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The Zrt-/Irt-like protein (ZIP) family mediates zinc influx from extracellular space or intracellular vesicles/organelles, playing a central role in systemic and cellular zinc homeostasis. Out of the 14 family members encoded in human genome, ZIP4 is exclusively responsible for zinc uptake from dietary food and dysfunctional mutations of ZIP4 cause a life-threatening genetic disorder, Acrodermatitis Enteropathica (AE). About half of the missense AE-causing mutations occur within the large N-terminal extracellular domain (ECD), and our previous study has shown that ZIP4–ECD is crucial for optimal zinc uptake but the underlying mechanism has not been clarified. In this work, we examined zinc binding to the isolated ZIP4–ECD from Pteropus Alecto (black fruit bat) and located zinc-binding sites with a low micromolar affinity within a histidine-rich loop ubiquitously present in ZIP4 proteins. Zinc binding to this protease-susceptible loop induces a small and highly localized structural perturbation. Mutagenesis and functional study on human ZIP4 by using an improved cell-based zinc uptake assay indicated that the histidine residues within this loop are not involved in preselection of metal substrate but play a role in promoting zinc transport. The possible function of the histidine-rich loop as a metal chaperone facilitating zinc binding to the transport site and/or a zinc sensor allosterically regulating the transport machinery was discussed. This work helps to establish the structure/function relationship of ZIP4 and also sheds light on other metal transporters and metalloproteins with clustered histidine residues.

To study the clinical profile and outcome of children with Inborn errors of metabolism. Thirty one newly diagnosed children with Inborn errors of metabolism over a 1 y period were studied for their relevant clinical, biochemical, diagnosis, treatment and follow-up details. Inborn errors of metabolism accounted for 2% of hospital admissions. Sixty five percent were born to parents of consanguineous marriage. Of the 31 children with Inborn errors of metabolism, 16 (51%) had lysosomal storage disorders, 8 (26%) had disorders of amino acid metabolism, 2 (6%) each had disorders of carbohydrate and bile acid metabolism, 1 (3%) each had disorders of fatty acid oxidation, mitochondrial and peroxisome metabolism. Acrodermatitis dysmetabolica, as a complication was observed in one child and the overall mortality rate in this series was 10%. Lysosomal storage disorders constituted the majority of Inborn errors of metabolism in this series and amino acidopathies/organic acidemias were successfully treated with special formulas.

Background: Chronic acrodermatitis continua of Hallopeau (ACH) is a rare form of pustular psoriasis predominantly affecting the distal phalanges of the fingers and toes. The disease manifests by pustular rash with marked infiltration, fissures, and often results into severe dystrophy of nail plates. ACH is refractory to most of psoriasis standard of care (SOC) therapies. Objective: The objective of this study is to assess the prospects of secukinumab therapy of ACH based on current clinical observation. Methods: We observed a female patient with ACH. Number of SOC treatments were applied in that case including local PUVA therapy, systemic retinoids, methotrexate, and biologic agents. Result: Secukinumab, a IL-17 inhibitor, demonstrated pronounced clinical effect in the case of ACH refractory to other SOC therapies. Conclusion: IL-17 inhibition provided by secukinumab was linked to clinically meaningful improvement in the heavily pretreated ACH. Further exploration and clinical studies may be important to provide more data on secukinumab effects in ACH.

The essential trace element zinc (Zn) plays a key role in the development, differentiation and growth of various human tissues. Zinc homeostasis is primarily regulated by two zinc transporter families (solute-linked carrier families, SLC). Disturbances in zinc metabolism may give rise to disorders that typically manifest themselves on the skin. An autosomal recessive zinc deficiency disorder, acrodermatitis enteropathica is caused by a mutation in the gene coding for the ZIP4 transporter. Due to intestinal malabsorption, affected infants develop clinical signs and symptoms shortly after weaning. Acquired zinc deficiency is a rare but underdiagnosed disorder associated with various etiologies and variable clinical manifestations. Depending on the patient's age, a multitude of causes have to be considered. Given the characteristic periorificial and acral lesions, the clinical diagnosis is usually made by dermatologists. Laboratory confirmation includes measurement of plasma zinc levels and - as a supplementary measure - zinc-dependent enzymes such as alkaline phosphatase. Oral zinc replacement therapy frequently leads to clinical remission within a few days. Depending on the cause, disease management should include cooperation with pediatricians and gastroenterologists in order to guarantee optimal patient care.

The trace element zinc (Zn) binds to over ten percent of proteins in eukaryotic cells. Zn flexible chemistry allows it to regulate the activity of hundreds of enzymes and influence scores of metabolic processes in cells throughout the body. Deficiency of Zn in humans has a profound effect on development and in adults later in life, particularly in the brain, where Zn deficiency is linked to several neurological disorders. In this review, we will summarize the importance of Zn during development through a description of the outcomes of both genetic and early dietary Zn deficiency, focusing on the pathological consequences on the whole body and brain. The epidemiology and the symptomology of Zn deficiency in humans will be described, including the most studied inherited Zn deficiency disease, Acrodermatitis enteropathica. In addition, we will give an overview of the different forms and animal models of Zn deficiency, as well as the 24 Zn transporters, distributed into two families: the ZIPs and the ZnTs, which control the balance of Zn throughout the body. Lastly, we will describe the TRPM7 ion channel, which was recently shown to contribute to intestinal Zn absorption and has its own significant impact on early embryonic development.

Since the onset of the COVID‐19 pandemic, the growing body of literature has largely focused on the adult population. Reported symptoms among children appear to be consistent with those in adults, including fever, respiratory symptoms, and gastrointestinal symptoms, though children may experience an overall milder disease course. Viral exanthems with possible association to COVID‐19 have been reported in pediatric patients. We describe a 10‐month‐old boy with Gianotti‐Crosti syndrome in the setting of recent SARS‐CoV‐2 RT‐PCR positive testing to increase physician awareness and add to the collection of cutaneous manifestations of COVID‐19.

ZIP4 is a representative member of the Zrt-/Irt-like protein (ZIP) transporter family and responsible for zinc uptake from diet. Loss-of-function mutations of human ZIP4 (hZIP4) drastically reduce zinc absorption, causing a life-threatening autosomal recessive disorder, acrodermatitis enteropathica (AE). These mutations occur not only in the conserved transmembrane zinc transport machinery, but also in the extracellular domain (ECD) of hZIP4, which is only present in a fraction of mammalian ZIPs. How these AE-causing ECD mutations lead to ZIP4 malfunction has not be fully clarified. In this work, we characterized all seven confirmed AE-causing missense mutations in hZIP4-ECD and found that the variants exhibited completely abolished zinc transport activity in a cell-based transport assay. Although the variants were able to be expressed in HEK293T cells, they failed to traffic to the cell surface and were largely retained in the ER with immature glycosylation. When the corresponding mutations were introduced in the ECD of ZIP4 from Pteropus Alecto, a close homolog of hZIP4, the variants exhibited structural defects or reduced thermal stability, which likely accounts for intracellular mistrafficking of the AE-associated variants and as such a total loss of zinc uptake activity. This work provides a molecular pathogenic mechanism for AE.

La paraqueratosis pustulosa es una entidad poco descrita en la literatura y se define como un proceso inflamatorio cutáneo, ungueal y periungueal en el area distal de un dedo habitualmente pulgar o indice, frecuentemente en la infancia. Su evolución suele ser benigna y la respuesta a emolientes tópicos es favorable. A continuación, se presenta un caso de esta enfermedad con el objetivo de resaltar su consideración en patologías ungueales pediátricas.

Pustular psoriasis refers to a heterogeneous group of chronic inflammatory skin disorders that are clinically, histologically, and genetically distinct from plaque psoriasis. Pustular psoriasis may present as a recurrent systemic illness (generalized pustular psoriasis [GPP]), or as localized disease affecting the palms and/or soles (palmoplantar pustulosis [PPP], also known as palmoplantar pustular psoriasis), or the digits/nail beds (acrodermatitis continua of Hallopeau [ACH]). These conditions are rare, but their possible severity and consequences should not be underestimated. GPP, especially an acute episode (flare), may be a medical emergency, with potentially life-threatening complications. PPP and ACH are often debilitating conditions. PPP is associated with impaired health-related quality of life and psychiatric morbidity, while ACH threatens irreversible nail and/or bone damage. These conditions can be difficult to diagnose; thus, primary care providers should not hesitate to contact a dermatologist for advice and/or patient referral. The role of corticosteroids in triggering and leading to flares of GPP should also be noted, and physicians should avoid the use of systemic corticosteroids in the management of any form of psoriasis.PLAIN LANGUAGE SUMMARYA brief guide to pustular psoriasis for primary care providersPustular psoriasis consists of a group of rare conditions that cause the skin to become red and painful. In these conditions, small blisters filled with pus (called pustules) appear suddenly. The pustules are not infectious. Pustular psoriasis is different from plaque psoriasis, in which people develop scaly patches of skin. People can have pustular psoriasis and plaque psoriasis at the same time. Pustular psoriasis can be widespread, affecting large areas of the body, arms, and legs. This is called generalized pustular psoriasis (GPP). GPP can cause life-threatening complications that may require emergency medical treatment. Pustular psoriasis can be more localized, occurring on the palms of the hands and soles of the feet. This is called palmoplantar pustulosis (PPP). It can also occur on the fingers, toes, and nail beds, called acrodermatitis continua of Hallopeau (ACH). PPP and ACH can make walking and other everyday activities difficult. Because GPP, PPP, and ACH are rare, primary care providers are unlikely to meet many people with pustular psoriasis, so they may not recognize these conditions immediately. This article aims to help primary care providers assess and diagnose people who may have GPP, PPP, or ACH, and advise when they should get help from a skin specialist (dermatologist). See Figure 1 for a full infographic version of this summary.

Background Palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH) are rare variants of psoriasis. Knowledge of the efficacy of biologics is scarce. Objectives To evaluate the real-life efficacy of tumour necrosis factor blockers and ustekinumab in PPP and in ACH. Methods A multicentre retrospective descriptive study was conducted in 19 dermatology departments, including all patients with PPP or ACH seen from 2014 to 2016 who received one of the studied biologics. The data were collected by a standardized document. Factors associated with complete clearance (CC) were analysed by multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Results Among 92 patients included, 50 received adalimumab, 44 ustekinumab, 36 etanercept and 31 infliximab. Improvement and CC were observed in 83.9% and 20.0% patients receiving infliximab, 75.0% and 38.6% ustekinumab, 57.1% and 20.0% etanercept and 60.4% and 29.2% adalimumab. We found no significant difference in CC rates or duration of treatment among the biological treatments (P = 0.18 and P = 0.10, respectively). On multivariate analysis, CC with etanercept was associated with the ACH form and not smoking [OR = 9.5 (95% CI 1.1-82.7), P = 0.04 and 0.1 (0.01-0.9), P = 0.04]; with ustekinumab, male sex and absence of obesity [6.0 (1.3-28.6), P = 0.02 and 4.7 (1.0-22.7), P = 0.05]; with adalimumab, the ACH form [11.9 (2.7-52.3), P = 0.001]; and with infliximab, obesity [5.6 (1.1-29.4), P = 0.04]. Conclusions We found no difference in efficacy between TNF blockers and ustekinumab and among the three different TNF blockers in real life for PPP or ACH, which reveals the heterogeneity of clinical response to biologics in pustular psoriasis as compared with plaque psoriasis.

International audience; Skins symptoms during COVID‐19 have been recently described but their relation to SARS‐CoV‐2 is unclear while results for real‐time reverse transcriptase polymerase chain reaction (rRT‐PCR) testing were variable. Recalcati et al. reported 14 cases of patients with skin symptoms consistent with previous described COVID‐19 lesions but all the patients were tested negative. They asked for a serology to validate the hypothesis that these lesions are related to COVID‐19.

The case of a 72-year-old female patient with exanthem and concomitant neuropathy of the instep of the foot and progressive ipsilateral lower leg pain is reported. Sonographically, a superficial vein thrombosis with extension into the deep venous system originating from the exanthem was observed. On the basis of the clinical picture as well as the serological and electrophysiological findings, a rare diagnosis of acrodermatitis chronica atrophicans with peripheral neuropathy was made, which could significantly promote the local development of venous thrombosis.

RESUMEN Introducción: La acrodermatitis enteropática es una dermatosis nutricional heredada o adquirida por deficiencia de zinc que clínicamente se caracteriza por eritema, escamocostras y erosiones, especialmente en la región perioral, en zonas acras y en la región anogenital. Además de una ingesta oral inadecuada, hay causas secundarias de esta deficiencia nutricional. Objetivo: Referir una dermatosis nutricional secundaria infrecuente en lactante femenina. Presentación de caso: Pequeñita de 6 meses de edad, fototipo III, alimentada con lactancia materna exclusiva, que acude a consulta especializada de dermatología en el hospital “William Soler” por cuadro clínico de 3 meses de evolución caracterizado por lesiones eritematocostrosas en regiónes acrales y periorificiales. Los padres refirieron lactancia materna exclusiva. Se realizaron complementarios Conclusiones: Las deficiencias de vitaminas y oligoelementos pueden ocasionar un amplio rango de hallazgos mucocutaneos. En el caso presentado diagnosticado como acrodermatitis enteropática adquirida, hay un aporte inadecuado de zinc en la leche materna.

No abstract available Keywords: IL-36; acrodermatitis continua of hallopeau; generalized pustular psoriasis; localized pustular psoriasis; pustular psoriasis; spesolimab.

Neutrophilic dermatoses are a heterogeneous group of inflammatory skin diseases that have unique clinical features, but are combined by the presence of a sterile, predominantly neutrophilic infiltrate at histopathological examination. Neutrophilic dermatoses include Sweet syndrome, gangrenous pyoderma, Behcet’s disease, neutrophilic urticaria, subcorneal pustular dermatosis, palmoplantaris pustulosis, acrodermatitis Allopo, acute generalized exentematous pustulosis, infant pustulosis, etc. The morphology of skin lesions associated with these diseases is heterogeneous, which makes diagnosis challenging. In addition, a thorough clinical evaluation of patients is necessary to exclude diseases that mimic these disorders and to diagnose potential concomitant infectious, inflammatory, and tumor processes. While some neutrophilic dermatoses may disappear spontaneously, most require treatment to achieve remission. A delay in diagnosis and treatment can lead to significant morbidity and even mortality in these patients. Glucocorticoids are the drugs of choice for the treatment of neutrophilic dermatoses. In case of their ineffectiveness, other biological disease-modifying antirheumatic drugs may be administered depending on the severity of the skin lesion, chronicity of the disease, the presence of systemic lesions, and refractory status. This work is devoted to epidemiology, etiopathogenesis, clinical features, diagnostic signs and modern methods of treating Sweet syndrome and gangrenous pyoderma based on a review of modern literature and our own clinical observations., Нейтрофильные дерматозы — гетерогенная группа воспалительных заболеваний кожи, которые имеют уникальные клинические особенности, но объединены наличием стерильного, преимущественно нейтрофильного инфильтрата, выявляемого по результатам гистопатологического исследования. К нейтрофильным дерматозом относят Свит- синдром, гангренозную пиодермию, болезнь Бехчета, нейтрофильную крапивницу, субкорнеальный пустулезный дерматоз, ладонно-подошвенный пустулез, акродерматит Аллопо, острый генерализованный экзентематозный пустулез, детский акропустулез и др. Морфология поражений кожи, ассоциированная с этими заболеваниями, не­однородна, что делает их диагностику сложной. Кроме того, необходима тщательная клиническая оценка состояния пациентов для исключения заболеваний, имитирующих эти расстройства, а также для диагностики потенциальных сопутствующих инфекционных, воспалительных и опухолевых процессов. В то время как некоторые нейтрофильные дерматозы могут исчезать самопроизвольно, большинство из них нуждается в лечении для достижения ремиссии. Задержка в диагностике и проведении лечения может привести к значительному повышению заболеваемости и даже смерти пациентов. Глюкокортикоиды являются препаратами выбора для лечения нейтро­фильных дерматозов, при неэффективности которых возможно применение других биологических болезнь-модифицирующих антиревматических препаратов, которые следует назначать в зависимости от степени тяжести поражения кожи, хронизации заболевания, наличия системного поражения и рефрактерности состояния. Данная работа посвящена освещению эпидемиологии, этиопатогенеза, клинических особенностей, диагностических признаков и современных методов лечения больных со Свит-синдромом и гангренозной пиодермией на основе обзора современной литературы и собственных клинических наблюдений., Нейтрофільні дерматози — гетерогенна група запальних захворювань шкіри, які мають унікальні клінічні особливості, але об’єднані наявністю стерильного, переважно нейтрофільного інфільтрату, виявленого за результатами гістологічного дослідження. До нейтрофільних дерматозів зараховують Світ-синдром, гангренозну піодермію, хворобу Бехчета, нейтрофільну кропив’янку, субкорнеальний пустульозний дерматоз, долонно-підошовний пустульоз, акродерматит Аллопо, гострий генералізований екзентематозний пустульоз, дитячий акропустульоз і ін. Морфологія уражень шкіри, асоційована з цими захворюваннями, неоднорідна, що робить їх діагностику складною. Крім того, необхідна ретельна клінічна оцінка стану пацієнтів для виключення захворювань, що імітують ці розлади, а також для діагностики потенційних супутніх інфекційних, запальних і пухлинних процесів. У той час як деякі нейтрофільні дерматози можуть зникати спонтанно, більшість потребують проведення лікування для досягнення ремісії. Затримка в діагностиці та проведенні лікування може призвести до значного підвищення захворюваності та навіть смерті пацієнтів. Глюкокортикоїди є препаратами вибору для лікування нейтрофільних дерматозів, при неефективності яких можливе застосування інших біологічних хворобомодифікуючих антиревматичних препаратів, які слід призначати залежно від ступеня тяжкості ураження шкіри, хронізації захворювання, наявності системного ураження і рефрактерності стану. Ця робота присвячена висвітленню епідеміології, етіопатогенезу, клінічних особливостей, діагностичних ознак і сучасних методів лікування хворих із Світ-синдромом і гангреноз­ною піодермією на основі огляду сучасної літератури і власних клінічних спостережень.

Acrodermatitis continua of Hallopeau (ACH) is a rare chronic inflammatory skin disease. Treatment is extremely challenging and mostly based on empirics as there is only scarce evidence from case reports and few small case series. In this retrospective study, patients with ACH treated at five university medical centers were analyzed according to patient and disease characteristics and treatment experience. We identified 39 patients with ACH with a mean age of 54.4 years at onset, of whom 22 (56.4%) were female. A total of 115 systemic treatment courses were analyzed with methotrexate as the most common therapy (27.0%). Overall, effectiveness of systemic treatments was low (excellent response rate: 14.8%). Among non-biologics, excellent response was noted in 21.1% (4/19) of treatment courses with methotrexate, followed by acitretin (13.3%; 2/15). Among biologics, guselkumab (excellent response: 100%; 2/2), secukinumab (excellent response: 42.9%; 3/7) and adalimumab (excellent response: 20.0%; 2/10) were most efficacious. The median drug survival was 7.0 months and did not differ significantly between the subgroup of non-biologic and biologic therapies. To our knowledge, this is the largest case series in ACH investigating patient characteristics and treatment outcomes. Based on our treatment experience, we suggest a treatment algorithm starting with acitretin or methotrexate as first-line therapy, followed by biologics. Cyclosporin may be used for short-term control. However, none of the applied systemic therapies yielded satisfying efficacy in our cohort. In patients with primary non-response, switch of treatment should be evaluated timely on an individual basis, considering possible irreversible disease complications such as nail loss. More research with prospective design is needed to further evaluate traditional and also particularly newer antipsoriatic drugs in ACH.

Contains fulltext : 220683.pdf (Publisher’s version ) (Closed access) Lyme borreliosis is the most common vectorborne disease in the northern hemisphere. It usually begins with erythema migrans; early disseminated infection particularly causes multiple erythema migrans or neurologic disease, and late manifestations predominantly include arthritis in North America, and acrodermatitis chronica atrophicans (ACA) in Europe. Diagnosis of Lyme borreliosis is based on characteristic clinical signs and symptoms, complemented by serological confirmation of infection once an antibody response has been mounted. Manifestations usually respond to appropriate antibiotic regimens, but the disease can be followed by sequelae, such as immune arthritis or residual damage to affected tissues. A subset of individuals reports persistent symptoms, including fatigue, pain, arthralgia, and neurocognitive symptoms, which in some people are severe enough to fulfil the criteria for post-treatment Lyme disease syndrome. The reported prevalence of such persistent symptoms following antimicrobial treatment varies considerably, and its pathophysiology is unclear. Persistent active infection in humans has not been identified as a cause of this syndrome, and randomized treatment trials have invariably failed to show any benefit of prolonged antibiotic treatment. For prevention of Lyme borreliosis, post-exposure prophylaxis may be indicated in specific cases, and novel vaccine strategies are under development.

Introduction: The treatment of acquired acrodermatitis enteropathica involves zinc supplementation; however, further research is required to establsih the optimal dose and duration of the supplementation. Case presentation: Female patient with a history of gastric bypass, intestinal resection, and 2 months of skin rash that required biopsy with histological findings compatible with dermatitis associated to nutritional deficiency. She received elemental zinc supplementation for 11 days, achieving improvement in skin lesions. She was later readmitted twice due to reactivation of the disease with the need to restart zinc supplementation. At the time of this study, she had been receiving oral elemental zinc treatment for 3 years, at doses of up to 240 mg/day. Discussion: In patients with gastric bypass and intestinal malabsorption, the usual zinc dose of 8-11 mg/day may be insufficient and put patients at risk for acquired acrodermatitis enteropathica. In similar case reports, the supplementation dose ranges from 2 mg/kg/day of venous elemental zinc to 300 mg/day orally, while the duration of supplementation has not been established. Conclusions: Oral supplementation for 3 years with a maximum dose of 240 mg/day has been adequate for controlling the disease. Monitoring blood zinc levels and physical examination of the skin have been key factors for adjusting the dose to be supplied. RESUMEN Introducción. El tratamiento de la acrodermatitis enteropática adquirida es la suplementación de zinc, sin embargo la dosis óptima y la duración de esta aún son objeto de estudio. Presentación del caso. Paciente femenino con antecedente de bypass gástrico, resección intestinal y 2 meses de erupción cutánea que ameritó biopsia lesional con hallazgos histológicos compatibles con una dermatitis carencial. La mujer recibió suplemento de zinc elemental por 11 días, con lo que se logró mejoría de lesiones cutáneas. Posteriormente, presentó 2 reingresos por reactivación de la enfermedad con necesidad de reiniciar suplementación y, hasta el momento de la presente investigación, había permanecido 3 años con zinc elemental oral con dosis de hasta 240 mg/día. Discusión. En pacientes con malabsorción intestinal la dosis de zinc de rutina de 8-11 mg/ día puede ser insuficiente y los puede colocar en riesgo de acrodermatitis enteropática adquirida. En reportes de caso similares la dosis de suplementación va desde 2 mg/kg/día de zinc elemental venoso hasta 300 mg/día oral, en tanto la duración de la suplementación no ha sido establecida. Conclusiones. La suplementación oral por 3 años con hasta 240 mg/día ha sido adecuada para el control de la enfermedad; el seguimiento a través de la medición de los niveles de zinc en sangre y la exploración física de la piel ha sido clave en el ajuste de la dosis a suplementar.

In elderly or chronically ill patients, nutritional deficiencies are common and the presence of related skin lesions is not unusual. Recognition of such cutaneous involvement is important regarding the diagnosis essentially based on clinical elements. By using some clinical case reports, we will describe several pathologies related to nutritional deficiencies like scurvy, pellagra and acquired acrodermatitis enteropathica.Dans nos populations de patients vieillissants ou atteints de maladies chroniques, les carences nutritionnelles sont fréquentes et la présence de manifestations dermatologiques associées n’est pas rare. La reconnaissance de telles atteintes cutanées est importante pour le diagnostic qui est essentiellement clinique. A l’aide de vignettes cliniques, nous allons discuter ici de pathologies carentielles comme le scorbut, la pellagre ainsi que l’acrodermatite entéropathique acquise.