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Nutrients Oct 2021Celiac disease (CD) is an immune-mediated enteropathy caused by gluten ingestion, affecting approximately 1% of the worldwide population. Extraintestinal symptoms may be... (Review)
Review
Celiac disease (CD) is an immune-mediated enteropathy caused by gluten ingestion, affecting approximately 1% of the worldwide population. Extraintestinal symptoms may be present as the first signs of CD, years before the CD diagnosis is made. A great variety of extraintestinal manifestations may be associated with CD. Cutaneous manifestations represent the main extraintestinal manifestations, with dermatitis herpetiformis being the most common in patients with CD. In adults, it has been demonstrated that the role of a gluten-free diet is crucial not only for the recovery of signs and symptoms associated with CD but also for cutaneous manifestations, which often improve after gluten avoidance. In children with CD, the association with skin disorders is well documented regarding dermatitis herpetiformis, but studies considering other dermatological conditions, such as psoriasis and atopic dermatitis, are few. The prevalence and manifestations of dermatological disorders in celiac children are often different from those in adults, explaining the gap between these populations. In addition, the therapeutic role of a gluten-free diet in the improvement in skin alterations is not fully understood in children and in adult population except for dermatitis herpetiformis. Therefore, cutaneous CD symptoms need to be known and recognized by physicians despite their specialties to improve early CD diagnosis, which is critical for a better prognosis. This review describes the current scientific evidence on skin manifestations associated with CD in the pediatric population.
Topics: Celiac Disease; Child; Humans; Skin; Skin Diseases
PubMed: 34684612
DOI: 10.3390/nu13103611 -
JAMA Dermatology Nov 2021Dermatologists submit direct immunofluorescence (DIF) biopsies on a daily basis, using an assay detecting immunoreactant deposition with a panel that has traditionally...
IMPORTANCE
Dermatologists submit direct immunofluorescence (DIF) biopsies on a daily basis, using an assay detecting immunoreactant deposition with a panel that has traditionally comprised immunoglobulin (Ig) G, IgA, IgM, C3, and fibrin, with or without albumin antibodies.
OBJECTIVES
To evaluate and compare the frequency of immunoreactants in DIF biopsies submitted over an 8-year period and assess use by dermatologists based on clinical impression.
DESIGN, SETTING, AND PARTICIPANTS
A quality improvement study was conducted in a community outreach reference laboratory associated with a large academic medical center. Results of 2050 consecutive DIF skin biopsies submitted to the laboratory between April 1, 2012, and June 12, 2020, were analyzed by final pathologic diagnosis and antibody subtype positivity, in comparison with clinical impression. Biopsies in which the submitting physician had not performed the biopsy were excluded.
MAIN OUTCOMES AND MEASURES
Histopathologic findings and the results of DIF biopsies using the standard 6-antibody panel were evaluated in correlation with the submitted clinical diagnosis to assess immunoreactivity of the assay.
RESULTS
Of 2050 DIF biopsies submitted, 367 (17.9%) were positive; IgG, IgA, and C3 alone identified all primary immunobullous disease cases (pemphigoid, pemphigus, linear IgA, and dermatitis herpetiformis), and IgA, C3, and fibrin antibodies alone identified all vasculitis cases. A panel of IgG, IgA, IgM, and fibrin identified all cases of lupus erythematosus. DIF results were positive in less than half of cases of hematoxylin and eosin biopsy-confirmed lupus erythematosus (23 of 47 [49%]). A total of 247 biopsies were submitted for clinical diagnoses not optimally supported on DIF: lichen planus, porphyria, and connective tissue disease.
CONCLUSIONS AND RELEVANCE
The findings of this study suggest that there is a knowledge gap among dermatologists relating to the opportunity for high-value, cost-conscious use of DIF. The practice of reflexive antibody testing using a 6-antibody panel for all DIF biopsies is likely unnecessary. DIF protocols tailored to the clinical diagnosis may enhance cost-effectiveness without loss of test sensitivity or specificity.
Topics: Fluorescent Antibody Technique, Direct; Humans; Linear IgA Bullous Dermatosis; Pemphigus; Skin; Skin Diseases
PubMed: 34613346
DOI: 10.1001/jamadermatol.2021.3892 -
Pharmaceuticals (Basel, Switzerland) Sep 2021Dermatologic pathologies are the fourth most common cause of non-fatal disease worldwide; however, they produce a psychosocial, economic, and occupational impact equal... (Review)
Review
Dermatologic pathologies are the fourth most common cause of non-fatal disease worldwide; however, they produce a psychosocial, economic, and occupational impact equal to or greater than other chronic conditions. The most prevalent are actinic keratosis, followed by basal-cell carcinoma, in a lesser proportion acne vulgaris, psoriasis, and hidradenitis suppurativa, among others, and more rarely dermatitis herpetiformis. To treat actinic keratosis and basal-cell carcinoma, 5-fluorouracil (5-FU) 0.5% is administered topically with good results, although in certain patients it produces severe toxicity. On the other hand, dapsone is a drug commonly used in inflammatory skin conditions such as dermatitis herpetiformis; however, it occasionally causes hemolytic anemia. Additionally, biologic drugs indicated for the treatment of moderate-to-severe psoriasis and hidradenitis suppurativa have proved to be effective and safe; nevertheless, a small percentage of patients do not respond to treatment with biologics in the long term or they are ineffective. This interindividual variability in response may be due to alterations in genes that encode proteins involved in the pathologic environment of the disease or the mechanism of action of the medication. Pharmacogenetics studies the relationship between genetic variations and drug response, which is useful for the early identification of non-responsive patients and those with a higher risk of developing toxicity upon treatment. This review describes the pharmacogenetic recommendations with the strongest evidence at present for the treatments used in dermatology, highlighting those included in clinical practice guides. Currently, we could only find pharmacogenetic clinical guidelines for 5-FU. However, the summary of product characteristics for dapsone contains a pharmacogenetic recommendation from the United States Food and Drug Administration. Finally, there is an enormous amount of information from pharmacogenetic studies in patients with dermatologic pathologies (mainly psoriasis) treated with biologic therapies, but they need to be validated in order to be included in clinical practice guides.
PubMed: 34577605
DOI: 10.3390/ph14090905 -
Frontiers in Immunology 2021
Topics: Animals; Celiac Disease; Humans; T-Lymphocytes
PubMed: 34539679
DOI: 10.3389/fimmu.2021.756087 -
Acta Dermato-venereologica Sep 2021Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease treated with a gluten-free diet. However, the itching and blistering rash alleviates slowly...
Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease treated with a gluten-free diet. However, the itching and blistering rash alleviates slowly after gluten withdrawal and occasionally persists despite a long-term gluten-free diet. This study investigated the prevalence and factors associated with prolonged (i.e. >2 years) and ongoing skin symptoms in 237 patients with dermatitis herpetiformis. Data were gathered from medical records and via questionnaires. Among patients with dermatitis herpetiformis, 38% had prolonged symptoms after diagnosis, and 14% had ongoing skin symptoms at follow-up (median duration of gluten-free diet 24 years). A severe rash at diagnosis was associated with both prolonged and ongoing cutaneous symptoms. In addition, patients with dermatitis herpetiformis with ongoing skin symptoms at follow-up had been on the dietary treatment for a shorter time (median duration 16 vs 25 years) and were less often on a strict diet (53% vs 78%) compared with patients with dermatitis herpetiformis without ongoing skin symptoms.
Topics: Celiac Disease; Dermatitis Herpetiformis; Diet, Gluten-Free; Glutens; Humans; Prevalence
PubMed: 34490466
DOI: 10.2340/00015555-3914 -
Diagnostics (Basel, Switzerland) Aug 2021Immune responses to tissue transglutaminase (tTG) and nonapeptides of gliadin (npG) are associated with dermatitis herpetiformis (DH), a gluten-related dermatosis....
Immune responses to tissue transglutaminase (tTG) and nonapeptides of gliadin (npG) are associated with dermatitis herpetiformis (DH), a gluten-related dermatosis. Recently, a bi-analyte immunoblot (b-aIB) was introduced to detect IgA antibodies in response to tTG and npG. We compared the utility of ELISA and b-aIB with tTG in serological diagnoses of DH and their agreement with direct immunofluorescence (DIF). In total, 55 sera (27 DIF-positive DH patients, 4 DIF-negative DH patients and 24 healthy controls) were examined. ELISA for anti-tTG IgA, b-aIB for anti-npG and anti-tTG IgA, and statistical analysis were performed. The b-aIB with tTG showed 78% sensitivity, 100% specificity, 100% positive predictive value, and 82% negative predictive value in relation to ELISA. A better rate of agreement (Cohen's kappa values) in IgA detection was observed in the pair tTG ELISA and b-aIB with npG (0.85) than in pairs tTG ELISA and b-aIB with tTG (0.78) or b-aIB with tTG and b-aIB with npG (0.78). No degree of agreement was found between serological tests and DIF. Both serological tests may be used to detect the anti-tTG IgA in DH patients. Still, DH diagnosing requires careful consideration of clinical data as well as results of tissue imaging (crucial DIF) and immunoserological techniques detecting DH-type features.
PubMed: 34441348
DOI: 10.3390/diagnostics11081414 -
Medicina (Kaunas, Lithuania) Aug 2021Dermatitis herpetiformis (DH), Duhring disease, is caused by gluten sensitivity and affects 11.2 to 75.3 per 100,000 people in the United States and Europe with an... (Review)
Review
Dermatitis herpetiformis (DH), Duhring disease, is caused by gluten sensitivity and affects 11.2 to 75.3 per 100,000 people in the United States and Europe with an incidence of 0.4 to 3.5 per 100,000 people per year. DH is characterized by a symmetrical blistering rash on the extensor surfaces with severe pruritus. The diagnosis continues to be made primarily by pathognomonic findings on histopathology, especially direct immunofluorescence (DIF). Recently, anti-epidermal transglutaminase (TG3) antibodies have shown to be a primary diagnostic serology, while anti-tissue transglutaminase (TG2) and other autoantibodies may be used to support the diagnosis and for disease monitoring. Newly diagnosed patients with DH should be screened and assessed for associated diseases and complications. A gluten-free diet (GFD) and dapsone are still mainstays of treatment, but other medications may be necessary for recalcitrant cases. Well-controlled DH patients, managed by a dermatologist, a gastroenterologist, and a dietician, have an excellent prognosis. Our review comprehensively details the current diagnostic methods, as well as methods used to monitor its disease course. We also describe both the traditional and novel management options reported in the literature.
Topics: Autoantibodies; Celiac Disease; Dermatitis Herpetiformis; Diet, Gluten-Free; Humans; Immunoglobulin A; Prognosis
PubMed: 34441049
DOI: 10.3390/medicina57080843 -
Postepy Dermatologii I Alergologii Apr 2021
Reply letter to "An update on direct immunofluorescence for diagnosing dermatitis herpetiformis". Could granular C3 deposits at the dermal epidermal junction be considered a marker of "cutaneous gluten sensitivity"?
PubMed: 34408602
DOI: 10.5114/ada.2021.106218 -
Dermatology Online Journal Jul 2021Dermatitis herpetiformis (DH) is a rare autoimmune blistering disorder in which patients with celiac disease, a gluten-sensitive enteropathy, present with a severely...
Dermatitis herpetiformis (DH) is a rare autoimmune blistering disorder in which patients with celiac disease, a gluten-sensitive enteropathy, present with a severely pruritic papulovesicular eruption over extensor surfaces such as the knees, elbows, lower back, buttocks, and neck. Patients are instructed to adhere to a gluten-free diet for purposes of improving their skin disease and gluten-sensitive enteropathy; this is the only treatment that lowers risk of enteropathy-associated T cell lymphoma. Patients who adhere to a strict gluten-free diet often have remission of their skin disease over months to years. Dapsone is a rapid and extremely effective first-line treatment option and often used while transitioning to a gluten-free diet. Aside from gluten-free diet and dapsone, second-line treatment options include sulfapyridine, sulfasalazine, and colchicine. Some patients have difficulty adhering to a gluten-free diet or develop intolerable side effects to systemic therapies. Furthermore, there is limited data on the use of the second-line treatments. Recent studies have shed light on the role of JAK-STAT-dependent pathways in the pathogenesis of dermatitis herpetiformis. We present a patient treated with tofacitinib, 5mg twice daily, an oral JAK1/3 inhibitor, who demonstrated clinical improvement of DH and control of new lesion development.
Topics: Aged; Celiac Disease; Dapsone; Dermatitis Herpetiformis; Diet, Gluten-Free; Drug Administration Schedule; Humans; Janus Kinase 1; Janus Kinase 3; Male; Patient Compliance; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Remission Induction; Treatment Outcome
PubMed: 34391330
DOI: 10.5070/D327754365 -
Kansas Journal of Medicine 2021
PubMed: 34367491
DOI: 10.17161/kjm.vol1415224