Azathioprine for Refractory Cutaneous Sarcoidosis: A Case Report

Dear Editor, Sarcoidosis is a chronic disorder with noncaseating granulomas in various organs, affecting the skin in about 25% of cases.[1] Here, we report a first case of steroid-resistant cutaneous sarcoidosis successfully treated with azathioprine. A 76-year-old man with heart failure, diabetes, and hyperlipidemia developed a facial, trunk, and limb rash. Seven months prior to presentation at our department, he developed a red papule on his left upper limb, which subsequently spread. Four months before his initial visit, he consulted a dermatologist and underwent a skin biopsy, resulting in a diagnosis of sarcoidosis. He was initiated on oral minocycline (200 mg/day). After three months of therapy, his symptoms failed to improve, and he was referred to our department for further evaluation. On referral to our department, the patient had multiple red papules, nodules, and plaques on the scalp, face, trunk, and limbs [Figure 1a and b]. Laboratory test showed mild elevations in aspartate aminotransferase, lactate dehydrogenase, creatinine, hemoglobin A1c, and C-reactive protein, and revealed elevated soluble IL-2 receptor (847 U/mL) and lysozyme (19.0 μg/mL). A second biopsy of a back lesion [Figure 1c] revealed dense noncaseating granulomas with epithelioid and Langhans giant cells [Figure 1d], negative Ziehl–Neelsen stain. Systemic tests showed no sarcoidosis in other organs. Ophthalmological and neurological exams were unremarkable. Based on these findings, a diagnosis of cutaneous sarcoidosis was made.Figure 1: (a and b) Multiple red papules, nodules, and plaques were found on the head, face, trunk, and limbs at our initial examination. (c) The site of rebiopsy on the back at our initial examination. (d) Histopathological analysis revealed numerous noncaseating epithelioid cell granulomas and Langhans-type giant cells in the dermis (Hematoxylin and Eosin staining, original magnification × 100). (e) At relapse (during oral administration of PSL 12.5 mg), multiple red papules appeared on the trunk and limbs. Clinical presentation before the initiation of azathioprine therapy. (f) These papules resolved six months after the initiation of azathioprineInitial treatment with oral roxithromycin (300 mg/day), tranilast (300 mg/day), and topical clobetasol propionate was ineffective. Four weeks after the initial treatment, oral prednisolone (PSL) at 20 mg/day and topical tacrolimus were then initiated. The lesions improved, and lysozyme and soluble IL-2 receptor levels normalized. However, lesions recurred whenever the PSL dose was tapered below 10 mg/day. At relapse, multiple red papules appeared on the trunk and limbs [Figure 1e]. Subsequent laboratory investigations revealed normal soluble IL-2 receptor levels, but an elevation of lysozyme levels, again. Histopathological features remained consistent with the previous biopsies, confirming recurrent cutaneous sarcoidosis. Methotrexate is frequently used as a steroid-sparing agent in cutaneous sarcoidosis. However, due to the patient’s renal dysfunction, methotrexate was contraindicated. Instead, oral azathioprine (100 mg/day) was started, leading to significant improvement and normalized lysozyme levels, allowing PSL tapering to 5 mg/day without recurrence [Figure 1e]. The patient remains stable with no side effects. Studies show azathioprine is effective for sarcoidosis involving the stomach, lungs, liver, and nerves,[1-5] but limited reports exist for isolated skin involvement. Müller-Quernheim et al.[3] reported the addition of azathioprine not only improved respiratory symptoms but also led to remission or improvement of skin symptoms in all five patients with cutaneous involvement, suggesting that azathioprine could be effective for cutaneous manifestations of sarcoidosis. Vorselaars et al.[5] conducted a comparative study suggesting that azathioprine may be as effective as methotrexate in sarcoidosis. Although methotrexate is often preferred, azathioprine is a useful alternative when methotrexate is not suitable. In conclusion, this case highlights that azathioprine could be a steroid-sparing option for cutaneous sarcoidosis, especially when other treatments fail or are contraindicated, but more research is needed to confirm this. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the. form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.