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Academic Pathology 2021http://journals.sagepub.com/doi/10.1177/2374289517715040..
http://journals.sagepub.com/doi/10.1177/2374289517715040..
PubMed: 33889719
DOI: 10.1177/23742895211006844 -
Frontiers in Immunology 2021Dermatitis herpetiformis is a cutaneous form of celiac disease manifesting as an itching rash typically on the elbows, knees and buttocks. It is driven by the ingestion... (Review)
Review
Dermatitis herpetiformis is a cutaneous form of celiac disease manifesting as an itching rash typically on the elbows, knees and buttocks. It is driven by the ingestion of gluten-containing cereals and characterized by granular deposits of immunoglobulin A in the papillary dermis. These antibodies target transglutaminase (TG) 3 and in the majority of patients they are also found in circulation. The circulating antibodies disappear and skin symptoms resolve as a result of gluten-free diet but the cutaneous anti-TG3 IgA deposits may persist for several years. In dermatitis herpetiformis, plasma cells secreting antibodies against TG3 are located in the intestinal mucosa similarly to those producing TG2 antibodies characteristic for celiac disease. In fact, both TG2- and TG3-specific plasma cells and gluten responsive T cells are found in dermatitis herpetiformis patients but the interplay between these cell populations is unknown. The small bowel mucosal damage in celiac disease is believed to be mediated by co-operation of cytotoxic intraepithelial T cells and the inflammatory milieu contributed by gluten-reactive CD4+ T cells, whereas the skin lesions in dermatitis herpetiformis appear to be devoid of gluten reactive T cells. Thus, how celiac disease-type intestinal T and B cell responses develop into an autoimmune condition affecting the skin is still incompletely understood. Finally, the skin and small bowel lesions may reappear upon reintroduction of gluten in patients treated with gluten-free diet but virtually nothing is known about the long-lived B cell and memory T cell populations activating in response to dietary gluten in dermatitis herpetiformis.
Topics: Animals; Autoimmunity; B-Lymphocytes; Biomarkers; Celiac Disease; Dermatitis Herpetiformis; Diagnosis, Differential; Disease Susceptibility; Epitopes; Glutens; Humans; Immunity, Cellular; Immunity, Humoral; Phenotype; Skin; T-Lymphocytes
PubMed: 33854513
DOI: 10.3389/fimmu.2021.657280 -
Journal of Investigative Medicine High... 2021Bullous pemphigoid (BP) is the most prevalent autoimmune blistering skin disease in the Western world affecting mainly the elderly population. The diagnosis is based on...
Bullous pemphigoid (BP) is the most prevalent autoimmune blistering skin disease in the Western world affecting mainly the elderly population. The diagnosis is based on clinical assessment along with specific immunopathologic findings on skin biopsy. Risk factors include genetic factors, environmental exposures, and several infections including hepatitis B, hepatitis C, , , and cytomegalovirus. A variety of drugs have been associated with BP including but not limited to dipeptidyl peptidase-4 inhibitors, loop diuretics, spironolactone, and neuroleptics. Associated neurologic disorders (dementia, Parkinson's disease, bipolar disorder, previous stroke history, and multiple sclerosis) have also been described. Common clinical presentation consists of extremely pruritic inflammatory plaques that resemble eczematous dermatitis or urticaria, followed by formation of tense bullae with subsequent erosions. Typical distribution involves the trunk and extremities. Mucosa is typically spared affecting only 10% to 30% of patients. Several unusual clinical presentations of BP have been described such as nonbullous forms with erythematous excoriated papules, plaques, and nodules. Other reported findings include urticarial lesions, prurigo-like nodules, multiple small vesicles resembling dermatitis herpetiformis or pompholyx, vegetating and purulent lesions localized in intertriginous areas, and even exfoliative erythroderma. Recognition and management of such cases can present a diagnostic challenge to clinicians. In this article, we describe another variant which to our knowledge is the first case to present with a cellulitis-like presentation in a patient with a known history of BP.
Topics: Aged; Blister; Cellulitis; Humans; Pemphigoid, Bullous; Skin
PubMed: 33847152
DOI: 10.1177/23247096211008585 -
Acta Dermato-venereologica Apr 2021Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease. Anaemia is a common finding in patients with untreated coeliac disease, but little is known...
Dermatitis herpetiformis is a cutaneous manifestation of coeliac disease. Anaemia is a common finding in patients with untreated coeliac disease, but little is known about the occurrence of anaemia in those with dermatitis herpetiformis. This study investigated the prevalence of anaemia and factors associated with anaemia in 250 patients with dermatitis herpetiformis, at diagnosis and one year after diagnosis. As controls, 139 patients with coeliac disease were included. Patient records were reviewed to gather baseline clinical, histological, and laboratory data. Follow-up data for patients with dermatitis herpetiformis were collected from patient records and via questionnaires or at follow-up visits. The prevalence of anaemia was 12% in patients with dermatitis herpetiformis and 17% in patients with coeliac disease at diagnosis (p = 0.257). Anaemia in patients with dermatitis herpetiformis was not associated with the severity of skin symptoms or small bowel damage. The prevalence of anaemia at a 1-year follow-up had increased to 19%, but it was associated mainly with dapsone treatment.
Topics: Anemia; Celiac Disease; Dermatitis Herpetiformis; Follow-Up Studies; Humans; Prevalence
PubMed: 33846758
DOI: 10.2340/00015555-3795 -
Case Reports in Dermatology 2021Chronic plaque psoriasis is often associated with autoimmune bullous diseases. Dermatitis herpetiformis (DH) is a rare immunobullous disease that has been linked to...
Chronic plaque psoriasis is often associated with autoimmune bullous diseases. Dermatitis herpetiformis (DH) is a rare immunobullous disease that has been linked to celiac disease (CD). To our knowledge, the coexistence of psoriasis and DH is uncommon, and has only been described in anecdotal reports. We report a case of chronic plaque psoriasis complicated by DH in a 60-year-old patient with no known history of CD or associated symptoms. In our patient, DH presented atypically as multiple vesicles along the edges of psoriatic plaques located on the back and hips, and as vesiculobullous eruptions on the fingers. The patient was successfully treated with a combination of dapsone and a gluten-free diet for DH, and secukinumab for psoriasis. This case highlights the importance of screening for CD in patients with psoriasis, as well as other concomitant autoimmune diseases. A gluten-free diet should be trialled in psoriatic patients with positive CD serology.
PubMed: 33790758
DOI: 10.1159/000512870 -
Dermatopathology (Basel, Switzerland) Feb 2021Bullous pemphigoid (BP) is an autoimmune bullous disease and is a rare condition in childhood. Acquired tense acral bullae and fixed urticarial annular lesions on the...
Bullous pemphigoid (BP) is an autoimmune bullous disease and is a rare condition in childhood. Acquired tense acral bullae and fixed urticarial annular lesions on the trunk are diagnostic clues of infantile BP. Diagnosis is supported by immunosorbent assay (IgG anti-BP180 and BP230) and direct immunofluorescence (linear deposition of IgG at the dermo-epidermal junction). Topical and/or systemic corticosteroids are the first-line treatment. The prognosis is good with a self-limited clinical course. Differential diagnoses include impetigo and other bullous diseases in children, such as dermatitis herpetiformis, linear IgA bullous dermatosis and erythema multiforme. The etiopathogenesis is still unknown, and the role of antigen stimuli such as infections, drugs and vaccination is still debated.
PubMed: 33672215
DOI: 10.3390/dermatopathology8010006 -
Medical Sciences (Basel, Switzerland) Feb 2021This short note presents previous research data supporting a pilot study of metronomic dapsone during the entire course of glioblastoma treatment. The reviewed data...
This short note presents previous research data supporting a pilot study of metronomic dapsone during the entire course of glioblastoma treatment. The reviewed data indicate that neutrophils are an integral part of human glioblastoma pathophysiology, contributing to or facilitating glioblastoma growth and treatment resistance. Neutrophils collect within glioblastoma by chemotaxis along several chemokine/cytokine gradients, prominently among which is interleukin-8. Old data from dermatology research has shown that the old and inexpensive generic drug dapsone inhibits neutrophils' chemotaxis along interleukin-8 gradients. It is on that basis that dapsone is used to treat neutrophilic dermatoses, for example, dermatitis herpetiformis, bullous pemphigoid, erlotinib-related rash, and others. The hypothesis of this paper is that dapsone will reduce glioblastomas' neutrophil accumulations by the same mechanisms by which it reduces dermal neutrophil accumulations in the neutrophilic dermatoses. Dapsone would thereby reduce neutrophils' contributions to glioblastoma growth. Dapsone is not an ideal drug, however. It generates methemoglobinemia that occasionally is symptomatic. This generation is reduced by concomitant use of the antacid drug cimetidine. Given the uniform lethality of glioblastoma as of 2020, the risks of dapsone 100 mg twice daily and cimetidine 400 mg twice daily is low enough to warrant a judicious pilot study.
Topics: Cimetidine; Dapsone; Glioblastoma; Humans; Interleukin-8; Pemphigoid, Bullous; Pharmaceutical Preparations; Pilot Projects
PubMed: 33669324
DOI: 10.3390/medsci9010012 -
Journal of Human Genetics Jun 2021The phenotype of coeliac disease varies considerably for incompletely understood reasons. We investigated whether established coeliac disease susceptibility variants...
The phenotype of coeliac disease varies considerably for incompletely understood reasons. We investigated whether established coeliac disease susceptibility variants (SNPs) are individually or cumulatively associated with distinct phenotypes. We also tested whether a polygenic risk score (PRS) based on genome-wide associated (GWA) data could explain the phenotypic variation. The phenotypic association of 39 non-HLA coeliac disease SNPs was tested in 625 thoroughly phenotyped coeliac disease patients and 1817 controls. To assess their cumulative effects a weighted genetic risk score (wGRS39) was built, and stratified by tertiles. In our PRS model in cases, we took the summary statistics from the largest GWA study in coeliac disease and tested their association at eight P value thresholds (P) with phenotypes. Altogether ten SNPs were associated with distinct phenotypes after correction for multiple testing (P ≤ 0.05). The TLR7/TLR8 locus was associated with disease onset before and the SH2B3/ATXN2, ITGA4/UBE2E3 and IL2/IL21 loci after 7 years of age. The latter three loci were associated with a more severe small bowel mucosal damage and SH2B3/ATXN2 with type 1 diabetes. Patients at the highest wGRS39 tertiles had OR > 1.62 for having coeliac disease-related symptoms during childhood, a more severe small bowel mucosal damage, malabsorption and anaemia. PRS was associated only with dermatitis herpetiformis (P = 0.2, P = 0.02). Independent coeliac disease-susceptibility loci are associated with distinct phenotypes, suggesting that genetic factors play a role in determining the disease presentation. Moreover, the increased number of coeliac disease susceptibility SNPs might predispose to a more severe disease course.
Topics: Adaptor Proteins, Signal Transducing; Adolescent; Adult; Aged; Ataxin-2; Celiac Disease; Child; Child, Preschool; Diabetes Mellitus; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Infant; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Toll-Like Receptor 7; Toll-Like Receptor 8; Young Adult
PubMed: 33446885
DOI: 10.1038/s10038-020-00888-5 -
American Journal of Clinical Dermatology May 2021Dermatitis herpetiformis (DH), presenting with an intense itch and blistering symmetrical rash, typically on the elbows, knees, and buttocks, is a cutaneous... (Review)
Review
Dermatitis herpetiformis (DH), presenting with an intense itch and blistering symmetrical rash, typically on the elbows, knees, and buttocks, is a cutaneous manifestation of celiac disease. Though overt gastrointestinal symptoms are rare, three-fourths of patients with DH have villous atrophy in the small bowel, and the rest have celiac-type inflammatory changes. DH affects mostly adults and slightly more males than females. The mean age at onset is about 50 years. DH diagnosis is confirmed by showing granular immunoglobulin A deposits in the papillary dermis. The DH autoantigen, transglutaminase 3, is deposited at the same site in tightly bound immune complexes. At present, the DH-to-celiac disease prevalence is 1:8. The incidence of DH is decreasing, whereas that of celiac disease is increasing, probably because of improved diagnostics. In DH, the treatment of choice for all patients is a gluten-free diet (GFD) in which uncontaminated oats are allowed. At onset, most patients need additional dapsone to rapidly control the rash and itching. Dapsone can be stopped after a mean of 2 years, and a strict lifelong GFD alone is required. Dietary adherence offers an excellent long-term prognosis for patients with DH, with a normal quality of life and all-cause mortality.
Topics: Adult; Age Factors; Celiac Disease; Combined Modality Therapy; Dapsone; Dermatitis Herpetiformis; Dermis; Diet, Gluten-Free; Female; Humans; Immunoglobulin A; Intestinal Mucosa; Intestine, Small; Male; Patient Compliance; Prevalence; Prognosis; Quality of Life; Risk Factors; Sex Factors; Treatment Outcome
PubMed: 33432477
DOI: 10.1007/s40257-020-00584-2 -
Acta Dermato-venereologica Feb 2021Granular deposits of IgA represent the specific cutaneous marker of dermatitis herpetiformis. The prevalence of IgA deposits in the skin of patients with coeliac disease...
Granular deposits of IgA represent the specific cutaneous marker of dermatitis herpetiformis. The prevalence of IgA deposits in the skin of patients with coeliac disease without dermatitis herpetiformis remains unknown. In this prospective case-control study, skin biopsies from newly diagnosed coeliac patients without dermatitis herpetiformis were analysed by direct immunofluorescence. Controls included healthy volunteers and patients with both bowel symptoms and skin eruptions unrelated to coeliac disease. Clinical data and serum level of anti-tissue transglutaminase and anti-epidermal transglutaminase IgA antibodies were collected from patients and controls. Granular deposits of IgA or IgA1 in the skin were found in 29 out of 45 patients with coeliac disease (64.4%), and in none of the included controls (specificity 100%; sensitivity 64.4%). Positive direct immunofluorescence correlated significantly with an increased serum level of anti-epidermal transglutaminase IgA antibodies (p < 0.005). This study shows that granular deposits of IgA represent a low sensitive, but highly specific, cutaneous marker of coeliac disease independent of dermatitis herpetiformis.
Topics: Case-Control Studies; Celiac Disease; Dermatitis Herpetiformis; Humans; Immunoglobulin A; Prospective Studies
PubMed: 33426564
DOI: 10.2340/00015555-3742