Sir,

Sebaceous hyperplasia (SH) is a benign pathology, generally affecting middle-aged individuals [1]. Azathioprine is one of the immunosuppressants initially indicated for patients with leukemia and organ transplant recipients. Over time, it has been shown to modulate the immune response long-term, which has been extrapolated to alter the therapeutic evolution of numerous autoimmune component pathologies, particularly ulcerative colitis, where it has found its place in the therapeutic arsenal. Numerous cutaneous side effects of azathioprine have been described in the literature, notably the occurrence of neutrophilic dermatoses, erythema nodosum, and pustular exanthematic eruption. However, azathioprine may more rarely cause eruptive sebaceous hyperplasia [2].

This was a 56-year-old patient followed in gastrology for hemorrhagic rectocolitis, under azathioprine, who consulted for facial lesions appearing several weeks after the beginning of treatment. A dermatological examination revealed a patient with phototype 4 with multiple normal skin-colored infracentimetric papules umbilicated at the center of the forehead (Fig. 1a). Dermoscopy showed small, yellowish-white clusters and peripheral linear vessels not reaching the center of the lesion, giving a crown-like appearance (Fig. 1b). The diagnosis of eruptive sebaceous hyperplasia was retained.

Figure 1: (a) Clinical image of the papulous eruption on the face during azathioprine treatment. (b) Dermoscopic image showing yellowish-white clusters and crown-like vascularization.

Moreover, the patient had a recent colonoscopy coming back without particularities, notably no tumor or suspicion of a degenerative zone, and did not present any family history of genetic cancer, particularly colorectal in the context of Muir–Torre syndrome.

A low-dose isotretinoin treatment was proposed yet refused by the patient.

SH is a benign affection due to the proliferation of sebaceous glands, usually affecting middle-aged male individuals. SH is most often the result of aging, whether chronological or extrinsic, notably photo-aging, and may also fit in the context of a genetic syndrome, particularly Muir–Torre syndrome [3].

Clinically, this condition presents as umbilicated, yellowish or normal skin-colored papules, predominantly located on the forehead and the medio-facial region. Histologically, SHs are characterized by three or four enlarged sebaceous lobules, which are located more superficially in the dermis when compared to their normal state.

Case reports of eruptive sebaceous hyperplasia following immunosuppressive treatment have increased in recent years, with the first cases reported secondary to cyclosporine in renal transplant recipients with a 30% occurrence rate in these subjects [4]. Other case reports have been signaled following the use of other often combined immunosuppressive treatments such as prednisone, tacrolimus, mycophenolate mofetil, and azathioprine [5–7].

Azathioprine is among the well-established treatments for inflammatory bowel diseases, particularly with the advent of effective immunosuppression, yet no data has been reported in the literature suggesting that azathioprine alone could be a causal factor of eruptive SH.

The pathophysiology of this eruption may be explained by the greater lipophilicity of the product and, therefore, its accumulation in the sebaceous glands.

Although only one case of eruptive SH has been reported in a patient with Crohn’s disease [1], we report a new case in a patient followed for chronic hemorrhagic rectocolitis.

To our knowledge, this was the first reported case of eruptive sebaceous hyperplasia secondary to the use of azathioprine alone in a patient with hemorrhagic rectocolitis. This should raise awareness of the side effect and the importance of informing patients about this potential side effect when prescribing the medication.

REFERENCES

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2.  Bidinger JJ, Sky K, Battafarano DF, Henning JS. The cutaneous and systemic manifestations of azathioprine hypersensitivity syndrome. J Am Acad Dermatol. 2011;651:184-91.

3.  Lazar AJ, Lyle S, Calonje E. Sebaceous neoplasia and Torre–Muir syndrome. Curr Diagn Pathol. 2007;134:301-19.

4.  Levandoski KA, Girardi NA, Loss MJ. Eruptive sebaceous hyperplasia as a side effect of oral tacrolimus in a renal transplant recipient. Dermatol Online J. 2017;235:13030/qt7x0125gz.

5.  Jung HY, Kim M, Cho BK, Park HJ. A case of cyclosporine-induced sebaceous hyperplasia in a renal transplant patient successfully treated with isotretinoin. Ann Dermatol. 2016;282:271-2.

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