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Nutrients Feb 2018The first manifestations that appear under zinc deficiency are skin defects such as dermatitis, alopecia, acne, eczema, dry, and scaling skin. Several genetic disorders... (Review)
Review
The first manifestations that appear under zinc deficiency are skin defects such as dermatitis, alopecia, acne, eczema, dry, and scaling skin. Several genetic disorders including acrodermatitis enteropathica (also known as Danbolt-Closs syndrome) and Brandt's syndrome are highly related to zinc deficiency. However, the zinc-related molecular mechanisms underlying normal skin development and homeostasis, as well as the mechanism by which disturbed zinc homeostasis causes such skin disorders, are unknown. Recent genomic approaches have revealed the physiological importance of zinc transporters in skin formation and clarified their functional impairment in cutaneous pathogenesis. In this review, we provide an overview of the relationships between zinc deficiency and skin disorders, focusing on the roles of zinc transporters in the skin. We also discuss therapeutic outlooks and advantages of controlling zinc levels via zinc transporters to prevent cutaneous disorganization.
Topics: Animals; Cation Transport Proteins; Deficiency Diseases; Homeostasis; Humans; Skin; Skin Absorption; Skin Diseases; Zinc
PubMed: 29462920
DOI: 10.3390/nu10020219 -
Journal of Dermatological Science May 2018Classifying inflammatory skin diseases is challenging, especially for the expanding group of disorders triggered by genetic factors resulting in hyperactivated innate... (Review)
Review
Classifying inflammatory skin diseases is challenging, especially for the expanding group of disorders triggered by genetic factors resulting in hyperactivated innate immunity that result in overlapping patterns of dermal and epidermal inflammation with hyperkeratosis. For such conditions, the umbrella term "autoinflammatory keratinization diseases" (AIKD) has been proposed. AIKD encompasses diseases with mixed pathomechanisms of autoinflammation and autoimmunity, and includes IL-36 receptor antagonist (IL-36Ra)-related pustulosis, CARD14-mediated pustular psoriasis, pityriasis rubra pilaris (PRP) type V, and familial keratosis lichenoides chronica (KLC). Mechanistically, the entities include generalized pustular psoriasis (GPP) without psoriasis vulgaris, impetigo herpetiformis and acrodermatitis continua, which are IL-36Ra-related pustuloses caused by loss-of-function mutations in IL36RN; GPP with psoriasis vulgaris and palmoplantar pustular psoriasis which are CARD14-mediated pustular psoriasiform dermatoses with gain-of-function variants of CARD14; PRP type V which is caused by gain-of-function mutations in CARD14; and, familial KLC in which mutations in NLRP1, an inflammasome sensor protein predominantly expressed in skin, have been identified. It is likely that further inflammatory keratinization disorders will also fall within the concept of AIKD, as elucidation of novel pathogenic mechanisms of inflammatory keratinization diseases emerges. A better understanding of the pathophysiology of AIKD is likely to lead to innovative, targeted therapies that benefit patients.
Topics: Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins; Autoimmune Diseases; CARD Signaling Adaptor Proteins; Dermatitis; Guanylate Cyclase; Humans; Immunity, Innate; Interleukins; Membrane Proteins; Mutation; NLR Proteins; Skin; Skin Diseases, Papulosquamous
PubMed: 29422292
DOI: 10.1016/j.jdermsci.2018.01.012 -
Journal of the European Academy of... Feb 2023
Topics: Humans; Acrodermatitis; COVID-19; COVID-19 Vaccines; Vaccination
PubMed: 36177535
DOI: 10.1111/jdv.18626 -
Biomolecules May 2022The human (h) transporter hZIP4 is the primary Zn importer in the intestine. hZIP4 is also expressed in a variety of organs such as the pancreas and brain. Dysfunction...
The human (h) transporter hZIP4 is the primary Zn importer in the intestine. hZIP4 is also expressed in a variety of organs such as the pancreas and brain. Dysfunction of hZIP4 can result in the Zn deficiency disease acrodermatitis enteropathica (AE). AE can disrupt digestive and immune system homeostasis. A limited number of hZIP4 expression strategies have hindered increasing knowledge about this essential transmembrane protein. Here, we report the heterologous expression of hZIP4 in . Both a wild-type and a mutant strain, in which the endogenous Zn transporters were deleted, were used to test the expression and localization of an hZIP4-GFP fusion protein. A full-length hZIP4-GFP and a truncated membrane-domain-only (mhZIP4-GFP) protein were observed to be present in the plasma membrane in yeast.
Topics: Acrodermatitis; Carrier Proteins; Cation Transport Proteins; Humans; Saccharomyces cerevisiae; Zinc
PubMed: 35625653
DOI: 10.3390/biom12050726 -
Journal of Nutritional Science and... 2015Zinc nutrition is of special practical importance in infants and children. Poor zinc absorption causes zinc deficiency, which leads to a broad range of consequences such... (Review)
Review
Zinc nutrition is of special practical importance in infants and children. Poor zinc absorption causes zinc deficiency, which leads to a broad range of consequences such as alopecia, diarrhea, skin lesions, taste disorders, loss of appetite, impaired immune function and neuropsychiatric changes and growth retardation, thus potentially threatening life in infants and children. In addition to dietary zinc deficiency, inherited zinc deficiency, which rarely occurs, is found during the infant stage and early childhood. Recent molecular genetic studies have identified responsible genes for two inherited zinc deficiency disorders, acrodermatitis enteropathica (AE) and transient neonatal zinc deficiency (TNZD), clarifying the pathological mechanisms. Both of these zinc deficiencies are caused by mutations of zinc transporters, although the mechanisms are completely different. AE is an autosomal recessive disorder caused by mutations of the ZIP4 gene, consequently resulting in defective absorption of zinc in the small intestine. In contrast, TNZD is a disorder caused by mutations of the ZnT2 gene, which results in low zinc breast milk in the mother, consequently causing zinc deficiency in the breast-fed infant. In both cases, zinc deficiency symptoms are ameliorated by a daily oral zinc supplementation for the patients. Zinc is definitely one of the key factors for the healthy growth of infants and children, and thus zinc nutrition should receive much attention.
Topics: Acrodermatitis; Breast Feeding; Cation Transport Proteins; Child, Preschool; Dietary Supplements; Genetic Predisposition to Disease; Growth Disorders; Humans; Infant; Milk, Human; Nutritional Requirements; Zinc
PubMed: 26598882
DOI: 10.3177/jnsv.61.S44 -
Oman Medical Journal Nov 2020Acrodermatitis enteropathica is a rare autosomal recessive disease caused by a genetic mutation leading to zinc deficiency. Clinical manifestation includes skin lesions,...
Acrodermatitis enteropathica is a rare autosomal recessive disease caused by a genetic mutation leading to zinc deficiency. Clinical manifestation includes skin lesions, diarrhea, and alopecia. We report the case of a two-month-old girl, admitted with erythematous scaly lesions in the neck and vesiculopustular lesions in the perioral region, associated with alopecia and diarrhea. Clinical diagnosis of the disease was made from her first presentation. She was started on zinc therapy and her lesions resolved entirely after one month of treatment.
PubMed: 33274070
DOI: 10.5001/omj.2020.97 -
Scientific Reports Dec 2022The human (h) ZIP4 is a plasma membrane transporter that functions to increase cytosolic zinc levels. hZIP4 encodes eight transmembrane domains and a large extracellular...
The human (h) ZIP4 is a plasma membrane transporter that functions to increase cytosolic zinc levels. hZIP4 encodes eight transmembrane domains and a large extracellular domain (ECD). This ECD is cleaved from the holo-transporter when cells are zinc-deficient. At the same time, mutations in the ECD can result in the zinc-deficiency disease Acrodermatitis enteropathica. Previously, it was shown that hZIP4's ECD is comprised of two structurally independent subdomains where contacts between the ECD monomeric units are centered at the PAL motif. These results lead to the hypothesis that ZIP4-ECD is essential to the dimerization of the holo-transporter. To test this hypothesis, we used Fluorescence Correlation Spectroscopy (FCS) to quantify the oligomeric state of full-length hZIP4 and hZIP4 lacking the ECD domain, each tagged with eGFP. Inspection of our experimental results demonstrate that both the full-length and truncated hZIP4 is a dimer when expressed in HEK293 cells. Parallel functional experiments demonstrate that the K and V for truncated and full-length hZIP4/eGFP are similar. Determining that truncated hZIP4/eGFP forms a dimer is a crucial step for understanding the function of the hZIP4-ECD, which provides more insight into how the diseases related to hZIP4 protein.
Topics: Humans; HEK293 Cells; Membrane Transport Proteins; Zinc
PubMed: 36473915
DOI: 10.1038/s41598-022-24782-6 -
Medicina (Kaunas, Lithuania) Aug 2020Background and Objectives Over the last years, inflammatory bowel disease (IBD) has been reported on a high incidence in pediatric populations and has been associated...
UNLABELLED
Background and Objectives Over the last years, inflammatory bowel disease (IBD) has been reported on a high incidence in pediatric populations and has been associated with numerous extraintestinal manifestations, making its management a real challenge for the pediatric gastroenterologist. Dermatological manifestations in IBD are either specific, related to the disease activity or treatment-associated, or non-specific. This literature review aims to identify and report the dermatological manifestations of IBD in children, the correlation between their appearance and the demographical characteristics, the relationship between these lesions and disease activity, and to highlight the impact of dermatological manifestations on an IBD treatment regime.
MATERIALS AND METHODS
A systemic literature review was performed, investigating articles and case reports on dermatological manifestations in children with IBD starting from 2005. A total of 159 potentially suitable articles were identified and after the exclusion process, 75 articles were selected.
RESULTS
The most common dermatological manifestations reported in pediatric IBD are erythema nodosum and pyoderma gangrenosum. More rare cases of metastatic Crohn's disease, epidermolysis bullosa acquisita, small-vessel vasculitis, necrotizing vasculitis, leukocytoclastic vasculitis, cutaneous polyarteritis nodosa, and Sweet's syndrome have been reported. Oral manifestations of IBD are divided into specific (tag-like lesions, mucogingivitis, lip swelling with vertical fissures, aphthous stomatitis, and pyostomatitis vegetans) and non-specific. IBD treatment may present with side effects involving the skin and mucosa. Anti-tumor necrosis factor agents have been linked to opportunistic skin infections, psoriasiform lesions, and a potentially increased risk for skin cancer. Cutaneous manifestations such as acrodermatitis enteropathica, purpuric lesions, and angular cheilitis may appear secondary to malnutrition and/or malabsorption.
CONCLUSIONS
The correct diagnosis of dermatological manifestations in pediatric IBD is of paramount importance because of their impact on disease activity, treatment options, and a patient's psychological status.
Topics: Biological Factors; Child; Colitis, Ulcerative; Crohn Disease; Humans; Immunosuppressive Agents; Malabsorption Syndromes; Receptors, Tumor Necrosis Factor; Skin Diseases
PubMed: 32842528
DOI: 10.3390/medicina56090425 -
Psoriasis (Auckland, N.Z.) 2017Psoriasis is the skin disease that most frequently affects the nails. Depending on the very nail structure involved, different clinical nail alterations can be observed.... (Review)
Review
Psoriasis is the skin disease that most frequently affects the nails. Depending on the very nail structure involved, different clinical nail alterations can be observed. Irritation of the apical matrix results in psoriatic pits, mid-matrix involvement may cause leukonychia, whole matrix affection may lead to red lunulae or severe nail dystrophy, nail bed involvement may cause salmon spots, subungual hyperkeratosis, and splinter hemorrhages, and psoriasis of the distal nail bed and hyponychium causes onycholysis whereas that of the proximal nail fold causes psoriatic paronychia. The more extensive the involvement, the more severe is the nail destruction. Pustular psoriasis may be seen as yellow spots under the nail or, in case of acrodermatitis continua suppurativa, as an insidious progressive loss of the nail organ. Nail psoriasis has a severe impact on quality of life and may interfere with professional and other activities. Management includes patient counseling, avoidance of stress and strain to the nail apparatus, and different types of treatment. Topical therapy may be tried but is rarely sufficiently efficient. Perilesional injections with corticosteroids and methotrexate are often beneficial but may be painful and cannot be applied to many nails. All systemic treatments clearing widespread skin lesions usually also clear the nail lesions. Recently, biologicals were introduced into nail psoriasis treatment and found to be very effective. However, their use is restricted to severe cases due to high cost and potential systemic adverse effects.
PubMed: 29387608
DOI: 10.2147/PTT.S126281 -
Indian Journal of Dermatology,... 2023
Topics: Humans; Argininosuccinic Aciduria; Acrodermatitis
PubMed: 37317759
DOI: 10.25259/IJDVL_75_2023