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Deep cutaneous mycoses (DCMs) are rare infections that extend throughout the dermis and subcutis, often occurring after inoculation with pathogenic fungi. Trends toward a growing incidence have been observed that may be partially related to an increasing population of solid organ transplant patients. The aim of this study is to describe the diagnostics and the outcomes of DCM among kidney transplant recipients so as to optimize their management. We performed a retrospective review of cases of DCM occurring among kidney transplant recipients in our institution over 12 years. Twenty cases were included. Lesions were only located on the limbs and presented mainly as single (10/20, 50%) nodular lesions (15/20, 75%), with a mean size of 3 cm. Direct mycological examination was positive for 17 patients (17/20, 85%) and the cultures were consistently positive. Thirteen different fungal species were observed, including phaehyphomycetes (n  = 8), hyalohyphomycetes (n  = 3), dermatophytes (n  = 1), and mucorale (n  = 1). The (1-3) beta-D-glucan antigen (BDG) was also consistently detected in the serum (20/20, 100%). Systematic imaging did not reveal any distant infectious lesions, but locoregional extension was present in 11 patients (11/14, 79%). Nineteen patients received antifungal treatment (19/20, 95%) for a median duration of 3 months, with surgery for 10 (10/20, 50%). There is a great diversity of fungal species responsible for DCMs in kidney transplant recipients. The mycological documentation is necessary to adapt the antifungal treatment according to the sensitivity of the species. Serum BDG positivity is a potentially reliable and useful tool for diagnosis and follow-up. [ABSTRACT FROM AUTHOR]

Background: The decline in estrogen levels from several years before (perimenopause) and during menopause has various negative effects, including skin specific issues, which often receive less attention than other menopausal symptoms despite having a significant negative effect on quality of life (QoL). The objective of this study was to evaluate the effectiveness of anti‐aging dermocosmetic products designed for women during the perimenopause and menopause. Materials and methods: An open study of 101 perimenopausal women (no menstruation for 4–12 months or irregular menstruation for <5 years) and 101 menopausal women (no menstruation for >12 months), not taking hormone replacement therapy, was conducted. Adapted dermocosmetic regimens, specific to each group (day cream, night cream and serum), were applied for 56 days. Assessments included automatic artificial intelligence diagnostics of eight clinical facial signs, hydration and transepidermal water loss (TEWL), and a menopause skin QoL questionnaire. Results: Mean age was 50 ± 3.9 years (range 41–57) and 59 ± 3.8 years (range 50–66) for the perimenopause and menopause groups, respectively. Significant improvements in wrinkles and vascular signs, increases in hydration, decreases in TEWL, and a positive impact on QoL were observed after 56 days of application of the respective dermocosmetic regimens for both the perimenopause and menopause groups. Conclusion: The anti‐aging skin care products designed specifically for perimenopausal and menopausal women increased skin hydration and improved wrinkles with a positive impact on QoL. [ABSTRACT FROM AUTHOR]

This article explores the effects of menopause on the skin and highlights the lack of awareness and information among women and healthcare professionals. Menopause, a natural process that occurs in women in their fifties, is associated with a decrease in estrogen levels, which can lead to changes in the skin such as dryness and increased wrinkles. A survey conducted in France revealed that a majority of menopausal women noticed changes in their skin, but less than 1% used skincare products specifically designed for menopause. The study suggests the need for increased awareness among healthcare professionals, better education for women about menopause, the development of specialized skincare products, and more research on the effects of menopause on the skin. [Extracted from the article]

Purpose: Tretinoin is a topical gold standard for photoaging treatment. However, patient adherence can be impaired by local tolerability in the first 1– 2 weeks of treatment. Mineral 89 Probiotic Fractions® (M89PF) containing Vichy volcanic mineralizing water®, probiotic fractions, hyaluronic acid, niacinamide and tocopherol was developed to fulfill the need for adjunctive products that can reinforce skin barrier and manage retinoid induced irritation. Patients and Methods: The study included 38 women, aged 44– 60 years, phototype II–VI, applying 0.025% tretinoin gel once nightly for 84 days. For 28 days, one hemi face was treated with M89PF and sunscreen SPF 50+ while other hemi face received sunscreen only. Then, M89PF application was changed to full face. Evaluations were performed at days 0, 7, 28 and 84. Erythema, dryness, fine lines, skin tone, radiance and pore appearance were assessed by a dermatologist. Tolerability was evaluated through self-assessment questionnaire. Skin hydration levels, inflammatory and oxidative stress biomarkers were analyzed by immunological assay: Interleukin(IL)-8, IL1-alpha, IL1-Receptor Antagonist (IL-1Ra), Prostaglandin E2 (PGE2), Catalase and Superoxide Dismutase (SOD). Results: Hemiface analysis showed that erythema, fine lines, skin tone, radiance, pore appearance, hydration, tightness, dryness, burning, itching and stinging sensations were improved (p< 0.05) on the M89PF side. At full face analysis on D84, erythema, fine lines, skin tone, radiance and pore appearance were improved compared to D0 (p< 0.001). Tightness, dryness, burning, itching and stinging were reduced when compared to D7 (p< 0.05). Dermatology Life Quality Index (DLQI) and Skindex 16 showed improvement in quality of life (p< 0.05). IL-1RA increased at D28 (p=0.003) and PGE2 decreased at D28 and D84 compared to D0 (p< 0.01). Conclusion: M89PF reduced retinoid induced irritation with a good tolerability profile and, used as an adjunct to topical tretinoin, significantly improved skin hydration, erythema, fine lines, skin tone, radiance and pore appearance. [ABSTRACT FROM AUTHOR]

Bothnian palmoplantar keratoderma (PPKB, MIM600231) is an autosomal dominant form of diffuse non-epidermolytic PPK characterized by spontaneous yellowish-white PPK associated with a spongy appearance after water-immersion. It is due to AQP5 heterozygous mutations. We report four patients carrying a novel AQP5 heterozygous mutation (c.125T>A; p.(Ile42Asn)), and belonging to the same French family. Early palmoplantar swelling (before one year of age), pruritus and hyperhidrosis were constant. The PPK was finally characterized as transgrediens, non-progrediens, diffuse PPK with a clear delineation between normal and affected skin. The cutaneous modifications at water-immersion test, "hand-in-the-bucket sign", were significantly evident after 3 to 6 min of immersion in the children and father, respectively. AQP5 protein is expressed in eccrine sweat glands (ESG), salivary and airway submucosal glands. In PPKB, gain of function mutations seem to widen the channel diameter of ESG and increase water movement. Thus, swelling seems to be induced by hypotonicity with water entrance into cells, while hyperhidrosis is the result of an increased cytosolic calcium concentration. [ABSTRACT FROM AUTHOR]

Albinism is a genetic disorder, present worldwide, caused by mutations in genes affecting melanin production or transport in the skin, hair and eyes. To date, mutations in at least 20 different genes have been identified. Oculo-cutaneous Albinism type IV (OCA4) is the most frequent form in Asia but has been reported in all populations, including Europeans. Little is known about the genotype-phenotype correlation. We identified two main phenotypes via the analysis of 30 OCA4 patients with a molecularly proven diagnosis. The first, found in 20 patients, is clinically indistinguishable from the classical OCA1 phenotype. The genotype-to-phenotype correlation suggests that this phenotype is associated with homozygous or compound heterozygous nonsense or deletion variants with frameshift leading to translation interruption in the SLC45A2 gene. The second phenotype, found in 10 patients, is characterized by very mild hypopigmentation of the hair (light brown or even dark hair) and skin that is similar to the general population. In this group, visual acuity is variable, but it can be subnormal, foveal hypoplasia can be low grade or even normal, and nystagmus may be lacking. These mild to moderate phenotypes are associated with at least one missense mutation in SLC45A2. [ABSTRACT FROM AUTHOR]

Biallelic mutations of the type XVII collagen (COLXVII) gene I COL17A1 i can result in intermediate JEB and rarely in severe nonlethal JEB phenotypes.[1],[2] In COLXVII-JEB, mucosal involvement remains inconsistent and is limited to the oral cavity and the oesophagus.[3] We documented the observation of a patient presenting with tracheal damage. Https://doi.org/10.1093/bjd/ljac135 Dear Editor, Junctional epidermolysis bullosa (JEB) is an autosomal recessive disorder characterized by skin blistering with a plane of cleavage through the lamina lucida of the cutaneous basement membrane. The predicted risk is 8.3% by age 1 year and 12.75% on or after age 9 in children with severe and intermediate generalized and nonlethal JEB (previously known as non-Herlitz JEB).[6] Lethal subglottic involvement is not reported in patients with COLXVII-JEB. [Extracted from the article]

Pachyonychia congenita (PC) is a genodermatosis associated with severe painful palmoplantar keratoderma (PPK) and thickened dystrophic nails caused by autosomal dominant-negative mutations in five genes encoding keratins 6A-B-C, 16, and 17. The mechanical, surgical, or medical options for painful PC are inefficient. Given ErbB/Her family members' role in epidermal homeostasis, this study sought to investigate the possibility of treating PC patients with PPK by blocking signaling either with EGFR (Her1) inhibitor erlotinib or lapatinib, a dual EGFR(Her1)/Her2. After 1 month of therapy with oral erlotinib treatment at 75 mg/day, the pain disappeared for patient #1, with partially reduced hyperkeratosis, while increasing the dose to 100 mg/day resulted in painful skin fissures. Therapy replacement with erlotinib cream at 0.2% was inconclusive, and substitution with oral lapatinib at alternating doses of 500 and 750 mg/day achieved a good compromise between pain reduction, symptom improvements, and side effects. Patient #2′s treatment with erlotinib cream failed to display significant improvements. Oral erlotinib started at 75 mg/day then reduced to 25 mg/day because of the formation of an acneiform rash. Treatment considerably improved the patient's condition, with an almost complete disappearance of pain. Oral Her1 or 1/2 inhibitors reduced pain, improved two PC patients' quality of life, and offered promising therapeutic perspectives. [ABSTRACT FROM AUTHOR]

Tuberous Sclerosis Complex (TSC) is a multisystem genetic disease characterized by cutaneous and extracutaneous hamartomas. The diagnosis is based on the association of major and minor criteria, defined by a consensus conference updated in 2012. The clinical examination of the skin is crucial because seven diagnostic criteria are dermatological: four major (hypomelanotic macules, angiofibroma or fibrous cephalic plaques, ungual fibromas, shagreen patches) and three minor criteria (confetti skin lesions, dental enamel pits, intraoral fibromas). Skin biopsy is commonly performed to assert the diagnosis of TSC when the clinical aspect is atypical. Histopathology of TSC cutaneous lesions have been poorly reported until now. In this article, we review the histologic features described in the literature and share our experience of TSC skin biopsies in our pediatric hospital specialized in genetic disorders. Both hypomelanotic lesions and cutaneous hamartomas (angiofibroma/fibrous cephalic plaques, ungual fibromas, shagreen patches) are discussed, including the recent entity called folliculocystic and collagen hamartoma, with a special emphasis on helpful clues for TSC in such lesions. [ABSTRACT FROM AUTHOR]

The onset of blisters in a neonate or an infant is often a source of great concern for both parents and physicians. A blistering rash can reveal a wide range of diseases with various backgrounds (infectious, genetic, autoimmune, drug-related, traumatic, etc.), so the challenge for the dermatologist and the pediatrician is to quickly determine the etiology, between benign causes and life-threatening disorders, for a better management of the patient. Clinical presentation can provide orientation for the diagnosis, but skin biopsy is often necessary in determining the cause of blister formations. In this article, we will provide information on the skin biopsy technique and discuss the clinical orientation in the case of a neonate or infant with a blistering eruption, with a focus on the histology for each etiology. [ABSTRACT FROM AUTHOR]

Autosomal recessive congenital ichthyosis (ARCI) belongs to a heterogeneous group of disorders of keratinization. To date, 10 genes have been identified to be causative for ARCI. NIPAL4 (Nipa‐Like Domain‐Containing 4) is the second most commonly mutated gene in ARCI. In this study, we present a large cohort of 101 families affected with ARCI carrying mutations in NIPAL4. We identified 16 novel mutations and increase the total number of pathogenic mutations in NIPAL4 to 34. Ultrastructural analysis of biopsies from six patients showed morphological abnormalities consistent with an ARCI EM type III. One patient with a homozygous splice site mutation, which leads to a loss of NIPAL4 mRNA, showed additional ultrastructural aberrations together with a more severe clinical phenotype. Our study gives insights into the frequency of mutations, a potential hot spot for mutations, and genotype–phenotype correlations. [ABSTRACT FROM AUTHOR]

Psoriasis vulgaris is a common skin inflammatory disease characterized by recurrent flare episodes associated with scaly well-demarcated skin plaques. Skin biopsies from psoriatic patients with high PASI score (22.67 ± 8.67) and fromHDwere used to study APN/CD13. APN/CD13 is over-expressed in LP and nLP compare to HD skins and fibroblasts. This overexpression is positively correlated with specific enzymatic activity enhancement. However, discrepancies between APN/CD13 expression in LP and nLP prompt us to focus our study on APN/CD13 modulation. Calcitonin Gene Related Peptide (CGRP), a neuropeptide, positively modulated expression and activity of APN/CD13. CGRP consistently induced IL4 secretion, which is also involved in the increase of APN/CD13 expression and activity, which is significantly reversed using IL-4 blocking antibody. Surprisingly, retinoic acid altered the APN/CD13 enzymatic activity only in nLP fibroblasts without modification of APN/CD13 expression. APN/CD13 is over-expressed on psoriatic fibroblasts and exerted high level of activity compare to HD fibroblasts. Taken together, several factors such as CGRP and IL-4 acted on positive regulation of APN/CD13 expression and activity. This study highlighted the interest of APN/CD13 as a new potential target, which should be investigated in psoriasis. [ABSTRACT FROM AUTHOR]

Background: A localized form of epidermolysis bullosa simplex (EBS-l) is considered one of the mildest forms of epidermolysis bullosa (EB), with blisters limited to the palms and soles. However, these lesions can be very painful. The aim of the study was to characterize pain in patients with EBS-l and evaluate its impact on quality of life (QoL). Patients were contacted via the Research Group of the French Society of Pediatric Dermatology and the association of EB patients (DEBRA France). One investigator used a standardized questionnaire that included validated scales for pain and QoL for a telephone interview.Results: We included 57 patients (27 children). All patients had pain: the mean pain on a 10-mm visual analog scale was >5 for most adults (90%) and children ≥8 years old (94%) when blisters were present and for most adults (73%) and about half of the children ≥ age 8 (53%) during dressing changes. Similar results were found for younger patients. Overall, 75% of patients had neuropathic pain; for 55% of children and 73% of adults, the pain had a moderate to severe impact on QOL. Only seven patients used premedication before changing dressings and seven regularly used oral treatment for chronic pain. A total of 21% and 23% of patients used non-steroidal anti-inflammatory drugs and grade 2 analgesics, respectively. These treatments were not effective for neuropathic pain. Six patients tried 5% lidocaine plasters on their feet, with good efficacy.Conclusions: EBS-l patients have frequent and severe pain with neuropathic characteristics. This pain is undertreated and affects QoL. [ABSTRACT FROM AUTHOR]

A 12-year-old girl, with atopic dermatitis since childhood, was referred for an acquired and painful transgradient palmoplantar keratoderma (PPK), thought to be inherited. Crusted scabies presentation in children is variable and can present as keratoderma over acral surfaces, onychodystrophy, subungual hyperkeratosis, or erythrodermic dermatitis.[[1], [3]] Pruritus is variable. The treatment remains difficult; crusted scabies is often resistant to topical treatment alone. [Extracted from the article]

Multicentric reticulohistyocytosis (MRH) is a rare multisystemic non-Langerhans histiocytosis characterized by cutaneous nodules and severe destructive polyarthritis, sometimes associated with constitutional symptoms and various organ involvements. Its treatment remains empirical and challenging. We first report herein, the successful treatment of a multicentric reticulohistiocytosis patient with anakinra based on cutaneous biopsy immunostaining and serum cytokines features. A first-line treatment associating methotrexate, cortisone and hydoxychloroquine showed none improvement. Therefore, while further tests were performed to rule out an associated malignancy, auto-immune disease or mycobacterial infection, a treatment with anakinra was chosen instead of anti-TNF-alpha drugs. As soon as the 5th day, anakinra allowed control of fever, then rapid improvement of constitutional symptoms, arthritis, cutaneous lesions, and normalization of C-reactive protein, IL-6, and especially IL-1β levels. Then methotrexate was added, while anakinra was removed at the 12th month, with persistent and complete remission over the two-year follow up. Further assessment of IL-1 pathogenic role and blockade on larger cohorts of patient could open new therapeutic perspectives for refractory/relapsing MRH, considering the good tolerance profile of specific targeting drugs. [ABSTRACT FROM AUTHOR]

Phacomatosis pigmentokeratotica is characterized by the coexistence of an organoid epidermal naevus, following Blaschko's lines, and a large speckled lentiginous naevus, typically arranged in a chequerboard pattern. This entity has been isolated from the group of epidermal naevus syndromes and is frequently associated with extracutaneous anomalies. We report here the first observation of phacomatosis pigmentokeratotica associated with nephroblastoma. In addition to this paediatric renal tumour, the coexistence of juvenile arterial hypertension suggests an associated vascular defect. The link between the extracutaneous manifestations and cutaneous twin spot phenotype is discussed. [ABSTRACT FROM AUTHOR]

Bi-allelic mutations in I LRMDA i gene (leucine-rich melanocyte differentiation-associated protein or I C10orf11 i gene, chromosome 10 open reading frame 11 or leucine-rich differentiation-associated protein), located on chromosome 10q22, are associated with the newly described and very rare OCA7 subtype (MIM615179). OCA7 was first described in 8 members from the same family from Faroe Islands and in one patient from Lithuania.[2] While ocular symptoms predominate, patients presented with pale skin, scalp hair colors varied from pale blond to dark brown. Notably, four patients (from Turkey, Lithuania and our two patients) carry the same c.66dupC suggesting a founder effect in the east part of Europe and Asia. [Extracted from the article]

The article discusses a study on a large Algerian family in which nine members presented with erythrokeratodermia variabilis (EKV)-P phenotypes associated with a novel mutation in the GJB4 gene. Characteristics of EKV include hyperkeratosis and transient erythematous areas. The possibility that EKV and progressive symmetrical erythrokeratodermia (PSEK) may be manifestations of the same genetic defect is also addressed.

PIK3CA -related overgrowth spectrum is caused by mosaicism mutations in the PIK3CA gene. These mutations, which are also observed in various types of cancer, lead to a constitutive activation of the PI3K/AKT/mTOR pathway, increasing cell proliferation. Heat shock transcription factor 1 (HSF1) is the major stress-responsive transcription factor. Recent findings indicate that AKT phosphorylates and activates HSF1 independently of heat-shock in breast cancer cells. Here, we aimed to investigate the role of HSF1 in PIK3CA -related overgrowth spectrum. We observed a higher rate of proliferation and increased phosphorylation of AKT and p70S6K in mutant fibroblasts than in control cells. We also found elevated phosphorylation and activation of HSF1, which is directly correlated to AKT activation. Specific AKT inhibitors inhibit HSF1 phosphorylation as well as HSF1-dependent gene transcription. Finally, we demonstrated that targeting HSF1 with specific inhibitors reduced the proliferation of mutant cells. As there is currently no curative treatment for PIK3CA -related overgrowth spectrum, our results identify HSF1 as a new potential therapeutic target. • PIK3CA -related overgrowth spectrum is characterized by increased cell proliferation. • Strong activation of HSF1 is found in PIK3CA -related overgrowth spectrum fibroblasts. • AKT inhibitors reduces HSF1 activation and HSF1-dependent gene transcription. • HSF1 inhibition blocks the PIK3CA -related overgrowth spectrum proliferation. [ABSTRACT FROM AUTHOR]

Background & Aim Several types of unexplained extra-hepatic manifestations, including haematological disorders, have been reported in the context of hepatitis E virus (HEV) infection. However, the underlying mechanism(s) of these manifestations are unknown. We provide evidence that HEV has an extra-hepatic endothelial tropism that can engage cutaneous T cells towards clonality. Methods A patient with a CD30(+) cutaneous T cell lymphoproliferative disorder (T-LPD) and biopsy-proven chronic HEV infection received three rounds of oral ribavirin treatment, administered either without or with interferon, and eventually achieved a sustained virologic response (SVR). Pathologic, virologic and immunologic investigations were carried out on biopsied skin lesion, and peripheral blood mononuclear cells between the 2nd and 3rd round of antiviral treatment and biopsied liver. Results Remission of T-LPD was observed upon antiviral treatment, and the patient remained in complete remission after achieving SVR. The T cell analysis showed large CD30(+) lymphocytes surrounding the blood vessels within the CD8(+) T cell infiltrate. HEV was detected within dermal microvascular endothelial cells using immunofluorescence staining, in situ hybridisation and electron microscopy. Infiltrating T cells mostly comprised memory CD8(+) T cells with a tissue-resident memory T cell phenotype. Overall, 98% of extracted T cells were CD8(+) T cells with a Vβ signature skewed towards Vβ4 and with an oligoclonal profile. T cell clones from T-LPD were more like T cells in the liver than T cells in the blood [odds ratio = 4.55, (3.70–5.60), p <0.0001]. No somatic mutations were found in the T-LPD exomes. Conclusion HEV has an extra-hepatic tissue tropism in humans, including dermal endothelium, and can induce CD30(+) T-LPD that is sensitive to antivirals. Lay summary Hepatitis E virus (HEV) has an extra-hepatic tissue tropism and should be added to the list of viruses associated with lymphoproliferative disorders. As such, HEV should be part of the laboratory workup of any lymphoproliferation, particularly those of the T cell phenotype that involve the skin. In the context of HEV-associated cutaneous T cell lymphoproliferative disorders, antiviral treatment could be considered a first-line treatment instead of chemotherapy. [ABSTRACT FROM AUTHOR]