Investigation of Nagashima-type palmoplantar keratoderma in China: A cross-sectional study of 234 patients.

Nagashima-type palmoplantar keratoderma (NPPK) is the most prevalent hereditary palmoplantar keratoderma (PPK) in China, but there is a paucity of epidemiological data on the Chinese population. To explore the clinical and genetic characteristics, evaluate the demographic distribution, and estimate the burden of disease of NPPK. A total of 234 Chinese patients with NPPK were enrolled from two medical centers and an online PPK support group. Next-generation sequencing and Sanger sequencing were performed to screen out and confirm pathogenic mutations in SERPINB7. Clinical features and quality of life (QOL) were evaluated using self-completed questionnaires. In total, 14 pathogenic mutations were identified in SERPINB7 from the cohort. The top four recurrent mutations were c.796C>T (355, 75.9%), c.522dupT (66, 14.1%), c.650_653delCTGT (24, 5.1%), and c.455G>T (12, 2.6%), accounting for 97.6% of Chinese NPPK patients. Other mutations (11, 2.4%) include c.455-1G>T, c.336+2T>G, c.635delG and seven novel mutations c.2T>C, c.434delG, c.455-16A>G, c.656T>C, c.745-553T>G, c.832C>T, c.1036G>T. The estimated prevalence of NPPK in China was found to be 0.975/10 000 based on Chinese databases. Clinically, there were no apparent genotype-phenotype correlations in NPPK patients. Pediatric patients mainly presented with palmoplantar peeling, while adults presented with scale (p < 0.001). The most common comorbidities in NPPK patients were onychomycosis (40.0%), eczema (36.8%), and tinea pedis (30.3%). As for burden of disease, NPPK patients' QOL was decreased by a moderate degree. In this study, pathogenic mutations' allele frequencies in SERPINB7 were updated, and prevalence of NPPK in China was estimated. This large-scale cohort study provides evidence-based recommendations for patient management. Identification of new mutations are important for timely diagnosis of NPPK. Palmoplantar peeling in children can be used as a hallmark for early recognition of NPPK.

Hiperqueratosis plantar / Plantar hyperkeratosis

RESUMEN La hiperqueratosis es un trastorno caracterizado por el engrosamiento de la capa externa de la piel, que está compuesta de queratina, una fuerte proteína protectora. Puede ser causada por fricción, conllevando la aparición de callosidades, inflamación crónica, eccema o trastornos genéticos, como la ictiosis ligada al cromosoma X. Se presentó el caso de un paciente de 47 años, que acudió al Servicio de Ortopedia por lesión escamosa a nivel de ambas regiones plantares con dificultad para la marcha. El tratamiento quirúrgico fue el empleado en este paciente para la obtención de la biopsia exerética. La evolución fue favorable en el postoperatorio mediato e inmediato, y el paciente se incorporó de forma rápida a su vida normal. Con este caso se identificaron las características clínicas de la hiperqueratosis plantar, así como el uso de la biopsia exerética como estándar de oro para el diagnóstico positivo en los tumores periféricos. Un diagnóstico adecuado por el médico inicial, la interrelación del Servicio de Ortopedia con la consulta de tumores periféricos, y el tratamiento quirúrgico seleccionado, constituyen factores determinantes en la evolución favorable de los pacientes con este diagnóstico (AU).

ABSTRACT Hyperkeratosis is a disorder characterized by thickening of the outer layer of the skin, which is composed of keratin, a strong protective protein. It can be caused by friction, leading to callosities, chronic inflammation, eczema or genetic disorders such as X chromosome-linked ichthyosis. We presented the case of a patient, aged 47 years, who attended the Orthopedic Service for scaly lesion at the level of both plantar regions with difficulties to walk. Surgical treatment was used in this patient to obtain an exeretic biopsy. The evolution was favorable in both the mediate and immediate postoperative period, and the patient quickly returned to his normal life. This case identified the clinical characteristics of plantar hyperkeratosis and the use of exeretic biopsy as a gold standard for positive diagnosis in the peripheral tumors. An adequate diagnosis by the initial physician, the interrelation of the orthopedic service with the consultation of peripheral tumors, and the chosen surgical treatment are determining factors in the favorable evolution of patients with this diagnosis (AU).

Identification of clinically useful predictive genetic variants in pachyonychia congenita.

BACKGROUND: Pachyonychia congenita (PC) refers to a group of autosomal dominant disorders caused by mutations in five keratin genes (KRT16,KRT6A,KRT17,KRT6B or KRT6C). Current disease classification is based on the gene harbouring disease-causing variants. AIMS: We harnessed the International Pachyonychia Congenita Research Registry (IPCRR) containing both clinical and molecular data on patients with PC worldwide, to identify genetic variants predicting disease severity. METHODS: We ascertained 815 individuals harbouring keratin mutations registered in the IPCRR. We looked for statistically significant associations between genetic variants and clinical manifestations in a subgroup of patients carrying mutations found in at least 10% of the cohort. Data were analysed using χ2 and Kruskal-Wallis tests. RESULTS: We identified five mutations occurring in at least 10% of the patients registered in the IPCRR. The KRT16 p.L132P mutation was significantly associated with younger age of onset, presence of palmar keratoderma oral leucokeratosis and a higher number of involved nails. By contrast, the KRT16 p.N125S and p.R127C mutations resulted in a milder phenotype featuring a decreased number of involved nails and older age of onset. Patients carrying the p.N125S mutation were less likely to develop palmar keratoderma while p.R127C was associated with an older age of palmoplantar keratoderma onset. Moreover, the KRT17 p.L99P mutation resulted in an increased number of involved fingernails and patients demonstrating 20-nail dystrophy, while the opposite findings were observed with KRT17 p.N92S mutation. CONCLUSIONS: We have identified novel and clinically useful genetic predictive variants in the largest cohort of patients with PC described to date.

Aquagenic acrokeratoderma due to frequent handwashing during the COVID-19 pandemic outbreak.

Aquagenic acrokeratoderma (AK) is a rare, transient type of acquired palmoplantar keratoderma resulting from short-term contact with water and characterized by white, transparent papules and plaques usually localized in the palmar regions of the hand. The pathogenesis of aquagenic acrokeratoderma is not fully understood and is assumed to be related to an increased salt concentration in the epidermal cells with an increase in the ability of stratum corneum to bind water. This report of patients developing AK following increased frequencies of handwashing in the COVID-19 Pandemic Outbreak is intended to contribute to our understanding of the pathogenesis.

Palmoplantar keratoderma, oral involvement, and homozygous CTSC mutation in two brothers from Cambodia.

Haim-Munk syndrome (HMS) and Papillon-Lefevre syndrome (PLS) are phenotypic variants of palmoplantar keratoderma (PPK) with progressive early-onset periodontitis and dental caries. HMS and PLS have been associated with homozygous or compound heterozygous mutations in the lysosomal protease gene Cathepsin C (CTSC). There have been only a few documented cases of CTSC mutations in patients from South-East Asia. We report the clinical findings of two Cambodian brothers who presented with diffuse, demarcated PPK with transgrediens extending to the elbows and knees, as well as pachyonychia and dental caries. Arachnodactyly and periodontitis were also found in the older brother. Next-generation sequencing unveiled a homozygous missense variant in CTSC (NM_001814.5: c.1337AC: p.(Asp446Ala)) in both brothers. Both parents were heterozygous for the variant, while an unaffected older brother was homozygous for the wild-type allele. Our study adds to the spectrum of mutations and associated clinical presentations for this rare genodermatosis.

Association of Transient Palmoplantar Keratoderma With Clinical and Immunologic Characteristics of Bullous Pemphigoid.

Importance: Development of transient palmoplantar keratoderma (PPK) with bullous pemphigoid (BP) has only been described in 2 isolated case reports. The clinical significance and the pathophysiologic mechanisms of this association are unknown. Objective: To examine the clinical characteristics and immunological profile of patients with BP who develop transient PPK and analyze therapeutic options and outcomes. Design, Setting, and Participants: In this case series, patients with BP who developed acquired, transient PPK, and were treated at a single institution from January 1, 2015, through December 31, 2017, were studied. Main Outcomes and Measures: Clinical and immunological activity of BP, treatment administrated before and after PPK appearance, and patient outcomes. Results: Six patients with BP and transient PPK were identified and included in the study. There were 5 women and 1 man with a mean age of 72 years. At baseline, all patients had a generalized, multibullous BP and high serum anti-BP180 antibodies (mean, 130 U/mL; range, 73-150), whereas anti-BP230 antibodies were elevated in only 1 case. The PPK appeared a mean 6.2 (range, 2-12) months after BP diagnosis, following a prolonged period of disease activity with recurrent flares. When the PPK occurred, BP was uncontrolled on therapy (mean Bullous Pemphigoid Disease Activity Index [BPDAI] score, 57; range, 34-105; mean anti-BP180 antibodies titer, 122 U/mL; range, 81-150). On administration of additional systemic immunosuppressive therapies, the PPK healed progressively in a mean 4.3 months (range, 2-9), along with BP clinical remission in 4 of 6 patients. No relationship was found between PPK occurrence and anti-BP180/230 antibodies profiles. In contrast, blister fluids collected at the time of PPK displayed a much higher level of interleukin 1ß (IL-1ß) compared with those collected in the absence of PKK. Expression of IL-17A, IL-17F, and IL-22 was also enhanced in the blister fluid of patients with BP who had PPK. Conclusions and Relevance: To our knowledge, this is the first report of 6 cases of BP with transient PPK with extensive immunological investigation. The PPK appeared after a prolonged period of clinical BP activity punctuated with recurrent relapses, was transient, and healed after BP control with additional immunosuppressive therapy. Enhanced expression of a particular cytokine panel in the blister fluid at time of PPK could support keratinocyte proliferation as described in patients with psoriasis. Transient PPK could represent a clinical marker of severe, treatment-resistant BP.

Importancia de la sensibilidad plantar en la regulación del control postural y del movimiento: revisión / Importance of plantar sensitivity in the regulation of postural control and movement: Review

El objetivo de esta revisión es analizar la influencia de la sensibilidad plantar en la mejora de la capacidad de reequilibración y de gestión del movimiento, analizando los mecanismos que permiten valorarla y describiendo los factores que en ella influyen. Para ello se realizó una búsqueda sistemática de la bibliografía publicada entre 2000 y 2016, en las bases de datos PubMed, Web of Science, Sport-Discus y en las referencias citadas en los artículos recuperados, cuyo idioma de publicación fuera español o inglés. Un total de 9 artículos fueron recuperados y analizados. La mayoría de los estudios sugieren que, la retroalimentación sensorial del pie resulta fundamental en el mantenimiento de los patrones generales (posturales y de desplazamiento) y específicos (deportivos). La alteración de la cantidad o calidad de la información aferente plantar no solo parece alterar la creación de los diferentes patrones, sino que podrá incrementar el riesgo de aparición de lesiones (AU)

The objective of this review is to analyse the influence of plantar sensitivity in improving the ability to rebalance and manage movement by analysing the mechanisms available to assess this and describing the factors that influence this. This project required a systematic search of the literature published between 2000 and 2016 in PubMed, Web of Science, and SPORTDiscus, as well as the references cited in relevant articles from these sources. The publication languages were Spanish and English, and a total of 9 items were collected and analysed. Most studies suggest that sensory feedback from the foot is essential in maintaining general (postural and displacement) and specific (sport) patterns. Altering the quantity or quality of plantar afferent information not only appears to alter the creation of different patterns but may also increase the risk of injury (AU)

Management of Plantar KeratodermasLessons from Pachyonychia Congenita.

Plantar keratodermas can arise due to a variety of genetically inherited mutations. The need to distinguish between different plantar keratoderma disorders is becoming increasingly apparent because there is evidence that they do not respond identically to treatment. Diagnosis can be aided by observation of other clinical manifestations, such as palmar keratoderma, more widespread hyperkeratosis of the epidermis, hair and nail dystrophies, or erythroderma. However, there are frequent cases of plantar keratoderma that occur in isolation. This review focuses on the rare autosomal dominant keratin disorder pachyonychia congenita, which presents with particularly painful plantar keratoderma for which there is no specific treatment. Typically, patients regularly trim/pare/file/grind their calluses and file/grind/clip their nails. Topical agents, including keratolytics (eg, salicylic acid, urea) and moisturizers, can provide limited benefit by softening the skin. For some patients, retinoids help to thin calluses but may lead to increased pain. This finding has stimulated a drive for alternative treatment options, from gene therapy to alternative nongenetic methods that focus on novel findings regarding the pathogenesis of pachyonychia congenita and the function of the underlying genes.

Mal de meleda - through history and today.

Meleda disease is an indigenous dermatological disease classified as a hereditary palmoplantar keratoderma. The disease was first described on the island of Mljet, Croatia, by Luko Stulli in 1826. We present a historical review of the literature data throughout the centuries till today. Recently, the gene responsible for the disease has been identified on chromosome 8qter within the cluster of Ly-6 homologous human genes. Various mutations in the secreted LY6/PLAUR-related protein1 gene (SLURP1) located on the aforementioned chromosome were identified as the cause of the disease. Due to similarity between the islands of Malta and Mljet, we are proud of the fact that, to the credit of Croatian researchers and scientists, Mal de Meleda entered the international scientific literature under that very name and has preserved it until today.

Symmetrical acrokeratoderma: A peculiar entity in China? Clinicopathologic and immunopathologic study of 34 new cases.

BACKGROUND: Symmetrical acrokeratoderma seems to be a new disorder in China, and 138 cases have been reported in the Chinese literature. OBJECTIVE: We sought to summarize the clinicopathologic features and immunophenotyping of inflammatory cells in 34 new cases. METHODS: Clinical data of 34 patients were prospectively collected over 4 years. Histopathology and immunostaining of infiltrated cells were performed in 27 and 9 patients, respectively. RESULTS: Brown to black hyperkeratotic patches were symmetrically distributed over the acral regions in 33 cases and on the scalp in 1 case, with a whitish change after water contact or sweating. The condition was aggravated in summer and alleviated in winter in 33 patients. History of ichthyosis vulgaris was seen in 23 cases. The typical histopathology included epidermal hyperkeratosis, acanthosis, and papillary dermal perivascular infiltrate of lymphohistiocytes. Number of CD3(+), CD4(+), and CD8(+) cells increased in lesional and perilesional skin compared with normal-appearing skin. The skin lesions developed slowly but were confined to the acral predilection sites after the mean follow-up of 25.4 ± 13.8 months. LIMITATIONS: The follow-up time was short. CONCLUSION: This disorder may represent a peculiar dermatosis that is frequently associated with ichthyosis vulgaris. No specific therapy is available for the disorder.

Use of arsenic-induced palmoplantar hyperkeratosis and skin cancers to predict risk of subsequent internal malignancy.

Hyperpigmentation, hyperkeratoses, and Bowen's disease are hallmarks of chronic arsenic exposure. The association between arsenic-induced skin lesions and subsequent internal cancers is examined by using a community-based prospective study. The cohort was enrolled from an arseniasis-endemic area in southwestern Taiwan, where 2,447 residents participated in skin examinations during the late 1980s. The number of participants diagnosed with hyperpigmentation was 673; with hyperkeratosis, 243; and with skin cancer (Bowen's disease or non-melanoma skin cancer), 378. Newly diagnosed internal cancers were ascertained through linkage with National Cancer Registry profiles. Cox regression was performed to estimate hazard ratios with 95% confidence intervals for potential risk predictors. Compared with participants without skin lesions, patients affected with skin cancers had a significantly increased risk of lung cancer (hazard ratio = 4.64, 95% confidence interval: 2.92, 7.38) and urothelial carcinoma (hazard ratio = 2.02, 95% confidence interval: 1.23, 3.30) after adjustment for potential confounders and cumulative arsenic exposure. Hyperkeratosis is significantly associated with an increased lung cancer risk (hazard ratio = 2.76, 95% confidence interval: 1.35, 5.67). A significant interactive effect on lung cancer risk between hyperkeratosis and cigarette smoking was identified, which suggests that patients with hyperkeratosis who have been exposed to arsenic should cease smoking.

Prevalence and treatment of palmoplantar keratoderma and tinea pedis in patients with Sézary syndrome.

BACKGROUND: Mycosis fungoides (MF) and the Sézary syndrome (SS) are non-Hodgkin's lymphomas that present with cutaneous lesions. Sézary syndrome is characterized by blood involvement, exfoliative eryrthroderma, lymphadenopathy, pruritus, keratoderma, and immunosuppression. This study was to estimate the prevalence of palmoplantar keratoderma and tinea pedis in Sézary syndrome and to analyze the effectiveness of anti-fungal treatment. METHODS: We conducted a retrospective review of 1562 prospectively collected patients at the MD Anderson Cancer Center Cutaneous Lymphoma Clinic over sixteen years. All patients' palms and soles were evaluated for clinical evidence of keratoderma (hyperkeratosis) and for dermatophytosis (tinea pedis or unguum) by examining scales under 10% potassium hydroxide by light microscopy for hyphae. RESULTS: Of 138 Sézary syndrome patients (88 men, 50 women, median age at diagnosis 64 years), 85 (61.6%) had palmoplantar keratoderma; 45 of the 85 Sézary syndrome patients (52.9%) also had coexisting tinea pedis. Only 14 (10.1%) had tinea pedis without keratoderma. Treatment for tinea pedis resulted in microscopy cure of keratoderma in 12 of 45 (26.7%) patients and clinical improvement. CONCLUSIONS: The prevalence of palmoplantar keratoderma in Sézary syndrome is 61.6%, with co-existing tinea pedis found in 52.9%. Palmoplantar keratoderma with tinea pedis showed clinical improvement with fungicidal therapy suggesting that tinea often contributes to the pathogenesis and severity of Sézary syndrome-related keratoderma.

Retrospective long-term follow-up in patients with chronic palmoplantar dermatoses after good response to bath PUVA therapy.

BACKGROUND: Numerous studies have confirmed the short-term effectiveness of 8-methoxypsoralen bath PUVA therapy in patients with chronic palmoplantar dermatoses; however, little is known about long-term results. PATIENTS AND METHODS: In this retrospective study we examined the long-term results in 79 patients (mean age: 48 years) with chronic palmoplantar dermatoses who were treated with bath PUVA three times a week over an 8-year period. A good clinical response (a reduction of more than 50% of the skin lesions) occurred after a mean of 23 treatments and a mean cumulative UVA dose of 39 J/cm(2) in 51 patients (65%). In 2007 a questionnaire was sent to these 51 patients to assess the long-term outcome. RESULTS: With bath PUVA treatment, the best results were found in patients with hyperkeratotic eczema (17/22; 77% good clinical response) followed by patients with palmoplantar psoriasis (26/41; 63%) and patients with dyshidrotic eczema (8/16; 50%). Thirty-four patients (67%) answered the questionnaire after a mean follow-up interval of 4.3 years (10-87 months). Among these patients, 36% reported an improved course of disease after PUVA therapy with reduced frequency and/or intensity of the skin rash, and 29% of patients reported continued complete clearance. 79% of our patients reported a long-term reduction in the use of topical corticosteroids during the follow-up period (mean: 4.3 years). In addition, 67% of patients reported a lasting improvement in quality of life. CONCLUSIONS: These data show that bath PUVA may have a long-term, beneficial influence on the course of disease in a majority of patients with recalcitrant chronic palmoplantar dermatoses.

A review of the clinical phenotype of 254 patients with genetically confirmed pachyonychia congenita.

BACKGROUND: Pachyonychia congenita (PC) is a group of autosomal dominant keratinizing disorders caused by a mutation in one of 4 keratin genes. Previous classification schemes have relied on data from case series and case reports. Most patients in these reports were not genetically tested for PC. OBJECTIVE: We sought to clarify the prevalence of clinical features associated with PC. METHODS: We surveyed 254 individuals with confirmed keratin mutations regarding their experience with clinical findings associated with PC. Statistical comparison of the groups by keratin mutation was performed using logistic regression analysis. RESULTS: Although the onset of clinical symptoms varied considerably among our patients, a diagnostic triad of toenail thickening, plantar keratoderma, and plantar pain was reported by 97% of patients with PC by age 10 years. Plantar pain had the most profound impact on quality of life. Other clinical findings reported by our patients included fingernail dystrophy, oral leukokeratosis, palmar keratoderma, follicular hyperkeratosis, hyperhidrosis, cysts, hoarseness, and natal teeth. We observed a higher likelihood of oral leukokeratosis in individuals harboring KRT6A mutations, and a strong association of natal teeth and cysts in carriers of a KRT17 mutation. Most keratin subgroups expressed a mixed constellation of findings historically reported as PC-1 and PC-2. LIMITATIONS: Data were obtained through questionnaires, not by direct examination. Patients were self- or physician-referred. CONCLUSIONS: We propose a new classification for PC based on the specific keratin gene affected to help clinicians improve their diagnostic and prognostic accuracy, correct spurious associations, and improve therapeutic development.

Estudio de prevalencia de patologías podológicas y grado de dependencia en personas mayores de 65 años / No disponible

La prevalencia de patologías podológicas sufre un incremento desde los sesenta años de edad, de igual forma que el nivel de dependencia de las personas. En el presente estudio realizado sobre 748 pacientes mayores de 65 años de 16 municipios gallegos, valoramos la relación entre patologías podológicas y el grado de dependencia. No se observa relación directa de la mayoría de las patologías podológicas con el grado de dependencia, tan solo la onicocriptosis y otras patologías ungueales poco frecuentes muestran datos estadísticos significativos que establecen el grado de dependencia como factor predisponente(AU)

The prevalence of podiatric pathologies suffers an increase from sixty years of age, of equal form that the level of dependence of the persons. For the present study realized on 748 patients 65 and older taken in the region of Galicia we value the relation between podiatric pathologies and the degree of dependence. Is not observed direct relation of the majority of the podiatric pathologies by the degree of dependence, only the onichocryptosis and other nail pathologies slightly frequent show statistical significant information that establish the degree of dependence as predisposing factor(AU)