Acantholytic Pityriasis Rubra Pilaris Associated with Imiquimod 3.75% Application

Abstract

Imiquimod is an immunomodulator with both antitumor and antiviral properties. It is currently available in two cream formulations as Aldara (imiquimod 5%) and the newly approved Zyclara (imiquimod 3.75%). Imiquimod has been associated with localized erythema, crusting, and scaling at the site of application. However, more severe generalized skin eruptions including erythema multiforme, psoriasis, and hyperpigmentation have been described. The newly approved imiquimod 3.75% cream is a presumably safer alternative due to its lower concentration. This paper describes the development of generalized acantholytic pityriasis rubra pilaris after the treatment of an actinic keratosis on the forehead with imiquimod 3.75% cream.

Pityriasis rubra pilaris induced by topical use of imiquimod 5%

“…Four more cases of PRP induced by imiquimod with some features in common ( Table 1 ) have been reported. It is remarkable that all of them showed acantholysis in light microscopy, 2 , 3 , 4 , 5 while it has been described in approximately only 30% of PRP biopsies in previous studies. 1 Imiquimod has been previously reported to be involved in developing acantholytic alterations with negative direct immunofluorescence studies.…”

“…It has been proposed that acantholysis could be a result of the increased levels of proinflammatory cytokines induced by imiquimod. 4 Also, it should be pointed out that most of the patients presented systemic symptoms. 5 Most of them showed an excellent response to conventional treatments, assuming imiquimod-induced PRP is likely to have a favorable prognosis.…”

“… 5 Most of them showed an excellent response to conventional treatments, assuming imiquimod-induced PRP is likely to have a favorable prognosis. 2 , 3 , 4 , 5 …”

Rare Cutaneous Side Effects of Imiquimod: A Review on Its Mechanisms, Diagnosis, and Management

“…Patients manifested with the typical PRP rash characterized by generalized erythematous-orange papulosquamous lesions, usually with unaffected skin and palmar and/or plantar keratoderma. The pathological examination of four patients showed the characteristics of classic PRP, including hyperparakeratosis alternated with orthokeratosis in both the horizontal and vertical directions, psoriasiform epidermal hyperplasia, and superficial perivascular lymphocytic infiltrates [ 96 – 99 ]. Of note, intraepidermal acantholysis was found in all patients and was thought to be a pathological indicator that differentiates PRP from psoriasis [ 100 ].…”

Plasmacytoid Dendritic Cells in Pityriasis Rubra Pilaris

“…Second, PRP has been associated with several inflammatory disorders such as LE, lichen planus, alopecia areata and vitiligo 5 6 , in which evidence suggests significant pDC role in their underlying pathogenesis 1 . Third, imiquimod, an immunomodulator known to be a potent pDC activator through its effect on TLR-7, has been reported to induce or exacerbate PRP 7 . Fourth, PRP relation to psoriasis may raise the possibility of similar underlying pathogenesis.…”