Enzymes can usually be unambiguously assigned to one of seven classes specifying the basic chemistry of their catalyzed reactions. Less frequently, two or more reaction classes are catalyzed by a single enzyme within one active site. Two examples are an isomerohydrolase and an isomero-oxygenase that catalyze isomerization-coupled reactions crucial for production of vision-supporting 11-cis-retinoids. In these enzymes, isomerization is obligately paired and mechanistically intertwined with a second reaction class. A handful of other enzymes carrying out similarly coupled isomerization reactions have been described, some of which have been subjected to detailed structure-function analyses. Herein we review these rarefied enzymes, focusing on the mechanistic and structural basis of their reaction coupling with the goal of revealing catalytic commonalities.

Acitretin is an oral retinoid with alopecia as a possible adverse effect. However, repigmentation of the hair color after acitretin is not a well-documented phenomenon. Herein, we introduce a case where a patient\'s hair color darkened after a course of acitretin.

Grover\'s disease, also known as transient acantholytic dermatosis (TAD), currently has no published randomized control trials regarding the treatment of the disease; thus, evidence for treatment is largely derived from case studies and case reports. In this case series, we summarize the current treatment options for Grover\'s disease and discuss two cases of refractory Grover\'s disease treated with low-dose oral isotretinoin in patients who previously failed to reach clearance with multiple treatment options. Our aim is to highlight the efficacy of low-dose systemic retinoid therapy in Grover\'s disease when other treatment options prove unsatisfactory.

A 39-year-old Caucasian woman affected by Noonan Syndrome (NS) mutated in RAF1 was referred to us with itchy lesions on her limbs that had appeared two months earlier. Clinically, there were multiple umbilicated papules with a hyperkeratotic central plug, localized on the upper and lower limbs (Figure 1, a-b). The patient had no personal history of diabetes mellitus or chronic renal failure, but suffered from hypertrophic cardiomyopathy. Blood tests showed no abnormalities. On histological examination of a skin lesion, an ectatic hair follicle with a hyperkeratotic ostium was observed with fragments of hair, inflammatory cells, and epidermal perforation. A final diagnosis of Kyrle disease (KD) was established. The patient underwent narrowband UVB (NB-UVB) phototherapy with residual atrophic scars (Figure 1, c-d), but with a complete and long-lasting resolution of symptoms. KD belongs to perforating dermatoses (PD), a heterogeneous group of skin diseases characterized by the transepidermal elimination of dermal components. Despite the classification of PD still being under debate, four primary forms are traditionally recognized: reactive perforating collagenosis, elastosis perforans serpiginosum, perforating folliculitis, and KD (1). The typical skin manifestation of KD is an eruption of dome-shaped papules and nodules, with a whitish central keratotic plug, mainly localized on the extremities and the buttocks. Described by Kyrle in 1916, KD is frequently associated with systemic diseases, especially chronic renal failure and diabetes mellitus. Other associated conditions include chronic hepatic disease, internal malignancies, and congestive heart disease (1). Despite the absence of a consensus, the control of the underlying disease remains the first therapeutic target. Both topical (keratolytics, retinoids, and corticosteroids) and systemic treatments (corticosteroids, retinoids, antibiotics, and phototherapy) have been reported to control skin manifestations (2). In our experience, NB-UVB is an effective option as first-line therapy in case of diffuse lesions, both in KD and in other PD (3). NS is a relatively common RASopathy, a heterogenous group of genetic diseases characterized by a defect of the Ras-mitogen-activated protein kinase (Ras-MAPK) pathway, with an estimated prevalence of 1/1000-2500. PTPN11 is the most frequent mutated gene, accounting for 50% of cases, but more than ten genes have been identified as causing NS (4). Classical features include a distinctive facial dysmorphism, short stature, pulmonic stenosis, and other anomalies of different organs. The skin is commonly involved. Keratinization disorders and hair abnormalities such as keratosis pilaris, ulerythema ophryogenes, wavy or curly hair, and scarce scalp hair, are often described. Other cutaneous signs include easy bruising, skin hyperlaxity, multiple lentigines, and café-au-lait spots (5). To the best of our knowledge, no cases of KD in patients with NS have been previously reported to date. The exact etiopathogenesis of KD is not clear, but it has been hypothesized that systemic diseases, such as diabetes and chronic renal failure, can cause a deposit of substances or dermis alterations, which triggers the inflammatory process with subsequent transepidermal extrusion (1). In our patient, we ruled out all the causes commonly associated with KD. It is however possible that this manifestation could be a direct result of the patient\'s illness. Our patient suffered from diffuse keratosis pilaris, and an abnormal epidermal keratinization with a secondary inflammatory dermic response is among the suggested possible pathogenetic mechanisms of KD (1). On the other hand, the hyperlaxity and fragility of the skin typical of NS suggest the presence of altered connective tissue, which could trigger an abnormal keratinization and, subsequently, the transepidermal extrusion, as well as perforating elastosis, which is associated with genetic connective tissue diseases (1). Moreover, our patient suffered from a cardiac disease, another condition associated with KD (5). Although these explanations have their appeal, there is currently insufficient evidence of a link between KD and NS, and it will be necessary to collect additional data to confirm this hypothesis.

Darier disease is an autosomal dominant disorder with hyperkeratotic papules affecting primarily seborrheic areas of the upper chest, back, forehead, scalp, nasolabial folds, ears, and, less frequently, the oral mucosa. A typical eruption consists of keratotic and crusted skin-colored papules and plaques. Pruritus occurs in 80% of patients, and pain is rare. Lesions can be triggered by exposure to ultraviolet light, heat, or stress. Secondary infections of the lesions are a common complication. A definitive diagnosis is obtained by a biopsy showing histological features such as acantholysis, suprabasal clefts, and \"corps rond and grains\". Here we present a 37-year-old woman admitted to the gynecology department with pruritic lesions she had noticed on her vulva and perineum for three months. A vulvar biopsy led to the diagnosis of Darier disease. She was referred to the dermatology department and treated with oral acitretin since systemic retinoids are offered as the first-line treatment of the disease.

BACKGROUND: Topical retinoids are a mainstay in acne management and have been shown to improve skin texture. Injectable non-animal stabilized hyaluronic acid (NASHATM) gel as skin booster is largely used in aesthetic treatments to improve skin quality including the appearance of atrophic acne scars.
OBJECTIVE: To evaluate a new sequential treatment with topical trifarotene and injectable skin booster NASHA gel in acne scars.
METHODS: 10 patients between 19 and 25 years (3 males and 7 females) with previous moderate to severe acne vulgaris on the face with the outcome of atrophic and post-inflammatory slightly hyperpigmented scars were prescribed home short contact therapy (SCT) with topical trifarotene 50 μg/g at the evening for 3 months. A proper skincare routine for sensitive skin was also recommended. The 3-month retinoid therapy was followed by an injectable medical procedure with NASHA gel 20 mg/ml as skin booster. A minimum of 3 sessions to 10 sessions were carried out according to the severity of acne scars and the skin response observed.
RESULTS: Adherence to the treatment was complete and the results evaluated by digital photography showed very effective results with high clinical improvement or almost complete resolution of atrophic acne scars.
CONCLUSIONS: The results observed in this case series show that the sequential treatment with topical trifarotene and injectable NASHA gel as skin booster can be effective in the progressive reduction of acne scarring, potentially related to a synergic effect of skin remodeling and collagen stimulation. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7630.

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Generalized verrucosis (GV) is a group of immunodeficiency disorders accompanied by widespread human papillomavirus infection. We revisit two cases of GV due to congenital interleukin-7 deficiency successfully treated with systemic retinoids. We also present a review of the literature on the use of systemic retinoids to treat GV. Our review suggests that systemic retinoids are a safe and effective option for managing recalcitrant wart lesions in cases of GV.

For decades, retinoids have been considered the gold standard of treatment for a variety of skin conditions.1,2 As the bioavailable form of vitamin A, retinoic acid has demonstrated the ability to reduce skin discoloration, stimulate collagen production, reduce rhytids, improve acne, and uneven skin texture.3,4 Retinoic acid is a potent drug with high bioavailability. Challenges with such a product include skin sensitivity and retinoid dermatitis.1,5 This potential irritation and discomfort may hinder patient compliance reducing visible results. The non-prescription vitamin A ingredient retinol is an effective and less irritating alternative, as it is converted into retinoic acid within the skin, causing little to no irritation when used topically. Intensive Age Refining Treatment: 0.5% pure retinol night by PCA SKIN® contains 0.5% retinol, protected and delivered into the skin with a multi-layered liposomal delivery technology. This development addresses the inherent instability of retinol,1,2,3 as well as the mitigation of irritation with the goal of enhancing patient compliance and visible results. This formulation also features niacinamide and terminalia chebula to further support the anti-aging benefits of retinol. The 12-week in vivo use of this potent, yet non-irritating retinol topical demonstrates improved patient compliance and satisfaction due to tolerability and enhanced efficacy in the improvement in overall signs of healthy skin. J Drugs Dermatol. 2022;21(7):784-788. doi:10.36849/JDD.6621.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease with a challenging treatment. Current guidelines reserve dapsone as a third line agent for patients with mild to moderate HS. To our knowledge, only four small case series have been reported. The objective of this study was to assess the effectiveness and safety of dapsone in our clinical practice. A retrospective observational single-center study of 56 HS patients who underwent treatment with dapsone from May 1, 2015, to June 1, 2021, was performed. The Hidradenitis Suppurativa Clinical Response (HiSCR) scale was used to evaluate the response to treatment. Fifty-six patients were included, 66% of which were men, with a median age of 33 years. Most of them had mild or moderate disease and belonged to LC2 follicular phenotype. All patients had been refractory to first-line treatments. Dapsone was prescribed at doses of 50-150 mg/day. 62.5% of the patients achieved HiSCR after 12 weeks of treatment. No serious adverse reactions were detected. The median duration of treatment was 8 months. After multivariate analysis, an association was found between the presence of fistulous tracts and the risk of non-response to the drug. In four of the dapsone responders, oral retinoids were added to achieve a sustained response. Limitations include the retrospective and non-controlled nature of this study. In conclusion, dapsone is an effective and well-tolerated option for long-term HS treatment, and in this series, it was mainly chosen for patients with LC2 phenotype. It would be interesting to study combination with retinoids and other management options.