Involution of classic Kaposi sarcoma lesions under acitretin treatment Kaposi sarcoma treated with acitretin

Acitretin, indicated for generalized pustular psoriasis, was effective in concomitant classic Kaposi sarcoma.


| CASE PRESENTATION
A 60-year-old woman without any past medical history was admitted to our department for a progressively developing pustulosis during the last 15 days. Physical examination showed high-grade fever, malaise, and a generalized eruption with a painful erythema and coalescent 2-3 mm pustules. Blood count revealed neutrophilia (30 000 elements/mm 3 ). C-reactive protein was elevated with a value of 173 mg/L. The procalcitonin test was negative. Histology showed spongiform pustules in the stratum corneum surrounded by parakeratosis and psoriasiform hyperplasia. The diagnosis of GPP was established. The patient was put on acitretin 30 mg daily (0.4 mg/kg) with an excellent improvement of both general and skin conditions. After 15 days of hospitalization, a few, red-brown to violaceous, infiltrated papules and F I G U R E 1 Angiomatous infiltrated papules and plaques on the left arm plaques appeared on her both forearms ( Figure 1). There was no mucosal involvement. A skin biopsy revealed the presence of newly formed cleft-like vascular spaces and diffuses dermal spindle cell neoplastic proliferation (Figure 2A,B). Immunohistochemistry showed the presence of HHV-8 confirming the diagnosis of KS ( Figure 2C). Tests for HIV were negative. Three months later, while the patient was only under acitretin treatment, we noticed the complete regression of angiomatous plaques of KS ( Figure 3).

| DISCUSSION
In our patient, although without major evidence, acitretin appears to be effective in a newly established KS.
Previous reports highlight the safeness of retinoid therapy in KS, mainly in the AIDS-related variant. [3][4][5][6] Retinoids have been also described as an effective treatment of classic KS.
Florek reported stabilization of KS with 35 mg oral acitretin daily in a 77-year-old man while tretinoin, imiquimod, and alitretinoin 0.1% gel twice daily did not result in significant improvement. 1 Morganroth had treated a classic KS with topical 0.1% alitretinoin gel in an 83-year-old woman. Remission of almost all the lesions was obtained after a few months with only mild irritative dermatitis. 7 Recently, topical alitretinoin (9-cis-retinoic acid) has been approved by the US Food and Drug Administration and European consensus-based interdisciplinary guideline as a treatment for the localized KS. 2,8 The Table 1 summarizes the reports in which the efficacy of retinoids in KS had been assessed.
Pharmacologically, it has been proved that retinoic acid and its synthetic analogs inhibit the proliferation of KS cells by down-regulation of IL-6 (an autocrine growth factor for KS cells). Their effects are exerted through two families of nuclear receptors, retinoic acid receptors, (RARs) and retinoid X receptors (RXRs), which belong to the superfamily of steroid-thyroid-vitamin D3 hormone receptors. These receptors antagonize the enhancer action of NF-IL6, a basic zipper family transcription factor and, therefore, inhibit IL-6 promoter action. 9 Corbeil has demonstrated that acitretin at low concentrations was sufficient to inhibit the growth of rapidly dividing early passage KS cells. Higher concentrations induced KS cells apoptosis but they are pharmacologically unachievable with oral systemic therapy. 10 Retinoic acid analogs also inhibit HHV8 replication. 11 The coexistence of psoriasis and KS is rarely reported in the literature. 9 In a large study conducted by Brambilla et al, of the 1407 patients followed for KS, 37 patients were identified with psoriasis. All of these patients had psoriasis vulgaris, and none of them had GPP. The average time latency time from psoriasis onset to KS onset was 18.8 years. 12 An intense cytokine dysregulation during GPP may explain the acceleration of the development of HHV-8 infection into KS in our case.
In summary, we would like to highlight that acitretin, prescribed for GPP in our patient, was an active antitumor drug for early classic KS with complete recovery within a few weeks. Our observation is also particular given the short latency time from GPP to KS onset. The efficacy of acitretin is interesting to assess in KS.

CONFLICT OF INTEREST
None declared.

AUTHORS' CONTRIBUTION
ND and AS: managed the patient and drafted the manuscript. IC: analyzed all histopathology specimens. MBS: referred the patient. MM: managed the patient and revised the manuscript. All authors have approved the final manuscript.

ETHICAL APPROVAL
Appropriate consent has been obtained, prior to submission, for the publication of images and data.

DATA AVAILABILITY STATEMENT
Data sharing was not applicable to this article as no datasets were generated or analyzed during the current study.