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Introduction: Cutaneous T-cell dyscrasia (CTCD) encompasses a heterogeneous group of T-cell infiltrates, often clonal and epitheliotropic. While the etiology remains unclear, certain medications, including statins, have been linked to cutaneous T-cell lymphocytic infiltrate development. Case Description: A patient presented with a pruritic, scaly eruption on her palms and soles unresponsive to topical steroids for 1 month. Histopathological examination revealed compact orthokeratosis, mild lymphocytic infiltrate with focal exocytosis, and atypical lymphocytes. Immunophenotyping demonstrated a predominance of CD3+ T cells with a 1:1 CD4/CD8 ratio and reduced CD7 expression. The clinical presentation, histopathology, and immunophenotype supported a diagnosis of statin-induced CTCD. Conclusion: Statin discontinuation led to complete symptom resolution, emphasizing the reversibility of drug-induced T-cell dyscrasia. This case highlights the importance of a detailed medication history as drug-induced T-cell dyscrasia, unlike classic CTCD with its characteristic lymphoid atypia, phenotypic abnormalities, and clonality leading to a refractory course, can be reversed by drug withdrawal. [ABSTRACT FROM AUTHOR]

Introduction: Cutaneous T-cell dyscrasia (CTCD) encompasses a heterogeneous group of T-cell infiltrates, often clonal and epitheliotropic. While the etiology remains unclear, certain medications, including statins, have been linked to cutaneous T-cell lymphocytic infiltrate development. Case Description: A patient presented with a pruritic, scaly eruption on her palms and soles unresponsive to topical steroids for 1 month. Histopathological examination revealed compact orthokeratosis, mild lymphocytic infiltrate with focal exocytosis, and atypical lymphocytes. Immunophenotyping demonstrated a predominance of CD3+ T cells with a 1:1 CD4/CD8 ratio and reduced CD7 expression. The clinical presentation, histopathology, and immunophenotype supported a diagnosis of statin-induced CTCD. Conclusion: Statin discontinuation led to complete symptom resolution, emphasizing the reversibility of drug-induced T-cell dyscrasia. This case highlights the importance of a detailed medication history as drug-induced T-cell dyscrasia, unlike classic CTCD with its characteristic lymphoid atypia, phenotypic abnormalities, and clonality leading to a refractory course, can be reversed by drug withdrawal.

Spiny keratoderma is a rare skin condition that presents on the palmar and plantar surfaces of the hands and/or feet. This condition is difficult to appreciate under ambient lighting but can be both physically and emotionally distressing to patients. Furthermore, because of the association with various neoplasms and systemic diseases, timely diagnosis and appropriate follow-up is of importance. We evaluate a case of spiny keratoderma in a patient with recently diagnosed hypothyroidism and emphasize the importance of proper lighting during a dermatology-focused physical examination. The patient's palmar lesions were only appreciable under LED light and with physical examination. A biopsy of the lesions confirmed the diagnosis of spiny keratoderma.

Spiny keratoderma (SKD) is a rare palmoplantar keratoderma that presents with few to numerous millimetric hyperkeratotic projections on the palms and soles. It has been described with both hereditary and acquired variants. The acquired form, which presents in older adults, has been associated with a variety of systemic diseases and malignant conditions. In patients suspected of having acquired spiny keratoderma, an evaluation for malignant conditions may be warranted. Treatment with topical keratolytics or topical and oral retinoids is usually insufficient. Herein, we present the case of a 58-year-old man diagnosed with idiopathic SKD.

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. 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. [ABSTRACT FROM AUTHOR]

Introduction: Palmoplantar psoriasis is a rare variant of psoriasis. Its impact on quality of life have been poorly investigated. Objectives: Our aim was to investigate the prevalence of localized palmoplantar psoriasis (PPP), to assess its severity using the modified-Palmoplantar Pustular Psoriasis Area and Severity Index (m-PPPASI), and to evaluate the correlation with the Dermatology Life Quality Index (DLQI). Methods: We conducted a descriptive study with prospective data-collection from January to June 2021. We enrolled 223 patients with psoriasis. We excluded patients without palmar/plantar involvement, and those with a body surface area (BSA) greater than or equal to 10%. Results: We included 33 patients with PPP. This corresponded to a 14.8% prevalence among all psoriasis phenotypes. The mean age was 45 years. The male to female ratio was 2.3. Pruritus was present in 27 cases. The mean m-PPPASI was 11.77. The mean DLQI was 8.33. A significant correlation was found between DLQI and m-PPPASI: Mean DLQI scores for patients with m-PPPASI less than or equal to 10 and m-PPPASI greater than 10 were 5.6 and 11.3, respectively (p=0.002). Only 11.8% of patients with m-PPPASI less than or equal to 10 had a DLQI greater than 10, whereas 50% of those with m-PPPASI greater than 10 had a DLQI greater than 10 (p=0.026). Conclusions: Based on the present work, we confirm that, although affecting a reduced BSA, PPP is a severe form of psoriasis. We consider the m-PPPASI to be a reliable tool which can be used to assess the severity of PPP.

Abstract Keratoderma climactericum is characterized by palmoplantar hyperkeratosis developing after the onset of menopause. Although rare, keratoderma climactericum can profoundly impact quality of life and may be refractory to prescription‐strength topical steroids and keratolytics. We report a 52‐year‐old female with a 1‐year history of palmoplantar keratoderma. She had a medical history of generalized anxiety disorder and had reached menopause 2 years before presentation. Previously failed treatments included clotrimazole 1% cream twice daily, triamcinolone 0.1% cream twice daily, and betamethasone 0.05% cream mixed with tazarotene 0.1% cream twice daily. She was diagnosed with keratoderma climactericum, and conjugated oestrogen 0.625 mg/g cream twice daily was initiated. After 4 weeks, she had dramatically reduced erythema and hyperkeratosis of her bilateral palms and soles. No adverse effects to treatment were reported. Although the utility of topical oestrogen for keratoderma climactericum has been debated, our case provides further evidence for its efficacy and safety.

BACKGROUND: Papillon-Lefevre syndrome is a rare genodermatosis characterized by hyperkeratosis of the palms and soles, aggressively progressive periodontitis that leads to premature loss of primary and permanent teeth due to an autosomal recessive hereditary disorder, caused by mutations in the gene for cathepsin C. CLINICAL CASE: Two female patients with disseminated dermatosis to the upper and lower extremities, which affected the palms, soles, back of the hands and feet at the level of the fingers and bone protrusions, bilateral and symmetrical, consisting of yellowish, erythematous keratoses and thick scales that converged to form plaques with well-defined erythematous borders, accompanied by onychodystrophy and anodontia. CONCLUSIONS: We consider relevant to share more cases of this type, because they are diseases of low prevalence and incidence, and knowing them can lead us to an ever-increasing understanding of the illness, so it is reasonable to maintain a positive perspective towards the future while waiting for new treatments. [ABSTRACT FROM AUTHOR]

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.

Simulated standardized patients (SSP) have emerged as close to a gold standard for measuring the quality of clinical care. This method resolves problems of patient mix across healthcare providers and allows care to be benchmarked against preexisting standards. Nevertheless, SSPs are not real patients. How, then, should data from SSPs be considered relative to clinical observations with real patients in a given health system? Here, we reject the proposition that SSPs are direct substitutes for real patients and that the validity of SSP studies therefore relies on their ability to imitate real patients. Instead, we argue that the success of the SSP methodology lies in its counterfactual manipulations of the possibilities available to real careseekers - especially those paths not taken up by them - through which real responses can be elicited from real providers. Using results from a unique pilot study where SSPs returned to providers for follow-ups when asked, we demonstrate that the SSP method works well to elicit responses from the provider through conditional manipulations of SSP behavior. At the same time, observational methods are better suited to understand what choices real people make, and how these can affect the direction of diagnosis and treatment. A combination of SSP and observational methods can thus help parse out how quality of care emerges for the patient as a shared history between care-seeking individuals and care providers.

Abstract Pityriasis rubra pilaris (PRP) can be triggered by viruses, such as cytomegalovirus, Epstein‐Barr virus, varicella zoster, human immunodeficiency virus and, more exceptionally, SARS‐CoV‐2. We report an additional case of PRP following COVID‐19 infection. Given the existing literature and the close temporal association, we suggest a possible causal relationship. We speculate that an altered immune response with a genetic predisposition for PRP may have played a role in our patient. We highlight the development of PRP as part of the spectrum of COVID‐19 skin‐related conditions.

Introduction: The present report describes the case of a 12-year-old patient with 17-year follow-up who was previously diagnosed with Papillon-Lefèvre Syndrome (PLS), which is a rare autosomal recessive irregularity in the cathepsin C gene (CTSC) characterized by palmoplantar hyperkeratosis and premature loss of primary and permanent teeth. Case Report: A specific mutation in the c.203 T > G gene inducing loss of function leading to PLS was detected, as was a mutation in the HLA-DRB1*11 allele, which is associated with this syndrome. There is no consanguinity of the parents, and the siblings are entirely healthy. Early identification of the main characteristics of this syndrome is imperative. Accurate diagnosis by genetic analysis allows differential diagnoses and timely comprehensive dental treatment. Conclusions: Additionally, it allows consultation with a dermatologist to maintain or improve the quality of life of patients with this condition due to progressive worsening and severity of the main physical manifestations.

Backgound Keratoderma is a manifestation of different skin diseases whether inherited or acquired, systemic or cutaneous diseases, and is demonstrated as the thickening of the epidermis of palms and soles singly or in combination. Objective To record all cases of keratoderma those are seen in daily clinical practice over a specified period. Methods This is a case series descriptive study where all patients with keratoderma of palms and or soles were recorded during years between 2014-2022years. Full history and clinical examination were carried out aiming to establish the right clinical diagnosis and all demographic features were recorded. Biopsies for histopathological assessment were carried out in suspected cases and a scrape for fungus was done in patients with tinea as a confirmatory test. Results Forty-two patients with keratoderma were seen during this specified period, their ages ranged from 6 months-30years with a median of 6 years, with 32 (94%) males and 2 (5.88%) females. Regarding the diagnosis of keratoderma, 13(30.95%) with congenital, 11 (26%) with pityriasis rubra pilaris, 7 (16.66%) with lichen planus, 6 (14.7%) with dermatophytes and 5 (11.9%) with psoriasis. Conclusion Kertatoderma is a disease of male patients which has different etiological factors commonly congenital, followed by pityriasis rubra pilaris, then lichen planus, dermatophytes, and Psoriasis. Keratoderma could be the only manifestation of these diseases where the diagnosis could be very difficult, especially in the acquired variants. [ABSTRACT FROM AUTHOR]

Abstract Acrokeratoelastoidosis (AKE) is a marginal papular keratoderma. It is a rare autosomal dominant condition that may also present in childhood or adulthood in sporadic cases. AKE is distinguished by its histological findings, with dermal elastorrhexis and an overlying epithelial dell. We report a 55‐year‐old woman with AKE and knuckle pads on the palms and soles, which are considered as an extension of AKE papules to the interphalangeal joints.

Rationale: Papillon-Lefèvre syndrome (PLS) is a rare genodermatosis with autosomal-recessive genetic inheritanceand has features mainly palmoplantar hyperkeratosis and rapidly progressing severe periodontitis leading to early loss of deciduous and permanent dentition. Patient Concerns: The patient in the presented report was concerned with loose teeth, gingival bleeding and oral malodour and wanted to get missing teeth replaced. Diagnosis: The diagnosis was made based on medical history, clinical and radiological findings. Interventions: Periodontal phase I therapy included extraction of hopeless teeth, manual and ultrasonic scaling, mechanical and chemical plaque control and periodic maintenance. Missing teeth were restored by removable and fixed prosthesis. Dermatological lesions were conservatively managed. Outcomes: A comprehensive treatment stabilised periodontal disease of the patient and prosthetic rehabilitation improved oral health related quality of life of PLS patient. Lessons: PLS patients require an early diagnosis and a team approach for dermatological, periodontal complications and prosthetic rehabilitation.

Pachydermoperiostosis (PDP) is a rare genodermatosis with prominent cutaneous, soft tissue and skeletal manifestations. It can mimic secondary causes of hypertrophic osteoarthropathy such as thyroid acropachy. Cutaneous manifestations can be debilitating and constitute critical clues to formulating an accurate diagnosis. Palmoplantar keratoderma is a seldom reported manifestation of the disease hence, its significance as a phenotypic variant of pachydermoperiostosis is unknown. We describe a rare case of complete pachydermoperiostosis with diffuse palmoplantar keratoderma in a young African man presenting with hyperhidrosis, hyper-defecation and weight loss who had been previously misdiagnosed with thyroid acropachy. The aim is to provide a detailed clinical description of both common and unconventional features of this rare disease. Pachydermoperiostosis manifests with diverse genotypic and phenotypic characteristics that can mimic treatable, secondary causes of hypertrophic osteoarthropathy. Keratoderma and hyper-defecation are seldom reported manifestations that may represent unique variants of PDP. Awareness of characteristic dermatological manifestations of the disease can enhance early and accurate clinical diagnosis and prevent needless investigations.

BACKGROUND: Acrokeratoelastoidosis of Costa is a genodermatosis that can be autosomal dominant with variable expressivity, although sporadic cases have also been described. It belongs to the group of palmoplantar keratoderma. Clinically, papules are observed in marginal areas of palms and soles. It belongs to the group of palmoplantar keratoderma, the histopathological findings help in the diagnosis showing hyperkeratosis, hypergranulosis, moderate acanthosis, homogenization of collagen fibers with elastorrhexis that can be better observed in special stains for elastic fiber. CLINICAL CASE: A 56-year-old female patient with lesions that started in childhood consisting of papules in the marginal zone of the palms and soles, which increased in size and progressively in number. She had a family history of first degree of consanguinity (mother) with the same lesions, with histopathology report showing compact orthokeratotic hyperkeratosis, acanthotic epithelium and prominent granular layer, the elastic fibers staining revealed foci of rupture and elastorrhexis. A diagnosis of acrokeratoelastoidosis of Costa was established, and management with 15% urea was started with partial improvement. CONCLUSIONS: Acrokeratoelastoidosis of Costa is an uncommon disease, so far without prevalence studies and with isolated case reports. whose diagnosis is based on clinical manifestations, histopathological study and stains for elastic fiber. It represents an important esthetic compromise. [ABSTRACT FROM AUTHOR]

Rationale: Papillon-Lefèvre syndrome (PLS) is a rare genodermatosis with autosomal-recessive genetic inheritanceand has features mainly palmoplantar hyperkeratosis and rapidly progressing severe periodontitis leading to early loss of deciduous and permanent dentition. Patient Concerns: The patient in the presented report was concerned with loose teeth, gingival bleeding and oral malodour and wanted to get missing teeth replaced. Diagnosis: The diagnosis was made based on medical history, clinical and radiological findings. Interventions: Periodontal phase I therapy included extraction of hopeless teeth, manual and ultrasonic scaling, mechanical and chemical plaque control and periodic maintenance. Missing teeth were restored by removable and fixed prosthesis. Dermatological lesions were conservatively managed. Outcomes: A comprehensive treatment stabilised periodontal disease of the patient and prosthetic rehabilitation improved oral health related quality of life of PLS patient. Lessons: PLS patients require an early diagnosis and a team approach for dermatological, periodontal complications and prosthetic rehabilitation. [ABSTRACT FROM AUTHOR]

Mutations in SLURP1, a secreted protein of keratinocytes, cause a palmoplantar keratoderma (PPK) known as mal de Meleda. Slurp1 deficiency in mice faithfully recapitulates the human disease, with increased keratinocyte proliferation and thickening of the epidermis on the volar surface of the paws. There has long been speculation that SLURP1 serves as a ligand for a receptor that regulates keratinocyte growth and differentiation. We were intrigued that mutations leading to increased signalling through the epidermal growth factor receptor (EGFR) cause PPK. Here, we sought to determine whether reducing EGFR signalling would ameliorate the PPK associated with SLURP1 deficiency. To address this issue, we bred Slurp1-deficient mice that were homozygous for a hypomorphic Egfr allele. The hypomorphic Egfr allele, which leads to reduced EGFR signalling in keratinocytes, did not ameliorate the PPK elicited by SLURP1 deficiency, suggesting that SLURP1 deficiency causes PPK independently (or downstream) from the EGFR pathway.

SLURP1, a member of the lymphocyte antigen 6 protein family, is secreted by suprabasal keratinocytes. Mutations in SLURP1 cause a palmoplantar keratoderma (PPK) known as mal de Meleda. SLURP2, another secreted lymphocyte antigen 6 protein, is encoded by a gene located ?20 kb downstream from SLURP1. SLURP2 is produced by suprabasal keratinocytes. To investigate the importance of SLURP2, we first examined Slurp2 knockout mice in which exon 2-3 sequences had been replaced with lacZ and neo cassettes. Slurp2(-/-) mice exhibited hyperkeratosis on the volar surface of the paws (i.e., palmoplantar keratoderma), increased keratinocyte proliferation, and an accumulation of lipid droplets in the stratum corneum. They also exhibited reduced body weight and hind limb clasping. These phenotypes are similar to those of Slurp1(-/-) mice. To solidify a link between Slurp2 deficiency and palmoplantar keratoderma and to be confident that the disease phenotypes in Slurp2(-/-) mice were not secondary to the effects of the lacZ and neo cassettes on Slurp1 expression, we created a new line of Slurp2 knockout mice (Slurp2X(-/-)) in which Slurp2 was inactivated with a simple nonsense mutation. Slurp2X(-/-) mice exhibited the same disease phenotypes. Thus, Slurp2 deficiency and Slurp1 deficiencies cause the same disease phenotypes.

Cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK) syndrome is an autosomal recessive neuro-cutaneous disorder characterized by a collection of clinical manifestations, including microcephaly, cerebral dysgenesis, palmoplantar keratoderma, facial dysmorphism, and ichthyosis. The etiology of this condition has been proved to be a homozygous mutation in the SNAP29 gene, which has an essential role in dermatological and neurological manifestations of this syndrome. In this report, we present the first documented Iranian patient with CEDNIK syndrome. So far, only 14 cases of this condition have been reported globally. [ABSTRACT FROM AUTHOR]

Keratoderma is a group of dermatoses characterized by a violation of keratinization processes, excessive horn formation mainly in the area of the palms and soles. Under our supervision in the Tashkent regional skin and venereal clinic in the Department of dermatology was a patient Z. born in 2007, who was undergoing inpatient treatment for Meleda island disease. The rash is localized in the area of the palm and soles, changes and dystrophy of the nails. As a result of inpatient treatment (12 days), the Horny layers on the palms and soles decreased, especially in the Central part. All the cracks have fused, no new ones have been found. The severity of inflammatory phenomena, hyperkeratotic layers decreased, the area of the lesion and the intensity of itching decreased. The patient was discharged from the hospital with clinical improvement. This case is of particular interest to practical dermatovenerologists as a rare dermatosis

Abstract Rapp–Hodgkin syndrome (RHS) is a rare condition that is characterized by ectodermal dysplasia and palatal abnormalities. Palmoplantar keratoderma (PPK) is an unusual manifestation of hidrotic ED. Ulcerations on the palms are also not common in RHS. We describe a 15‐year‐old boy who has RHS associated with PPK.

Cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK) syndrome is an autosomal recessive neuro-cutaneous disorder characterized by a collection of clinical manifestations, including microcephaly, cerebral dysgenesis, palmoplantar keratoderma, facial dysmorphism, and ichthyosis. The etiology of this condition has been proved to be a homozygous mutation in the SNAP29 gene, which has an essential role in dermatological and neurological manifestations of this syndrome. In this report, we present the first documented Iranian patient with CEDNIK syndrome. So far, only 14 cases of this condition have been reported globally.

Arrhythmogenic cardiomyopathy (AC) is associated with mutations in genes encoding intercalated disc proteins and ultimately results in sudden cardiac death. A subset of patients with AC have the autosomal recessive cardiocutaneous disorder Naxos disease, which is caused by a 2-base pair deletion in the plakoglobin-encoding gene JUP that results in a truncated protein with reduced expression. In mice, cardiomyocyte-specific plakoglobin deficiency recapitulates many aspects of human AC, and overexpression of the truncated Naxos-associated plakoglobin also results in an AC-like phenotype; therefore, it is unclear whether Naxos disease results from loss or gain of function consequent to the plakoglobin mutation. Here, we generated 2 knockin mouse models in which endogenous Jup was engineered to express the Naxos-associated form of plakoglobin. In one model, Naxos plakoglobin bypassed the nonsense-mediated mRNA decay pathway, resulting in normal levels of the truncated plakoglobin. Moreover, restoration of Naxos plakoglobin to WT levels resulted in normal heart function. Together, these data indicate that a gain of function in the truncated form of the protein does not underlie the clinical phenotype of patients with Naxos disease and instead suggest that insufficiency of the truncated Naxos plakoglobin accounts for disease manifestation. Moreover, these results suggest that increasing levels of truncated or WT plakoglobin has potential as a therapeutic approach to Naxos disease.

Mutations in SLURP1 cause mal de Meleda, a rare palmoplantar keratoderma (PPK). SLURP1 is a secreted protein that is expressed highly in keratinocytes but has also been identified elsewhere (e.g., spinal cord neurons). Here, we examined Slurp1-deficient mice (Slurp1(-/-)) created by replacing exon 2 with β-gal and neo cassettes. Slurp1(-/-) mice developed severe PPK characterized by increased keratinocyte proliferation, an accumulation of lipid droplets in the stratum corneum, and a water barrier defect. In addition, Slurp1(-/-) mice exhibited reduced adiposity, protection from obesity on a high-fat diet, low plasma lipid levels, and a neuromuscular abnormality (hind-limb clasping). Initially, it was unclear whether the metabolic and neuromuscular phenotypes were due to Slurp1 deficiency, because we found that the targeted Slurp1 mutation reduced the expression of several neighboring genes (e.g., Slurp2, Lypd2). We therefore created a new line of knockout mice (Slurp1X(-/-) mice) with a simple nonsense mutation in exon 2. The Slurp1X mutation did not reduce the expression of adjacent genes, but Slurp1X(-/-) mice exhibited all of the phenotypes observed in the original line of knockout mice. Thus, Slurp1 deficiency in mice elicits metabolic and neuromuscular abnormalities in addition to PPK.

La acroqueratoelastoidosis de Costa es una rara genodermatosis autosómica dominante con expresividad variable, que se caracteriza por la presencia de múltiples pápulas hiperqueratósicas en la zona marginal de las manos, los pies o ambas. Debuta predominantemente en la niñez y vida adulta temprana, es de curso crónico y generalmente asintomática. Su diagnóstico diferencial del resto de las acroqueratodermias es un desafío para el clínico, sin embargo, el hallazgo histológico de elastorrexis nos permite categorizarla. Presentamos un caso esporádico de una paciente joven, con características clínicas e histopatológicas típicas de la enfermedad.

Keratolytic winter erythema (KWE) is a rare autosomal dominant keratoderma affecting primarily the palms and soles, manifesting with recurrent waves of erythema followed by epidermal peeling. The condition is so named in view of its anecdotal worsening during the winter months. It is highly penetrant but shows considerable individual clinical variability, waning and reappearing throughout the life course. Histologically, early established lesions of KWE manifest with degenerative changes involving the Malpighian layer, with associated absence of the stratum granulosum. The damaged zone undergoes parakeratotic transformation and subsequent centrifugal ejection. Thick peeling occurs when the stratum corneum eventually separates off as a result of a keratolytic split occurring above, through or below the parakeratotic zone. Reconstitution of the stratum granulosum ensues. KWE is caused by a duplication of an intergenic enhancer element upstream of the cathepsin B gene on chromosome 8. This leads to the upregulation of cathepsin B in the stratum granulosum and subsequent peeling of the epidermis as the end result. With elucidation of the molecular pathology of KWE, new therapeutic approaches to KWE may be considered.

N/a.

Mal de Meleda (MdM) is an autosomal recessive form of palmoplantar keratoderma, that is characterized by transgradient keratoderma with associated scleroatrophy, nail changes, pseudoainhum around digits and perioral erythema, without a tendency for spontaneous resolution. Mal de Meleda can lead to severe flexion contractures in some patients as well as mycotic over-rinfections with significant impact on quality of life and daily activity. Mal de Meleda is a rare genetic disorder but no standardized treatment has been established. Treatment options for this disease include topical keratolytic agents, propylene glycol, topical 5-fluorouracil and surgical treatment. In addition, it has been reported that etretinate and acitretin, usually produce improvement. Herein, we present a case of Mal de Meleda with lips involvement which showed significant clinical improvement with acitritin.

Inherited monogenic palmoplantar keratodermas are a heterogeneous group of conditions characterised by persistent epidermal thickening of the palmoplantar skin. Palmoplantar keratodermas are grouped depending on the morphology of the keratoderma into diffuse, focal/striate or papular/punctate. Some palmoplantar keratodermas just affect the skin of the palms and soles and others have associated syndromic features which include changes in hair, teeth, nails, hearing loss or cardiomyopathy. Next generation sequencing has helped discover genes involved in many of these conditions and has led to reclassification of some palmoplantar keratodermas. In this review, we discuss the diagnostic features of palmoplantar keratodermas and management options.

Mutations in the genes encoding desmosomal proteins cause a wide range of diseases associated with abnormalities of the skin, hair and heart. In 45-50% these mutations determine the development of arrhythmogenic right ventricular cardiomyopathy. Today, more than 120 autosomal dominant and autosomal recessive mutations of the desmoplakin (DSP) gene are known, causing skin and cardiac disorders. The article presents a rare clinical case of Carvajal syndrome (OMIM 605676), associated with compound heterozygous mutations, with the classic triad of symptoms (the phenotype of dilated cardiomyopathy, keratoderma, and woolly hair), which was first identified in Eastern Europe (Belarus). A brief literature review of the problems and issues of differential diagnosis are presented in the article in the form of a comparative analysis of Carvajal syndrome with phenotypically similar pathology - Naxos syndrome, caused by mutations in the gene encoding another desmosomal protein - Placoglobin (Naxos syndrome, OMIM 601214), and leading to the development of arrhythmogenic right ventricular cardiomyopathy.

Abstract Hyperkeratosis presents as thickened skin. It can be congenital or acquired. Typically, it affects the palms and soles; the distribution of epidermal involvement is either diffuse, focal, or punctate. Microscopically, the pathologic signature of hyperkeratosis is marked orthokeratosis of the stratum corneum. Topical treatments provide the mainstay of therapy for hyperkeratosis. These include keratolytics (such as urea, salicylic acid, and lactic acid) and retinoids; physical debridement, topical corticosteroids, and phototherapy (using topical psoralen and ultraviolet A phototherapy) are other local therapeutic modalities. Selenium is a non-metallic essential element; its water-insoluble salt, selenium sulfide, is an active ingredient that is used (in either a foam, lotion, or shampoo) to treat not only seborrheic dermatitis but also tinea versicolor. Three individuals with hyperkeratosis involving their palms and/or soles are described; the hyperkeratosis was successful treated with topical selenium sulfide in either a 2.5% lotion/shampoo or a 2.75% foam. The response to topical selenium sulfide was not only rapid but also complete and sustained; none of the patients experienced any adverse events secondary to the therapy. In conclusion, we recommend that topical selenium sulfide be added to the therapeutic armamentarium for congenital or acquired hyperkeratosis—particularly for those patients with involvement of their palms and soles.

Mal de Meleda is a rare genodermatosis with an autosomal recessive inheritance. Mutations in the SLURP1 gene are the cause of this disease. Clinically, it is characterized by progressive palmoplantar hyperkeratosis exhibiting a transgradiens pattern extending to the dorsal aspects of the hands and feet in a glove and stocking pattern. It is also associated with hyperhidrosis, nail changes, subungual hyperkeratosis and perioral erythema. Here we report the first case of Gamborg-Nielsen variant of Mal de Meleda disorder in a patient of an Egyptian origin.

Schopf–Schulz–Passarge syndrome (SSPS) is a rare type of ectodermal dysplasia that has autosomal recessive inheritance. It is characterized by palmoplantar keratoderma, hypodontia, hypotrichosis, nail dystrophy, and multiple periocular and eyelid apocrine hidrocystomas. A 36-year-old male presented with multiple eyelid and periocular apocrine hidrocystomas, ichthyosis, palmoplantar keratoderma, hypodontia, nail dystrophy, and thin scalp hair. Skin biopsy from a periocular lesion revealed cyst lined with smooth, thin epithelium, and few areas revealed foci of decapitation secretion consistent with apocrine hidrocystoma. The patient was diagnosed with SSPS.

Hereditary ectodermal dysplasias, a group of disorders affecting skin, hair, nails, and teeth, consist of two main clinical forms – hypohidrotic and hidrotic. Clouston syndrome is a hidrotic ectodermal dysplasia characterized by a triad of generalized hypotrichosis, palmoplantar hyperkeratosis, and nail dystrophy. This paper reports a large Indian family with Clouston syndrome but with the absence of palmoplantar keratoderma, one of the features of the typical triad, thus representing phenotypic heterogeneity, in spite of the presence of a common known mutation in GJB6 gene (p.Gly11Arg).

Rapp–Hodgkin syndrome (RHS) is a rare condition that is characterized by ectodermal dysplasia and palatal abnormalities. Palmoplantar keratoderma (PPK) is an unusual manifestation of hidrotic ED. Ulcerations on the palms are also not common in RHS. We describe a 15‐year‐old boy who has RHS associated with PPK. [ABSTRACT FROM AUTHOR]

The discovery of genetic causes of inherited skin disorders has been pivotal to the understanding of epidermal differentiation, function, and renewal. Here we show via exome sequencing that mutations in ASPRV1 (aspartic peptidase retroviral-like 1) cause a dominant Mendelian disorder featuring palmoplantar keratoderma and lamellar ichthyosis, a phenotype that has otherwise been exclusively recessive. ASPRV1 encodes a mammalian-specific and stratified epithelia-specific protease important in processing of filaggrin, a critical component of the uppermost epidermal layer. Three different heterozygous ASPRV1 missense mutations in four unrelated ichthyosis kindreds segregate with disease and disrupt protein residues within close proximity to each other and autocatalytic cleavage sites. Expression of mutant ASPRV1 proteins demonstrates that all three mutations alter ASPRV1 auto-cleavage and filaggrin processing, a function vital to epidermal barrier integrity. [ABSTRACT FROM AUTHOR]

Erythrokeratoderma (EK) is heterogeneous clinical entity characterized by excessive scaling with resulting erythrokeratotic plaques. Several genes have been linked to EK and they encode a number of proteins that are important for the integrity of the keratinocyte layer of the epidermis. PERP is a transcription factor that is activated by both p53 and p63. However, its deficiency in a mouse model appears to only recapitulate p63‐mediated role in skin development and organization. We report an extended multiplex consanguineous family in which an EK phenotype with a striking similarity to that observed in Perp−/− mice, is mapped to an autozygous region on chromosome 6 that spans PERP. Whole‐exome sequencing revealed a novel variant in PERP that fully segregated with the phenotype. Functional analysis of patient‐ and control‐derived keratinocytes revealed a deleterious effect of the identified variant on the intracellular localization of PERP. A previous report showed that PERP mutation causes a dominant form of keratoderma but a single patient in that report with a homozygous variant in PERP suggests that recessive inheritance is also possible. Our results, therefore, support the establishment of an autosomal recessive PERP‐related EK phenotype in humans. [ABSTRACT FROM AUTHOR]

Inherited monogenic palmoplantar keratodermas are a heterogeneous group of conditions characterised by persistent epidermal thickening of the palmoplantar skin. Palmoplantar keratodermas are grouped depending on the morphology of the keratoderma into diffuse, focal/striate or papular/punctate. Some palmoplantar keratodermas just affect the skin of the palms and soles and others have associated syndromic features which include changes in hair, teeth, nails, hearing loss or cardiomyopathy. Next generation sequencing has helped discover genes involved in many of these conditions and has led to reclassification of some palmoplantar keratodermas. In this review, we discuss the diagnostic features of palmoplantar keratodermas and management options. [ABSTRACT FROM AUTHOR]

Punctate palmoplantar keratoderma (PPPK) is a rare entity with an estimated prevalence rate of 1.17/100,000. PPPK usually presents with bilateral asymptomatic, tiny, hyperkeratotic punctate papules and plaques on the palmoplantar surface. Among the PPPK varieties, the linear presentation is much rarer, and so far there have been only 3 case reports. Here, we report the case of a 27-year-old female Thai patient who presented to our outpatient clinic with unilateral asymptomatic linear thickening lesions on her right sole since childhood. There were no similar lesions on other parts of the body. A histopathologic examination revealed epidermal hyperplasia and hyperkeratosis without columns of parakeratosis or cornoid lamella. The other examinations were normal. The clinical and histological contexts were consistent with a diagnosis of unilateral linear PPPK. The patient was treated with topical 10% urea cream and 10% salicylic acid cream twice daily. To the best of our knowledge, this is the first reported case of unilateral linear PPPK in Thailand, and the fourth reported case worldwide.

Papillon–Lefevre syndrome is a rare autosomal recessive disorder, in which the clinical manifestations are periodontitis which results in premature loss of both deciduous and permanent teeth and palmoplantar keratinization. The palmoplantar keratoderma typically has its onset between the ages of 1 and 4 years and severe periodontitis starts at the age of 3 or 4 years. The deciduous teeth frequently fall out by about age five and most of the permanent teeth may also be lost by approximately age 17. In the present case, a young, edentulous male of this syndrome having most the characteristic features was treated by modified complete denture prosthesis considering his young age and low socioeconomic status.

The acrokeratoelastoidosis of Costa is a rare genodermatosis of autosomal dominant inheritance with variable expressivity. It is characterized by the presence of multiple hyperkeratotic papules in the marginal zone of the hands and / or feet, which appears predominantly in childhood and early adulthood. It is generally asymptomatic and chronic. Its differential diagnosis from the rest of acrokeratodermias is a challenge for the physician; however, the histological finding of elastorhexis allows us to categorize it. We present a sporadic case of a young female patient, with clinical and histopathological characteristics typical of the disease. [ABSTRACT FROM AUTHOR]

Aquagenic keratoderma is a benign entity that is characterized by producing whitish or translucent papules, a few seconds after contact with water. We present the case of a 16-year-old patient with multiple confluent papules that appear in the palms after contact with water and disappear after drying. The patient had a skin biopsies after water exposure. The histopathological findings showed changes of the superficial layers of the stratum corneum and dilatation of sweat gland ducts. This entity of unknown etiology has been related to neuronal and eccrine gland dysfunction. More recently it has been associated to alterations of aquaporins. The "hand-in-the-bucket" sign, is a useful clinical tool for the diagnosis as histopathological findings may be nonspecific. Topical treatments included include barrier mechanisms and botulinum toxin. [ABSTRACT FROM AUTHOR]