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Nada C. Macaron, MD; Cynthia Cohen, MD; Suephy C. Chen, MD, MS; Jack L. Arbiser, MD, PhD

Arch Dermatol. 2005;141:259-262.

Background  Sarcoidosis, which occurs most commonly in African American women, is a granulomatous multisystem disorder affecting the skin, lungs, and central nervous system. In a previous immunohistochemistry study of keloids, a scar granuloma stained highly positive for glioma-associated oncogene homologue (gli)-1.

Observation  This observation led us to study whether gli-1, one of the vertebrate zinc finger transcription factor genes of the gli superfamily, is expressed in granulomatous skin disorders such as cutaneous sarcoidosis, granuloma annulare (GA), and necrobiosis lipoidica diabeticorum (NLD). Immunohistochemistry studies for gli-1 were performed on biopsy specimens from patients with cutaneous sarcoidosis, GA, and NLD. All sarcoid lesions were highly positive for gli-1 expression, and 75% of the cells demonstrated positivity with a stain intensity of 3 on a scale of 1 to 3. The gli-1 expression was confined to cutaneous granulomas. CD68 staining was highly positive in the sarcoid lesions as well. Similarly, GA and NLD lesions were uniformly positive for gli-1 expression.

Conclusions  We found that gli-1 is inappropriately expressed in granulomatous lesions of the skin such as cutaneous sarcoidosis, GA, and NLD. These findings provide a rationale for clinical trials of inhibitors of gli-1 signaling, including tacrolimus and sizolimus, for the treatment of cutaneous sarcoidosis and other granulomatous disorders of the skin.

Author Affiliations: Departments of Pathology and Laboratory Medicine (Drs Macaron and Cohen) and Dermatology (Drs Chen and Arbiser), and Emory Center for Outcomes Research (Dr Chen), Emory University School of Medicine, Atlanta, Ga; and Department of Health Services Research and Development (Dr Chen) and Division of Dermatology, Atlanta Veterans Affairs Medical Center, Atlanta (Drs Chen and Arbiser).

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