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Olmsted syndrome is a rare genetic disorder characterized by severe thickening of the palms and soles, often resistant to conventional treatments. We present the case of a patient with Olmsted syndrome with a 16-year follow-up. The patient presented at five years of age with treatment-resistant palmoplantar keratoderma despite three years of dermatological management, leading to complications. Surgical interventions included initial debridement down to the deep dermis, which resulted in recurrence after three months. This was followed by a decision for extensive excision down to the subcutaneous tissue, use of a bilayer wound matrix dressing followed by negative pressure wound therapy, and a thin split-thickness graft, resulting in full resolution. The patient, now a college student, has regained normal daily activities. This case underscores the challenges and highlights a novel surgical approach for managing Olmsted syndrome, demonstrating a 16-year follow-up and aiming to improve patient outcomes in these complex cases.
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Symmetrical acral keratoderma (SAK) is a rare skin disorder with symmetric hyperkeratotic patches on the acral regions. Variants in the filaggrin gene (FLG) have been associated with SAK since 2020. To explore the clinical and genetic basis in six patients with SAK. Whole-exome sequencing, direct sequencing, and prediction of protein structure and function were performed. In this study, we identified two novel variants, c.3320del and c.4909del, and seven previously reported variants, c.3099C>G, c.4544C>A, c.6950_6957del, c.7264G>T, c.7945del, c.8117C>G, c.12064A>T. The findings of this study bolster the existing evidence implicating FLG variants in SAK, introducing two novel variants to the database of FLG variants associated with the condition.
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Proteínas Filagrinas , Proteínas de Filamentos Intermediários , Humanos , Proteínas de Filamentos Intermediários/genética , Feminino , Masculino , Sequenciamento do Exoma , Adulto , Ceratodermia Palmar e Plantar/genética , Pessoa de Meia-IdadeRESUMO
PLACK syndrome (OMIM 616295) is a rare genodermatosis associated with peeling skin, leukonychia, acral punctate keratosis, cheilitis, and knuckle pads and is caused by loss-of-function mutations in the CAST gene, which encodes calpastatin, a calcium-dependent protease. This case report highlights a case of PLACK syndrome presenting with the unique findings of striate hyperkeratosis on the palms as well as life-threatening cardiomyopathy. We review why CAST mutations might impact cardiac function and raise awareness of the potential association between PLACK syndrome and cardiac manifestations.
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Reactive arthritis(ReA), a form of arthritis occurring post-infection, manifests with antecedent infection symptoms, arthritis, and extra-articular manifestations, categorizing it as spondyloarthritis. "Keratoderma blennorrhagicum" (characterized by pustular hyperkeratosis on palms and soles, resembling pustular psoriasis) represents the most typical skin manifestation of ReA, occurring in acute or chronic phases. Severe lesions necessitate systemic disease modifying anti-rheumatic drugs (DMARDs) or biologic therapies. This article reports a case of ReA with sacroiliitis and widespread pustular eruptions following a urinary tract infection. Treatment with sulfasalazine and thalidomide significantly improved sacroiliitis, but the skin rash remained persistent and recurring. Subsequent use of adalimumab and secukinumab resulted in worsening skin rash, prompting a switch to tofacitinib, leading to a remarkable improvement in pustular eruptions after 20 days of treatment. This case demonstrates successful application of tofacitinib in treating severe keratoderma blennorrhagicum refractory to conventional DMARDs and biologics, offering insights into JAK inhibition for challenging rheumatic diseases with skin involvement.
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Artrite Reativa , Piperidinas , Pirimidinas , Humanos , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Artrite Reativa/tratamento farmacológico , Artrite Reativa/etiologia , Masculino , Feminino , Adulto , Resultado do Tratamento , Antirreumáticos/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Janus Quinases/uso terapêuticoRESUMO
Palmoplantar keratoderma (PPK) is a multi-faceted skin disorder characterized by the thickening of the epidermis and abrasions on the palms and soles of the feet. Among the genetic causes, biallelic pathogenic variants in the FAM83G gene have been associated with PPK in dogs and humans. Here, a novel homozygous variant (c.794G>C, p.Arg265Pro) in the FAM83G gene, identified by whole exome sequencing in a 60-year-old female patient with PPK, is reported. The patient exhibited alterations in the skin of both hands and feet, dystrophic nails, thin, curly and sparse hair, long upper eyelid eyelashes, and poor dental enamel. FAM83G activates WNT signalling through association with ser/thr protein kinase CK1α. When expressed in FAM83G-/- DLD1 colorectal cancer cells, the FAM83GR265P variant displayed poor stability, a loss of interaction with CK1α and attenuated WNT signalling response. These defects persisted in skin fibroblast cells derived from the patient. Our findings imply that the loss of FAM83G-CK1α interaction and subsequent attenuation of WNT signalling underlie the pathogenesis of PPK caused by the FAM83GR265P variant.
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Caseína Quinase Ialfa , Ceratodermia Palmar e Plantar , Via de Sinalização Wnt , Humanos , Feminino , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/patologia , Pessoa de Meia-Idade , Caseína Quinase Ialfa/metabolismo , Caseína Quinase Ialfa/genética , Sequenciamento do Exoma , Ligação Proteica , Fibroblastos/metabolismoRESUMO
Palmoplantar keratoderma (PPK) is a group of -disorders with genetic and phenotypic heterogeneity featuring skin thickening of the palms and soles. More than 60 genes involved in various biological processes are implicated in PPK. PIK3CA is an oncogene encoding p110α, and its somatic variants contribute to a spectrum of congenital overgrowth disorders, including epidermal nevi (EN). To identify the genetic basis and elucidate the pathogenesis of a patient with unilateral focal PPK. Whole-exome sequencing and Sanger sequencing combined with laser capture microdissection (LCM) were performed on genomic DNA extracted from the patient's peripheral blood and skin lesion. Skin biopsies were taken from the lesion of the patient and normal controls for immunofluorescence. Molecular docking was performed using Alphafold2-multimer. A three-year-old girl presented with unilateral focal PPK with an identified missense -variant (c.3140A>G, p.His1047Arg) in PIK3CA from affected tissue. This variant only existed in the lesional epidermis. Elevated PI3K/AKT/mTOR signalling in the affected epidermis and an increased number of Ki67-positive keratinocytes were demonstrated. Molecular docking indicated instability of the p110α-p85α dimer caused by the PIK3CA His1047Arg variant. We describe the first PPK case associated with a variant in PIK3CA, which expands the spectrum of PIK3CA-related disorders. Our study further underscores the importance of the PI3K/AKT/mTOR pathway in the homeostasis of skin keratinization.
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Classe I de Fosfatidilinositol 3-Quinases , Ceratodermia Palmar e Plantar , Mutação de Sentido Incorreto , Transdução de Sinais , Pré-Escolar , Feminino , Humanos , Classe I de Fosfatidilinositol 3-Quinases/genética , Sequenciamento do Exoma , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Mal De Meleda is a rare genetic disorder characterized by palmoplantar keratoderma, often presenting challenges in diagnosis and management. This case report discusses an 18-year-old male presenting with thickened, yellowish skin on both palms and soles, accompanied by itching and cracking. A diagnosis of the transgradiens variant of Mal De Meleda was established through clinical and histopathological examination. Treatment with oral acitretin and topical moisturizers resulted in significant improvement. This report highlights the importance of recognizing rare variants of palmoplantar keratoderma and the need for a multidisciplinary approach to diagnosis and management.
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This article addresses the diagnostic challenges of palmoplantar dermatoses (PPD) within the scope of Primary Health Care (PHC). These common skin conditions, encountered in daily practice, exhibit a diverse range of symptoms and morphologies, complicating their diagnosis. They are etiologically classified into infectious inflammatory, non-infectious inflammatory, and hereditary keratodermas. While various dermatoses may affect the palms and soles, few are specific to this area. Notable examples include palmoplantar pustulosis, dyshidrosis, erythema pernio, and Bazex syndrome. Given the high prevalence of dermatological consultations in PHC, this article underscores the significance of PHC professionals' knowledge regarding these conditions. It proposes a diagnostic algorithm to facilitate their management and timely referral.
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Nagashima-type palmoplantar keratoderma is an autosomal recessive genodermatosis caused by loss-of-function variants in SERPINB7 and is the most prevalent form of inherited palmoplantar keratodermas among Asians. However, there is currently no effective therapy for Nagashima-type palmoplantar keratoderma because its pathogenesis remains unclear. In this study, Serpinb7-/- mice were generated and spontaneously developed a disrupted skin barrier, which was further exacerbated by acetone-ether-water treatment. The skin of these Serpinb7-/- mice showed weakened cytoskeletal proteins. In addition, SERPINB7 deficiency consistently led to decreased epidermal differentiation in a 3-dimensional human epidermal model. We also demonstrated that SERPINB7 was an inhibitory serpin that mainly inhibited the protease legumain. SERPINB7 bound directly with legumain and inhibited legumain activity both in vitro and in vivo. Furthermore, we found that SERPINB7 inhibited legumain in a protease-substrate manner and identified the cleavage sites of SERPINB7 as Asn71 and Asn343. Overall, we found that SERPINB7 showed the nature of a cysteine protease inhibitor and identified legumain as a key target protease of SERPINB7. Loss of SERPINB7 function led to overactivation of legumain, which might disrupt cytoskeletal proteins, contributing to the impaired skin barrier in Nagashima-type palmoplantar keratoderma. These findings may lead to the development of therapeutic strategies for Nagashima-type palmoplantar keratoderma.
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SLURP1 and SLURP2 are both small secreted members of the Ly6/u-PAR family of proteins and are highly expressed in keratinocytes. Loss-of-function mutations in SLURP1 lead to a rare autosomal recessive palmoplantar keratoderma (PPK), Mal de Meleda (MdM), which is characterized by diffuse, yellowish palmoplantar hyperkeratosis. Some individuals with MdM experience pain in conjunction with the hyperkeratosis that has been attributed to fissures or microbial superinfection within the affected skin. By comparison, other hereditary PPKs such as pachyonychia congenita and Olmsted syndrome show prevalent pain in PPK lesions. Two mouse models of MdM, Slurp1 knock-out and Slurp2X knock-out, exhibit robust PPK in all four paws. However, whether the sensory experience of these animals includes augmented pain sensitivity remains unexplored. In this study, we demonstrate that both models exhibit hypersensitivity to mechanical and thermal stimuli as well as spontaneous pain behaviors in males and females. Anatomical analysis revealed slightly reduced glabrous skin epidermal innervation and substantial alterations in palmoplantar skin immune composition in Slurp2X knock-out mice. Primary sensory neurons innervating hindpaw glabrous skin from Slurp2X knock-out mice exhibit increased incidence of spontaneous activity and mechanical hypersensitivity both in vitro and in vivo. Thus, Slurp knock-out mice exhibit polymodal PPK-associated pain that is associated with both immune alterations and neuronal hyperexcitability and might therefore be useful for the identification of therapeutic targets to treat PPK-associated pain.
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Antígenos Ly , Ceratodermia Palmar e Plantar , Camundongos Knockout , Ativador de Plasminogênio Tipo Uroquinase , Animais , Feminino , Masculino , Camundongos , Antígenos Ly/genética , Antígenos Ly/metabolismo , Modelos Animais de Doenças , Hiperalgesia/genética , Hiperalgesia/fisiopatologia , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/patologia , Camundongos Endogâmicos C57BL , Limiar da Dor/fisiologia , Ativador de Plasminogênio Tipo Uroquinase/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismoRESUMO
Key Clinical Message: Keratosis palmoplantaris striata type I (SPPK-I) is a rare autosomal-dominant type of hereditary epidermolytic palmoplantar keratoderma, which can be caused by mutations in desmoglein-1 (DSG-1). Patients suffer from hyperkeratotic plaques and painful palmoplantar fissures. Unfortunately, treatment options including salicylic vaseline, topical corticosteroids, phototherapy, and retinoids are inefficient. Abstract: Hereditary palmoplantar keratodermas (PPKs) represent a heterogeneous group of rare skin disorders with epidermal palmoplantar hyperkeratosis. Mutations in the desmoglein 1 gene (DSG1), a transmembrane glycoprotein, have been reported primarily in striate PPKs. We report a patient with keratosis palmoplantaris striata type I (SPPK-I) with a specific pathogenic variant [c.349C>T, p.(Arg117*)] in DSG1. Despite increased understanding, effective treatment options for PPK, including SPPK-I, remain limited.
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Background: Crusted scabies is a rare form of parasitic infection provoked by a massive infestation of the ectoparasite Sarcoptes scabiei varietas hominis on human skin. It is an extremely contagious type of disease and can even lead to a social stigma. In European countries like Greece, many cases remain undiagnosed for long periods, causing extreme distress in the patient's everyday life and social environment. Case Description: Herein, we present a case of an 86-year-old woman with crusted scabies in Greece, who remained undiagnosed for 5 months. Massive hyperkeratotic plaques on the extremities, and face, palmoplantar keratoderma, and numerous small erythematous papules on the torso with extreme itch were the main clinical manifestations of the patient. Dermoscopy revealed the parasite. All necessary decontamination measures were taken by personnel. Treatment was administered and a complete cure of the disease was observed. Conclusions: In this case, the use of dermoscopy has attributed to precise crusted scabies diagnosis and acute pharmacological management of the patient. Early diagnosis of such diseases not only saves patients from lethal secondary infections, but also reduces the risk of a massive scabies outbreak. We also conducted a mini-review, analyzing all recent data concerning crusted scabies macroscopic, dermatoscopic, and histological images. All new information concerning the pathophysiological mechanism of crusted scabies manifestation, updated treatment options, and potential resistance to widely-used treatments are provided.