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Frontiers in Medicine 2023Heat shock protein 90 alpha (Hsp90α) is one of the key intra- and extracellular chaperones responsible for the biological activity of various signaling molecules that...
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 ( = 31), DH ( = 26), CD ( = 15), and healthy controls ( = 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; < 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.
PubMed: 38249962
DOI: 10.3389/fmed.2023.1327144 -
Alimentary Pharmacology & Therapeutics Mar 2024Data on mortality in coeliac disease are contrasting. (Review)
Review
BACKGROUND
Data on mortality in coeliac disease are contrasting.
AIMS
To systematically review the literature on all-cause and cause-specific mortality in coeliac disease compared to the general population, and evaluate differences across clinical phenotypes, geographical regions, and over time.
METHODS
We searched PubMed and Embase from 1 January 1970 to 31 December 2022 for eligible studies reporting on all-cause and cause-specific mortality in coeliac disease compared to the general population or controls. The protocol was registered on Open Science Framework (https://doi.org/10.17605/OSF.IO/852DN).
RESULTS
We included 25 studies. All-cause mortality (HR 1.16, 95% CI 1.05-1.27, I = 89%), mortality due to malignancies (HR 1.21, 95% CI 1.08-1.36, I = 65%) and respiratory disease (HR 1.39, 95% CI 1.04-1.86, I = 76%) were increased. Mortality due to non-Hodgkin lymphoma (HR 10.14, 95% CI 2.19-46.88, I = 96%) was markedly increased. Mortality significantly decreased in recent decades: 1989-2004 (HR 1.61, 95% CI 1.27-2.03, I = 91%), 2005-2014 (HR 1.16, 95% CI 0.99-1.36, I = 89%), 2015-2022 (HR 1.19, 95% CI 1.05-1.35, I = 93%). All-cause mortality was not increased in dermatitis herpetiformis (HR 0.85, 95% CI 0.73-0.99, I = 40%) and undiagnosed coeliac disease (HR 1.09, 95% CI 0.95-1.25, I = 0%). Mortality was increased in the UK (HR 1.23, 95% CI 1.03-1.47, I = 91%) but not Scandinavia (HR 1.01, 95% CI 0.91-1.13, I = 81%). Limitations include high heterogeneity and lack of data for many countries.
CONCLUSION
Mortality in coeliac disease is increased, predominantly due to malignancies-particularly non-Hodgkin lymphoma-although differing significantly across disease phenotypes. Mortality of patients with coeliac disease has significantly decreased in recent decades. These results may influence diagnosis and management.
Topics: Humans; Celiac Disease; Lymphoma, Non-Hodgkin; Neoplasms
PubMed: 38204404
DOI: 10.1111/apt.17867 -
Nutrients Dec 2023Celiac disease (CD) is an immune-mediated systemic gluten-related disorder characterized by a wide spectrum of intestinal and extra-intestinal manifestations, including... (Review)
Review
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.
Topics: Humans; Celiac Disease; Skin Diseases; Dermatitis; Glutens; Autoimmune Diseases
PubMed: 38201912
DOI: 10.3390/nu16010083 -
Diagnostics (Basel, Switzerland) Dec 2023Autoimmune bullous diseases (ABDs) are a rare but significant group of dermatoses that pose great challenges to the treating dermatologist. ABDs are characterized by the...
BACKGROUND
Autoimmune bullous diseases (ABDs) are a rare but significant group of dermatoses that pose great challenges to the treating dermatologist. ABDs are characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Most epidemiological studies have focused on a single ABD. More than that, there are few data about the incidence and prevalence of autoimmune blistering diseases in Romania.
METHODS
In this study, between 2015 and 2019, we retrospectively investigated a total of 225 patients with autoimmune bullous diseases from the northeastern region of Romania. The diagnosis was based on the clinical and histo- and immunohistological findings.
RESULTS
Pemphigus was the most frequently encountered ABD, with an incidence of 8.16/1,000,000 inhabitants, representing 58.7% (132 cases), followed by 24% cases of bullous pemphigoid (54 cases), 15.4% of patients were diagnosed with dermatitis herpetiformis (37 cases), and 0.9% other subepidermal autoimmune bullous dermatoses. The average age of onset of pemphigus vulgaris was 59.4 years, the majority of patients being male, while the average age of patients diagnosed with bullous pemphigoid was 73.8 years, the majority being female.
CONCLUSIONS
Pemphigus vulgaris is the most frequently encountered ABDs in the northeast of Romania, with a higher incidence than in Western European countries, and this may be due to specific peculiarities of the geographical area, as well as to a genetic susceptibility of the population in this region.
PubMed: 38201366
DOI: 10.3390/diagnostics14010057 -
Cureus Jan 2024[This corrects the article DOI: 10.7759/cureus.48045.].
[This corrects the article DOI: 10.7759/cureus.48045.].
PubMed: 38179325
DOI: 10.7759/cureus.c150 -
Antibodies (Basel, Switzerland) Dec 2023Celiac disease (CD) is an autoimmune condition that is initiated in genetically susceptible individuals by the exposure of the intestines to gluten, and the early start... (Review)
Review
Celiac disease (CD) is an autoimmune condition that is initiated in genetically susceptible individuals by the exposure of the intestines to gluten, and the early start of symptoms is related to malabsorption. Atypical variants of the illness are often identified in adulthood and are frequently associated with manifestations outside of the intestines, including metabolic osteopathy, anemia, and dermatitis herpetiformis. But also, empirical data suggest a correlation between CD and reproductive abnormalities, including repeated abortions. Infertility and repeated miscarriages frequently manifest in women diagnosed with CD and may serve as the initial clinical indication of a subclinical form. Furthermore, the condition may manifest as amenorrhea, infertility, and the delivery of infants with a low birth weight. Regarding the mechanisms of CD in infertility, along with the anti-tTG action to hinder the invasiveness of trophoblast, these antibodies could damage endometrial angiogenesis, which has been shown in in vitro models with human endometrial cells and in vivo in murine models. Another important aspect is the role of nutrient deficiencies, such as zinc deficiency (connected to impaired hormone production, secondary amenorrhea, and pre-eclampsia) and folic acid, etc. Therefore, our objective was to conduct a comprehensive review of the existing literature pertaining to this specific topic and to elucidate the role of the autoantibodies in its pathogenesis.
PubMed: 38131801
DOI: 10.3390/antib12040079 -
The Journal of International Medical... Dec 2023Impetigo herpetiformis is a rare skin disease that most often occurs in the third trimester of pregnancy. It is currently considered as a form of generalized pustular... (Review)
Review
Impetigo herpetiformis is a rare skin disease that most often occurs in the third trimester of pregnancy. It is currently considered as a form of generalized pustular psoriasis and the typical skin lesions comprise small sterile pustules. Here, a case of impetigo herpetiformis in the second trimester of pregnancy after 7 weeks of hydroxychloroquine administration for suspected Sjogren's syndrome is reported. Treatment with anti-infective, anti-inflammatory and immunosuppressive medication did not improve the patient's condition. Following delivery of a live male by emergency caesarean section at 29 weeks' gestation, the rash was reported to be completely resolved by 3 months postpartum. Previously published cases of impetigo herpetiformis in the second trimester of pregnancy that were retrieved from a search of the PubMed database are also reviewed and discussed.
Topics: Female; Humans; Pregnancy; Cesarean Section; Dermatitis Herpetiformis; Exanthema; Impetigo; Pregnancy Complications, Infectious; Pregnancy Trimester, Second; Psoriasis
PubMed: 38102997
DOI: 10.1177/03000605231217950 -
Cureus Oct 2023Objectives The aim of this study was to describe the clinical, serological, and histopathological features of patients with dermatitis herpetiformis (DH) in Saudi...
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.
PubMed: 38034235
DOI: 10.7759/cureus.48045 -
Medicina (Kaunas, Lithuania) Nov 2023HLA class II molecules are key factors determining susceptibility to autoimmune disorders, and their role in immune-mediated skin conditions such as psoriasis has been... (Review)
Review
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.
Topics: Humans; Child; Pemphigus; Autoimmune Diseases; Pemphigoid, Bullous; Skin; HLA Antigens; Alleles; Genetic Predisposition to Disease; HLA-DRB1 Chains; Gene Frequency
PubMed: 38003999
DOI: 10.3390/medicina59111950 -
Acta Dermato-venereologica Nov 2023Dermatitis herpetiformis has been investigated in the past; however, only a limited number of studies have reported its incidence based on validated nationwide...
Dermatitis herpetiformis has been investigated in the past; however, only a limited number of studies have reported its incidence based on validated nationwide population-based registries. To address this gap, the aims of this study are to estimate the incidence of dermatitis herpetiformis in Sweden and to validate the National Patient Register (NPR) for diagnosis of dermatitis herpetiformis. A population-based open cohort study was conducted, including all patients diagnosed with dermatitis herpetiformis (International Classification of Diseases 10th revision; ICD-10 code L13.0) in Sweden from 2005 to 2018 (n = 1,724), identified from the NPR. The diagnosis of dermatitis herpetiformis in the NPR was validated using medical records, histopathological and immunopathological data, yielding a positive predictive value (PPV) of 62.5%. The mean annual incidence of dermatitis herpetiformis was 0.93/100,000 (95% confidence interval 0.79-1.08), female to male ratio 1:1, and mean age at diagnosis 60.9 years. In conclusion, this large nationwide cohort study showed a low validity for diagnosis of dermatitis herpetiformis in the NPR, and the adjusted incidence rate of dermatitis herpetiformis in Sweden was estimated to be 0.93/100,000, which is lower than that in previous Swedish studies.
Topics: Humans; Male; Female; Middle Aged; Cohort Studies; Sweden; Incidence; Dermatitis Herpetiformis; Retrospective Studies
PubMed: 37971253
DOI: 10.2340/actadv.v103.13210