Therapeutic Options for the Treatment of Darier’s Disease: A Comprehensive Review of the Literature

Darier’s disease (also known as keratosis follicularis or dyskeratosis follicularis) is an autosomal dominant inherited disorder which manifests as hyperkeratotic greasy papules in the first or second decade of life. Aside from symptom management and behavioral modifications to avoid triggers, there are currently no validated treatments for Darier’s disease (DD). However, a variety of treatments have been proposed in the literature including retinoids, steroids, vitamin D analogs, photodynamic therapy, and surgical excision. The purpose of this review article is to identify therapeutic options for treating DD and to outline the evidence underlying these interventions. A search was conducted in Medline for English language articles from inception to July 4, 2020. Our search identified a total of 474 nonduplicate studies, which were screened by title and abstract. Of these, 155 full text articles were screened against inclusion/exclusion criteria, and 113 studies were included in our review. We identified Grade B evidence for the following treatments of DD: oral acitretin, oral isotretinoin, systemic Vitamin A, topical tretinoin, topical isotretinoin, topical adapalene gel, topical 5-flououracil, topical calciptriol and tacalcitol (with sunscreen), grenz ray radiation, and x-ray radiation. All other evidence for treatments of DD consisted of case reports or case series, which is considered grade C evidence. Considering the quality and quantity of evidence, clinicians may consider initiating a trial of select topical or oral retinoids first in patients with localized or generalized DD, respectively.

Pembrolizumab-induced follicular eruption and response to isotretinoin

Background: Pembrolizumab is a monoclonal antibody targeting PD-1. Folliculitis secondary to pembrolizumab has rarely been reported in the treatment of malignant melanoma. Case: A 49-year-old with a history of mild lower limb folliculitis developed metastatic malignant melanoma, and immunotherapy with pembrolizumab was initiated. Following 19 doses of pembrolizumab, a folliculocentric pustular eruption developed on the lower legs. Biopsy was consistent with folliculitis. Treatment with topical corticosteroids, high-dose prednisolone, lymecycline, clarithromycin, trimethoprim and clindamycin was unsuccessful. Pembrolizumab was stopped after 22 cycles, but the folliculitis persisted. Oral isotretinoin was required for disease control. Discussion: Drug-induced follicular eruptions have rarely been described with anti PD-1 therapy. Isotretinoin may be required to achieve remission.

EFFECT OF ISOTRETINOIN ORAL ON ACNE VULGARIS (A REVIEW OF SYSTEMATIC AND METAANALYSIS STUDIES ON ALANINE AMINOTRANSFERASE LEVELS, ASPARTATE AMINOTRANSFERASE, LIPID PROFILE, HOMEOSTATIC MODEL ASSESSMENT FOR INSULIN RESISTANCE, COMPLETE BLOOD COUNT, FASTING BLOOD GLUCOSE)

Background: Oral isotretinoin is known to has a large role in the treatment of acne vulgaris, but unfortunately has signicant side effects. Observation of laboratory changes during oral isotretinoin intake is important in order to ensure safety. Medline Pubmed, Scopus, Methods: ProQuest, Cochrane library, ClinicalTrials.gov, the reference list, conference proceedings, researchers in eld of eligible studies were searched. Result: 17 studies (1573 patients) were included into meta-analysis. Mean difference values (95% CI) increase for triglycerides 25,81 mg/dL, total cholesterol 16,11 mg/dl, Low-Density Lipoprotein cholesterol (LDL) 15,11 mg/dL, Aspartate Aminotransferase (AST) 3,08 U/L, Alanine Aminotransferase (ALT) 1.61 U/L, hemoglobin 0,18 g/dl, fasting glucose 0,55mg/dL. High-Density Lipoprotein cholesterol (HDL) decrease 3,09 3 3 mg/dl, White Blood Cell (WBC) decrease 0.23 x10 /μL, neutrophils decrease 0,26 x10 /μL. The qualitative analysis found that HOMA IR had increase in mean value. Longer laboratory evaluation time, can reduce the cost Conclusion: of treatment and discomfort of patients in acne therapy. Acne patient with abnormal baseline values of laboratory parameters should avoid taking oral isotretinoin

Rapid-onset oral isotretinoin-induced acne fulminans without systemic symptoms in a male adolescent

Isotretinoin-induced acne fulminans without systemic symptoms (IIAF-WOSS) is an uncommon clinical variant of acne, not exhibiting systemic symptoms but with potentially severe skin lesions. Some authors believe that its occurrence is dose-dependent. Herein, we present the case of a sixteen-year-old boy with IIAF-WOSS, which developed two weeks after starting treatment with isotretinoin 0.6 mg/kg/day. The patient was successfully treated with a systemic steroid. IIAF-WOSS may cause significant disfiguring scarring, thus the physician needs to be aware of this condition, even early with low doses of isotretinoin.

Analysis of the effects of isotretinoin on the premature epiphyseal closure in pediatric populations: a literature review

Context Oral isotretinoin, a systemic retinoid and a vitamin A derivative, has been widely utilized to treat acne in both adult and pediatric populations. Additionally, systemic retinoids have also been utilized to treat neuroblastoma in pediatric patients. Common side effects associated with oral isotretinoin include dry eyes, dry mouth, elevated liver enzymes, depression, and arthralgia. Less common side effects of isotretinoin include hearing loss, pseudotumor cerebri, anaphylaxis, and skeletal abnormalities including growth arrest. The U.S. Food and Drug Administration (FDA) has received reports of premature epiphyseal closure in patients treated with isotretinoin retinoids, which are commonly prescribed by primary care providers as a treatment for acne. It is important to raise awareness of the potential side effects of isotretinoin to enable informed treatment decisions before beginning an isotretinoin regimen. Objectives This chapter aims to elucidate that isotretinoin, given at various doses and durations, has been associated with growth plate abnormalities, which can lead to premature epiphyseal closure. Methods Two databases were utilized for the literature review and were conducted at different time periods. Our literature review was conducted between December 2020 and June 2021, utilizing PubMed with the following search terms: “isotretinoin” and “isotretinoin and premature epiphyseal closure.” In April 2021, we searched the FDA’s “Drug Data and Adverse Event Report System” utilizing the terms “isotretinoin” and “epiphysis premature fusion.” We included in our query reports of patients worldwide under 18 years of age with premature epiphyseal closure or growth plate damage secondary to isotretinoin. Studies published in English between 1980 and 2020 were also included, as well as background sources relating to an isotretinoin profile with side effects and dosing. We narrowed our search to exclude patients with a history of growth plate disorders due to trauma, malignancy, or other pathological processes, as well as patients with growth arrest due to endocrine factors. Growth plate abnormalities associated with retinoid derivatives other than isotretinoin were also excluded. Results A total of 28 items were selected for our literature review including: one FDA drug label, one FDA website of adverse reactions, 19 supplemental articles, six case reports, and one case series of premature epiphyseal closure secondary to isotretinoin. The FDA received 41 reports worldwide of premature epiphyseal closure related to isotretinoin in patients under 18 years of age. Additionally, premature epiphyseal closure and growth plate abnormalities occurred in nine patients with various durations and doses of isotretinoin ranging from the lowest dose of 0.5 mg/kg/day for a few months to 3.5 mg/kg/day for years. Conclusions Isotretinoin-induced premature epiphyseal closure and growth plate deformities seem to be linked to higher doses of isotretinoin for the duration of months to years. There have been reported cases of premature epiphyseal closure in individuals receiving therapeutic doses of isotretinoin for acne treatment, which are much lower compared to the high doses utilized for neuroblastoma. Based on this study, isotretinoin appears to impact the growth plates of proximal tibia and distal femur. A cause-and-effect relationship between isotretinoin and premature epiphyseal closure cannot be concluded.

Response of Bowenoid Papulosis to Combination Treatment of Oral Isotretinoin and Topical 1% 5-Fluorouracil

Bowenoid papulosis (BP) is a rare benign disease which can have spontaneous regression but can sometimes turn malignant.1 It is characterised by solitary or multiple verruca-like papules or plaques usually present on genitalia having a close histological resemblance to Bowen's disease and a predilection for sexually active young adults.2 It affects all races equally and has almost same male to female ratio. There are an estimated 5 cases per 100000 women. The exact prevalence is unknown.3 We hereby present a case report of bowenoid papulosis. Bowenoid papulosis is an uncommon form of intraepithelial neoplasia. It is caused by human papilloma virus (HPV) infection and clinically resembles viral wart while histologically resembling in situ squamous cell carcinoma (SCC). We hereby report a case of an adult male with multiple verrucous lesions on penis and scrotum. The histopathology showed features of bowenoid papulosis. The patient was treated with oral isotretinoin and topical 1 % 5 - fluorouracil following which the lesions reduced remarkably in the span of 3 weeks.