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Oral Minocycline in Treatment of Cutaneous Sarcoidosis

Oral Minocycline in Treatment of Cutaneous Sarcoidosis Currently, therapeutic techniques used to treat cutaneous sarcoidosis rely on limited data from evidenced-based research.1,2 Bachelez et al3 conducted a prospective study in which 10 of 12 patients showed improvement after minocycline therapy, and Antonovich and Callen4 reported the case of 1 woman who was successfully treated with doxycycline. On the basis of these encouraging reports, our clinic began to use minocycline, a commonly used anti-inflammatory acne therapy that does not require laboratory monitoring, as a first-line treatment for cutaneous sarcoidosis. The present retrospective study sought to evaluate our experience with minocycline treatment and to compare its effectiveness across sex and race. Methods This retrospective study was approved by our institutional review board. The primary data sources were paper and electronic medical records of patients with cutaneous sarcoidosis treated with minocycline at the University of Pittsburgh Department of Dermatology in the UPMC Falk Dermatology Clinic between 2005 and 2012. The data obtained from medical records included the patient's age, race, sex, extent of skin disease, systemic involvement, prior therapies, duration of minocycline use, and the outcome of this therapy. The outcomes were categorized into 3 groups based on the percentage of body surface area (BSA) that showed remission of lesions: complete remission indicated resolution across 100% of the affected BSA; partial remission indicated 50% BSA resolution; and no remission indicated 0% BSA resolution. Patients met inclusion criteria if they sought treatment for disfiguring, biopsy-proven cutaneous sarcoidosis lesions that were extensive enough to require oral therapy. The outcome of oral therapy was recorded after at least 2 months of use, unless adverse events caused premature discontinuation. In addition, these patients were required to undergo and adhere to the regimen of minocycline treatment as prescribed by a UPMC dermatologist (J.C.E.). Statistical analysis (significance, P < .05) included the 1-proportion z test to evaluate difference in response to therapy across ages, the Mann-Whitney U test with a null probability of 50% to determine if more patients responded to therapy than not, and the Fisher exact test to determine all other differences, such as differences in response across race and sex. Results Twenty-seven patients met the inclusion criteria. Twenty-five had moderately extensive lesions (maculopapular, nodular, or plaque lesions on the face, torso, and/or extremities), and 2 had severe ulcerative lesions (scalp); no patients had classic lupus pernio (infiltrative and/or indurated plaquelike lesions). The average age of the patients at time of diagnosis of cutaneous sarcoidosis was 43 years. There were 14 men and 13 women; 17 were black, and 10 were white. Seven patients experienced lesions on the skin only; 17 had pulmonary and skin involvement; and 1 had ocular, pulmonary, and skin involvement. Sinus, muscle, and parotid involvement occurred with skin disease individually once as well. At the time of presentation, 2 patients were undergoing steroid treatment for pulmonary sarcoidosis and had persistent cutaneous lesions prior to minocycline therapy, and they continued prednisone treatment to preserve lung function. Minocycline was prescribed as first-line treatment in 18 patients and as second-line treatment in the remaining 9 (for 8 of these 9 patients, hydroxychloroquine treatment had failed, and prednisone had failed for 1 with skin-only disease). Owing to the extent of granuloma load in the skin, topical and intralesional steroids were not used during oral treatment. The average length of time until the initial therapy was assessed was 4.1 months. Of 27 patients, 6 (22%) had complete remission; 14 (52%) had partial remission; and 7 (26%) had no remission. Of the 2 severe ulcerative cases, 1 achieved a partial remission and 1 no remission. In total, 20 of 27 (74%) patients showed response to the treatment, and the proportion of those who responded was significantly greater than those who did not respond (P = .02) (Figures 1 and Figure 2). There was no difference in the response of minocycline across age, race, or sex. Adverse events often included dizziness, nausea, and blue skin hyperpigmentation. Six patients experienced hyperpigmentation, limited in 4 of these cases to the site of the lesion. White patients were significantly more likely to experience an adverse event than black patients (P = .04), but there was no significant difference across sex. Discussion As a whole, this study is limited by its retrospective nature, but it appears that minocycline therapy is a promising option for treating moderate cutaneous sarcoidosis. In total, 20 of 27 patients responded to therapy (74%), and significantly more patients responded than those who did not respond. After reviewing the current literature, our clinic chooses to treat cutaneous sarcoidosis using a monotherapeutic ladder in which minocycline is prescribed as first-line therapy, followed by hydroxychloroquine, methotrexate, thalidomide, and biological agents. Randomized controlled trials are needed to further establish and compare the effectiveness of minocycline as well as all other treatments. Back to top Article Information Correspondence: Dr English, Department of Dermatology, University of Pittsburgh, Presbyterian South Tower, Ste 3880, Pittsburgh, PA 15213 (englishjc@upmc.edu). Accepted for Publication: November 22, 2012. Author Contributions: Dr English and Ms Steen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: English. Acquisition of data: Steen. Analysis and interpretation of data: Steen and English. Drafting of the manuscript: Steen and English. Critical revision of the manuscript for important intellectual content: English. Obtained funding: Steen. Administrative, technical, or material support: English. Study supervision: English. Conflict of Interest Disclosures: None reported. Funding/Support: Ms Steen received a stipend from the University of Pittsburgh Medical School, Dean's Summer Research Program, for her contribution. Role of the Sponsors: The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; or in the preparation, review, or approval of the manuscript. Additional Contributions: We are indebted to statisticians Dan Winger, MS, and Li Wang, MS, who are supported by National Institutes of Health grants UL1 RR024153 and UL1TR000005. References 1. Izikson A, English JC III. Cutaneous sarcoidosis. In: Williams H, Bigby M, Diepgen T, Herxheimer A, Naldi L, Rzany B, eds. Evidence-Based Dermatology. London, England: Wiley-Blackwell; 2008:595-607 2. Badgwell C, Rosen T. Cutaneous sarcoidosis therapy updated. J Am Acad Dermatol. 2007;56(1):69-8317190623PubMedGoogle ScholarCrossref 3. Bachelez H, Senet P, Cadranel J, Kaoukhov A, Dubertret L. The use of tetracyclines for the treatment of sarcoidosis. Arch Dermatol. 2001;137(1):69-7311176663PubMedGoogle Scholar 4. Antonovich DD, Callen JP. Development of sarcoidosis in cosmetic tattoos. Arch Dermatol. 2005;141(7):869-87216027303PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Dermatology American Medical Association

Oral Minocycline in Treatment of Cutaneous Sarcoidosis

JAMA Dermatology , Volume 149 (6) – Jun 1, 2013

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Publisher
American Medical Association
Copyright
Copyright © 2013 American Medical Association. All Rights Reserved.
ISSN
2168-6068
eISSN
2168-6084
DOI
10.1001/jamadermatol.2013.2977
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Abstract

Currently, therapeutic techniques used to treat cutaneous sarcoidosis rely on limited data from evidenced-based research.1,2 Bachelez et al3 conducted a prospective study in which 10 of 12 patients showed improvement after minocycline therapy, and Antonovich and Callen4 reported the case of 1 woman who was successfully treated with doxycycline. On the basis of these encouraging reports, our clinic began to use minocycline, a commonly used anti-inflammatory acne therapy that does not require laboratory monitoring, as a first-line treatment for cutaneous sarcoidosis. The present retrospective study sought to evaluate our experience with minocycline treatment and to compare its effectiveness across sex and race. Methods This retrospective study was approved by our institutional review board. The primary data sources were paper and electronic medical records of patients with cutaneous sarcoidosis treated with minocycline at the University of Pittsburgh Department of Dermatology in the UPMC Falk Dermatology Clinic between 2005 and 2012. The data obtained from medical records included the patient's age, race, sex, extent of skin disease, systemic involvement, prior therapies, duration of minocycline use, and the outcome of this therapy. The outcomes were categorized into 3 groups based on the percentage of body surface area (BSA) that showed remission of lesions: complete remission indicated resolution across 100% of the affected BSA; partial remission indicated 50% BSA resolution; and no remission indicated 0% BSA resolution. Patients met inclusion criteria if they sought treatment for disfiguring, biopsy-proven cutaneous sarcoidosis lesions that were extensive enough to require oral therapy. The outcome of oral therapy was recorded after at least 2 months of use, unless adverse events caused premature discontinuation. In addition, these patients were required to undergo and adhere to the regimen of minocycline treatment as prescribed by a UPMC dermatologist (J.C.E.). Statistical analysis (significance, P < .05) included the 1-proportion z test to evaluate difference in response to therapy across ages, the Mann-Whitney U test with a null probability of 50% to determine if more patients responded to therapy than not, and the Fisher exact test to determine all other differences, such as differences in response across race and sex. Results Twenty-seven patients met the inclusion criteria. Twenty-five had moderately extensive lesions (maculopapular, nodular, or plaque lesions on the face, torso, and/or extremities), and 2 had severe ulcerative lesions (scalp); no patients had classic lupus pernio (infiltrative and/or indurated plaquelike lesions). The average age of the patients at time of diagnosis of cutaneous sarcoidosis was 43 years. There were 14 men and 13 women; 17 were black, and 10 were white. Seven patients experienced lesions on the skin only; 17 had pulmonary and skin involvement; and 1 had ocular, pulmonary, and skin involvement. Sinus, muscle, and parotid involvement occurred with skin disease individually once as well. At the time of presentation, 2 patients were undergoing steroid treatment for pulmonary sarcoidosis and had persistent cutaneous lesions prior to minocycline therapy, and they continued prednisone treatment to preserve lung function. Minocycline was prescribed as first-line treatment in 18 patients and as second-line treatment in the remaining 9 (for 8 of these 9 patients, hydroxychloroquine treatment had failed, and prednisone had failed for 1 with skin-only disease). Owing to the extent of granuloma load in the skin, topical and intralesional steroids were not used during oral treatment. The average length of time until the initial therapy was assessed was 4.1 months. Of 27 patients, 6 (22%) had complete remission; 14 (52%) had partial remission; and 7 (26%) had no remission. Of the 2 severe ulcerative cases, 1 achieved a partial remission and 1 no remission. In total, 20 of 27 (74%) patients showed response to the treatment, and the proportion of those who responded was significantly greater than those who did not respond (P = .02) (Figures 1 and Figure 2). There was no difference in the response of minocycline across age, race, or sex. Adverse events often included dizziness, nausea, and blue skin hyperpigmentation. Six patients experienced hyperpigmentation, limited in 4 of these cases to the site of the lesion. White patients were significantly more likely to experience an adverse event than black patients (P = .04), but there was no significant difference across sex. Discussion As a whole, this study is limited by its retrospective nature, but it appears that minocycline therapy is a promising option for treating moderate cutaneous sarcoidosis. In total, 20 of 27 patients responded to therapy (74%), and significantly more patients responded than those who did not respond. After reviewing the current literature, our clinic chooses to treat cutaneous sarcoidosis using a monotherapeutic ladder in which minocycline is prescribed as first-line therapy, followed by hydroxychloroquine, methotrexate, thalidomide, and biological agents. Randomized controlled trials are needed to further establish and compare the effectiveness of minocycline as well as all other treatments. Back to top Article Information Correspondence: Dr English, Department of Dermatology, University of Pittsburgh, Presbyterian South Tower, Ste 3880, Pittsburgh, PA 15213 (englishjc@upmc.edu). Accepted for Publication: November 22, 2012. Author Contributions: Dr English and Ms Steen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: English. Acquisition of data: Steen. Analysis and interpretation of data: Steen and English. Drafting of the manuscript: Steen and English. Critical revision of the manuscript for important intellectual content: English. Obtained funding: Steen. Administrative, technical, or material support: English. Study supervision: English. Conflict of Interest Disclosures: None reported. Funding/Support: Ms Steen received a stipend from the University of Pittsburgh Medical School, Dean's Summer Research Program, for her contribution. Role of the Sponsors: The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; or in the preparation, review, or approval of the manuscript. Additional Contributions: We are indebted to statisticians Dan Winger, MS, and Li Wang, MS, who are supported by National Institutes of Health grants UL1 RR024153 and UL1TR000005. References 1. Izikson A, English JC III. Cutaneous sarcoidosis. In: Williams H, Bigby M, Diepgen T, Herxheimer A, Naldi L, Rzany B, eds. Evidence-Based Dermatology. London, England: Wiley-Blackwell; 2008:595-607 2. Badgwell C, Rosen T. Cutaneous sarcoidosis therapy updated. J Am Acad Dermatol. 2007;56(1):69-8317190623PubMedGoogle ScholarCrossref 3. Bachelez H, Senet P, Cadranel J, Kaoukhov A, Dubertret L. The use of tetracyclines for the treatment of sarcoidosis. Arch Dermatol. 2001;137(1):69-7311176663PubMedGoogle Scholar 4. Antonovich DD, Callen JP. Development of sarcoidosis in cosmetic tattoos. Arch Dermatol. 2005;141(7):869-87216027303PubMedGoogle ScholarCrossref

Journal

JAMA DermatologyAmerican Medical Association

Published: Jun 1, 2013

Keywords: minocycline,cutaneous sarcoidosis

References