Fixed drug eruption induced by cyclophosphamide

ARTICLE

ejd.2012.1666

Auteur(s) : Kenji Sakurai beautifulskyblue58@yahoo.co.jp, Atsushi Otsuka, Yoshiki Miyachi, Kenji Kabashima

Department of Dermatology, Kyoto University, 54 Shogoin Kawara, Sakyo Kyoto 606-8507, Japan

Fixed drug eruption (FDE) is a cutaneous adverse reaction to drugs, characterized by recurrent site-specific skin lesions following intake of the responsible drug [1]. A variety of drugs are known to induce FDE [2]; however, to the best of our knowledge, there have been no reports of FDE after administration of cyclophosphamide. Cyclophosphamide is known to stabilize the lung functions in systemic scleroderma patients with interstitial lung disease (ILD), and is also used as an anticancer drug for the treatment of lung and breast cancers; the drug exerts its anticancer activity via its inhibitory effect on DNA synthesis [3, 4]. Here we report a case, for the first time, of FDE induced by cyclophosphamide.

A 54-year-old woman, who had suffered from scleroderma and ILD for 3 years, consulted our clinic for a skin eruption. She had been receiving cyclophosphamide pulse therapy (500 mg/m²). After the 14th course of pulse therapy, she developed well-demarcated, round deep-red erythematous patches with itching on the right elbow, right lower leg and left thigh, which eventually resolved with pigmentation, but reappeared at the same sites after each pulse therapy (3 episodes in total) (figure 1A-B). Routine laboratory examinations showed no abnormalities. A histological examination revealed lymphocytic infiltration at the epidermal-dermal junction, spongiform degeneration of the epidermis, edema of the superficial layer of the dermis, and perivascular lymphocytic and eosinophilic infiltration in the dermis; the findings were consistent with FDE (figure 1C-D). Challenge tests with metoclopramide and transfusion fluids used at the time of intravenous cyclophosphamide pulse therapy were negative. Although this patient had been receiving beraprost sodium for pulmonary hypertension and a proton pump inhibitor for reflux esophagitis, these drugs seemed to be causally unrelated to the eruption.

Based on the above findings, the patient was diagnosed as having FDE due to cyclophosphamide or metabolites of cyclophosphamide, including 4-hydroperoxycyclophosphamide and phosphoramide mustard. The FDE in this case did not develop immediately after the drug dosing, but about 8 hours afterwards. Considering this fact and the knowledge that some time is required for the formation of metabolites, it is probable that the FDE in this case represented a reaction to a metabolite of cyclophosphamide rather than to cyclophosphamide itself.

After discontinuation of the cyclophosphamide pulse therapy, no recurrence of the cutaneous manifestations was noted. In this case, the drug-lymphocyte stimulation test was not performed, since cyclophosphamide has an inhibitory effect on DNA synthesis. This is the first case of FDE induced by cyclophosphamide, to the best of our knowledge. Although limited to a single case, our case suggests that cyclophosphamide has the potential to induce FDE.

Disclosure

Financial support: none. Conflict of interest: none

References

1. Ozkaya E, Mirzoyeva L, Jhaish MS. Ceftriaxone-induced fixed drug eruption: first report. American Journal of Clinical Dermatology 2008; 9: 345-7.

2. Baykal C, Erkek E, Tutar E et al. Cutaneous fixed drug eruption to paclitaxel; a case report. European Journal of Gynaecological Oncology 2000; 21: 190-1.

3. Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Annals of the Rheumatic Diseases 2007; 66: 940-4.

4. Steen VD, Conte C, Owens GR et al. Severe restrictive lung disease in systemic sclerosis. Arthritis and Rheumatism 1994; 37: 1283-9.