Impetigo herpetiformis in the second trimester: a case report and review of the literature.

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.

Piel y tubo digestivo: dermatitis herpetiforme y enfermedad celíaca / Small bowel and skin: celiac disease and dermatitis herpetiformis

La dermatitis herpetiforme, también denominada Enfermedad de Dühring-Brocq, es una dermatosis autoinmune crónica que evoluciona por brotes, caracterizada por la presencia de ampollas pequeñas que tienden a agruparse, en codos, rodillas y glúteos, con disposición simétrica, intensamente pruriginosas. Es considerada una manifestación cutánea de la enfermedad celíaca. Afecta a adultos jóvenes (20 a 50 años). El estudio histopatológico evidencia ampollas subepidérmicas. La inmunofluorescencia directa es característica: depósitos granulares de IgA en las puntas de las papilas dérmicas. Aún ante falta de sintomatología digestiva debe investigarse enfermedad celíaca en todos los pacientes. La dieta libre de gluten es la clave del tratamiento. En aquellos pacientes con intenso prurito o con una dermatosis muy extensa se puede utilizar dapsona vía oral, que alivia rápidamente las manifestaciones cutáneas, pero no modifica el curso de la enfermedad digestiva. Se presenta un paciente en quien a partir de las lesiones cutáneas se realizó diagnóstico de dermatitis herpetiforme primero y de enfermedad celíaca luego

Dermatitis herpetiformis, also known as Dühring-Brocq disease, is a chronic autoimmune dermatosis that evolves in outbreaks. It is characterized by the presence of small blisters that tend to cluster on the elbows, knees, and buttocks, with a symmetrical distribution and intense itching. It is considered a cutaneous manifestation of celiac disease. It affects young adults (20 to 50 years old). Histopathological examination reveals subepidermal blisters. Direct immunofluorescence is characteristic, showing granular deposits of IgA at the tips of the dermal papillae. Even in the absence of digestive symptoms, celiac disease should be investigated in all patients. A gluten-free diet is the key to treatment. In patients with intense itching or extensive dermatosis, oral dapsone can be used to quickly relieve cutaneous manifestations, but it does not alter the course of the digestive disease. We present a patient in whom the diagnosis of dermatitis herpetiformis was made initially, followed by a diagnosis of celiac disease based on the skin lesions

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.

Antibody Responses to Transglutaminase 3 in Dermatitis Herpetiformis: Lessons from Celiac Disease.

Dermatitis herpetiformis (DH) is the skin manifestation of celiac disease, presenting with a blistering rash typically on the knees, elbows, buttocks and scalp. In both DH and celiac disease, exposure to dietary gluten triggers a cascade of events resulting in the production of autoantibodies against the transglutaminase (TG) enzyme, mainly TG2 but often also TG3. The latter is considered to be the primary autoantigen in DH. The dynamics of the development of the TG2-targeted autoimmune response have been studied in depth in celiac disease, but the immunological process underlying DH pathophysiology is incompletely understood. Part of this process is the occurrence of granular deposits of IgA and TG3 in the perilesional skin. While this serves as the primary diagnostic finding in DH, the role of these immunocomplexes in the pathogenesis is unknown. Intriguingly, even though gluten-intolerance likely develops initially in a similar manner in both DH and celiac disease, after the onset of the disease, its manifestations differ widely.

Significant improvement of dermatitis herpetiformis with tofacitinib.

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.

Dermatitis Herpetiformis: Novel Perspectives.

Dermatitis herpetiformis (DH) is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac disease (CD). Both DH and CD occur in gluten-sensitive individuals, share the same Human Leukocyte Antigen (HLA) haplotypes (DQ2 and DQ8), and improve following the administration of a gluten-free diet. Moreover, almost all DH patients show typical CD alterations at the small bowel biopsy, ranging from villous atrophy to augmented presence of intraepithelial lymphocytes, as well as the generation of circulating autoantibodies against tissue transglutaminase (tTG). Clinically, DH presents with polymorphic lesions, including papules, vesicles, and small blisters, symmetrically distributed in typical anatomical sites including the extensor aspects of the limbs, the elbows, the sacral regions, and the buttocks. Intense pruritus is almost the rule. However, many atypical presentations of DH have also been reported. Moreover, recent evidence suggested that DH is changing. Firstly, some studies reported a reduced incidence of DH, probably due to early recognition of CD, so that there is not enough time for DH to develop. Moreover, data from Japanese literature highlighted the absence of intestinal involvement as well as of the typical serological markers of CD (i.e., anti-tTG antibodies) in Japanese patients with DH. Similar cases may also occur in Caucasian patients, complicating DH diagnosis. The latter relies on the combination of clinical, histopathologic, and immunopathologic findings. Detecting granular IgA deposits at the dermal-epidermal junction by direct immunofluorescence (DIF) from perilesional skin represents the most specific diagnostic tool. Further, assessing serum titers of autoantibodies against epidermal transglutaminase (eTG), the supposed autoantigen of DH, may also serve as a clue for the diagnosis. However, a study from our group has recently demonstrated that granular IgA deposits may also occur in celiac patients with non-DH inflammatory skin diseases, raising questions about the effective role of eTG IgA autoantibodies in DH and suggesting the need of revising diagnostic criteria, conceivably emphasizing clinical aspects of the disease along with DIF. DH usually responds to the gluten-free diet. Topical clobetasol ointment or dapsone may be also applied to favor rapid disease control. Our review will focus on novel pathogenic insights, controversies, and management aspects of DH.

Gluten Challenge Induces Skin and Small Bowel Relapse in Long-Term Gluten-Free Diet-Treated Dermatitis Herpetiformis.

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of celiac disease causing an itchy, blistering rash. Granular IgA deposits in the skin are pathognomonic for DH, and the treatment of choice is a lifelong gluten-free diet (GFD). Preliminary evidence suggests that there are patients with DH who redevelop gluten tolerance after adherence to a GFD treatment. To evaluate this, we performed a 12-month gluten challenge with skin and small-bowel mucosal biopsy samples in 19 patients with DH who had adhered to a GFD for a mean of 23 years. Prechallenge biopsy was negative for skin IgA and transglutaminase 3 deposits in 16 patients (84%) and indicated normal villous height-to-crypt depth ratios in the small bowel mucosa in all 19 patients. The gluten challenge caused a relapse of the rash in 15 patients (79%) in a mean of 5.6 months; of these 15 patients, 13 had skin IgA and transglutaminase 3 deposits, and 12 had small-bowel villous atrophy. In addition, three patients without rash or immune deposits in the skin developed villous atrophy, whereas one patient persisted without any signs of relapse. In conclusion, 95% of the patients with DH were unable to tolerate gluten even after long-term adherence to a GFD. Therefore, lifelong GFD treatment remains justified in all patients with DH.

[Dermatitis herpetiformis]. / Dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is a genetically determined, gluten sensitive autoimmune bullous dermatosis related to celiac disease in which granular, insoluble aggregates in the papillary dermis of epidermal transglutaminase (TG3), immunoglobulin A (IgA), and fibrinogen are present. Detection of the dermal IgA-TG3 immune complex is the gold standard of diagnosis. DH develops in a subpopulation of patients with gluten sensitive enteropathy, characterized by itching, erythematous, excoriated papules showing characteristic distribution over the knees, elbows and buttocks; vesicles are rarely seen. The primary therapy of DH is a strict, lifelong gluten-free diet, and it may be necessary to temporarily give dapsone in case of severe symptoms.

Clinical, pathologic, and immunologic features of pemphigus herpetiformis: a literature review and proposed diagnostic criteria.

Pemphigus herpetiformis (PH), a rare type of pemphigus, is characterized by immunologic findings consistent with pemphigus but with a unique clinical and pathologic presentation. PH was first described as resembling dermatitis herpetiformis clinically, but because of its variable presentation, it can also resemble linear immunoglobulin A bullous dermatosis and bullous pemphigoid. We reviewed reported cases to analyze the most frequent clinical, pathologic, and immunologic characteristics and to propose corresponding diagnostic criteria. Through a comprehensive review of Medline and PubMed databases, 96 publications and 158 cases were identified. After reviewing the reported characteristics of PH, we suggest the following diagnostic criteria: Clinical: 1) pruritic herpetiform intact blisters with/without erosions; and/or 2) pruritic annular or urticarial erythematous plaques with/without erosions; Pathologic: 1) intraepidermal eosinophils or neutrophils, or both; and/or 2) intraepidermal split with/without acantholysis; Immunologic: 1) direct immunofluorescence showing immunoglobulin G with/without C3 intercellular deposits; and/or 2) indirect immunofluorescence showing immunoglobulin G to epithelial cell surface; and/or 3) detection of serum autoantibodies against desmogleins (1,3) or desmocollins (1,2,3), or both. Diagnosis requires one clinical, one pathologic, and one immunologic feature. We also report three new cases diagnosed at our institution to demonstrate the applicability of the suggested criteria.

A Case of Dermatitis Herpetiformis With Fibrillar Immunoglobulin A Deposition: A Rare Pattern Not to Be Missed.

Dermatitis herpetiformis is a rare, chronic autoimmune disorder characterized by intense pruritic papules and vesicles, which can be associated with celiac disease and other autoimmune disorders. Its histologic characteristic is the accumulation of neutrophils within the papillary dermis with granular deposition of immunoglobulin A (IgA) observed under direct immunofluorescence. Herein, we report a 58-year-old woman who presented with a vesicular rash on the buttocks. The patient reported a recent history of genital herpes, Entamoeba histolytica colitis, recurrent hives, and eczema. A representative biopsy demonstrated features of spongiotic dermatitis and focal papillary dermal neutrophilic aggregates. Direct immunofluorescence revealed fibrillary IgA deposition in the papillary dermis, granular C3 deposition at the dermal-epidermal junction, and dermal papillae. The overall clinical, histologic, and DIF findings were consistent with those of dermatitis herpetiformis. The fibrillar IgA pattern is rare and easily overlooked by the unwary. Pathologists should be aware of this rare pattern, especially when the histologic findings are not classic.

Treatment resistant impetigo herpetiformis treated with infliximab.

Impetigo herpetiformis is a rare disease of pregnancy with the onset being in the second half of pregnancy and resolution after delivery. It is associated with a high rate of perinatal mortality and fetal abnormalities. Clinical and histological features of the disease are consistent with pustuler psoriasis. We reported a case of 25-year-old female gravida 1 para 0, who responded poorly to consecutive treatments with systemic steroids, cyclosporine, intravenous immunoglobulin, and acitretin. Good response was obtained with adding infliximab to the treatment.

Herpetiform pemphigus with characteristic transmission electron microscopic findings of various-sized ballooning vacuoles in keratinocytes without acantholysis.

We report a unique case of a Japanese woman with herpetiform pemphigus (HP) who had IgG autoantibodies reactive with nondesmosomal sites of keratinocytes and presented characteristic transmission electron microscopic (TEM) findings of various-sized vacuoles in keratinocytes without acantholysis. The patient presented with pruritic annular oedematous erythemas with small blisters lining the margins on the trunk and extremities. Histopathological examinations showed intraepidermal blisters with prominent infiltrations of eosinophils. Direct and indirect immunofluorescence tests revealed the presence of in vivo bound and circulating IgG autoantibodies to the keratinocyte cell surfaces. However, enzyme-linked immunosorbent assays for desmoglein (Dsg) 1, Dsg3 and desmocollins 1-3 showed negative results. Immunoblotting using the full-length human Dsg1 recombinant protein showed a positive band. TEM examination showed various-sized vacuoles squashing the nuclei in many keratinocytes, resulting in rupture of the cells. Immunoelectron microscopic examination revealed IgG deposition over the entire keratinocyte cell surfaces, which spared the desmosomes. IgG antibodies were also present on the inside walls of the vacuoles around the nuclei of keratinocytes and on the cell surfaces of infiltrating eosinophils. This patient also had marked eosinophilia and high levels of thymus and activation-regulated chemokine and interleukin-5 in the serum. These results indicated a novel autoantigen on the nondesmosomal keratinocyte cell surfaces and the pathogenesis of bullous spongiotic change with inflammation in HP.