Psoriasis following isotretinoin therapy: Paradoxical effect or a Koebner phenomenon?

Dear Editor, Isotretinoin is a synthetic retinol analog that is effective in the treatment of recalcitrant, nodulocystic acne. Mucocutaneous adverse effects of isotretinoin include cheilitis, facial xerosis, rashes, pruritus, eczema, conjunctivitis, and dermatitis.[1] A 26-year-old man with a medical history of acne vulgaris was treated with isotretinoin (0.5 mg/kg/day). One month after introducing isotretinoin, the patient presented to the dermatology department with erythematosquamous lesions on the trunk. Physical examination showed multiple, well-circumscribed and erythematous plaques of various sizes on his lower back. The eruption was localized mainly on old burn scars [Figure 1a]. His mucous membranes and nails were not involved. All other physical examinations were normal. The patient had no personal or family history of psoriasis. He had a history of burns 2 years ago. Burns sequelae were localized mainly on the lower back. The laboratory tests were normal, including liver and kidney tests and serum concentrations of C3 and C4. Testing for antinuclear antibodies and viral hepatitis was negative.Figure 1: (a) Multiple, circular, psoriasiform plaques present on the lower back. (b) Psoriasiform hyperplasia with diminution of the granular cell layer. There was a mild pericapillary mononuclear inflammatory infiltrate and dilated dermal tortuous capillaries.The histopathological analysis showed psoriasiform hyperplasia with a diminished granular cell layer. There was a mild pericapillary mononuclear inflammatory infiltrate and dilated dermal tortuous capillaries [Figure 1b]. All external factors including viral or bacterial infections, neoplasia, alcohol consumption, and smoking were ruled out. The list of differential diagnoses for psoriasis is extensive and includes infectious, inflammatory, and neoplastic processes that mimic its papulosquamous presentation. Atopic dermatitis is distinguished by the absence of clear demarcation from uninvolved skin, important pruritus, and predilection for flexural areas. Lichen simplex chronicus is located in areas of the skin that are accessible to scratching. The most common areas are on self-accessible areas of the body, such as the head, scalp, hands, arms, neck, and genitals. Our patient denied the presence of pruritus. Other skin diseases that may also be considered are subacute cutaneous lupus erythematosus, lichen planus, nummular eczema, and cutaneous T-cell lymphoma. The skin biopsy of our patient excludes many of these differential diagnoses. Therefore, drug-induced psoriasis was suspected, and isotretinoin treatment was withdrawn. The evolution was favorable, and the patient improved with topical corticosteroids within 3 weeks after withdrawal of isotretinoin. During a 20-month follow-up period, our patient did not experience any more episodes of cutaneous eruption. The temporal relationship between isotretinoin administration and our patient’s development of psoriasis, combined with the resolution of the skin lesions within several days of withdrawal of the drug, was consistent with the pathogenic role of isotretinoin. No cases of isotretinoin-induced psoriasis have been reported in PUBMED. The lesions in our patient may theoretically be explained by a Koebner phenomenon. Koebner’s phenomenon was initially reported as the emergence of psoriatic lesions after skin trauma in the uninvolved skin of psoriatic patients. Recently, the definition of Koebner phenomenon has been extended even further to describe patients who did not have preexisting dermatosis before trauma or in whom the response did not reoccur on additional trauma. The exact pathogenesis of the Koebner phenomenon is unknown. Different triggers including cutaneous trauma, chronic pressure on the skin, solar exposure, hot water burn, and drugs are reported to induce the development of psoriasiform eruptions through activation of the Koebner phenomenon.[2] Drugs may exacerbate psoriasis and induce Koebnerization by chemical interaction with genetically susceptible epidermal cells.[2,3] Skin fragility is a well-known complication of isotretinoin therapy.[4] Skin fragility could theoretically induce Koebnerization. The molecular basis of the retinoids’ clinical effectiveness in the treatment of psoriasis is still ambiguous. High doses of isotretinoin (1.5–2 mg/kg/day) induced a significant improvement of patients with generalized pustular psoriasis in small studies.[5] Another facet of the retinoids’ action on skin is their hyperproliferative effects.[6] The hyperproliferative effect of isotretinoin on the epidermis may explain the paradoxical effect of this drug. With our unique case, it is not definitively concluded that this case is classified neither as drug-induced psoriasis nor a Koebner phenomenon. Additional studies on similar reports are warranted not only to precisely interpret the clinical significance of this paradoxical reaction but also to further explore and clarify these hypotheses. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent form. In the form the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Data availability statement The data supporting the findings of this study are available from the corresponding author upon reasonable request. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.