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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 -
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 -
Dermatology Online Journal Jul 2007A 13-year-old girl presented with a history of red scaly plaques involving the chest, arms and legs beginning in infancy. Punch biopsy revealed psoriasiform hyperplasia...
A 13-year-old girl presented with a history of red scaly plaques involving the chest, arms and legs beginning in infancy. Punch biopsy revealed psoriasiform hyperplasia and pallor of the epidermis. The patient's serum zinc level was 36 mug/dl [nl. 66-144 mug/dl]. A diagnosis of acrodermatitis enteropathica was established and the patient responded well to zinc replacement therapy. Acrodermatitis enteropathica is a rare autosomal recessive disorder caused by mutations in SLC39A4, which encodes the tissue-specific zinc transporter ZIP4.
Topics: Acrodermatitis; Adolescent; Astringents; Biopsy; Cation Transport Proteins; Diagnosis, Differential; Female; Follow-Up Studies; Genetic Predisposition to Disease; Humans; Mutation; Skin; Zinc; Zinc Sulfate
PubMed: 18328205
DOI: No ID Found -
Biochemical Society Transactions Dec 2008The SLC39A (solute carrier 39A) [ZIP (Zrt-Irt-like protein)] family consists of 14 members which are thought to control zinc uptake into the cytoplasm. Among these, ZIP4... (Review)
Review
The SLC39A (solute carrier 39A) [ZIP (Zrt-Irt-like protein)] family consists of 14 members which are thought to control zinc uptake into the cytoplasm. Among these, ZIP4 is known to be particularly important for zinc homoeostasis. Mutations in this gene cause acrodermatitis enteropathica, a rare recessive-lethal human genetic disorder. In the present paper, our studies of the regulation and function of the mouse Zip4 gene are briefly reviewed. Mouse Zip4 is expressed at highest levels in tissues involved in absorption of dietary or maternal zinc, and the gene and protein are dynamically regulated by multiple post-transcriptional mechanisms in response to zinc availability. ZIP4 accumulates at the apical surface of enterocytes and endoderm cells when zinc is deficient, because of increased stability of the mRNA and stabilization of the protein. In contrast, when zinc is replenished, the mRNA is destabilized and the protein is internalized and degraded rapidly. The critical importance of ZIP4 in zinc homoeostasis is revealed in mice with targeted deletions of this gene. Homozygous Zip4-knockout embryos die during early morphogenesis and heterozygous offspring are significantly underrepresented and display an array of developmental defects, including exencephalia, anophthalmia and severe growth retardation. Mice heterozygous for Zip4-knockout are hypersensitive to zinc deficiency, which suggests that humans heterozygous for this gene may also be very sensitive to zinc deficiency.
Topics: Acrodermatitis; Animals; Cation Transport Proteins; Humans; Zinc
PubMed: 19021533
DOI: 10.1042/BST0361242 -
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 -
Allergologie Select 2023Tick bite-induced IgE-mediated reactions to the oligosaccharide galactose α-1,3-galactose (alpha-gal) are increasingly recognized. This study investigated alpha-gal...
BACKGROUND
Tick bite-induced IgE-mediated reactions to the oligosaccharide galactose α-1,3-galactose (alpha-gal) are increasingly recognized. This study investigated alpha-gal sensitization in three groups with different tick bite exposure.
MATERIALS AND METHODS
Specific IgE antibodies to alpha-gal and total IgE were investigated in 485 patients with Lyme borreliosis with different disease manifestations and compared to a control group of 200 randomly selected patients without increased exposure to tick bites. A group of 232 hunters and forest workers served as a model for multiple tick bites.
RESULTS
Specific IgE (sIgE) antibodies to alpha-gal (> 0.1 kU/L) were found in 12.6% of all borreliosis samples compared to the control group with 9% (relative risk 1.4; 95% CI 0.85 - 2.3; not significant (n.s.). The highest prevalence of sIgE to alpha-gal was observed in hunters and forest service employees (22.8%, relative risk 2.5; 95% CI 1.5 - 4.2; p < 0.001). Higher age and elevated total IgE were also associated with alpha-gal sensitization.
CONCLUSION
IgE sensitization to alpha-gal tends to be more frequent in tick-exposed patients with borreliosis than in controls (n.s.). Moreover, hunters and forest workers show an even higher rate of elevated IgE to alpha-gal. Thus, frequent tick contact may result in alpha-gal sensitization. In the area of Munich, the prevalence of alpha-gal sensitization appears lower than in the state of Baden-Württemberg and lower than in the USA, which may be due to the difference in tick species or the frequency of tick exposure. This study could show that alpha-gal sensitization and presumably alpha-gal syndrome does not seem to be a modern problem but existed already more than 30 years ago.
PubMed: 37705677
DOI: 10.5414/ALX02424E -
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