Chronic verrucous sarcoidosis associated with human papillomavirus infection: Improvement with adalimumab.

To the Editor: Verrucous sarcoidosis is a rare variant of cutaneous sarcoidosis observed most commonly on the lower extremities of patients with severe pulmonary disease. A case of a skin-colored to violaceous verrucous hyperplasia overlying sarcoidal plaques associated with human papillomavirus (HPV) was previously reported in this journal (Fig 1). At that time, we postulated that the virus inoculated the skin after facial trauma. In addition, sarcoidal plaques appeared to produce an immunocompromised district that favored HPV growth. In the absence of any previously reported cases of verrucous sarcoidosis of the face, the optimal approach for targeting both HPV and the underlying sarcoidal plaques was unknown. The response to a variety of treatments was instructive.

Fig 1

Lesion at initial presentation shows annular verrucous lesions overlying sarcoidal papules and plaques.

Treatment course

Initially, hydroxychloroquine, 200 mg twice a day, was used to target cutaneous sarcoidosis in combination with imiquimod 5% cream 3 times a week to target the HPV. Unfortunately, severe irritation led us to discontinue imiquimod after 2 weeks. The patient was lost to follow-up but returned 2 years later with thickening and expansion of verrucous lesions. Treatment was initiated with hydroxychloroquine, 200 mg twice a day, methotrexate, 5 mg weekly, and topical pimecrolimus 1% cream twice daily to suppress pruritus. Methotrexate was titrated to 15 mg weekly. No significant improvement was noted after 4 months. In addition, several test areas were treated with liquid nitrogen cryotherapy, but no improvement was noted (Fig 2, A and B).

Fig 2

A, Lesion progression 2 years later. Worsening disease shows thickened annular verrucous lesions overlying sarcoidal changes despite a variety of treatments including cryotherapy, intralesional triamcinolone, hydroxycholorquine, methotrexate, and imiquimod. B, Close-up view of the right nasal sidewall and right cheek refractive to treatments noted in previous figure.

The previous medications were discontinued, and subcutaneous adalimumab was administered with a loading dose of 80 mg followed by a 40-mg injection the next week and then 40-mg injections every other week. After 4 months, all of the dermal plaques correlating with sarcoidal granulomas resolved. Perhaps, surprisingly, significant improvement was also noted with 95% improvement in verrucous plaques on the cheeks and thinning of the advancing verrucous border on the forehead (Fig 3, A and B). No adverse events occurred during treatment.

Fig 3

A, Annular lesions 4 months after starting adalimumab treatment. Note significant improvement in background sarcoidosis papules and plaques in addition to thinning borders of verrucous lesions. B, Close-up view with near-complete thinning of the verrucous border and resolution of hyperpigmentated annular lesions 4 months after adalimumab initiation.

Discussion

Adalimumab is a fully human monoclonal antibody directed against tumor necrosis factor (TNF)-α and is currently approved by the US Food and Drug Administration for autoimmune conditions including rheumatoid arthritis and Crohn's disease. The distinguishing characteristic of sarcoidosis, noncaseating granulomas, consists of macrophages, lymphocytes, and neutrophils that release TNF-α. This cytokine triggers the inflammatory cascade by inducing immature lymphocytes to differentiate into T helper 1 cells. Elevated levels of TNF-α have been documented in sarcoidosis patients.

Because of these findings, anti-TNF biologic drugs have been used to break up sarcoidal granulomas. The TNF- α inhibitors, etanercept and infliximab, improve cutaneous and extracutaneous sarcoidosis. Only 1 double-blind, randomized, controlled trial studied the effects of adalimumab in cutaneous sarcoidosis patients, the results of which show significant improvement in lesion area, volume, and quality of life among patients. In this case, it appears that complete resolution of sarcoidal granulomas normalized local immunity (resolution of immunocompromised district) leading to marked improvement of the associated HPV infection. We know of no other mechanism that would explain this phenomenon.