Targeted serum proteome profiling reveals nicotinamide adenine dinucleotide phosphate (NADPH)-related biomarkers to discriminate linear IgA bullous disorder from dermatitis herpetiformis.

Linear IgA bullous dermatosis (LABD) and dermatitis herpetiformis (DH) represent the major subtypes of IgA mediated autoimmune bullous disorders. We sought to understand the disease etiology by using serum proteomics. We assessed 92 organ damage biomarkers in LABD, DH, and healthy controls using the Olink high-throughput proteomics. The positive proteomic serum biomarkers were used to correlate with clinical features and HLA type. Targeted proteomic analysis of IgA deposition bullous disorders vs. controls showed elevated biomarkers. Further clustering and enrichment analyses identified distinct clusters between LABD and DH, highlighting the involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Comparative analysis revealed biomarkers with distinction between LABD and DH and validated in the skin lesion. Finally, qualitative correlation analysis with DEPs suggested six biomarkers (NBN, NCF2, CAPG, FES, BID, and PXN) have better prognosis in DH patients. These findings provide potential biomarkers to differentiate the disease subtype of IgA deposition bullous disease.

State-of-the-art diagnosis of autoimmune blistering diseases.

Autoimmune blistering disorders (AIBDs) are a heterogeneous group of approximately a dozen entities comprising pemphigus and pemphigoid disorders and dermatitis herpetiformis. The exact diagnosis of AIBDs is critical for both prognosis and treatment and is based on the clinical appearance combined with the detection of tissue-bound and circulating autoantibodies. While blisters and erosions on the skin and/or inspectable mucosal surfaces are typical, lesions may be highly variable with erythematous, urticarial, prurigo-like, or eczematous manifestations. While direct immunofluorescence microscopy (IFM) of a perilesional biopsy is still the diagnostic gold standard, the molecular identification of the major target antigens opened novel therapeutic avenues. At present, most AIBDs can be diagnosed by the detection of autoantigen-specific serum antibodies by enzyme-linked immunosorbent assay (ELISA) or indirect IFM when the clinical picture is known. This is achieved by easily available and highly specific and sensitive assays employing recombinant immunodominant fragments of the major target antigens, i.e., desmoglein 1 (for pemphigus foliaceus), desmoglein 3 (for pemphigus vulgaris), envoplakin (for paraneoplastic pemphigus), BP180/type XVII collagen (for bullous pemphigoid, pemphigoid gestationis, and mucous membrane pemphigoid), laminin 332 (for mucous membrane pemphigoid), laminin ß4 (for anti-p200 pemphigoid), type VII collagen (for epidermolysis bullosa acquisita and mucous membrane pemphigoid), and transglutaminase 3 (for dermatitis herpetiformis). Indirect IFM on tissue substrates and in-house ELISA and immunoblot tests are required to detect autoantibodies in some AIBD patients including those with linear IgA disease. Here, a straightforward modern approach to diagnosing AIBDs is presented including diagnostic criteria according to national and international guidelines supplemented by long-term in-house expertise.

A Critical Appraisal of Gluten in Skin Disorders, the Evidence So Far, and Updated Recommendations.

Gluten, a polypeptide hapten, found in many cereals such as barley, wheat, rye, oats, and others, has been recently implicated in a range of cutaneous disorders ranging from chronic plaque psoriasis through psoriatic arthritis, urticaria (chronic as well as paediatric onset), and angioedema to lichen planus, vitiligo, and rosacea. The evidence for them is still not well reviewed. To generate evidence for the causal role of gluten in various dermatological disorders. The Pubmed, MedLine, and EMBASE databases were searched using the keywords "Gluten" and one of the dermatoses, namely, "Atopic Dermatitis", "Vasculitis", "Psoriasis", "Psoriatic Arthritis", "Acne", "Alopecia Areata", and "Immunobullous disorders". All articles published in English for which free full text was available were taken into consideration. The search strategy returned in a total of 1487 articles which were screened for relevance and elimination of duplicates. Ultimately, around 114 articles were deemed suitable. The data were extracted and presented in the narrative review format. A simple and cost-effective solution to many of these chronic and lifelong conditions is to restrict gluten in the diet. However, the dermatologist would do well to remember that in the vast majority of dermatological disorders including the ones listed here, gluten restriction is not warranted and can even lead to nutritional deficiencies. The evidence varied from Grade I for some disorders like psoriatic arthritis to Grade IV to most disorders like acne, vitiligo, vasculitis, and atopic dermatitis. Herein, we review the evidence for each of these conditions and make practical recommendations for gluten restriction in them.

[The disease under chronic urticaria: beyond itching]. / La enfermedad crónica bajo la urticaria: más allá del prurito.

BACKGROUND: Brief erythematous-papular skin rashes suggest the diagnosis of urticaria; However, it may be another type of dermatitis, and complementary examinations must be carried out to establish its diagnosis. CASE REPORT: 53-year-old female patient, diagnosed in 2016 with diffuse large B cell lymphoma, in complete remission. Since 2010, he has had episodes of erythematous-papular lesions lasting 24-36 hours. He received antihistamines, corticosteroids and omalizumab without clinical improvement. The ANA determination was positive (1/320), nuclear mitotic pattern. The skin biopsy was compatible with dermatitis herpetiformis. The study of celiac and locus antibodies showed positivity for HLA-DQ2 and DQ2.5 in heterozygosity. The diagnosis of dermatitis herpetiformis was established. Treatment consisted of a gluten-free diet and prescription of dapsone, with satisfactory results. CONCLUSION: It is important to establish the differential diagnosis of patients with chronic urticaria who do not respond to the reference treatment, in addition to carrying out a thorough clinical examination and physical examination before starting treatment and relying on a multidisciplinary team to establish an accurate diagnosis and treatment. appropriate. Due to the side effects of dapsone, subsequent follow-up of patients is essential.

ANTECEDENTES: Los exantemas cutáneos eritemato-papulares de breve duración sugieren el diagnóstico clínico de urticaria; no obstante, puede tratarse de otro tipo de dermatitis, y para establecer el diagnóstico deben llevarse a cabo exploraciones complementarias. REPORTE DE CASO: Paciente femenina de 53 años, diagnosticada en 2016 con linfoma difuso de células B grandes, en remisión completa. Desde el 2010 manifestó episodios de lesiones eritemato-papulosas, de 24-36 horas de duración. Recibió antihistamínicos, corticoides y omalizumab sin mejoría clínica. La determinación de ANA resultó positiva (1/320), con patrón mitótico nuclear. La biopsia cutánea fue compatible con dermatitis herpetiforme. El estudio de anticuerpos de celiaquía y locus mostró positividad para HLA-DQ2 y DQ2.5 con heterocigosis. Se estableció el diagnosticó de dermatitis herpetiforme. El tratamiento consistió en dieta exenta de gluten y prescripción de dapsona, con resultados satisfactorios. CONCLUSIÓN: Es importante establecer el diagnóstico diferencial de pacientes con urticaria crónica que no responden al tratamiento de referencia, además de efectuar el examen clínico y la exploración física exhaustivos antes de iniciar el protocolo, y apoyarse de un equipo multidisciplinario para establecer el diagnóstico certero y tratamiento adecuado. Debido a los efectos secundarios de la dapsona, es imprescindible el seguimiento posterior de los pacientes.

Improving the Diagnosis of Dermatitis Herpetiformis Using the Intraepithelial Lymphogram.

Dermatitis herpetiformis is a cutaneous manifestation of celiac disease. Phenotyping of intraepithelial lymphocytes in the small bowel mucosa can strengthen the diagnosis of celiac disease when it is not clear-cut. We aim to evaluate the usefulness of the intraepithelial lymphogram to confirm dermatitis herpetiformis in equivocal cases. We performed a retrospective multicenter study on patients diagnosed with dermatitis herpetiformis and collected data from the intraepithelial lymphogram assessed by flow cytometry. A total of 36 patients were analyzed in relation to the severity of intestinal damage (18 had non-atrophic mucosa) at baseline (N = 28) and/or after the adoption of a gluten-free diet (median follow-up of three years, N = 16). We observed that patients with atrophy more often had positive celiac serology (p = 0.019), celiac clinical symptoms (p = 0.018), and iron-deficiency anemia (p = 0.018), but the severity of skin damage was similar in both groups (p = 0.79). At baseline, increased TCRγδ+ cells were present in 94% of patients with atrophy and 67% with non-atrophic lesions (p = 0.13). After a gluten-free diet, increased TCRγδ+ cells persisted in 100% and 63% of cases, respectively (p = 0.21). We concluded that increased TCRγδ+ cells may be helpful in confirming the diagnosis of dermatitis herpetiformis in equivocal cases, even in patients who were started on a gluten-free diet.

Clinicopathological Profile of Dermatitis Herpetiformis Patients in Saudi Arabia.

Objectives The aim of this study was to describe the clinical, serological, and histopathological features of patients with dermatitis herpetiformis (DH) in Saudi Arabia. Methods We retrospectively reviewed the medical charts of all patients diagnosed with DH in the dermatology departments of National Guard Health Affairs (NGHA) hospitals in five different cities, from 2016 to 2022. We included patients who had been diagnosed by a dermatologist and had a combination of typical DH skin lesions, positive immunoglobulin A (IgA) on direct immunofluorescence (DIF), and/or positive tissue transglutaminase (tTG) IgA. Results A total of 11 patients were included. Their average age was 43.6 ± 12.5 years, and the ratio of females: males was 2.7: 1. Among the eight skin biopsies performed, IgA was detected on DIF in five patients. Seven out of nine patients (77.8%) had positive tTG IgA. Nine patients were managed with dapsone and a gluten-free diet (GFD); they had excellent responses within months. Conclusion The profiles of Saudi patients with DH were similar to those of Caucasian patients, but DH appears to be less common in Saudi Arabia. The high positive rates of tTG IgA make it an important tool for diagnosis in unclear cases. Dermatitis herpetiformis is likely associated with underlying gluten-sensitive enteropathy in Saudi patients.

Role of Human Leukocyte Antigen Class II in Antibody-Mediated Skin Disorders.

HLA class II molecules are key factors determining susceptibility to autoimmune disorders, and their role in immune-mediated skin conditions such as psoriasis has been extensively investigated. However, there is currently little understanding of their role in antibody-mediated skin diseases such as autoimmune blistering disorders. We researched the available literature using PubMed to narratively review the current knowledge on HLA associations in antibody-mediated blistering skin pathologies. Our results summarized the risk alleles that are identified in the literature, together with certain known protective alleles: in the pemphigus group, alleles HLA-DQB1*0503 and HLA-DRB1*0402 are most commonly associated with disease; in the pemphigoid group, the most studied allele is HLA-DQB1*0301; in epidermolysis bullosa acquisita, few genetic studies are available; in dermatitis herpetiformis, the association with haplotypes HLA-DQ2 and HLA-DQ8 is strongly established; finally, in linear IgA bullous disease, specific HLA alleles may be responsible for pediatric presentations. Our current pathogenic understanding of this group of disorders assigns a key role to predisposing HLA class II alleles that are able to bind disease autoantigens and therefore stimulate antigen-specific autoreactive T cells. The latter engage B lymphocytes that will produce pathogenic autoantibodies. The distribution of HLA alleles and their disease associations are variable across demographics, and an in-depth pathogenetic understanding is needed to support associations between HLA alleles and disease phenotypes. Additionally, in a personalized medicine approach, the identification of HLA alleles associated with the risk of disease may become clinically relevant in identifying susceptible subjects that should avoid exposure to known triggers, such as medication, when possible.

Exploring Celiac Disease: A Case Analysis of Multi-Systemic Symptoms and Effective Dietary Intervention in a Young Female.

This study presents the case of a 23-year-old woman diagnosed with celiac disease (CD), a condition triggered by an immune response to gluten, leading to inflammation in the small intestine. The patient manifested typical gastrointestinal symptoms, including diarrhea, abdominal pain, and vomiting, complemented by extra-intestinal signs such as fatigue and skin rashes. Diagnosis was corroborated through the presence of tTG-IgA antibodies and distinct histological changes in the duodenum. A notable finding was the patient's iron deficiency anemia, directly linked to the duodenal damage caused by CD. Effective management, encompassing a strict gluten-free diet and iron supplementation, resulted in marked improvement in her condition. This case accentuates the significance of early CD detection, especially in patients exhibiting a combination of gastrointestinal and extra-intestinal symptoms. Emphasis is placed on the pivotal role of timely diagnosis, adherence to a gluten-free regimen, and sustained monitoring to ensure patient well-being and prevent complications.

Dermatitis herpetiforme en mujer joven de la Amazonía peruana

La dermatitis herpetiforme es una enfermedad autoinmune que se caracteriza por la presencia de lesiones vesiculares y prurito en la superficie extensora de las extremidades, nalgas y parte baja de la espalda. Se presenta el caso clínico de una mujer de 21 años, natural y procedente de Iquitos, que presentó múltiples vesículas dolorosas, pruriginosas, de base eritematosa y purulentas en ambos codos durante un mes. Posteriormente, estas lesiones se diseminaron a ambas rodillas y se agregó prurito intenso. La paciente experimentó períodos alternantes de remisión y exacerbación. La correlación del cuadro clínico, resultados serológicos y de biopsia, junto con respuesta terapéutica a la dapsona confirmaron el diagnóstico de dermatitis herpetiforme, con una evolución favorable y remisión de la enfermedad.

Dermatitis herpetiforme is an autoimmune disease characterized by the presence of vesicular lesions and itching on the extensor surface of the limbs, buttocks, and lower back. The clinical case of a 21-year-old woman, a native of and from Iquitos, is presented. She presented multiple painful, itchy vesicles with an erythematous and purulent base on both elbows for a month. Subsequently, these lesions spread to both knees, and intense itching was added. The patient experienced alternating periods of remission and exacerbation. The correlation of the clinical picture, serological and biopsy results, along with the therapeutic response to dapsona, confirmed the diagnosis of dermatitis herpetiforme, with a favorable evolution and remission of the disease.

Separate Gut Plasma Cell Populations Produce Auto-Antibodies against Transglutaminase 2 and Transglutaminase 3 in Dermatitis Herpetiformis.

Dermatitis herpetiformis (DH) is an inflammatory skin disorder often considered as an extra intestinal manifestation of celiac disease (CeD). Hallmarks of CeD and DH are auto-antibodies to transglutaminase 2 (TG2) and transglutaminase 3 (TG3), respectively. DH patients have auto-antibodies reactive with both transglutaminase enzymes. Here it is reported that in DH both gut plasma cells and serum auto-antibodies are specific for either TG2 or TG3 with no TG2-TG3 cross reactivity. By generating monoclonal antibodies from TG3-specific duodenal plasma cells of DH patients, three conformational epitope groups are defined. Both TG2-specific and TG3-specific gut plasma cells have few immunoglobulin (Ig) mutations, and the two transglutaminase-reactive populations show distinct selection of certain heavy and light chain V-genes. Mass spectrometry analysis of TG3-specific serum IgA corroborates preferential usage of IGHV2-5 in combination with IGKV4-1. Collectively, these results demonstrate parallel induction of anti-TG2 and anti-TG3 auto-antibody responses involving separate B-cell populations in DH patients.

Patient-reported burden of skin disorders in coeliac disease.

OBJECTIVES: The current knowledge on the associations between coeliac disease and different skin diseases is contradictory and the patient's perspective on the burden of these is lacking. This study aimed to investigate patient-reported frequency, severity and quality of life effects of skin disorders in coeliac disease patients compared to controls and moreover to study the impacts of gluten-free diet on these skin diseases. MATERIALS AND METHODS: A study questionnaire designed for the purposes of this study and a validated Dermatology Life Quality Index (DLQI) questionnaire were posted to 600 adult members of the Finnish Coeliac Society and 1173 matched controls. Responses from 327 coeliac disease patients and 382 non-coeliac controls were compared. RESULTS: Coeliac disease patients were shown to be at no increased risk of atopic dermatitis, acne, rosacea, psoriasis, alopecia areata, vitiligo or chronic urticaria. The severity of these skin diseases did not differ between study groups, but the risk for at least moderate effects on quality of life caused by dermatological diseases was increased among those with coeliac disease. Positive response from gluten-free diet was most commonly experienced by coeliac disease patients with atopic dermatitis. CONCLUSIONS: Even though the risk for skin diseases was shown not to be increased among coeliac disease patients, there is still an increased burden related to experienced skin symptoms among these patients, which non-dermatologists treating coeliac disease patients should acknowledge.

Skin gluten-related disorders: new and old cutaneous manifestations to be considered.

The term gluten-related disorders (GRD) refer to a spectrum of different clinical manifestations triggered by the ingestion of gluten in genetically susceptible individuals, including coeliac disease (CD), wheat allergy and non-celiac gluten sensitivity (NCGS). GRD are characterized by a large variety of clinical presentations with both intestinal and extra-intestinal manifestations. The latter may affect almost every organ of the body, including the skin. Besides the well-known association between CD and dermatitis herpetiformis, considered as the cutaneous specific manifestation of CD, many other muco-cutaneous disorders have been associated to GRD. In this review, we analyzed the main features of dermatological diseases with a proven association with GRD and those that improve after a gluten-free diet, focusing on the newly described cutaneous manifestations associated with NCGS. Our main hypothesis is that a "cutaneous-gluten sensitivity," as specific cutaneous manifestation of NCGS, may exist and could represent a diagnostic marker of NCGS.

Risk of vascular diseases in patients with dermatitis herpetiformis and coeliac disease: a long-term cohort study.

INTRODUCTION: Dermatitis herpetiformis (DH) is a cutaneous manifestation of coeliac disease. Increased cardiovascular morbidity has been reported in coeliac disease, but in DH only little is known about this. In this cohort study with a long-term follow-up, the risk for vascular diseases in patients with dermatitis herpetiformis (DH) and coeliac disease was assessed. METHODS: The study consisted of 368 DH and 1072 coeliac disease patients with biopsy-proven diagnosis performed between 1966 and 2000. For each DH and coeliac disease patient three matched reference individuals were obtained from the population register. Data regarding all outpatient and inpatient treatment periods between 1970 and 2015 were reviewed for diagnostic codes of vascular diseases from the Care Register for Health Care. Cox proportional hazard model was used to assess the risks for the diseases studied and the HRs were adjusted for diabetes mellitus (aHR). RESULTS: The median follow-up time of DH and coeliac disease patients was 46 years. The risk for cardiovascular diseases did not differ between DH patients and their references (aHR 1.16, 95% CI 0.91-1.47), but among coeliac disease patients, the risk was increased (aHR 1.36, 95% CI 1.16-1.59). The risk for cerebrovascular diseases was found to be decreased in DH patients when compared with references (aHR 0.68, 95% CI 0.47-0.99) and increased in coeliac disease patients (aHR 1.33, 95% CI 1.07-1.66). The risk for venous thrombosis was increased in coeliac disease patients (aHR 1.62, 95% CI 1.22-2.16) but not in DH. CONCLUSIONS: The risk for vascular complications appears to differ between DH and coeliac disease. In DH the risk for cerebrovascular diseases seems to be decreased, while in coeliac disease an elevated risk for cerebrovascular and cardiovascular diseases was observed. These differing vascular risk profiles between the two manifestations of the same disease merit further investigation.

An increased risk for cardiovascular diseases was observed among patients with coeliac disease, but not among patients with dermatitis herpetiformis, a cutaneous manifestation of coeliac disease.The risk for cerebrovascular diseases was shown to be decreased in dermatitis herpetiformis patients, but conversely, an increased risk for cerebrovascular diseases was identified in coeliac disease patients.Coeliac disease, but not dermatitis herpetiformis, was shown to be associated with increased risk for venous thrombosis.

A Rare Case of COVID-19-Induced Acute Exacerbation of Oral Dermatitis Herpetiformis in a Geriatric Patient.

Introduction: Dermatitis herpetiformis (DH) is an autoimmune vesiculobullous disease associated with celiac enteropathy. The clinical manifestation of DH is the occurrence of a papulovesicular rash on the skin. Oral mucosal involvement in DH is very rare. This study aimed to describe the impact of COVID-19 on the acute exacerbation of oral dermatitis herpetiformis. Case Report: A 74-year-old woman was referred to the Oral Medicine Department with a chief complaint of the blisters on the skin for a week and ulcers in the oral cavity appeared two days ago. Extraoral examination revealed crusts on the neck and extremities. The lips appeared dry and desquamative. Intraoral examination revealed erosive lesions covered with a white-yellowish plaques on the right and left sides of the buccal mucosa, an ulcer with a diameter of 0.5 cm, and purpura hemorrhagic on left buccal mucosa and right lateral border of the tongue. Histopathological examination of the skin lesion revealed a subepithelial blister with eosinophils and neutrophil cells. The definitive diagnosis of dermatitis herpetiformis was made. She was given 5 mg intravenous dexamethasone, cetirizine 10 mg, and clindamycin 300 mg by the dermatologist. We gave hyaluronic acid 0.025% mouthwash for oral ulcers and petroleum jelly for the lips. The oral lesions had significant improvement after 4 weeks of treatment. Two months later, the patient experienced acute exacerbation after being infected with COVID-19 (anti-SARS-CoV-2 IgG S-RBD >40,000 AU/mL). The oral lesions healed after a month of treatment. Conclusion: COVID-19 can trigger the acute exacerbation of dermatitis herpetiformis. SARS-CoV-2 causes an immune dysregulation and hypersensitivity reaction.

Atypical Dermatitis Herpetiform and Scalp Psoriasis in Ulcerative Colitis Patient Treated With Adalimumab.

Adalimumab is a blocker of tumor necrosis factor (TNF)-alpha with established efficacy in the treatment of ulcerative colitis. However, literature indicated that adalimumab can, occasionally, induce paradoxical psoriasis reactions and, very rarely, dermatitis herpetiformis. We present a unique case of a 26-year-old female patient who developed a combination of dermatitis herpetiformis and scalp psoriasis paradoxically as a result of adalimumab treatment for ulcerative colitis. To the best of our knowledge, this is the first case of such a combination within the context of adalimumab therapy. The etiopathological underpinning of such a reaction remains elusive but is speculated to be complex and involves the interaction of several immunological and dermatological mechanisms. Adalimumab therapy is associated with a genuine risk for the development of paradoxical psoriasis and dermatitis herpetiformis. We, through this case report, added to the evidence confirming such an association. Clinicians should follow these potential adverse effects and make every effort to warn patients of their likelihood.

Immunopathological Assessment of the Oral Mucosa in Dermatitis Herpetiformis.

Dermatitis herpetiformis (Duhring's disease, DH) is a chronic blistering cutaneous condition with pruritic polymorphic lesions, consisting of vesicles, papules or nodules and erythema, found predominantly on the extensor surfaces of the limbs, buttocks, and neck. Diagnosis is based on characteristic clinical and immunopathological findings. Oral manifestations of DH have rarely been described. The aim of the study was to evaluate IgA, IgG, IgM and C3 complement deposits in the oral mucosa in DH patients. Direct immunofluorescence (DIF) was performed on the oral mucosa specimens collected from 10 DH patients. Biopsy was taken in a local anesthesia from perilesional site from the buccal mucosa and then preserved in a standard procedure using polyclonal rabbit IgG, IgA, IgM and C3 antibodies. Granular IgA and C3 deposits were found in 6 patients (60%), and in 3 subjects (30%) the result was indeterminate. Significant fluorescence of the deposits along the basement membrane was observed in 2 patients, moderate fluorescence in 3 patients, and in 4 cases the result was indeterminate. C3 deposits were found in 5 subjects (50%), 3 of them being moderate and 2 indeterminate. No IgM and IgG deposits were detected in the collected buccal mucosa specimens.

Oral immune-mediated disorders with malignant potential/association: An overview.

A group of oral disorders or conditions, which may result from, or could be triggered by an abnormality in the normal immune response of an individual are known as oral immune-mediated disorders. Some of these disorders have malignant potential, while others are associated with malignancy. In this overview, we will discuss a few of the oral diseases (such as oral lichen planus, primary Sjogren's syndrome, systemic lupus erythematosus, dermatitis herpetiformis, and linear immunoglobulin A bullous dermatosis, to name a few), which are caused due to irregularity in the immune system and are either associated with malignancy or capable of undergoing malignant transforming, thereby increasing the morbidity and mortality rate.

Differences in the detection of circulating Hsp90 alpha between patients with atopic dermatitis and dermatitis herpetiformis.

Heat shock protein 90 alpha (Hsp90α) is one of the key intra- and extracellular chaperones responsible for the biological activity of various signaling molecules that are involved in (auto)immune-mediated inflammatory diseases. Recent epidemiologic data suggest that patients with atopic dermatitis (AD) are at risk for several autoimmune diseases, including dermatitis herpetiformis (DH), an extraintestinal manifestation of celiac disease (CD). In addition, pruritic diseases such as AD may be confused clinically with DH. In this study, we aimed to determine the role of circulating Hsp90α in patients with AD in relation to patients with DH, CD, and healthy controls. Using an enzyme-linked immunosorbent assay, levels of circulating Hsp90α were determined in serum samples derived from patients with AD (n = 31), DH (n = 26), CD (n = 15), and healthy controls (n = 55). Although serum concentrations of Hsp90α were similar between patients with DH, CD, and healthy controls, we found that serum levels of Hsp90α were significantly higher (mean value of 5.08-fold; p < 0.0001) in patients with AD when compared to patients with DH. A cutoff value calculated as 2 × standard deviation above the mean concentration of Hsp90α in DH patients revealed that 83.9% (26/31) of AD patients were Hsp90α positive, whereas none of the DH patients (0/26) displayed such a positivity. This preliminary study suggests a distinct role for extracellular Hsp90α in the pathogenesis of AD compared to DH and its potential use in distinguishing AD from DH. Nevertheless, the potential role of the evaluation of extracellular Hsp90α for distinguishing between AD and DH is at present speculative and requires further and careful observations.

Cutaneous Disorders Masking Celiac Disease: Case Report and Mini Review with Proposal for a Practical Clinical Approach.

Celiac disease (CD) is an immune-mediated systemic gluten-related disorder characterized by a wide spectrum of intestinal and extra-intestinal manifestations, including damage to cutaneous and connective tissue. We report a rare case of chronic severe dermatitis involving connective tissue and cutaneous vascular vessels as the main clinical presentation of undiagnosed seronegative gluten disorder. A gluten-free diet dramatically improved the intestinal and cutaneous clinical damage in the patient. Pitfalls and the steps of differential diagnosis are described. We also review the literature regarding studies of CD and connective tissue diseases to extend the knowledge of these rare associations. We propose a practical diagnostic approach in suspected CD in autoimmune cutaneous disorders.