RESUMO
We have observed a distinct phenomenon of transient oral lingual leukoplakia in infancy and report 22 healthy infants with gray-white plaques on the dorsal tongue with sparing of the tip from four medical centers in three countries. The onset of the eruption ranged from 1 week to 7 months of life and resolved in 19 patients (86%, with 3 patients lost to follow-up). None of the eight patients examined at 1 year of age had residual findings. We believe this is a common entity that can be distinguished from oral candidiasis on clinical and/or laboratory examination and name this entity "transient infantile lingual leukoplakia."
Assuntos
Leucoplasia Oral , Humanos , Masculino , Lactente , Feminino , Leucoplasia Oral/diagnóstico , Leucoplasia Oral/patologia , Recém-Nascido , Doenças da Língua/diagnóstico , Doenças da Língua/patologia , Língua/patologia , Diagnóstico DiferencialRESUMO
BACKGROUND: Short anagen hair (SAH) is a rare paediatric hair disorder characterized by a short anagen phase, an inability to grow long scalp hair and a negative psychological impact. The genetic basis of SAH is currently unknown. OBJECTIVES: To perform molecular genetic investigations in 48 individuals with a clinical phenotype suggestive of SAH to identify, if any, the genetic basis of this condition. METHODS: Exome sequencing was performed in 27 patients diagnosed with SAH or with a complaint of short, nongrowing hair. The cohort was screened for variants with a minor allele frequency (MAF) < 5% in the general population and a Combined Annotation Dependent Depletion (CADD) score > 15, to identify genes whose variants were enriched in this cohort. Sanger sequencing was used for variant validation and screening of 21 additional individuals with the same clinical diagnosis and their relatives. Genetic association testing of SAH-related variants for male pattern hair loss (MPHL) was performed using UK Biobank data. RESULTS: Analyses revealed that 20 individuals (42%) carried mono- or biallelic pathogenic variants in WNT10A. Rare WNT10A variants are associated with a phenotypic spectrum ranging from no clinical signs to severe ectodermal dysplasia. A significant association was found between WNT10A and SAH, and this was mostly observed in individuals with light-coloured hair and regression of the frontoparietal hairline. Notably, the most frequent variant in the cohort [c.682T>A;p.(Phe228Ile)] was in linkage disequilibrium with four common WNT10A variants, all of which have a known association with MPHL. Using UK Biobank data, our analyses showed that c.682T>A;p.(Phe228Ile) and one other variant identified in the SAH cohort are also associated with MPHL, and partially explain the known associations between WNT10A and MPHL. CONCLUSIONS: Our results suggest that WNT10A is associated with SAH and that SAH has a genetic overlap with the common phenotype MPHL. The presumed shared biologic effect of WNT10A variants in SAH and MPHL is a shortening of the anagen phase. Other factors, such as modifier genes and sex, may also play a role in the clinical manifestation of hair phenotypes associated with the WNT10A locus.
Assuntos
Displasia Ectodérmica , Cabelo , Humanos , Masculino , Criança , Alopecia , Fenótipo , Displasia Ectodérmica/genética , Frequência do Gene , Proteínas Wnt/genéticaRESUMO
Importance: Kidney-urinary tract (KUT) manifestations cause substantial morbidity in patients with junctional epidermolysis bullosa (JEB), but the spectrum of disease severity and the clinical course have been poorly characterized. Objective: To examine in a large cohort of patients with intermediate JEB the KUT manifestations, diagnostic and therapeutic procedures, genotype-phenotype correlations, and outcomes as a basis for recommendations, prognosis, and management. Design, Setting, and Participants: In this retrospective, longitudinal case series study, 99 patients with a diagnosis of JEB based on clinical and genetic findings who were treated in a single dermatology department in Freiburg, Germany, were assessed during an 18-year period (January 1, 2003, to December 31, 2021). Clinical, laboratory, and molecular genetic parameters were extracted from patients' medical records. Main Outcomes and Measures: Clinical characteristics, natural history, management of KUT manifestations, and genotype-phenotype correlations of intermediate JEB. Results: Of the 183 patients with JEB, 99 (54%) had intermediate JEB and were included in this cohort. The cohort included 49 female patients and 50 male patients. None of 49 female patients and 15 of 50 male patients had KUT involvement affecting different levels of the urinary tract, resulting in a prevalence of 30% for males; thus, the overall prevalence was 15%. The mean age at onset of KUT manifestations was 6.9 years (range, first weeks of life to 20 years; age was not available for 1 patient). Median follow-up after diagnosis of KUT involvement was 13 years (range, 3 months to 54 years). Patients with laminin 332 or integrin ß4 deficiency had at least 1 missense or splice site genetic variant, leading to residual expression of laminin 332 or integrin α6ß4, respectively. Severity of KUT complications did not correlate with the extent of skin involvement but with the affected protein. Conclusions and Relevance: Physicians and patients with JEB should be aware of the risk for KUT involvement in intermediate JEB, and physicians should apply interdisciplinary and individualized diagnostic and therapeutic procedures for management of these complications. Because this disorder is so rare, multicenter studies are required to make general recommendations.
Assuntos
Epidermólise Bolhosa Juncional , Sistema Urinário , Epidermólise Bolhosa Juncional/diagnóstico , Epidermólise Bolhosa Juncional/genética , Feminino , Humanos , Integrina alfa6beta4 , Integrina beta4 , Rim/metabolismo , Masculino , Estudos Retrospectivos , Sistema Urinário/metabolismoRESUMO
Sleep problems are frequently reported in infants treated with propranolol for infantile hemangiomas, possibly serving as a marker for a negative impact on central nervous system function. In this cohort study, we objectively investigate the sleep behavior of infants with infantile hemangiomas on propranolol compared to a healthy, untreated control group. Sleep of propranolol-treated infants and controls was investigated using ankle actigraphy and a 24-h diary for 7-10 days at ages 3 and 6 months. The main outcome measures were the Number of Nighttime Awakenings and Sleep Efficiency. The main secondary outcome measures included 24-hour Total Sleep, daytime sleep behavior, and parent-rated infant sleep quality and behavioral development based on the Brief Infant Sleep Questionnaire (BISQ) and the age-appropriate Ages-and-Stages Questionnaire (ASQ), respectively. Fifty-four term-born infants were included in each cohort. No group difference in any investigated parameter was seen at age 3 months. At age 6 months, the propranolol group exhibited a decrease in Sleep Efficiency and a trend towards an increased Number of Nighttime Awakenings compared to the control group. Treated infants at 6 months also had shorter daytime waking periods. 24-hour Total Sleep was unaffected by propranolol. No negative impact of propranolol on subjective sleep quality and behavioral development was noted.Conclusion: Propranolol exerts a measurable yet mild impact on objectively assessed infants' sleep measures. Behavioral developmental scores were unaffected. Our results support propranolol as first-line therapy for complicated infantile hemangiomas. What is Known: ⢠Sleep disorders are frequently reported in infants with infantile hemangiomas treated with propranolol and often lead to treatment discontinuation. ⢠Investigations of the sleep pattern in this patient group using objective measures are lacking. What is New: ⢠The sleep pattern of propranolol-treated infants is assessed using actigraphy and a 24-h sleep diary and compared to healthy, untreated controls. ⢠Propranolol leads to a decreased sleep efficiency at night and an increased demand of daytime sleep, yet effects are mild overall.
Assuntos
Hemangioma , Neoplasias Cutâneas , Transtornos do Sono-Vigília , Antagonistas Adrenérgicos beta , Estudos de Coortes , Humanos , Lactente , Propranolol/uso terapêutico , Sono , Transtornos do Sono-Vigília/etiologia , Resultado do TratamentoRESUMO
Pansclerotic morphea (PSM) is a rare skin disease characterized by progressive stiffening of the skin with or without the typical superficial skin changes usually seen in morphea (localized scleroderma). Standard therapy, consisting of a combination of systemic glucocorticoids and methotrexate or mycophenolate mofetil, does rarely stop disease progression, which may lead to severe cutaneous sclerosis and secondary contractures. Little is known about the efficacy of newer biologicals such as abatacept, a fusion protein antibody against CTLA-4, or tocilizumab, a fully humanized IL-6R antibody, in the treatment of this pathology. We present the case of an 8 years old girl with an unusual, progressive stiffening of the skin, which was eventually diagnosed as pansclerotic morphea. A treatment with systemic glucocorticoids and methotrexate combined with tocilizumab led to a good clinical response within 2 months after initiation. In this paper, we discuss differential diagnoses to be considered and this new promising treatment option based on a case review of the literature.
Assuntos
Esclerodermia Localizada/diagnóstico , Dermatopatias/diagnóstico , Biomarcadores , Biópsia , Criança , Diagnóstico Diferencial , Gerenciamento Clínico , Feminino , Humanos , Imuno-Histoquímica , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Pele/patologia , Avaliação de Sintomas , Resultado do TratamentoRESUMO
Dystrophic epidermolysis bullosa (DEB) is a hereditary skin fragility disorder, characterized by trauma-induced blistering followed by soft tissue fibrosis. One of the most feared complications is the early development of aggressive cutaneous squamous cell carcinomas (SCC). For patients with locally advanced or metastasized SCCs treatment with cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), has been proposed and so far, treatment of five DEB patients with cetuximab has been published. With this report, we extend the spectrum of EB patients treated with cetuximab by adding two additional patients. Taking together all DEB cases treated with cetuximab, we propose that cetuximab should be administered as early as possible, since it seems to be more efficient and is accompanied by rather mild adverse effects. We also show that EGFR is frequently expressed in DEB-associated SCCs, although there were noticeable differences in the level of expression, which may influence responsiveness to EGFR-targeting therapies. Although only limited experiences with targeted cancer treatments in EB exist, such reports highlight the treatments' effects in this specific cohort and assist our therapeutic decisions.
Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Cetuximab/uso terapêutico , Epidermólise Bolhosa Distrófica/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Adolescente , Adulto , Epidermólise Bolhosa Distrófica/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
BACKGROUND: Epidermolysis bullosa (EB) is a group of rare, genetic diseases that affect the integrity of epithelial tissues, most notably the skin. Patients experience recurrent skin wounding, with severity depending on type, sub-type, and mutation. Oleogel-S10, a formulation of birch bark extract, has demonstrated efficacy in a Phase 2 trial assessing re-epithelialization of wounds in EB. EASE (NCT03068780, EudraCT 2016-002066-32) is a randomized, Phase 3, placebo-controlled study designed to determine the efficacy of Oleogel-S10 versus placebo in patients with EB. METHODS: EASE is a Phase 3, two-phase study comprising a 90-day, double-blind, randomized, placebo-controlled phase, followed by 24 months of open-label, single-arm follow-up. Patients with junctional EB, dystrophic EB, or Kindler syndrome and target wounds (10 - 50cm2) present for > 21 days and < 9 months, are randomized in a 1:1 ratio to receive wound dressings according to local standard of care with or without Oleogel-S10. Placebo is based on the Oleogel-S10 vehicle, which is sunflower oil formulated to have a consistency indistinguishable from that of the active product. The primary endpoint of the trial, directed by the US health authority according to the required study endpoints for chronic cutaneous ulcer and burn wounds, is to compare the efficacy of Oleogel-S10 versus placebo according to the proportion of patients with complete closure of the target wound within 45 ± 7 days of treatment. Additional EB-focused endpoints include wound burden, patient-reported outcomes, and safety. RESULTS: Results of the primary endpoint are anticipated to be available by H2 2019. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03068780 . EudraCT, 2016-002066-32. Registered on 3 March 2017.
Assuntos
Betula , Epidermólise Bolhosa/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Projetos de Pesquisa , Método Duplo-Cego , Epidermólise Bolhosa/psicologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Compostos Orgânicos/uso terapêutico , Satisfação do Paciente , Casca de Planta , Qualidade de VidaRESUMO
Epidermolysis bullosa (EB) is a group of rare heterogeneous, genetic disorders. Currently, there is no effective pharmacological or genetic therapy for all EB subtypes. Dry extract from birch bark and betulin upregulate some pro-inflammatory mediators and downregulate others. The increase in pro-inflammatory cytokines is temporary and attenuated over long-term treatment. This inflammatory stimulus is thought to be prerequisite for a secondary anti-inflammatory response. Dry extract from birch bark and its active marker substances have also been shown to increase the migration of primary human keratinocytes, accelerate wound closure, and promote differentiation of keratinocytes in vitro and in vivo-processes that are essential for reepithelialization and maintenance of the skin barrier. Comprehensive clinical data are available to support the use of Oleogel-S10 in the treatment of partial thickness wounds of different etiologies, and a proof-of-concept Phase 2 study in patients with dystrophic EB has suggested the potential for faster reepithelialization of wounds treated with Oleogel-S10.
Assuntos
Epidermólise Bolhosa/tratamento farmacológico , Triterpenos/administração & dosagem , Citocinas/metabolismo , Fármacos Dermatológicos/administração & dosagem , Epidermólise Bolhosa/patologia , Humanos , Compostos Orgânicos/administração & dosagem , Resultado do TratamentoRESUMO
Congenital hemangiomas are vascular tumors that are fully formed at birth, typically without postnatal growth. Noninvoluting congenital hemangiomas (NICH) have a distinctive clinical, radiologic, and histopathological profile and lack of expansion or involution over time. Herein, we describe two cases of NICH with atypical postnatal growth.
Assuntos
Progressão da Doença , Hemangioma Capilar/congênito , Hemangioma Capilar/fisiopatologia , Neoplasias Cutâneas/congênito , Neoplasias Cutâneas/fisiopatologia , Braço , Face , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Monitorização Fisiológica/métodos , Prognóstico , Medição de RiscoRESUMO
Two unrelated patients with GATA2-haploinsufficiency developed a hemophagocytic lymphohistiocytosis (HLH)-like disease during a varicella zoster virus (VZV) infection. High copy numbers of VZV were detected in the blood, and the patients were successfully treated with acyclovir and intravenous immunoglobulins. After treatment with corticosteroids for the HLH, both patients made a full recovery. Although the mechanisms leading to this disease constellation have yet to be characterized, we hypothesize that impairment of the immunoregulatory role of NK cells in GATA2-haploinsufficiency may have accentuated the patients' susceptibility to HLH. Expansion of a double negative T-lymphocytic population identified with CyTOF could be a further factor contributing to HLH in these patients. This is the first report of VZV-triggered HLH-like disease in a primary immunodeficiency and the third report of HLH in GATA2-haploinsufficiency. Since HLH was part of the presentation in one of our patients, GATA2-haploinsufficiency represents a potential differential diagnosis in patients presenting with the clinical features of HLH-especially in cases of persisting cytopenia after recovery from HLH.
Assuntos
Deficiência de GATA2/imunologia , Fator de Transcrição GATA2/imunologia , Herpesvirus Humano 3/imunologia , Linfo-Histiocitose Hemofagocítica/imunologia , Linfócitos T/imunologia , Infecção pelo Vírus da Varicela-Zoster/imunologia , Criança , Feminino , Deficiência de GATA2/virologia , Humanos , Linfo-Histiocitose Hemofagocítica/virologia , Masculino , Projetos Piloto , Linfócitos T/virologia , Infecção pelo Vírus da Varicela-Zoster/virologiaRESUMO
BACKGROUND/OBJECTIVES: Infantile hemangiomas (IHs) involving the conjunctiva are only anecdotally reported in the literature and little is known about their clinical course. In a retrospective case series we aimed to better delineate the clinical presentation, complications, and response to treatment of this uncommon subtype of IH. A classification of conjunctival IH is proposed. METHODS: Medical charts at three academic pediatric dermatology institutions were retrospectively analyzed. Data were collected on the clinical characteristics, ophthalmologic findings, treatments, and outcomes of 22 individuals with conjunctival IH. RESULTS: Growth characteristics of conjunctival IH closely mirrored those of their cutaneous counterparts. Ophthalmologic abnormalities were associated with the IH in six individuals (27%); in three, they were considered severe. Seventeen subjects (77%) required treatment, most commonly because of risk of ocular compromise. All treated individuals responded favorably to topical timolol or systemic propranolol. CONCLUSION: Conjunctival IH have clinical characteristics similar to those of cutaneous IH and respond readily to beta-blocker treatment. Ocular complications may occur in a minority of individuals receiving treatment.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Túnica Conjuntiva/patologia , Neoplasias da Túnica Conjuntiva/diagnóstico , Hemangioma/diagnóstico , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Feminino , Seguimentos , Hemangioma/complicações , Hemangioma/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
INTRODUCTION: Skin fragility and recurrent wounds are hallmarks of hereditary epidermolysis bullosa (EB). Treatment options to accelerate wound healing are urgently needed. Oleogel-S10 contains a betulin-rich triterpene extract from birch bark. In this study, we tested the wound healing properties of topical Oleogel-S10 in patients with dystrophic EB. METHODS: We conducted an open, blindly evaluated, controlled, prospective phase II pilot trial in patients with dystrophic EB (EudraCT number 2010-019945-24). Healing of wounds treated with and without topical Oleogel-S10 was compared. Primary efficacy variable was faster reepithelialization as determined by 2 blinded experts. The main secondary outcome variable of the study was percentage of wound epithelialization. RESULTS: Twelve wound pairs of 10 patients with dystrophic EB were evaluated. In 5 of 12 cases, both blinded reviewers considered epithelialization of the intervention wounds as superior. In 3 cases, only one reviewer considered Oleogel-S10 as superior and the other one as equal to control. Measurements of wound size showed a trend towards accelerated wound healing with the intervention but without reaching statistical significance. CONCLUSION: Our results indicate a potential for faster reepithelialization of wounds in patients with dystrophic EB when treated with Oleogel-S10 but larger studies are needed to confirm significance.
RESUMO
The clinical significance of timely re-epithelialization is obvious in burn care, since delayed wound closure is enhancing the risk of wound site infection and extensive scarring. Topical treatments that accelerate wound healing are urgently needed to reduce these sequelae. Evidence from preliminary studies suggests that betulin can accelerate the healing of different types of wounds, including second degree burns and split-thickness skin graft wounds. The goal of this combined study program consisting of two randomized phase III clinical trials in parallel is to evaluate whether a topical betulin gel (TBG) is accelerating re-epithelialization of split-thickness skin graft (STSG) donor site wounds compared to standard of care. Two parallel blindly evaluated, randomised, controlled, multicentre phase III clinical trials were performed in adults undergoing STSG surgery (EudraCT nos. 2012-003390-26 and 2012-000777-23). Donor site wounds were split into two equal halves and randomized 1:1 to standard of care (a non-adhesive moist wound dressing) or standard of care plus TBG consisting of 10% birch bark extract and 90% sunflower oil (Episalvan, Birken AG, Niefern-Oeschelbronn, Germany). The primary efficacy assessment was the intra-individual difference in time to wound closure assessed from digital photographs by three blinded experts. A total of 219 patients were included and treated in the two trials. Wounds closed faster with TBG than without it (15.3 vs. 16.5 days; mean intra-individual difference=-1.1 days [95% CI, -1.5 to -0.7]; p<0.0001). This agreed with unblinded direct clinical assessment (difference=-2.1 days [95% CI, -2.7 to -1.5]; p<0.0001). Adverse events possibly related to treatment were mild or moderate and mostly at the application site. TBG accelerates re-epithelialization of partial thickness wounds compared to the current standard of care, providing a well-tolerated contribution to burn care in practice.
Assuntos
Queimaduras/terapia , Géis/uso terapêutico , Reepitelização , Transplante de Pele , Ferida Cirúrgica/tratamento farmacológico , Triterpenos/uso terapêutico , Administração Cutânea , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The genetic basis of epidermolysis bullosa, a group of genetic disorders characterized by the mechanically induced formation of skin blisters, is largely known, but a number of cases still remain genetically unsolved. Here, we used whole-exome and targeted sequencing to identify monoallelic mutations, c.1A>G and c.2T>C, in the translation initiation codon of the gene encoding kelch-like protein 24 (KLHL24) in 14 individuals with a distinct skin-fragility phenotype and skin cleavage within basal keratinocytes. Remarkably, mutation c.1A>G occurred de novo and was recurrent in families originating from different countries. The striking similarities of the clinical features of the affected individuals point to a unique and very specific pathomechanism. We showed that mutations in the translation initiation codon of KLHL24 lead to the usage of a downstream translation initiation site with the same reading frame and formation of a truncated polypeptide. The pathobiology was examined in keratinocytes and fibroblasts of the affected individuals and via expression of mutant KLHL24, and we found mutant KLHL24 to be associated with abnormalities of intermediate filaments in keratinocytes and fibroblasts. In particular, KLHL24 mutations were associated with irregular and fragmented keratin 14. Recombinant overexpression of normal KLHL24 promoted keratin 14 degradation, whereas mutant KLHL24 showed less activity than the normal molecule. These findings identify KLHL24 mutations as a cause of skin fragility and identify a role for KLHL24 in maintaining the balance between intermediate filament stability and degradation required for skin integrity.
Assuntos
Alelos , Códon de Iniciação/genética , Mutação , Proteínas Repressoras/genética , Anormalidades da Pele/genética , Pele/patologia , Adulto , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Linhagem , Pele/metabolismoAssuntos
Moléculas de Adesão Celular/genética , Epidermólise Bolhosa Juncional/genética , Mutação , Sítios de Splice de RNA , Adolescente , Adulto , Sequência de Bases , Biópsia , Moléculas de Adesão Celular/metabolismo , Análise Mutacional de DNA , Epidermólise Bolhosa Juncional/diagnóstico , Epidermólise Bolhosa Juncional/metabolismo , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Fenótipo , Pele/metabolismo , Pele/ultraestrutura , CalininaRESUMO
Mutations in genes encoding for desmosomal components are associated with a broad spectrum of phenotypes comprising skin and hair abnormalities and account for 45-50% of cases of arrhythmogenic right ventricular cardiomyopathy. Today, more than 120 dominant and recessive desmoplakin (DSP) gene mutations have been reported to be associated with skin, hair and/or heart defects. Here we report on 3 cases with yet unreported DSP mutations, c.7566_7567delAAinsC, p.R2522Sfs*39, c.7756C>T, p.R2586*, c.2131_2132delAG and c.1067C>A, p.T356K, that were associated with variable woolly hair or hypotrichosis, palmoplantar keratoderma, and cardiac manifestations. In addition, we review and summarise the clinical features and DSP mutations of the patients described in the literature, which illustrates the complexity of this group of disorders and of their genotype-phenotype correlations, which cannot be easily predicted. Early diagnosis is crucial and cardiac examinations have to be performed on a regular basis.
Assuntos
Cardiomiopatias/genética , Desmoplaquinas/genética , Doenças do Cabelo/congênito , Ceratodermia Palmar e Plantar/genética , Mutação , Adolescente , Cardiomiopatias/diagnóstico , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/genética , Hereditariedade , Humanos , Ceratodermia Palmar e Plantar/diagnóstico , Masculino , Linhagem , Fenótipo , Fatores de RiscoRESUMO
Acral peeling skin syndrome (APSS) is an autosomal recessive skin disorder characterized by acral blistering and peeling of the outermost layers of the epidermis. It is caused by mutations in the gene for transglutaminase 5, TGM5. Here, we report on clinical and molecular findings in 11 patients and extend the TGM5 mutation database by four, to our knowledge, previously unreported mutations: p.M1T, p.L41P, p.L214CfsX15, and p.S604IfsX9. The recurrent mutation p.G113C was found in 9 patients, but also in 3 of 100 control individuals in a heterozygous state, indicating that APSS might be more widespread than hitherto expected. Using quantitative real-time PCR, immunoblotting, and immunofluorescence analysis, we demonstrate that expression and distribution of several epidermal differentiation markers and corneodesmosin (CDSN) is altered in APSS keratinocytes and skin. Although the expression of transglutaminases 1 and 3 was not changed, we found an upregulation of keratin 1, keratin 10, involucrin, loricrin, and CDSN, probably as compensatory mechanisms for stabilization of the epidermal barrier. Our results give insights into the consequences of TGM5 mutations on terminal epidermal differentiation.
Assuntos
Diferenciação Celular/fisiologia , Dermatite Esfoliativa/genética , Dermatite Esfoliativa/patologia , Epiderme/patologia , Mutação/genética , Transtornos da Pigmentação/genética , Transtornos da Pigmentação/patologia , Transglutaminases/genética , Adulto , Biópsia , Estudos de Casos e Controles , Células Cultivadas , Criança , Pré-Escolar , Dermatite Esfoliativa/fisiopatologia , Epiderme/metabolismo , Epiderme/fisiopatologia , Glicoproteínas/metabolismo , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intercelular , Queratina-1/metabolismo , Queratina-10/metabolismo , Queratinócitos/metabolismo , Queratinócitos/patologia , Transtornos da Pigmentação/fisiopatologia , Precursores de Proteínas/metabolismo , Dermatopatias/congênitoRESUMO
Immunosuppression is necessary in a large number of conditions to modify immune responses and control disease severity. It is a vital part of treatment regimes following organ and bone marrow transplants. However, the use of immunosuppressive drugs has been shown to cause infections with common and unusual pathogens. We present the case of a 5-year-old female heart transplant recipient. Nine months after the transplant, she developed a tender acneiform eruption on her face consisting of numerous small yellowish to pink papules and pustules. Many of the lesions had a central, firm, small spinulous excrescence or a central dell. Histopathology demonstrated abnormal maturation of the hair follicles, nucleated eosinophilic cells with trichohyalin granules. The clinical presentation and histological features were in keeping with trichodysplasia spinulosa, a rare complication in immunosuppressed subjects. Treatment trials included reduction of immunosuppression combined with topical and oral retinoids, topical acyclovir, and oral valganciclovir with limited success.