Mutations in SDR9C7 gene encoding an enzyme for vitamin A metabolism underlie autosomal recessive congenital ichthyosis.

Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of hereditary skin disorder characterized by an aberrant cornification of the epidermis. ARCI is classified into a total of 11 subtypes (ARCI1-ARCI11) based on their causative genes or loci. Of these, the causative gene for only ARCI7 has not been identified, while it was previously mapped on chromosome 12p11.2-q13.1. In this study, we performed genetic analyses for three Lebanese families with ARCI, and successfully determined the linkage interval to 9.47 Mb region on chromosome 12q13.13-q14.1, which was unexpectedly outside of the ARCI7 locus. Whole-exome sequencing and the subsequent Sanger sequencing led to the identification of missense mutations in short chain dehydrogenase/reductase family 9C, member 7 (SDR9C7) gene on chromosome 12q13.3, i.e. two families shared an identical homozygous mutation c.599T > C (p.Ile200Thr) and one family had another homozygous mutation c.214C > T (p.Arg72Trp). In cultured cells, expression of both the mutant SDR9C7 proteins was markedly reduced as compared to wild-type protein, suggesting that the mutations severely affected a stability of the protein. In normal human skin, the SDR9C7 was abundantly expressed in granular and cornified layers of the epidermis. By contrast, in a patient's skin, its expression in the cornified layer was significantly decreased. It has previously been reported that SDR9C7 is an enzyme to convert retinal into retinol. Therefore, our study not only adds a new gene responsible for ARCI, but also further suggests a potential role of vitamin A metabolism in terminal differentiation of the epidermis in humans.

Successful treatment of hydroquinone-resistant melasma using topical methimazole.

Melasma is an acquired hyperpigmentation skin disorder in sun-exposed areas. It occurs almost exclusively over the face, and is most commonly seen in women. Several depigmenting agents have been used for the treatment of melasma among which hydroquinone has been the most widely used due to its efficacy and safety in short-term use. However, hydroquinone is recently reported to be a cytotoxic and mutagenic compound in mammalian cells and is thus banned in several countries. Hydroquinone ban has caused investigators to search for alternative depigmenting agents for the treatment of melasma in recent years. Methimazole is an antithyroid agent orally used in humans since several decades and has been shown that when applied topically, it inhibits melanin synthesis and causes skin depigmentation in lab animals as well as human subjects. Herein, we report two hydroquinone-resistant melasma patients who were successfully treated with methimazole cream. Application of 5% methimazole cream once daily resulted in significant improvement of melasma in both patients after 8 weeks. The efficacy of methimazole for melasma treatment as well as its advantages over other known depigmenting compounds (non-mutagenicity, non-cytotoxicity and high tolerability profile) suggests that topical methimazole should be added to the armamentarium of anti-melasma treatment.

Genitogluteal porokeratosis: 10 years to make the diagnosis!

Genitogluteal porokeratosis, a relatively rare presentation of porokeratosis of Mibelli, often manifests in an atypical way due to its verrucous appearance that may obscure the characteristic annular keratotic rim. For this reason, misdiagnosis as other common papulosquamous diseases is not uncommon. We report a 44-year-old man with a 10-year-history of slowly progressive pruritic psoriasiform/lichenified plaques over the buttocks. Despite multiple skin biopsies, the lesions were misdiagnosed as psoriasis, lichen simplex chronicus, pityriasis rubra pilaris, and mycosis fungoides, until the last biopsy revealed findings characteristic of porokeratosis. Dermatologists and dermatopathologists should be aware of this rare and unique variant of porokeratosis, which, in addition to the atypical clinical presentation and the occasional misleading histology, may portend a better prognosis in terms of malignant degeneration.

Localized involutional lipoatrophy with epidermal and dermal changes.

Localized involutional lipoatrophy (LIL) was first described in 1986 as a distinctive idiopathic form of localized lipoatrophy characterized by loss of adipose tissue without antecedent inflammation. Clinically, LIL usually presents as a solitary, asymptomatic, well-demarcated, atrophic depression and often involves areas of antecedent intramuscular or intra-articular injections. Histologically, changes in the subcutaneous fat in LIL resemble fetal adipose tissue. Only rarely has there been any description of epidermal or dermal changes occurring with LIL. We describe two cases of LIL with overlying hypopigmentation and atrophy, and with morphea-like changes on histology. Recognition of these changes may have clinical and diagnostic implications.

Use of Topical Glycolic Acid Plus a Lovastatin-Cholesterol Combination Cream for the Treatment of Autosomal Recessive Congenital Ichthyoses.

Importance: Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders caused by defects in signaling pathways involved in epidermal proliferation and differentiation, leading to a wide range of skin manifestations. Therapeutic options are limited and often unsatisfactory. Topical cholesterol and statin as a combined formulation has proven successful in the treatment of patients with CHILD syndrome (congenital hemidysplasia ichthyosis and limb defects). Objective: To assess change in disease severity score after a 3-month therapeutic regimen consisting of a glycolic acid, 10% to 20%, cream and a combination cream of lovastatin, 2%, with cholesterol, 2%, in the treatment of ARCI. Design, Setting, and Participants: This case series of 15 patients with ARCI was conducted at the American University of Beirut, a referral center in the Middle East region for genodermatoses, between May 2017 and January 2018. No age groups were excluded; all patients were from the Middle East area; and all were initially not responsive to treatment with hydrating creams in combination with urea creams, 30% to 40%, or glycolic acid, 10% to 20%. Excluded were patients who had been taking systemic retinoids within 3 months before the start of the study. Interventions: A 3-month therapeutic regimen of glycolic acid, 10% to 20%, cream and a combination of lovastatin, 2%, with cholesterol, 2%, cream. Main Outcomes and Measures: Percentage change in disease severity scores following 2 and 3 months of study treatment. Results: Of the 15 patients included in the study, 10 were male (mean age, 11.2 years; age range, 2-38 years). The average percentage reduction in the disease severity score was 33.7% at 2 months (from 60.8 to 40.2) and 57.5% at 3 months (from 60.8 to 21.9). Adverse effects were mild and consisted mainly of irritation and burning. Conclusions and Relevance: These findings suggest a benefit from a treatment regimen consisting of glycolic acid, 10% to 20%, and a combination of lovastatin, 2%, with cholesterol, 2%, in the treatment of ARCI. This combination of creams might also prove to be beneficial in other types of ichthyoses and other dermatological diseases with a defective skin barrier.

Frontal fibrosing alopecia presenting with components of Piccardi-Lassueur-Graham-Little syndrome.

Frontal fibrosing alopecia (FFA), a cicatricial alopecia of the frontoparietal hairline affecting mainly postmenopausal women, is commonly associated with nonscarring alopecia of the eyebrows. This association has led some authors to relate it to Piccardi-Lassueur-Graham-Little syndrome (PLGLS), which is characterized by the triad of multifocal scalp cicatricial alopecia, nonscarring alopecia of the axillae and/or groin, and keratotic follicular papules. This is in spite of the absence of the follicular keratotic papules typical of PLGLS, and the different patterns of the cicatricial alopecias. We report a 37-year-old premenopausal woman with FFA associated with nonscarring alopecia of the eyebrows and axillae and follicular lichen planus-like lesions of the face. This case illustrates that FFA and PLGLS may share characteristics that, in addition to the overlap between FFA and PLGLS reported in the literature, would suggest they may be phenotypically related.

Acral pseudolymphomatous angiokeratoma of children in an elderly man: report of a case and review of the literature.

Acral pseudolymphomatous angiokeratoma of children (APACHE) is clinically characterized by angiomatous papules that preferentially affect acral areas of children. It is currently believed to be a variant of pseudolymphoma rather than angiokeratoma. Histopathologically, a mixed inflammatory cell infiltrate comprising B- and T-lymphocytes and a proliferation of thick-walled blood vessels are the hallmark. In the literature, although more adult cases are being described, the clinical, epidemiologic and histopathologic data of this presentation is scant. We report a 76-year-old man who presented with a 5-year history of progressively increasing asymptomatic dusky dome-shaped papules and plaques on his upper and lower extremities. Histology was consistent with APACHE. After reviewing all the adult cases in the literature and comparing them to the classical variant in children, we found no significant difference warranting separating these two variants. We prefer the designation "papular angiolymphoid hyperplasia" to APACHE as it encompasses all the childhood and adult cases involving acral and nonacral sites and highlights the histological and sometimes clinical similarities this entity shares with angiolymphoid hyperplasia with eosinophilia.

Adrenergic urticaria in a patient with anti-double-stranded DNA antibodies.

Adrenergic urticaria, a rare but distinct subtype of the physical urticarias, is characterized by wheals that are typically surrounded by a white halo of vasoconstriction, and by a positive response to intradermal adrenaline and noradrenaline injections. The pathogenesis of adrenergic urticaria is unknown. We report here a case of a 64-year-old woman with adrenergic urticaria who was found to have high levels of anti-double-stranded DNA antibodies without features of systemic lupus erythematosus. This is the first report associating adrenergic urticaria with anti-double-stranded DNA antibodies. The significance of this association is unknown.

Red scrotum syndrome: successful treatment with oral doxycycline.

BACKGROUND: Red scrotum syndrome often follows the prolonged application of topical corticosteroids to the scrotal area and is characterized by persistent erythema of the scrotum associated with severe itching, hyperalgesia, and a burning sensation. Several topical and systemic treatments have been used in the past without success. OBJECTIVE: To assess the efficacy of oral doxycycline, in addition to corticosteroid abstinence, in the treatment of red scrotum syndrome. METHODS: In a retrospective chart review, seven patients with red scrotum syndrome, who presented between 2004 and 2007 to the outpatient clinic at the American University of Beirut Medical Center, were identified as having been treated with oral doxycycline and steroid abstinence. RESULTS: All patients reported significant improvement (between 50%and 80%) of their symptoms within 2 weeks of starting doxycycline and had marked improvement of the erythema and complete resolution of symptoms in a period ranging from 2 to 3 months. CONCLUSION: We suggest that doxycycline may be effective in the treatment of red scrotum syndrome.