GEORGE J.HRUZAMDDEE ANNAGLASERMDELAINESIEGFRIEDMD
A 70-year-old man presented with a 2-year history of bloody gums and fetid breath. He was initially treated with topical corticosteroids and courses of oral prednisone starting at 60 mg/d and tapered over several weeks. When this treatment failed to produce any durable clinical improvement, he was treated sequentially with griseofulvin, dapsone, azathioprine, etretinate, and cyclosporine. His current medication was cyclophosphamide, 100 mg/d for 5 months. He reported that the only therapy that decreased his pain, swelling, and bleeding was the prednisone and brief courses of azithromycin, which had been discovered serendipitously while he was being treated for an upper respiratory infection.
Examination showed erosions and ulcerations of the hard palate; severe desquamative gingivitis, involving facial (Figure 1A) and palatal gingiva; and atrophy and striae of the buccal mucosa (Figure 2A) and tongue. A biopsy specimen from involved buccal mucosa showed hyperkeratosis, hypergranulosis, a dense lymphocytic infiltrate below the epithelium associated with basal cell vacuolization, and necrotic epithelial cells consistent with lichen planus. No atypia was identified. Serologic tests were negative for hepatitis C virus antibodies.
A, Severe desquamative gingivitis of the upper and lower gingival ridge. B, Lower ridge after 4 months of treatment with thalidomide.
A, Striae of left buccal mucosa. B, Left buccal mucosa after 4 months of treatment with thalidomide.
This patient's oral erosive lichen planus was recalcitrant to every systemic agent tried, including potent immunosuppressive agents. The only treatment that was temporarily successful at improving his condition was prednisone, which may have been associated with his subsequent development of diabetes, osteoporosis, and back pain. We needed to find a novel nonsteroidal therapy that could improve the man's quality of life, if not cure the condition.
In 1998, when thalidomide became available, we prescribed it at a starting dosage of 50 mg/d for 2 weeks and gradually increased the dosage over 3 months to 200 mg/d. All other therapy was discontinued. The patient experienced dizziness, edema of the lower extremities, and a mild erythematosquamous rash of the face and trunk, necessitating a decrease in dosage to 100 mg/d, with a reduction of adverse effects to a tolerable level. Concomitantly, after 4 months of treatment, he reported a decrease in pain, redness, bleeding with brushing, and fetid breath. Overall, he indicated a 75% improvement in his condition. After 11 months of treatment, examination showed nearly complete resolution of desquamative gingivitis (Figure 1B) and striae (Figure 2B).
Thalidomide therapy was discontinued after 1 year 5 months. About 2 weeks later, the patient reported gum pain; examination 5 weeks later revealed punctate erosions of the hard palate and recurrence of desquamative gingivitis.
Oral lichen planus is a common disease of unknown origin that affects 1% to 2% of the population. While most cases are reticular and relatively asymptomatic, the erosive variant can be debilitating and is typically resistant to standard therapies for lichen planus. Remission rates are as low as 5%. The possibility that there is an association with hepatitis C virus infection is still controversial. Systemic corticosteroid therapy results in temporary improvement but no long-term resolution. Immunosuppressive treatment with agents such as azathioprine, cyclophosphamide, and cyclosporine may allow reduction of the steroid dosage or induce remission, but their use is limited by toxic effects and cost.
Thalidomide was initially used in Europe and Canada as a sedative and antiemetic for pregnant women. Its use was terminated after severe teratogenic effects were recognized. Thalidomide was approved by the Food and Drug Administration in 1998 for the treatment of erythema nodosum leprosum. Since then, its off-label uses have proliferated. In 1985, Naafs and Faber1 reported the successful treatment of lichen planus with thalidomide. Their patient achieved remission and remained disease free after the use of the drug was discontinued. Two subsequent patients with oral erosive lichen planus have responded to treatment with thalidomide at a dosage of 150 mg/d and have maintained improvement at a dosage of 50 mg every other day.2
Thalidomide has many adverse effects besides teratogenicity. Headache, nausea, constipation, rash, sedation, dry mouth, erythema nodosum–like lesions, weight gain, and peripheral edema have all been documented.3 Also, a peripheral neuropathy may develop, and it has been suggested that patients be monitored every 6 months with nerve conduction studies while taking the drug.4
We were able to alleviate most of the sedation and dizziness caused by the use of thalidomide by having our patient take the drug in a single daily dose at bedtime. His peripheral edema resolved when the dosage was reduced. Although he still has a faint rash, he tolerates it and prefers to continue the treatment because of the dramatic improvement in his symptoms and in the appearance of the desquamative gingivitis.
Thalidomide distribution is strictly regulated. Physicians who want to prescribe thalidomide must first register with the manufacturer (Celgene Corp, Warren, NJ). The drug may be dispensed only by registered pharmacies. Physicians and patients must follow the System for Thalidomide Education and Prescribing Safety, or STEPS, Program. This program mandates a signed consent and enrollment in a long-term epidemiological follow-up study. Thalidomide may be given to women of child-bearing potential only if 2 effective forms of birth control are used and monthly STEPS questionnaires and pregnancy tests are obtained.
Accepted for publication July 31, 2000.
Corresponding author: Charles Camisa, MD, 9500 Euclid Ave, Desk A-61, Cleveland OH 44195 (e-mail: firstname.lastname@example.org).
Camisa C, Popovsky JL. Effective Treatment of Oral Erosive Lichen Planus With Thalidomide. Arch Dermatol. 2000;136(12):1442-1443. doi:10.1001/archderm.136.12.1442