-1609
   CrossRef