Trichophyton tonsurans‐induced kerion celsi with decreased defensin expression and paradoxically increased interleukin‐17A production

We report a case of kerion celsi due to Trichophyton tonsurans. An 18‐year‐old male student judo practitioner had alopecic patches, black dots and subcutaneous abscesses on the right temporal region. The damaged hair represented endothrix infection with T. tonsurans, as assessed by mycological examinations. He was treated with oral itraconazole without any therapeutic effect, followed by terbinafine with good effect. A skin biopsy showed neutrophil, lymphocyte and histiocyte infiltration into the dermis and subcutaneous tissue with abscesses around a number of dilated hair follicles. Immunostaining showed that the expression level of human β‐defensin 2 (HBD‐2) was decreased in the epidermis of the alopecic and adjacent skin. Because interleukin (IL)‐17A generally induces HBD‐2 production by epidermal keratinocytes, we also immunohistochemically investigated IL‐17A expression. Unexpectedly, many IL‐17A‐bearing cells were found around destructed hair follicles, indicating that IL‐17A expression was not attenuated, but rather increased in the skin lesion. Our case suggests that IL‐17A‐upregulated antimicrobial peptide expression is disordered in kerion celsi, and severe inflammation with IL‐17A may cause tissue damage and resultant scar.     

R164C mutation in FOXQ1 H3 domain affects formation of the hair medulla

A number of single gene mutations in laboratory mice produce hair follicle defects resulting in deformed hair shafts. The radiation‐induced (SB/LeJ‐Foxq1^sa) satin mutant mice have a satin‐like sheen to their hair and dilute colouration. This sheen is due to failure of the hair shafts to develop normal medullas, while the pigment dilution is due to the unrelated beige (lysosomal trafficking regulator, Lyst^bg) mutation. A new allelic mutation, Foxq1^sa‐J, arose spontaneously on the albino (tyrosinase, Tyr^c) MRL/MpJ‐Fas^lpr background. The Foxq1^sa‐J allele has a C to T transition at position 490. By contrast, the Foxq1^sa mutant allele was confirmed to be a 67 base pair deletion followed by two base changes (GA to AT). Morphologic changes were similar to those seen in Hoxc13 transgenic and targeted mutant mice. This new allelic mutation provides yet another tool to investigate formation of the interior structures of hair shafts.     

Modulating hair follicle size with Wnt10b/DKK1 during hair regeneration

Hair follicles have characteristic sizes corresponding to their cycle‐specific stage. However, how the anagen hair follicle specifies its size remains elusive. Here, we showed that in response to prolonged ectopic Wnt10b‐mediated β‐catenin activation, regenerating anagen hair follicles grew larger in size. In particular, the hair bulb, dermal papilla and hair shaft became enlarged, while the formation of different hair types (Guard, Awl, Auchene and Zigzag) was unaffected. Interestingly, we found that the effect of exogenous WNT10b was mainly on Zigzag and less on the other kinds of hairs. We observed dramatically enhanced proliferation within the matrix, DP and hair shaft of the enlarged AdWnt10b‐treated hair follicles compared with those of normal hair follicles at P98. Furthermore, expression of CD34, a specific hair stem cell marker, was increased in its number to the bulge region after AdWnt10b treatment. Ectopic expression of CD34 throughout the ORS region was also observed. Many CD34‐positive hair stem cells were actively proliferating in AdWnt10b‐induced hair follicles. Importantly, subsequent co‐treatment with the Wnt inhibitor, DKK1, reduced hair follicle enlargement and decreased proliferation and ectopic localization of hair stem cells. Moreover, injection of DKK1 during early anagen significantly reduced the width of prospective hairs. Together, these findings strongly suggest that Wnt10b/DKK1 can modulate hair follicle size during hair regeneration.     

TINEA CAPITIS IN NORTHWESTERN EUROPE 1963–1993: ETIOLOGIC AGENTS AND THEIR CHANGING PREVALENCE

Background. Although tinea capitis is endemic in many countries, its prevalence in Northwestern Europe (Belgium and the Netherlands) has not been established. Materials and Methods. Scales, pus, and hair were examined from 435 cases of tinea capitis for etiologic agents and their relative percentages calculated for 5-year periods between 1963 and 1992. Results. There was a change in organisms associated with tinea capitis in the Netherlands from Trichophyton schoenleinii to Trichophyton violaceum. Increased immigration from the Mediterranean is held partly responsible for the increased prevalence of T. violaceum infections. Infection with zoophilic dermatophytes, such as T. canis, has also become more frequent in the Netherlands. Conclusions. The zoophilic dermatophytes have supplanted the anthropophilic dermatophytes as the cause of tinea capitis in the Netherlands.     

Effects of topical application of EGCG on testosterone-induced hair loss in a mouse model

Abstract: We investigated the effect of topical epigallocatechin‐3‐gallate (EGCG) on testosterone (T)‐induced hair loss in mice. Marked hair loss was observed at the T‐injected site, and topical EGCG significantly reduced the hair loss (P < 0.05). TUNEL staining showed apoptosis of follicular epithelial cells in the T‐injected groups where topical EGCG was found to significantly diminish T‐induced apoptosis (P < 0.05). Topical EGCG down‐regulated the T‐induced expression of androgen receptor but did not down‐regulate 17β‐hydroxysteroid dehydrogenase (HSD) and three β‐HSD expression. Analysis using liquid chromatography tandem mass spectrometry (LC‐MS/MS) on serum and tissue samples revealed no significant difference in T and dihydrotestosterone concentrations between the T‐injected and T + EGCG groups. Thus, we found that T injection in a mouse model induces hair loss by apoptosis of the hair follicles rather than through the androgen metabolic pathway and also saw that T‐induced apoptosis of hair follicles was reduced by topical EGCG.     

Hair shaft abnormalities after chemotherapy and tamoxifen therapy in patients with breast cancer evaluated by optical coherence tomography

Background Antineoplastic treatment for breast cancer is frequently associated with alopecia. Increasingly, changes in the texture and shape of regrowing hair after chemotherapy have been reported, without evaluation on a scientific basis. Optical coherence tomography (OCT) provides highly reproducible measurements of hair shaft parameters. Objectives This study aims to evaluate hair shaft alterations using OCT in chemotherapy‐induced alopecia and in patients taking tamoxifen. Methods The measurements of this prospective case series were performed on women aged 29–68 years, receiving either tamoxifen (n = 17) or chemotherapy (n = 17) prior to (T1) and after (T2) treatment. Each time, 20 hairs from two different sites of the scalp (frontal, occipital) were examined by OCT. The hair parameters were characterized by cross section (CS) and form factor (FF). The ratio of maximal to minimal hair diameters determined the FF. Results After chemotherapy, the CS of hairs was significantly lower compared with hairs taken at T1. The FF did not vary between T1 and T2 for the frontal area, but it did for the occipital area. In patients treated with tamoxifen, changes were observed neither in CS nor in FF. However, comparing both therapeutic groups, there were significant differences in CS and FF for T2, but not for T1. Conclusions Reported changes in hair structure after chemotherapy may be due to reduction of hair shaft calibre and increase of FF in regrowing hair. The OCT technique is a promising method to gain more insight into chemotherapy‐induced changes of hair morphology.     

Marie Unna hereditary hypotrichosis accompanied by multiple familial trichoepithelioma in a Chinese family

Marie Unna hereditary hypotrichosis (MUHH) and multiple familial trichoepithelioma (MFT) are both autosomal dominant disorders. Recently, certain genes (HR and EPS8L3) have been found to be responsible for MUHH, while CYLD has been demonstrated to be the main pathogenic gene in MFT patients. However, there exist a number of CYLD mutation‐negative MFT cases, for which the causative gene has been unknown. Here, we identified a large, five‐generation Han Chinese family with several patients presenting with MUHH and MFT. Sanger sequencing of three genes in 13 family members was performed. We found that the c.1A>G mutation in an inhibitory upstream open‐reading frame of HR (U2HR) was present in all MUHH patients, while no pathogenic variants were found in the 3?‐ or 5?‐untranslated regions, exons or flanking intronic sequences of EPS8L3 or CYLD in any family members. Subsequently, whole‐genome sequencing was performed for five affected and one unaffected family member. We found no CYLD variants but identified an FABP12 variant (rs536105592 G>A) in the patients with both MUHH and MFT. These results suggest that the U2HR mutation was responsible for MUHH and the FABP12 variant may be coincidental in the accompanying MFT in this unique pedigree. This report deepens our understanding of the genetic basis of hair follicle diseases.     

Novel ERCC2 mutation in two siblings with trichothiodystrophy

Trichothiodystrophy describes a group of recessively inherited multisystem neuroectodermal disorders that takes its name from the characteristic feature of brittle, sulfur‐deficient hair. We describe two siblings with trichothiodystrophy due to a novel genotype. The maternal mutation (p.Arg722Trp) is a previously described pathogenic mutation in ERCC2 that has been shown to result in a severe phenotype, while the paternal mutation (c.1480‐1G > C) has not been previously reported. Our cases confirm the severe phenotype associated with the p.Arg722Trp mutation and expand the known genetic mutations associated with trichothiodystrophy by demonstrating a novel pathogenic mutation in ERCC2.     

Novel IL36RN mutation in a Japanese case of early onset generalized pustular psoriasis

Generalized pustular psoriasis is a distinct type of psoriasis characterized by recurrent febrile attacks with disseminated subcorneal pustules on generalized skin rashes. Recently, homozygous and compound heterozygous mutations of the IL36RN gene, which encodes the anti‐inflammatory cytokine interleukin (IL)‐36 receptor antagonist, were identified in familial and sporadic cases of various ethnicities with generalized pustular psoriasis. Here we report a 39‐year‐old Japanese male patient who had suffered from repeated attacks of generalized pustular psoriasis since infancy with intervals of several years. At presentation, erythematous lesions with a few pustules were found only on some parts of the body and controlled with topical corticosteroids. An analysis of the IL36RN gene revealed compound heterozygous mutations of c.28C>T and c.368C>T. While the former mutation causing the premature termination p.Arg10X is recurrent in Japanese cases, the latter missense mutation causing p.Thr123Met substitution is novel, but another mutation in the same position has been reported in one Japanese case. Our report further supports the presence of the Japanese‐specific hot spots in the IL36RN gene, 28C and 368C, and suggests the functional significance of Thr123. This special type of generalized pustular psoriasis caused by IL36RN mutations has been designated as deficiency for IL‐36 receptor antagonist, a new hereditary autoinflammatory disease, and its phenotypes have emerged to include other related pustular disorders, palmoplantar pustulosis, acrodermatitis continua of Hallopeau, and acute generalized exanthematous pustulosis. The genetic analysis of the cases with these diseases would be important for establishment and application of the specific treatments targeting the IL‐36 signaling.     

Novel homozygous mutation,c.400C>T (p.Arg134*), in the PVRL1 gene underlies cleft lip/palate‐ectodermal dysplasia syndrome in an Asian patient

Cleft lip/palate‐ectodermal dysplasia syndrome is a rare, autosomal recessive disorder caused by homozygous loss‐of‐function mutations of the poliovirus receptor‐like 1 (PVRL1) gene encoding nectin‐1. Nectin‐1 is a cell–cell adhesion molecule that is important for the initial step in the formation of adherens junctions and tight junctions; it is expressed in keratinocytes, neurons, and the developing face and palate. Clinical manifestations comprise a unique facial appearance with cleft lip/palate, ectodermal dysplasia, cutaneous syndactyly of the fingers and/or toes, and in some cases, mental retardation. We present the first report, to our knowledge, of an Asian individual with cleft lip/palate‐ectodermal dysplasia syndrome with a novel PVRL1 mutation. A 7‐year‐old Japanese boy, the first child of a consanguineous marriage, showed hypohidrotic ectodermal dysplasia with sparse, brittle, fine, dry hair and hypodontia, the unique facial appearance with cleft lip/palate, cutaneous syndactyly of the fingers and mild mental retardation. Scanning electron microscopic examination of the hair demonstrated pili torti and pili trianguli et canaliculi. Mutation analysis of exon 2 of PVRL1 revealed a novel homozygous nonsense mutation, c.400C>T (p.Arg134*). His parents were heterozygous for the mutant alleles. All four PVRL1 mutations identified in cleft lip/palate‐ectodermal dysplasia syndrome to date, including this study, resulted in truncated proteins that lack the transmembrane domain and intracellular domain of nectin‐1, which is necessary to initiate the cell–cell adhesion process.     

tert-butyl hydroperoxide, an organic peroxide, causes temporary delay in hair growth in a neonatal rat model

tert‐Butyl hydroperoxide (tBHP), an organic peroxide, has been shown to cause irreversible damage to keratinocytes in vitro with prolonged administration at high concentrations, and reversible damage with short‐term administration at low concentrations. To investigate the effects of tBHP on keratinocytes in vivo, we analysed hair growth in tBHP‐treated neonatal rats. Sprague–Dawley and Long–Evans rat pups were injected subcutaneously with tBHP or vehicle once daily for 6 days, and hair growth was monitored. The tBHP‐treated rats had a significant delay in hair growth. However, this delay reversed within days, and the hair coats, including hair pigmentation, of tBHP‐treated and sham‐treated rats were indistinguishable 2 weeks later. Histological analysis and BrdU labelling of S phase cells confirmed the delay in hair‐follicle growth and its reversal in tBHP‐treated rats. Our results indicated that the changes incurred in hair follicles by short‐term use of high‐dose oxidants in vivo are temporary and reversible.     

Identification of two Chinese oculocutaneous albinism type 6 patients and mutation updates of the SLC24A5 gene

Oculocutaneous albinism (OCA) is a rare and heterogeneous disorder characterized by hypopigmentation of the skin, hair and eyes. Thirty OCA type 6 (OCA6) patients with 24 mutations in SLC24A5 have been reported across various populations; however, only one patient has been identified in a Chinese population. This study identifies two novel SLC24A5 frame‐shift variants in two unrelated Chinese patients and both are predicted to be pathogenic by American College of Medical Genetics guidelines. The genotypes and phenotypes of all three Chinese OCA6 patients are unique compared with those identified in other populations. All of the mutations identified to date in Chinese OCA6 patients are predicted to be non‐functional, a finding that is useful in guiding genetic diagnosis and counseling for OCA6 in China.     

Comparative regenerative biology of spiny (Acomys cahirinus) and laboratory (Mus musculus) mouse skin

Wound‐induced hair follicle neogenesis (WIHN) has been demonstrated in laboratory mice (Mus musculus) after large (>1.5 × 1.5 cm²) full‐thickness wounds. WIHN occurs more robustly in African spiny mice (Acomys cahirinus), which undergo autotomy to escape predation. Yet, the non‐WIHN regenerative ability of the spiny mouse skin has not been explored. To understand the regenerative ability of the spiny mouse, we characterized skin features such as hair types, hair cycling, and the response to small and large wounds. We found that spiny mouse skin contains a large portion of adipose tissue. The spiny mouse hair bulge is larger and shows high expression of stem cell markers, K15 and CD34. All hair types cycle synchronously. To our surprise, the hair cycle is longer and less frequent than in laboratory mice. Newborn hair follicles in anagen are more mature than C57Bl/6 and demonstrate molecular features similar to C57Bl/6 adult hairs. The second hair cycling wave begins at week 4 and lasts for 5 weeks, then telogen lasts for 30 weeks. The third wave has a 6‐week anagen, and even longer telogen. After plucking, spiny mouse hairs regenerate in about 5 days, similar to that of C57Bl/6. After large full‐thickness excisional wounding, there is more de novo hair formation than C57Bl/6. Also, all hair types are present and pigmented, in contrast to the unpigmented zigzag hairs in C57Bl/6 WIHN. These findings shed new light on the regenerative biology of WIHN and may help us understand the control of skin repair vs regeneration.     

EMILIN3, an extracellular matrix molecule with restricted distribution in skin

EMILIN3 is an extracellular matrix glycoprotein that displays a dynamic and restricted expression pattern in connective tissues during post‐natal life. In this study, we report the characterization of EMILIN3 deposition in the skin. In addition, to unravel the functions of this protein in skin homeostasis, we generated Emilin3 null mice and provide evidence that EMILIN3 is dispensable for hair follicle growth and maintenance throughout adult life.     

Topical tacrolimus suppresses the expression of vascular endothelial growth factor and insulin‐like growth factor‐1 in late anagen

Tacrolimus has shown promising results in the treatment of various dermatological diseases, including hair loss. The direct effect of tacrolimus on hair follicles and its underlying mechanisms have rarely been investigated. In this study, we investigated the effects of topical tacrolimus on anagen in the hair cycle and on the expression of vascular endothelial growth factor (VEGF) and insulin‐like growth factor‐1 (IGF‐1) mRNAs in mouse skin. Topical tacrolimus 0.1% ointment was applied to one side of the skin of depilated C57BL/6 mice. Skin samples from both sides were taken during the study. Vegf and Igf‐1 mRNA were determined by quantitative RT‐PCR. No obvious difference in skin colour, hair cycling or histological features was found between the treated and untreated skin, but the levels of Vegf mRNA and Igf‐1 mRNA were markedly decreased in the treated skin in late anagen, compared with those in untreated skin.     

FAM83G/Fam83g genetic variants affect canine and murine hair formation

FAM83G/Fam83g genetic variants have been described in dogs, mice and recently also in humans. They are associated with palmoplantar keratoderma and altered hair or coat phenotype, reported as wooly phenotype in mice. FAM83G/Fam83g is an unexplored effector of temporally and spatially coordinated Wnt and BMP signalling which are key pathways in pre‐ and postnatal hair follicle morphogenesis and differentiation. The aim of this study was to unravel phenotypic consequences of FAM83G/Fam83g variants on hair coat formation in dogs and mice. Our results show differences in hair types and hair shaft structures in both species. Additionally, mice exhibit deregulated hair cycle progression which timely correlates with defective Wnt signalling (Axin2) and Bmp2/4 expression. These results affirm the involvement of FAM83G in hair morphogenesis, hair follicle differentiation and cycling.     

A somewhat unexpected result from the deconvolution of DSC curves for human hair: There is no apparent relation between cortical cell fractions and hair curliness

A deconvolution process has been developed for curves obtained by differential scanning calorimetry in water for Merino wool and the main ethnic hair types. This enables estimation of the fractions of ortho‐ and para‐type cell groups. The results also indicate that hair may contain a further, low‐sulphur subgroup of ortho‐type cells. The sizes of the major cell fractions are in line with expectations from microscopical investigations. The fractions are comparable for hair types, and no consistent association between cell‐type fractions and hair curvature is observed.     

Serotonin signalling is crucial in the induction of PUVA‐induced systemic suppression of delayed‐type hypersensitivity but not local apoptosis or inflammation of the skin

Psoralen and UVA (PUVA) has immunosuppressive and proapoptotic effects, which are thought to be responsible alone or in combination for its therapeutic efficacy. However, the molecular mechanism by which PUVA mediates its effects is not well understood. Activation of the serotonin (5‐hydroxytryptamine, 5‐HT) pathway has been suggested to be involved in the modulation of T‐cell responses and found to mediate UVB‐induced immune suppression. In particular, the activation of the 5‐HT_2A receptor has been proposed as one mechanism responsible for UV‐induced immune suppression. We therefore hypothesized that 5‐HT may play a role in PUVA‐induced effects. The model of systemic suppression of delayed‐type hypersensitivity (DTH) to Candida albicans was used to study immune function after exposure of C3H and KIT^{W‐Sh/W‐Sh} mice to a minimal inflammatory dose of topical PUVA. The intra‐peritoneal injection of the 5‐HT₂ receptor antagonist ketanserin or cyproheptadine or an anti‐5‐HT antibody immediately before PUVA exposure entirely abrogated suppression of DTH but had no significant effect on inflammation, as measured by swelling and cellular infiltration of the skin, and apoptosis as determined by the number of sunburn cells in C3H mice. Importantly, the systemic injection of 5‐HT recapitulated PUVA immune suppression of DTH but did not induce inflammation or apoptosis in the skin. KIT^{W‐Sh/W‐Sh} mice (exhibiting myelopoietic abnormalities, including lack of 5‐HT‐containing mast cells) were resistant to PUVA‐induced suppression of DTH but not local skin swelling. Thus, this points towards a crucial role of 5‐HT signalling in PUVA‐induced immune suppression but not inflammation or apoptosis in situ in the skin.