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Olmsted syndrome (OS) is a rare congenital skin disorder, typically characterized by symmetrical, severe palmoplantar and periorificial keratoderma, often accompanied by alopecia, and onychodystrophy, with varying degrees of pruritus and pain. Gain-of-function variants of the transient receptor potential cation channel subfamily V member 3 (TRPV3) were described as a cause of OS. Here, we report an atypical case of OS caused by a novel mutation in the TRPV3 gene that has not been described before in OS. The patient presented with disabling, bilateral palmoplantar keratoderma, and subsequently developed squamous cell carcinoma on the right sole. Genetic analysis identified a novel heterozygous p.Val306Met missense mutation in the exon 8 of TRPV3. Our findings expand the phenotypic spectrum of TRPV3-related OS and underscore the need for vigilant long-term monitoring of these patients. [ABSTRACT FROM AUTHOR]

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 antirheumatic 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Connexin hemichannels (HCs) expressed at the plasma membrane of mammalian cells are of paramount importance for intercellular communication. In physiological conditions, HCs can form gap junction (GJ) channels, providing a direct diffusive path between neighbouring cells. In addition, unpaired HCs provide conduits for the exchange of solutes between the cytoplasm and the extracellular milieu, including messenger molecules involved in paracrine signalling. The synergistic action of membrane potential and Ca2+ ions controls the gating of the large and relatively unselective pore of connexin HCs. The four orders of magnitude difference in gating sensitivity to the extracellular ([Ca2+]e) and the cytosolic ([Ca2+]c) Ca2+ concentrations suggests that at least two different Ca2+ sensors may exist. While [Ca2+]e acts as a spatial modulator of the HC opening, which is most likely dependent on the cell layer, compartment, and organ, [Ca2+]c triggers HC opening and the release of extracellular bursts of messenger molecules. Such molecules include ATP, cAMP, glutamate, NAD+, glutathione, D-serine, and prostaglandins. Lost or abnormal HC regulation by Ca2+ has been associated with several diseases, including deafness, keratitis ichthyosis, palmoplantar keratoderma, Charcot–Marie–Tooth neuropathy, oculodentodigital dysplasia, and congenital cataracts. The fact that both an increased and a decreased Ca2+ sensitivity has been linked to pathological conditions suggests that Ca2+ in healthy cells finely tunes the normal HC function. Overall, further investigation is needed to clarify the structural and chemical modifications of connexin HCs during [Ca2+]e and [Ca2+]c variations. A molecular model that accounts for changes in both Ca2+ and the transmembrane voltage will undoubtedly enhance our interpretation of the experimental results and pave the way for developing therapeutic compounds targeting specific HC dysfunctions. [ABSTRACT FROM AUTHOR]

Palmoplantar keratoderma (PPK) is a heterogeneous group of rare skin diseases characterized by hyperkeratosis on the palms or soles. The subtype isolated punctate PPK is caused by heterozygous variants in AAGAB. We investigated if the variant AAGAB c.370C>T, p.Arg124Ter in patients with punctate PPK in the Region of Southern Denmark represented a founder variant and estimated the age to the most recent common ancestor. We performed haplotype analysis on samples from 20 patients diagnosed with punctate PPK and the AAGAB c.370C>T, p.Arg124Ter variant. Using the Gamma Method, we calculated the years to the most recent common ancestor. We also explored the presence of the variant in other populations through literature and databases (HGMD, ClinVar, and gnomAD). Our analysis revealed a shared haplotype of 3.0 Mb, suggesting shared ancestry. The ancestral haplogroup was estimated to an age of 12.1 generations (CI: 4.9–20.3) equivalent to approximately 339 years (CI: 137–568). This study confirms that the frequently observed variant AAGAB c.370C>T, p.Arg124Ter in punctate PPK among patients in the Region of Southern Denmark is caused by a founder variant. We recommend testing for the variant as initial screening in our region and potentially for all Danish patients presenting with punctate PPK. [ABSTRACT FROM AUTHOR]

Background: Acral amelanotic melanomas (AAMs), a rare subset of melanomas located on acral sites such as the palms, soles, and subungual areas, are diagnostically challenging due to their lack of typical pigmentation and often benign clinical appearance. Misdiagnosis is common, leading to delays in treatment and potentially worse outcomes. This systematic review aims to synthesise evidence on cases of AAM initially misdiagnosed as other conditions, to better understand their clinical and epidemiological characteristics, diagnostic pitfalls, and management strategies. Methods: A comprehensive search of the MEDLINE/PubMed, EMBASE, and SCOPUS databases was conducted up to March 2024. Case reports and small case series of AAMs initially misdiagnosed as other conditions were included. Data on patient demographics, clinical presentation, and diagnostic methods were collected and analyzed. Results: Of the 152 records identified, 26 cases from 23 articles met the inclusion criteria. A demographic analysis revealed that the gender distribution appears to be perfectly balanced, with an age range of 38 to 91 years. Misdiagnoses included non-healing ulcers or traumatic lesions (37.5%), benign proliferative lesions (29.2%) and infectious lesions (20.8%). The foot was the most affected site (53.8%). Notably, a histological evaluation was performed in 50% of cases involving the upper extremities, in contrast to only 7.1% of cases involving the foot and 0% of cases of the heel. This discrepancy suggests a reluctance to perform biopsies in the lower extremities, which may contribute to a higher misdiagnosis rate in these areas. Conclusions: The underutilization of biopsy in the diagnosis of lower extremity lesions contributes significantly to the misdiagnosis and delay in treatment of AAMs. Especially when the clinical assessment and dermoscopy are inconclusive, biopsies of suspicious lesions are essential. Immunohistochemistry and markers such as PRAME are critical in differentiating melanoma from other malignancies such as clear cell sarcoma. This review highlights the need for increased vigilance and a proactive diagnostic approach to increase early detection rates and improve prognostic outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lichen nitidus is an infrequent dermatosis and especially prevalent in the pediatric population, although it also affects adults. It is typically characterized by papules with a smooth or umbilicated surface located on the extremities, trunk, and genitals. However, it exhibits various clinical manifestations that may vary according to location and subtype, making its diagnosis in these cases a challenge for the dermatologist. CLINICAL CASE: A 60-year-old female patient with a 9-month history of generalized, pruritic and some purpuric lesions, associated with keratoderma-type palmoplantar involvement. A biopsy was taken from one of the lesions located on the left forearm, compatible with generalized lichen nitidus. CONCLUSIONS: It is important to know the clinical varieties of this dermatosis, especially the generalized form. In these cases, the identification of typical lichen nitidus lesions in some body segments, central palmar involvement, and histological findings are key. [ABSTRACT FROM AUTHOR]

Background: Changes in skin, hair, and nails may be initial manifestations of an underlying thyroid hormone deficiency. Symptomatic treatment of cutaneous manifestations without treatment of underlying hypothyroidism contributes to long-term morbidity in patients. Aims and Objectives: The aim of the study was to study the cutaneous manifestations and demographic profile of patients with hypothyroidism. Materials and Methods: We conducted a hospital-based cross-sectional study of 200 patients presenting with cutaneous changes in primary hypothyroidism for a period of 18 months. A detailed history, clinical examination, and relevant investigations were performed. Results: Out of 200 patients, cutaneous manifestations were more prevalent in the age group between 30 and 49 years. The ratio of male to female was 1.0:6.4. A family history of hypothyroidism was present in 34.5% of patients. The most common cutaneous features were alteration in skin texture (53.0%), dry skin (48.5%), generalized pruritus (42.5%), urticaria (17%), followed by pigmentation of the skin (34.5%), out of which vitiligo was 9.0%, melasma was 5.5%, and others were 20.0%. Other changes include xerosis (32.5%), eczematous disorder (13%), acquired palmoplantar keratoderma (11.5%), and brittle nails (3.5%). 39.5% had hair changes, out of which diffuse hair loss was 17.5%, coarse hair wa s 12%, alopecia areata was 4.5%, and lateral loss of eyebrows was 4.5%. Changes in the oral cavity and mucous membrane were present in 3.0% of the patients, which included lip vitiligo (1.5%), oral lichen planus (1%), and oral candidiasis (0.5%). Menstrual abnormalities were present in 50.84% of females. The percentage of hypothyroid patients who complained of easy fatigability, facial puffiness, cold intolerance, weight gain, constipation, neck swelling, hoarseness of voice, increased sleeping pattern, and non-pitting edema of feet were 38.5%, 36.5%, 26.0%, 23.5%, 17.0%, 9%, 8%, 7.5%, and 6.5%, respectively. Conclusion: Based on our study, it can be concluded that the presence of certain skin conditions, such as alteration in skin texture, dry skin, generalized pruritus, urticaria, skin pigmentation, and diffuse hair loss, may indicate the possibility of hypothyroidism. These cutaneous manifestations may occur earlier than the diagnosis of hypothyroidism through biochemical testing. Therefore, it is important to consider the possibility of hypothyroidism when examining patients with these skin conditions. [ABSTRACT FROM AUTHOR]

Pachyonychia congenita (PC) is a group of rare hereditary disorders, characterised by hypertrophic nails and palmoplantar keratoderma (PPK), particularly localised to the pressure areas of the feet. At a molecular level, it is caused by mutations in genes encoding KRT6A, KRT6B, KRT6C, KRT16, or KRT17. To identify the underlying gene mutation in a Chinese family with PC presenting with disabling palmoplantar keratoderma and subsequent associated acral melanoma. Genomic DNA was extracted from peripheral blood samples of three available individuals in the Chinese family, which included the patient and his two unaffected sisters. The index patient presented with severe palmoplantar keratoderma as well as a newly diagnosed acral malignant melanoma (MM). Whole-exome sequencing (WES) was carried out with amplification of exon 1 of KRT16 by polymerase chain reaction (PCR). PCR products were then sequenced to identify potential mutations. We identified the proline substitution mutation p.Arg127Pro (c.380G>C) in our patient's 1A domain of KRT16. The same mutation was not found in his sisters or unrelated healthy controls. The mutation (p.Arg127Pro (c.380G>C)) in KRT16 has been reported in Dutch patients with PC. However, it is the first such report of a patient with a PC of Chinese origin. In addition, the acral MM occurred under the background of genetic PPK caused by KRT16 mutation in this patient. [ABSTRACT FROM AUTHOR]

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.

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: Dermatological conditions extend beyond physical symptoms, profoundly impacting the psychological well-being of patients. This study explores the intricate relationship between depressive symptoms, quality of life (QoL), and personality traits in individuals diagnosed with specific genodermatoses. Methods: The study cohort comprised 30 patients with genodermatoses treated at the dermatology clinic, and a healthy control group. Standardized survey questionnaires: The Dermatology Life Quality Index (DLQI), Beck's Depression Inventory (BDI), and NEO Five-Factor Inventory (NEO-FFI) were employed for assessments. Results: The findings indicate a significantly elevated risk of severely or very severely reduced QoL in the study group compared to matched controls (OR = 22.2, 95% CI: 2.7–184.8). Specifically, individuals with ichthyosis exhibited a staggering 131-fold higher risk of diminished QoL compared to the control group. Furthermore, the prevalence of depression was higher in the study group than in the control group (36.7% vs. 10%; p = 0.0086). A detailed analysis revealed that patients with low or average agreeableness exhibited a notably higher incidence of depression compared to those with high agreeableness (100% or 75% vs. 28.6%; p = 0.0400). Similarly, individuals with high levels of neuroticism had a significantly higher incidence of depression compared to those with average or low levels of neuroticism (rates: 66.7% vs. 9.1% or 0%, respectively; p = 0.0067). Conclusions: The study underscores a substantial correlation between genodermatoses and the mental health of affected individuals, underscoring the imperative consideration of psychological factors in the management of hereditary skin disorders. Our study's primary limitation is the small sample size, stemming from difficulties in recruiting participants due to the rare nature of the studied conditions. [ABSTRACT FROM AUTHOR]

Pachyonychia Congenita (PC) is a rare genetic disorder characterised by excessive keratinisation of the skin, nails, and mucous membranes, leading to thickened nail beds and skin on pressure points, notably on the soles of the feet. A 10-year-old girl came to the Outpatient Department (OPD) with her 38-year-old mother. Both of them had same complaints regarding their nails and callous formation over soles. They both had thickened nail plates with thickened pressure points on sole [Table/Fig-1a-c,2a-c]. In PC, oral manifestations are found but on the day of visit they didn’t have any lesion in mouth. Both of them had difficulty and pricking sensation during walking. Both of them had anorexia due to the heinous presentation of the nails. They had taken lots of medicines for the conditions of nails but of no use. Other family members were not affected. Dyskeratosis congenita, pterygium inversum unguis, and onycholysis can be differential diagnosis. The final diagnosis is PC type I. In [Table/Fig-1a-c,2a,b], onychodystrophy can be seen clearly. In [Table/Fig-2c], plantar keratoderma can be seen, which are the cardinal features for the diagnosis of PC.

Laila Tsaqilah,1 Keshia Amalia Mivina Mudia,1 Hermin Aminah Usman,2 Hartati Purbo Dharmadji,1 Risa Miliawati Nurul Hidayah,1 Erda Avriyanti1 1Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran–Dr. Hasan Sadikin General Hospital, Bandung, West Java, Indonesia; 2Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran–Dr. Hasan Sadikin General Hospital, Bandung, West Java, IndonesiaCorrespondence: Laila Tsaqilah, Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran–Dr. Hasan Sadikin General Hospital, Jl. Pasteur 38, Bandung, West Java, 40161, Indonesia, Tel +6282284474849, Email lailazuardy@gmail.comAbstract: Acquired palmoplantar keratoderma (PPK) is a non-hereditary hyperkeratosis of the palms and soles that is caused by various factors, including chemotherapeutic agents. The purpose of this case report is to present a rare case of acquired PPK caused by the chemotherapeutic agent capecitabine. A 54-year-old female complained of painful erythematous plaques on her palms and soles with history of consuming capecitabine. Physical examination revealed scaly erythematous plaques on the palmoplantar surface and knuckle pads on both hands. Histopathological features showed hyperkeratosis, acanthosis, vasodilatation, and perivascular lymphocytic infiltration. Therefore, the patient was diagnosed with acquired PPK due to capecitabine. The dose of capecitabine was reduced and the patient was administered topical corticosteroid and emollient. Improvement of skin lesions was strongly observed after discontinuation of capecitabine. The underlying cause of PPK should be identified to determine the appropriate treatment. Dose reduction or drug discontinuation is the mainstay therapy for patients with acquired PPK caused by chemotherapeutic agents.Keywords: capecitabine, chemotherapy, palmoplantar keratoderma

Abstract Papillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disease that presents clinically with palmoplantar keratoderma and periodontitis and results in early‐onset dental loss. PLS management is difficult. We report a 30‐year‐old female with PLS who had unfavourable response to topical keratolytic creams, oral isotretinoin and narrow‐band ultraviolet‐B (NB‐UVB) phototherapy but showed significant clinical improvement to adalimumab.

Abstract Background Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECTIN4 gene. Objective The main objective of the study was to identify the pathogenic sequence variant(s) for family screening and identification of carriers. Methods In the present study, the authors have investigated a large consanguineous family of Pakistani origin segregating autosomal recessive EDSS1. All the coding exons of the NECTIN4 gene were directly sequenced using gene-specific primers. Results The affected individuals presented the classical EDSS1 clinical features including sparse hair, hypoplastic nails with thick flat discolored nail plates, peg-shaped, conical, and widely spaced teeth with enamel hypoplasia, proximal cutaneous syndactyly of fingers and toes. Sequence analysis of the coding region of the NECTIN4 identified a novel nonsense variant [c.163C>T; p.(Arg55*)] in exon-2 of the gene. Computational analysis of protein structure revealed that the variant induced premature termination at Arg55 located in Ig-like V-loop region leading to loss of Ig-C2 type domains and transmembrane region, and most likely Nectin-4 function will be lost. Study limitation Gene expression studies are absent that would have strengthened the findings of computational analysis. Conclusion The present study expanded the phenotypic and mutation spectrum of the NECTIN4 gene. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.

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Introduction. Despite the availability of effective biologic therapies for psoriasis, there is no gold-standard treatment for nonpustular palmoplantar psoriasis (ppPsO). Methods. G-PLUS, a phase IIIb, double-blind, placebo-controlled, multicentre clinical trial, randomised adults with moderate-to-severe nonpustular ppPsO and limited plaque psoriasis (Psoriasis Area and Severity Index (PASI) ≥3 but <10) to guselkumab (an interleukin-23p19 blocker) or placebo. Placebo participants were crossed over to receive guselkumab at week (Wk) 16. The primary efficacy endpoint was the proportion of participants achieving palmoplantar PASI (ppPASI) 75 response at Wk16; clinical, biomarker, and quality-of-life endpoints were assessed through Wk48 and safety through Wk56. Results. At Wk16, ppPASI75 response was achieved by 35.9% of the guselkumab participants compared with 28.2% in the placebo group, resulting in a 7.7% difference in response rates (95% confidence interval: −11.5 and 24.7), which was not statistically significant (p = 0.533). More pronounced numerical improvements favouring guselkumab were observed for more stringent efficacy endpoints, such as Wk16 palmoplantar Investigator's Global Assessment (ppIGA) 0/1 response (guselkumab 34.6% vs. placebo 15.4%). Through Wk48, further improvements were observed in ppPASI75 response (55.1% and 64.1%) and ppIGA 0/1 response (42.3% and 48.7%) for the guselkumab and placebo-crossover groups, respectively. Dermatology Life Quality Index responses showed comparable trends at both timepoints. Safety and pharmacodynamic findings were consistent with the established profile for guselkumab. Serum biomarker levels were significantly reduced with guselkumab and correlated with the baseline PASI score but not the ppPASI score. Conclusion. Although the primary endpoint was not met, analysis of stringent secondary endpoints and post hoc analyses showed numerical improvements favouring guselkumab at Wk16. There were no new safety signals. Further studies are warranted to better understand the impact of guselkumab treatment in patients with ppPsO. This trial is registered with NCT03998683. [ABSTRACT FROM AUTHOR]

Background: Palmoplantar keratoderma (PPK) is a heterogeneous group of hereditary or acquired disorders characterised by excessive epidermal thickening of the palms and soles. Proper knowledge about the aetiology of the disease and clinico-demographic profile helps in planning management and predicting outcomes. Aims and Objective: To determine the prevalence of different dermatoses and describe their clinico-histological correlation in acquired palmoplantar keratoderma. Materials and Methods: An institution-based cross-sectional study conducted after obtaining Ethics-Committee permission and consent from participants. Patients of any age or gender presenting with acquired PPK were recruited. The calculated sample size was 67 by using the prevalence rate (p) of 22.2%, allowable error (L) of 10%, the confidence level of 95% (z = 1.96), and an infinite population size of 20,000. Patients were evaluated by taking demographic and clinical data in a pre-designed case record form, necessary laboratory investigations and histopathological examination that wereevaluated by three blinded experts. The pooled data were analysed with statistical software. Results: Among the 67 participants, Psoriasis was diagnosed clinically in 39 (58.2%) and histologically in 7 (10.4%), Lichen planus (LP) clinically in 16 (23.9%) and histologically in 9 (13.4%), Pityriasis rubra pilaris (PRP) in 8 (11.9%) patients clinically and 7 (10.4%) histologically and Hyperkeratotic eczema (HKE) in 4 (6%) clinically and 43 (64.2%) histopathologically. There was very poor inter-rater agreement (Kappa = 0.148, SE 0.0047, 95% CI 0.057 to 0.24). The clinico-pathological correlation was found to be agreeable in 17.9% Psoriasis, 56.2% LP and 87.5% PRP. HKE was commonly misdiagnosed as Psoriasis in 65.1% of patients. Conclusion: Hyperkeratotic lesions of the palm and sole often present with overlapping clinical features and a skin biopsy has to be done to aid in diagnosis. Limitation: Stratification of the clinical expertise of clinicians was done during the analysis. [ABSTRACT FROM AUTHOR]

Palmoplantar pustulosis (PPP) is a stubborn skin disease involving repeated aseptic small pustules on the palms and soles of the feet, which is triggered and exacerbated by metals and dental focal infections. There are few reports of an exacerbation of PPP symptoms after orthognathic surgery. The patient is a 40-year-old female who consulted an orthodontist at our hospital, complaining of a protruding maxilla and malocclusion. Under the diagnosis of skeletal prognathism, she underwent surgery for jaw deformity. Although no allergic symptoms were observed during the orthodontic treatment prior to surgery, postoperative scaling on the palms and soles of her feet worsened, and itching was observed on the skin, especially on the titanium plate used to secure the bone fragments. Under the diagnosis of metal allergy, treatment with steroids and vitamin D ointment failed to improve the condition, so surgery was performed to replace the metal plate with a non-metallic absorbable plate in the third postoperative month. Afterwards, the pruritus resolved, and erythema and scale on the palms and soles nearly disappeared. In the present case, though, oral bacterial infection, a past history of smoking, and stress from surgery were also considered to be possible causes of PPP exacerbation, and we concluded that one of the causes of PPP exacerbation was metal allergy from the plates or screws used to fix the bone fragments. [ABSTRACT FROM AUTHOR]

Eccrine Syringofibroadenoma (ESFA) is an infrequent benign adnexal cutaneous lesion distinguished by hyperplastic epithelium and differentiation into eccrine ducts, displaying diverse clinical presentations. In the present case, a 48-year-old Chinese female patient exhibited a decade-long history of palmoplantar erythema, which clinically resembled Dyshidrotic Eczema. Histological examination suggested the presence of ESFA. Ultimately, considering both the clinical manifestations and histological outcomes, the patients received a diagnosis of reactive ESFA. [ABSTRACT FROM AUTHOR]

Introduction: The involvement of palms and soles is variable among disease entities belonging to autoimmune bullous diseases (AIBD). We present our own clinical-laboratory experience concerning presentations of skin lesions on palms and soles in the pemphigus diseases group, pemphigoid diseases group, epidermolysis bullosa acquisita (EBA), and lichen planus pemphigoides (LPP) and discuss the pertinent literature. Methods: Lesions on palms and soles were assessed retrospectively on the basis of just photographic archives from the beginning of 2014 to March 2023. We comparatively evaluated 462 Slavic patients with AIBD. Results: Palmoplantar involvement was observed in only 21 patients with AIBD (12 females and 9 males). There was no statistically significant difference between palmoplantar involvement in the pemphigus diseases group compared to the pemphigoid diseases group and no statistically significant difference between the pemphigus diseases group compared to the subepithelial AIBD. Discussion: Nevertheless, particularly in LPP and EBA, and occasionally in pemphigus diseases and pemphigoid diseases groups of AIBD, localization on palms and soles may be diagnostically important at the clinical level. [ABSTRACT FROM AUTHOR]

Ectodermal dysplasias (ED) encompass a collection of conditions wherein the development of two or more structures derived from the ectoderm exhibits abnormal patterns. One example of such a rarity within the spectrum of ectodermal dysplasias is hidrotic ectodermal dysplasia, also known as Clouston syndrome. This particular variant is distinguished by a triad of clinical characteristics, which encompass partial-to-complete alopecia, nail dystrophy, and palmoplantar hyperkeratosis. It stands as a scarcely encountered autosomal-dominant inherited disorder, resulting from a mutation in the GJB6 gene that encodes the gap junction protein connexin 30. We hereby document the case of a forty-five-year-old Jordanian woman who presented with alopecia affecting the scalp, eyebrows, and eyelashes, in addition to nail dystrophy. Interestingly, she did not manifest palmoplantar keratoderma. It is worth mentioning that several members of her extended family also manifested similar clinical features. Subsequent genetic testing conclusively established the diagnosis of Clouston syndrome. In light of this diagnosis, comprehensive counseling was extended to the patient. [ABSTRACT FROM AUTHOR]

Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease that affects men and women of all ages, including children. PRP is characterized by follicular and palmoplantar hyperkeratosis and salmon-colored scaling plaques. The exact pathogenesis of PRP is still unknown; most PRP cases are acquired, but some cases may show a familial occurrence, often associated with a mutation in the CARD14 gene. Due to the rarity of PRP, treatment recommendations are based mainly on case reports, small case series and expert opinions and still represent a major therapeutic challenge, especially in children. A growing number of reports on treatment with biologicals, particularly anti-TNFα, has been published. However, an involvement of the IL-23/Th17 axis in both psoriasis and PRP pathogenesis may suggest that this pathway may be a potential therapeutic target. Here, we present three pediatric patients with PRP successfully treated with risankizumab. All patients exhibited a severe course of PRP and lack of response to conventional therapy, including acitretin, cyclosporine and phototherapy. A single dose of 75 mg risankizumab resulted in almost complete clearance of skin lesions in case 1 and 2 at week 4. In patient 3, clear skin was achieved after the second administration of risankizumab (150 mg). All patients continue the treatment with risankizumab, and no adverse effects have been reported up to the present time. Our study demonstrates that risankizumab, an IL-23 blocker, shows good efficacy and safety among pediatric patients with PRP. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated the anti-interleukin-36 receptor antibody spesolimab in patients with moderate-to-severe palmoplantar pustulosis (PPP). Methods: This phase IIb trial comprised a loading dose period to week (W) 4, then maintenance dosing to W52. Patients were randomised 2:1:1:1:2 to subcutaneous spesolimab 3000 mg to W4 then 600 mg every 4 weeks (q4w), spesolimab 3000 mg to W4 then 300 mg q4w, spesolimab 1500 mg to W4 then 600 mg q4w, spesolimab 1500 mg to W4, 300 mg q4w to W16 then 300 mg every 8 weeks (q8w), or placebo switching to spesolimab 600 mg q4w at W16. The primary efficacy endpoint was percentage change from baseline in Palmoplantar Pustular Area and Severity Index (PPP ASI) at W16. Secondary endpoints included a Palmoplantar Pustular Physician's Global Assessment (PPP PGA) score of 0/1. Safety (including adverse events [AEs], local tolerability) was assessed. Results: 152 patients were treated. The primary endpoint was not met; mean differences for spesolimab versus placebo ranged from − 14.6% (95% confidence interval [CI]: − 31.5%, 2.2%) to − 5.3% (95% CI: − 19.1%, 8.6%); none reached significance. At W16, 23 (21.1%) and two (4.7%) patients in the combined spesolimab and placebo groups, respectively, achieved PPP PGA 0/1 (mean difference 16.4%; 95% CI: 3.8%, 25.7%), increasing to 59 (54.1%; combined spesolimab) and 12 (27.9%; placebo switch to spesolimab) patients at W52. Non-Asian patients had significant improvements in the primary endpoint (mean difference − 17.7%; nominal P = 0.0394) and PPP PGA 0/1 at W16 with spesolimab versus placebo. Rates of AEs and AE-related discontinuations were similar for spesolimab and placebo. Local tolerability events and injection-site reactions were more frequent with spesolimab than placebo. Conclusion: The primary objective to demonstrate a non-flat dose–response relationship and proof-of-concept was not achieved; improvements with spesolimab occurred in secondary endpoints and in non-Asian patients, indicating potential modest benefits. Spesolimab was generally well tolerated (ClinicalTrials.gov NCT04015518). Plain Language Summary: A clinical trial of spesolimab for patients with palmoplantar pustulosis. Palmoplantar pustulosis (PPP) is a painful, difficult-to-treat skin disease that is found on patients' palms and the soles of their feet. In this clinical trial, we studied an injected medicine called spesolimab for treating patients with PPP. Patients were split into five groups; four groups received different doses of spesolimab and one received placebo (an injection without spesolimab). After 16 weeks, patients receiving placebo switched to spesolimab. We measured the body area affected by PPP and how severe PPP was at week 16. Patients' doctors also assessed skin affected by PPP. At 16 weeks of treatment, there was no significant difference between spesolimab and placebo in terms of the PPP-affected area and severity. However, more patients had clear or almost clear skin with spesolimab than placebo. Among non-Asian patients, more showed an improvement in their PPP with spesolimab than with placebo; this was not the case with Asian patients. Patients taking spesolimab or placebo reported side effects, of which the most common were colds, aches and headaches. More patients receiving spesolimab reported a reaction at the injection site compared with placebo. We monitored patients for up to 1 year, and results remained similar. We showed that spesolimab may have a modest effect on the body area affected by PPP, as well as the severity of PPP, and did not seem to cause more side effects than placebo, except for reactions at the injection site. [ABSTRACT FROM AUTHOR]

Eccrine poroma (EP) is an uncommon benign tumor of intra-epidermal portion of sweat ducts, usually affecting palmoplantar area in middle-aged patients. In this report, we describe the case of a 66-year-old man with an asymptomatic, rapidly growing, pedunculated nodule on his neck. The lesion was removed by simple excision. Histopathologic studies confirmed eccrine poroma as final diagnosis. No sign of recurrence was seen during 6 months of follow-up. Pedunculated presentation, rapid growth and the site of the lesion in our case is rare. [ABSTRACT FROM AUTHOR]

The article discusses a case of Papillon-Lefèvre syndrome (PLS), a rare hereditary disorder characterized by palmoplantar keratoderma and severe periodontitis leading to premature tooth loss. The case study involves a thirteen-year-old child with erythemato-squamous lesions and severe periodontal destruction. PLS is a genotypic condition with dermatological and dental manifestations, often associated with parental consanguinity. Treatment involves oral retinoids to manage skin lesions and slow alveolysis. [Extracted from the article]

The article discusses Chanarin-Dorfman syndrome (DCS), a rare autosomal recessive disorder caused by mutations in the ABHD5 gene, leading to lipid overload in various tissues. Symptoms include congenital ichthyosiform non-bullous erythroderma, growth retardation, and various systemic manifestations. Treatment is symptomatic, with emollients, a low-fat diet, and acitretin being common approaches. The case study presented a six-month-old infant with ichthyosis and hypertriglyceridemia, highlighting the importance of considering hypertriglyceridemia in congenital ichthyosis cases. [Extracted from the article]

Periungual pyogenic granulomas are benign vascular tumors that present as painful, round, spontaneously bleeding lesions composed of rapidly proliferating capillaries and excess tissue. The vast majority of pyogenic granulomas are caused by physical trauma or infectious agents and they may resolve spontaneously. Herein, we highlight a very rare case of periungual pyogenic granulomas induced by the regularly prescribed oral retinoid acitretin during treatment for congenital palmoplantar keratoderma. This unique case showed that it is feasible to continue acitretin therapy in the presence of pyogenic granuloma development if proper dose reduction and topical therapies are utilized. The patient's lesions resolved within two weeks of this protocol's initiation and the pyogenic granulomas did not recur over the course of a six-month follow-up observation period. In addition, we performed a systematic review of the literature using PubMed databases for the clinical features and treatments in other reported acitretin-induced pyogenic granuloma cases; we compiled a comprehensive list of other prescription drugs known to cause pyogenic granulomas up-to-date.

Hyalohyphomycosis includes infections caused by various fungal species that produce hyaline, septate, branched hyphae. Fusarium is one such species which usually causes multiple papulo-nodules, ecthyma gangrenosum-like ulcers in immunocompromised individuals. Also, fusariosis is usually difficult to manage and responds favorably to amphotericin B, voriconazole, and posaconazole in disseminated cases. Here, we report an atypical case of cutaneous fusariosis in an immunocompetent individual who presented with multiple large cystic swellings, psoriasiform plaques, and palmoplantar keratoderma, and the patient responded completely to itraconazole. [ABSTRACT FROM AUTHOR]

Darier's disease is an infrequently encountered autosomal dominant condition characterised by complete penetrance but variable expression. It is characterised by abnormal keratinisation and epidermal adhesion deficiency, clinically presenting as greasy keratotic or warty papules and plaques, primarily affecting seborrheic regions and flexures. Additional manifestations include palmar pits, nail abnormalities, cobble-stoning of the oral mucosa, and even neuro-psychiatric issues. In extremely rare cases, mucosal involvement can occur in the oral, laryngeal, Oesophageal, or rectal areas. Familial Darier's disease typically emerges during puberty. Here, the authors present a unique case of 55 years old male patient of Darier's disease with delayed onset, despite a significant family history of the condition. The clinico-pathological aspects, highlighting the presence of palmo-plantar keratoderma are also discussed. Treatment included the application of topical hydrocortisone 1% cream twice daily for two weeks, then once daily for two weeks along with dexpanthenol once daily for eight weeks. [ABSTRACT FROM AUTHOR]

KID syndrome is a congenital disorder combining keratitis, ichthyosis, and deafness. Herein, we report a case diagnosed in adulthood. A 29-year-old male patient with deafness and progressive loss of visual acuity in early childhood was consulted because of generalized scaly lesions that worsened over time. A skin examination revealed large blackish ichthyosiform scaly patches on the limbs, marked follicular keratosis on the trunk, palmoplantar keratoderma, small papules, sometimes hyperpigmented, on the mediofacial area, and significant xerosis. Dental anomalies such as malocclusion and several decayed teeth were present. The combination of ichthyosis lesions, deafness, and visual abnormalities led to the diagnosis of KID syndrome. Emollients and keratolytics were applied with a slight improvement in the skin lesions. The uniqueness of this observation was the late diagnosis of KID syndrome. Ichthyosis associated with neurosensory deficits should evoke KID syndrome despite the difficulty of molecular diagnosis in developing countries. [ABSTRACT FROM AUTHOR]

Ichthyoses are genetically determined cornification disorders of the epidermis characterized by the presence of different degrees of scaling, hyperkeratosis, and erythroderma often associated with palmoplantar keratoderma. Different classifications of these diseases have been proposed, often based upon the involved genes and/or the clinical presentation. The clinical features of these diseases present some overlap of phenotypes among distinct genetic entities, depending mainly on the penetrance of mutations. In this study, using a clinical, genetic, and molecular approach, we analyzed a family with two affected members who had clinical and histological features resembling erythrokeratodermia variabilis (EKV) or a type of erythrodermic hyperkeratosis with palmoplantar keratoderma. Despite of the clinical presentation, we demonstrated that the affected patients were genetically double heterozygous for two different mutations in the ABCA12 gene, known to be responsible for harlequin ichthyosis. To explain the mild phenotype of our patients, we performed a molecular characterization of the skin. In the upper layers of the epidermis, the results showed a patchy presence of the glucosyl-ceramides (GlcCer), which is the lipid transported by ABCA12, fundamental in contributing to skin impermeability. Indeed, the two mutations detected do not completely abolish ABCA12 activity, indicating that the mild phenotype is due to a partial loss of function of the enzyme, thus giving rise to an intermediate phenotype resembling EKVP, due to a partial depletion of GlcCer deposition. [ABSTRACT FROM AUTHOR]

Background: An association between punctate palmoplantar keratoderma type 1 (PPPK1) and malignancy has been proposed for decades. Some authors suggest that individuals with PPPK1 should undergo screening for various types of malignancies while others caution that an association is not well-established. In this systematic review, we summarized and evaluated the current evidence for a possible association between PPPK1 and malignancy. Methods: The review was conducted along PRISMA guidelines. The search used Embase, MEDLINE, Scopus, and the Human Gene Mutation Database up to March 2022. All studies reporting on individuals with the diagnosis of PPPK1 with or without history of malignancy were included. Two authors screened for eligible studies, extracted predefined data, and performed a quality assessment. Results: Of 773 studies identified, 45 were included. Most studies were reports on single families (24 of 45 studies) or multiple families (10 of 45 studies). The number of index cases with PPPK1 across all included studies was 280, and when family members reported with PPPK1 were added, a total of 817 individuals were identified. Overall, 23 studies reported on individuals with PPPK1 with a history of malignancy, whereas 22 studies reported on individuals with PPPK1 without a history of malignancy. Although the extracted data were not considered to be of sufficient quality to synthesize and answer our research question, the review did not confirm an association between PPPK1 and malignancy. Conclusion: This review shows that there is a lack of well-designed studies on this topic to conclude whether individuals with PPPK1 have an increased risk of malignancy. Based on the present literature, however, we could not confirm an association between PPPK1 and malignancy and find it highly questionable if patients with PPPK1 should be offered surveillance for malignancies. [ABSTRACT FROM AUTHOR]

Mal de Meleda (MDM) is a rare autosomal palmoplantar keratoderma (PPK) skin disorder (estimated incidence of 1 per 100,000 people) commonly associated with consanguinity and early childhood onset. MDM is characterized by bilateral diffusion of PPK plaques with delimited yellowish lesions that transgredien to the dorsum of the hands and feet. Additional features include nail dystrophy, lichenoid lesions, hyperhidrotic maceration, involvement of the knees and elbows, malodor, fungal superinfections, and digital constrictions. A male patient aged 42 years presented with asymptomatic, chronic, and diffused PPK lesions that progressed to the dorsal surface of the hands and feet, along with knees and elbows involvement. On clinical examination, asymmetrical lesions were observed on the hands, the left palm with yellowish waxy hyperkeratotic plaques, and the right palm with erythematous scaling and hyperkeratotic interphalangeal rings. The soles of the feet presented with yellow waxy hyperkeratotic plaques. In addition, nail dystrophy and loss of dermatoglyphics were observed. Initially, symptomatic topical treatment was established. However, owing to the lack of clinical response, a biopsy was performed, which revealed thickened corneal layer, acanthosis, spongiosis, and perivascular lymphohistiocytic infiltrate. MDM diagnosis was confirmed based on a personal history of consanguinity, clinical presentation with absence of systemic symptoms, and transgredien pattern of the lesions. Systemic treatment with low doses of isotretinoin (10 mg orally everyday) was initiated, and two months later, slight clinical improvement has been observed until date. The present case report describes MDM in a Hispanic patient, who presented with asymmetric PPK lesions on the hands and received isotretinoin treatment. [ABSTRACT FROM AUTHOR]

Palmoplantar pustulosis (PPP) is a chronic, relapsing, inflammatory disease that can occur alone or in association with arthritis. There is still controversy about whether it should be separated from psoriasis or classified as pustular psoriasis. Furthermore, drug-induced paradoxical PPP is a special variant of PPP that differs from classic PPP in several ways. Treatment of PPP is still challenging, and there are a number of treatment-resistant cases. This review summarizes the risk factors for the development of PPP and the currently available treatment modalities. Female sex, smokers or ex-smokers, obesity, thyroid dysfunction, and treatment with a tumor necrosis factor (TNF)-α inhibitor have been identified as risk factors for the disease's development, severity, and course. Topical treatments and phototherapy are effective for some patients and are used as a first-line or adjuvant treatment modality. Conventional treatments including retinoids and fumaric acid show good effects and can increase the efficacy of treatment with psoralen + ultraviolet light therapy (PUVA). Ciclosporin is fast acting, but relapse mostly occurs immediately after cessation. TNF-α inhibitors are efficient, and an even better response can be achieved with IL-17 and IL-23 blockers as well as apremilast. The effect of Janus kinase inhibitors seems to be promising according to case reports, but further investigations with larger cohorts are needed. [ABSTRACT FROM AUTHOR]

Carvajal syndrome is a rare hereditary cardiocutaneous syndrome caused by the variants of the desmoplakin (DSP) gene. In this study, we report a patient of Carvajal syndrome with a novel homozygous missense variant of DSP gene. We diagnosed a 7-year-old female patient with Carvajal syndrome characterized by dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia, who disclosed a novel homozygous missense variant c.4597C > T (p.Q1533X) in exon 6 of the DSP gene found for the first time. Both her parents were heterozygous for the identified nonsense variant c.4597C > T (p.Q1533X) in DSP gene but neither showed evidence of Carvajal syndrome, indicating that this novel variant causes the disease in an autosomal recessive manner. Genotypes of Carvajal syndrome are even broader than so far anticipated. When patients with dilated cardiomyopathy, palmoplantar keratoderma, woolly hair, and dental dysplasia are found in clinical practice, Carvajal syndrome should be highly suspected, and family gene sequencing should be actively carried out. [ABSTRACT FROM AUTHOR]

Background: Recent knowledge of psoriasis pathogenesis has led to the development of selective drugs. Among these, brodalumab is a monoclonal antibody targeting the interleukin (IL)-17A receptor approved for the treatment of moderate-to-severe plaque psoriasis. Biologics may be considered in patients with milder diseases in case of active psoriatic arthritis, severe impact on patient's quality of life, and involvement of sensitive and difficult-to-treat areas. These skin locations commonly require systemic drugs. Recently, psoriasis severity monitoring has also changed. Indeed, the clinical evaluation by means of specific efficacy scores was combined with serological evaluation by means of the assay of specific inflammatory biomarkers.Methods: An observational study enrolled patients affected by moderate-to-severe plaque psoriasis involving difficult-to-treat areas, undergoing treatment with brodalumab to evaluate the effectiveness and safety of brodalumab in patients with psoriasis affecting difficult-to-treat areas (scalp and palmoplantar regions). Secondary outcomes were the assessment of the development of serum markers of inflammation during the treatment period as well as the evaluation of the dermoscopic features of the affected sites to quantify disease activity and response to treatment.Results: Twenty-five patients were included in the study. A statistically significant reduction from baseline in PASI, PSSI, ppPASI and DLQI values as early as week 24 was observed, with further improvement up to week 52. Plasma levels of MMP-3, VEGF-A, and hs-PCR decreased during treatment from week 0 to week 52.Conclusion: Our real-life experience suggests brodalumab as a valuable option for the management of psoriasis located in difficult-to-treat areas. Moreover, our study highlights that the use of brodalumab reduces the plasmatic levels of inflammatory biomarkers (MMP-3, VEGF-A and hs-PCR), showing how the drug modulates the skin inflammatory response by reducing systemic inflammation. [ABSTRACT FROM AUTHOR]

The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment standards and significantly enhanced patient prognoses. However, the utilization of these groundbreaking therapies has led to the observation and reporting of various types of adverse events, commonly known as immune-related adverse events (irAEs). In the following article, we present four patients who encountered uncommon toxicities induced by ICIs. The first patient was a 59-year-old female diagnosed with stage 4 lung adenocarcinoma. She received immunotherapy (pembrolizumab) together with chemotherapy and subsequently developed autonomic neuropathy (AN). The next two patients also received chemo-immunotherapy (pembrolizumab) and were both 63-year-old males with stage 4 lung adenocarcinoma. One of the two experienced palmoplantar keratoderma, while the other presented with Reiter's syndrome (urethritis, conjunctivitis and arthritis). The 4th patient, an 80-year-old male with stage 4 squamous cell carcinoma of the lung, received chemo-immunotherapy (pembrolizumab) and developed myasthenia gravis. [ABSTRACT FROM AUTHOR]

Objective: In Ayurveda, majority of skin diseases are dealt under broader term Kushta. As per acharya Charaka, Vipadika kushta is classified under Kshudra kushta. This can be correlated with Palmoplantar psoriasis, which mainly effects palms and soles of a person causing cracks associated with severe pain, itching, discolouration and burning sensation. In the present study, an effort is made to compare clinical efficacy of Vipadikahara ghrita and taila prepared using go ksheera and arka ksheera in two different batches for the treatment of Vipadika kushta. Intervention: Vipadikahara ghrita & taila is a yamaka preparation that is mentioned in both charaka samhitha and ashtanga hridaya kushta chikitsa adhyaya, in the context of vipadika kushta. In this formulation ksheera is one of the ingredients, where specific type of ksheera to be used is not specified in charaka samhitha. Whereas in ashtanga hridaya commentary by Kaviraj Athrideva Gupta, usage of arka ksheera is mentioned. As specific ksheera is not mentioned in Charaka samhitha, go ksheera is taken and its effect is compared with the arka ksheera. Vipadikahara Ghrita & taila is administered externally for 15 days and changes are noted. Results: Vipadikahara ghrita & taila prepared with go ksheera helped in reducing only pain, whereas that prepared with arka ksheera reduced pain, itching, discolouration and size of the lesion. Conclusion: Hence it can be said that arka ksheera is found to be more effective in the present case study. [ABSTRACT FROM AUTHOR]

Background: Mal de Meleda is an autosomal recessive palmoplantar keratoderma, with SLURP1 identified as the pathogenic gene responsible. Although over 20 mutations in SLURP1 have been reported, only the mutation c.256G > A (p.G87R) has been detected in Chinese patients. Here, we report a novel heterozygous SLURP1 mutation in a Chinese family. Methods: We assessed the clinical manifestations of two Chinese patients with Mal de Meleda and collected specimens from the patients and other family members for whole-exome and Sanger sequencing. We used algorithms (MutationTaster, SIFT, PolyPhen-2, PROVEAN, PANTHER, FATHMM, mCSM, SDM and DUET) to predict the pathogenetic potential of the mutation detected. We also employed AlphaFold2 and PyMOL for protein structure analysis. Results: Both patients displayed the typical manifestation of palmoplantar keratoderma. In Proband 1, we detected a novel compound heterozygous mutation (c.243C > A and c.256G > A) in exon 3 of SLURP1. Proband 2 was an adult female born to a consanguineous family and carried a homozygous mutation (c.211C > T). Algorithms indicated both mutations to be probably disease causing. We used AlphaFold2 to predict the protein structure of these mutations and found that they cause instability, as shown by PyMOL. Conclusions: Our study identified a novel compound heterozygous mutation (c.243C > A and c.256G > A) in a Chinese patient with Mal de Meleda that has the potential to cause instability in protein structure. Moreover, this study expands on the existing knowledge of SLURP1 mutations and contributes to knowledge of Mal de Meleda. [ABSTRACT FROM AUTHOR]

Hereditary palmoplantar keratodermas (PPKs) are a clinically and genetically heterogeneous group of disorders characterized by excessive epidermal thickening of palms and soles. Several genes have been associated with PPK including PERP, a gene encoding a crucial component of desmosomes that has been associated with dominant and recessive keratoderma. We report a patient with recessive erythrokeratoderma (EK) in which whole exome sequencing (WES) prioritized by human phenotype ontology (HPO) terms revealed the presence of the novel variant c.153C > A in the N-terminal region the PERP gene. This variant is predicted to have a nonsense effect, p.(Cys51Ter), resulting in a premature stop codon. We demonstrated a marked reduction in gene expression in cultured skin fibroblasts obtained from the patient. Despite the PERP gene is expressed at low levels in fibroblasts, our finding supports a loss-of-function (LoF) mechanism for the identified variant, as previously suggested in recessive EK. Our study underscores the importance of integrating HPO analysis when using WES for molecular genetic diagnosis in a clinical setting, as it facilitates continuous updates regarding gene–clinical feature associations. [ABSTRACT FROM AUTHOR]

Objective To study the demography and clinical spectrum of icthyosis in children below twelve years of age. Methods A prospective randomized hospital based study was conducted between June 2013 and June 2015 in a district hospital in North India. The children were thoroughly examined and routine investigations were carried out. Results In two years duration, 2523 children coming to the dermatology OPD were screened for icthyosis. Conclusion There were 21 patients (70%) of icthyosis vulgaris, 3 patients(10%) of X linked recessive icthyosis, 2 patients (6.66%) of lamellar icthyosis, 2 patients (6.66%) of non bullous icthyosiform erythroderma, 1 patient (3.33%) of bullous icthyosiform erythroderma and 1 patient (3.33%) of Netherton syndrome. Palmoplantar keratoderma was seen in 5 patients(16.66%), impairment of sweating was seen in 6 patients (20%), keratosis pilaris was seen in 3 patients (10%), atopic diathesis was seen in 3 patients (10%), colloidon membrane was seen in 2 patients (6.66%) and eye involvement in the form of corneal opacity was seen in 1 patient (3.33%). [ABSTRACT FROM AUTHOR]

We examined the effect of a dietary seaweed extract—sulfated xylorhamnoglucuronan (SXRG84)—on individuals with inflammatory skin conditions. A subgroup analysis of a larger trial was undertaken, where 44 participants with skin conditions were enrolled in a double-blind placebo-controlled crossover design. Subjects ingested either SXRG84 extract (2 g/day) for six weeks and placebo for six weeks, or vice versa. At baseline, six- and twelve-weeks inflammatory markers and the gut microbiota were assessed, as well as skin assessments using the dermatology quality of life index (DQLI), psoriasis area severity index (PASI) and visual analogue scales (VAS). There were significant differences at weeks six and twelve for pro-inflammatory cytokines IFN-γ (p = 0.041), IL-1β (p = 0.030), TNF-α (p = 0.008) and the anti-inflammatory cytokine IL-10 (p = 0.026), determined by ANCOVA. These cytokines were all significantly higher at six weeks post placebo compared to twelve weeks post placebo followed by SXRG84 treatment. A total of 23% of participants reported skin improvements, as measured by VAS (mean difference 3.1, p = 0.0005) and the DQLI score (mean difference -2.0, p = 0.049), compared to the 'non-responders'. Thus, the ingestion of SXRG84 for 6 weeks reduced inflammatory cytokines, and a subset of participants saw improvements. [ABSTRACT FROM AUTHOR]

Background: A major worry of juvenile penile LS is potential malignant degeneration to spinocellular carcinoma (SCC) in adulthood. LS is characterized by increased CD8+ and CD57+ cells, dermal sclerosis, epidermal atrophy, and hyperkeratosis. p53 and Ki67 are reliable premalignant markers. Our aim was to define the LS immunohistochemical profile of foreskin in children, focusing on tissue immune response and cell proliferation. Methods: Thirty specimens of foreskins removed from pediatric patients during circumcision were included: six from ritual operation (A), twelve from phimosis (B), and twelve from phimosis with LS (C). Formalin-fixed paraffin-embedded sections were stained for histomorphology and immunohistochemistry. A quantitative evaluation for CD8, CD57, p53, and Ki-67 and a statistical analysis were performed. Results: As compared to groups A and B, the samples from group C patients showed an acanthotic epidermis, a dermal band of lymphoid infiltrate with a significant enhancement of CD8+ CD57+ lymphocytes, and a keratinocytic hyperplasia with an overexpression of Ki67+ and p53+ cells. Conclusions: Immunohistological findings confirmed an immune reaction and proliferative behavior in juvenile LS of foreskin. We believe that radical circumcision should be the first treatment of choice in pediatric patients with clinical suspicious of LS for the potential risk of transformation to SCC in adulthood. [ABSTRACT FROM AUTHOR]

We report a 6-year-old girl showing epidermolytic ichthyosis/epidermolytic hyperkeratosis (EI/EH). Targeted Next Generation Sequencing revealed a de novo, previously unidentified KRT1 mutation. The findings of this study expands the clinical and  spectrum and genotype-phenotype correlation associated with EI/EH.

Acrokeratoelastoidosis (AKE) is a rare, benign papular keratoderma that presents as keratotic papules on the lateral margins of the palms and soles. It is most commonly inherited in an autosomal dominant fashion, although sporadic cases are also described. We present a sporadic case of AKE in an 11-year-old girl with a past medical history significant for asthma. On literature review, we found three other cases presenting in children with a past medical history of asthma. We suggest a possible association between asthma and sporadic cases of AKE in children. Current understanding of the pathophysiology of AKE and its associated risk factors is limited and no effective treatment exists. Awareness of a possible association with asthma and atopy, careful history recording in young patients presenting with sporadic cases of AKE, and further research may help to delineate the likelihood of an association between AKE and asthma or atopy. Developing a better understanding of the associated factors that may contribute to the disease process may help guide more effective, targeted treatments in the future.

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]