MEDICAL DERMATOLOGY OF JOURNAL

MEDICAL DERMATOLOGY OF JOURNAL

Drug-Induced Pemphigus after six years of treatment  with phenytoin and Carbamazepine

                                                                                                            

Phenytoin and Carbamazepine-induced pemphigus vulgaris is seldom reported. Herein, We present a case of pemphigus vulgaris occurring after six years of treatment with phenytoin and carbamazepine.

In 2001, a 57-year-old female patient presented with oral ulcers of 18 months’ duration and scattered blistering lesions of six months’ duration. The patient had a seven year medical history of multiple sclerosis and experienced recurrent episodes of seizures and numbness, weakness, and prickling pain in all four limbs. She had been treated daily with 0-3 g phenytoin and 0,6 g carbamazepine for greater than six years. Dermatological examination revealed an oral ulcer and vesicles measuring 2-5 mm in diameter scattered over most of her body, especially the trunk. The vesicles were negative for nikolsky’s sign. A histopathologic examination of the skin lesions was consistent with pemphigus vulgaris (Fig. 1). Direct immunofluorescence revealed intercellular staining for complement fragment 3 (C3) in the epidermis. Lupus band test was positive, with deposits of IgM at the juncture between the dermis and epidermis. Laboratory investigation revealed positive antinuclear antibidy (ANA), anti-deoxyribonucleoprotein (anti-DNP), anti-doublestanded  DNA (anti-dsDNA), and anti-Ro/SSA. Full blood cell count, urinalysis, renal and liver function tests, and serum levels of complements C3 and C4 revealed no abnormalities. Drug-induced lupus erythematosus or indiopathic systemic lupus erythematosus (SLE) were ruled out because of the lack arthralgia and multisystem organ involvement and the evidence of typical pemphigus presentation in the epidermis. Pemphigus vulgaris was diagnosed  in line with the clinical and histopathologic findings.

Oral ulcers and skin vesicles improved quickly and healed  one month after the withdrawal of phenytoin and start of steroid treatment. Carbamazepine was also discontinued one month after the withdrawal of phenytoin. Ten months later,an oral ulcer and vesicles recurred after phenytoin and carbamazepine were reintroduced to treat multiple sclerosis. Another biopsy os skin lesions revealed acantholysis at the suprabasal layers but showed scarce inflammatory cells (Fig. 2). Direct immunofluorescence revaled intercellular staining for IgG and C3 in the epidermis. Recurrent eruptions continued after the  withdrawal of phenytoin only but were quickly well controlled after the withdrawal of both phenytoin and carbamazepine. There was no other relapse of skin or oral conditions; in addition, anti-dsDNA and anti-DNP returned to normal, whereas ANA and anti-Ro/SSA tested positive after the permanent discontionuatian of phenytoin and carbamazepine over the six years to the present. No internal organ damage was found between the episodes of bullous disease and recent follow-up.

In the literature, carbamazepine-induced pemphigus is reported only once in a 13-year-old girl after six years of treatment with carbamazepine for epilepsy.¹ Phenytoininduced erythematous pemphigus has not been reported in the English-language literature but was reported in the Chinese literature in 1995.² Furthermore, phenytoin and carbamazepine have been reported to cause ANA in drug-induced lipus,^3-4 in our case, anti-dsDNA and anti-DNP may have been induced by phenytoin and/or carbamazepine. We consider that higher-than-normal ANA and anti-Ro/SSA values may not be suggestive of SLE or Sjogren’s syndrome but may indicate immunoaberrance often found in multiple sclerosis patients.⁵

Drug-induced pemphigus should be considered as a possibility in a patient with bullous disease and long-termuse of antiepleptic medication. The withdrawel of theseculprit drugs and steroid administration proves effective in the treatment of drug-inducced pemphigus.

References

1.      Patterson CR, Davies MG. Carbamazepine-induced pemphigus. Clin Exp Dermatol 2003; 28: 98-99.

2.      Zhang X, Tong J, He D, et al. A Case report of Phenytoin-induced pemphigus erythematosus. Chin J Dermatol 1995; 28:57.

3.      Pelizza L, de Luca P, La Pesa M, et al. Drug-induced systemic lupus erytematosus after 7 years of treatment with carbamazepine. Acta Biomed 2006; 77: 17-19

4.      Ross S, Ormerod AD, Robert C, et al. Subacute cutaneous lupus erythematosus associated with phenytoin. Clin Exp Dermatol 2002; 27:474-476.

5.      De Andres C, Guillem A, Rodriguez-Mahou M, et al. Frequency and siqnificance of anti-Ro (SS-A) antibodies in multiple sclerosis patients. Acta Neurol Scand 2001; 104: 83-87.