Facial Dermatitis Herpetiformis.

A 34-year-old African-American woman with a past medical history of human immunodeficiency virus (HIV) and hypertension presented to the clinic with a blister that was appearing about once a month on her nose or cheeks over the past 8 months. The blister was occasionally pru- ritic and would resolve spontaneously. At the time of presentation, the patient had only post-inflammatory hyperpigmentation on her nasal dorsum. The patient had photos of the blister on her phone to show what it originally looked like (Figure 1).

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.

Sweet Syndrome as a Herpetiform Mimic: A Diagnostic Challenge.

ABSTRACT: The authors present a singular case of Sweet syndrome (acute febrile neutrophilic dermatosis) manifesting with an unusual herpetiform clinical presentation, underscoring the imperative for its inclusion in differential diagnoses of herpetic infections. A 26-year-old female patient with a systemic lupus erythematosus history presented with facial edema, hyperthermia, cephalalgia, and polyarticular pain. Dermatological examination revealed clustered, vesicle-like papules on erythematous, edematous skin, mimicking herpetic infection. Elevated acute-phase reactants and urine anomalies were noted. Histopathology confirmed Sweet syndrome, characterized by superficial and deep neutrophilic dermatitis, karyorrhexis, and papillary dermal edema. The patient responded to corticosteroid therapy and a brief antibiotic course, resolving both systemic and cutaneous symptoms. This case is remarkable for its atypical herpetiform presentation, a clinical rarity in Sweet syndrome, challenging the conventional diagnostic process. It emphasizes the necessity of considering Sweet syndrome in differential diagnoses when encountering herpetiform lesions, particularly in patients with autoimmune backgrounds. This case contributes significantly to the understanding of Sweet syndrome's clinical variability and highlights the critical role of thorough clinicopathological evaluation in achieving accurate diagnosis in complex dermatological disorders.

[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.

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.

Incidence of Dermatitis Herpetiformis in Sweden 2005 to 2018: A Nationwide Retrospective Cohort Study.

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.

Serum reactivity in dermatitis herpetiformis: an international multicentre study.

BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-induced skin disorder characterized predominantly by IgA autoantibodies against endomysium, tissue transglutaminase (TG2/tTG), epidermal transglutaminase (TG3/eTG) and deamidated gliadin. To date, circulating autoantibody reactivity has not been systematically described. OBJECTIVES: Characterization of serum reactivities in DH. METHODS: This multicentre international study analysed sera from 242 patients with DH taken at the time of initial diagnosis. DH-specific IgA and IgG serum autoantibodies were analysed by indirect immunofluorescence (IF) on monkey oesophagus, and by enzyme-linked immunosorbent assay (ELISA) based on recombinant TG2/tTG, TG3/eTG and deamidated gliadin (GAF3X). RESULTS: IgA indirect IF microscopy on monkey oesophagus revealed the highest reactivity (84.3%; specificity 100%) followed by IgA TG2/tTG ELISA (78.5%, specificity 99.0%), IgA TG3/eTG ELISA (72.7%, specificity 95.0%) and IgA GAF3X ELISA (69.0%, specificity 98.5%). CONCLUSIONS: Serum IgA and IgG autoantibodies against endomysium, TG2/tTG, TG3/eTG and deamidated gliadin are highly prevalent in DH. Indirect IF microscopy on monkey oesophagus (IgA) provides the highest diagnostic accuracy that can be further enhanced by 4.5% when combined with IgA TG2/tTG ELISA.

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.

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.

Guidelines of the Italian societies of gastroenterology on the diagnosis and management of coeliac disease and dermatitis herpetiformis.

INTRODUCTION: Coeliac disease and dermatitis herpetiformis are immune-mediated diseases triggered by the consumption of gluten in genetically predisposed individuals. These guidelines were developed to provide general practitioners, paediatricians, gastroenterologists, and other clinicians with an overview on the diagnosis, management and follow-up of coeliac patients and those with dermatitis herpetiformis. METHODS: Guidelines were developed by the Italian Societies of Gastroenterology. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists and a paediatrician with expertise in this field. RESULTS: These guidelines provide a practical guidance for the diagnosis, management and follow-up of coeliac patients and dermatitis herpetiformis in children and adults, both in primary care and in specialist settings. We developed four sections on diagnosis, gluten-free diet, follow-up and risk of complications in adults, one section focused on diagnosis and follow-up in children and one on the diagnosis and management of dermatitis herpetiformis. CONCLUSIONS: These guidelines may support clinicians to improve the diagnosis and management of patients with coeliac disease.

[Dermatitis herpetiformis and other forms of wheat sensitivity]. / Dermatitis herpetiformis und sonstige Formen der Weizensensitivität.

BACKGROUND: Wheat sensitivity is a collective term for several, especially gastrointestinal, diseases that occur as part of a hypersensitivity reaction after wheat consumption. The symptoms, which are mostly similar to those of irritable bowel syndrome, are often accompanied by skin lesions. In addition to celiac disease and dermatitis herpetiformis, the cutaneous manifestation of celiac disease, wheat sensitivity also includes nonceliac gluten sensitivity (NCGS), allergic nickel contact mucositis, wheat allergy, amylase-trypsin inhibitor intolerance, and fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) intolerance. OBJECTIVES: This review article aims to provide an overview of the clinical, especially dermatological and gastrointestinal features of the different forms of wheat sensitivity. Diagnosis and therapeutic management are also discussed. MATERIALS AND METHODS: A selective literature search was carried out with evaluation of our own clinical data. RESULTS: The skin lesions in dermatitis herpetiformis are very disease-specific. In contrast, wheat allergy often shares signs and symptoms with many other diseases. Other forms of wheat sensitivity cause primarily gastrointestinal abnormalities, but extra-intestinal manifestations can also occur. Their diagnosis is often complex and requires cross-disciplinary collaboration with experts in gastroenterology. The therapy consists of a wheat- or gluten-free diet. CONCLUSIONS: Knowledge of the different and frequently occurring dermatological signs of wheat sensitivity is of great importance, because dermatological manifestations associated with gastrointestinal pathology, intolerance reactions, and allergies appear more and more frequently.

An arcane presentation of pustular psoriasis in pregnancy: case report.

Pustular psoriasis of pregnancy (PPP) also known as impetigo herpetiformis is a well-described dermatosis of pregnancy characterized by the fatal progression of disease for both the mother and the foetus if left untreated. A 28-year-old G2P1L1 pregnant mother at 28 weeks of gestation, came to outpatient department (OPD) with complaints of scaly skin lesions all over her body along with fever, nausea and generalised weakness. On examination, there were erythematous scaly patches in the trunk, back, hands and legs accompanied by formation of pustules in the periphery of the lesions. Histopathological examination was consistent with pustular psoriasis. Patient was managed with prednisolone (40 mg/day which was later tapered). Serial antenatal visits and ultrasounds were done to monitor the health of the mother and foetal growth. Under the support of obstetrician, patient delivered a healthy female baby through caesarean section under general anaesthesia. Her lesions persisted in the postpartum period, which later started reducing gradually.

[Stiff person syndrome associated with dermatitis herpetiformis: a case report]. / Syndrome de la personne raide associé à une dermatite herpétiforme: à propos d'un cas.

Stiff person syndrome (SPS) is a rare disease affecting the central nervous system which can be autoimmune, paraneoplastic or idiopathic in origin. Its typical classic presentation is characterized by progressive stiffness of the trunk and limbs, associated with spasms. The diagnosis is supported by the existence of continuous and spontaneous muscle activity on electroneuromyogram detection, the presence of serum anti-GAD antibodies, and a response to benzodiazepines. We report the case of a 46-year-old patient with a classic form of autoimmune stiff person syndrome associated with dermatitis herpetiformis.

A Case of Possible Concurrence of Dermatitis Herpetiformis and Linear Immunoglobulin A / Immunoglobulin G Bullous Dermatosis.

Dear Editor, Linear immunoglobulin (Ig) A bullous dermatosis (LABD), one subtype of subepidermal autoimmune bullous skin diseases (AIBDs), is characterized by linear deposit of only IgA along the basement membrane zone (BMZ) on direct immunofluorescence (DIF) (1,2). Patients showing linear deposits of both IgA and IgG are diagnosed with linear IgA/IgG bullous dermatosis (LAGBD) (3,4). Dermatitis herpetiformis (DH) is another type of subepidermal AIBD characterized by clinically pruritic erythematous skin lesions with vesicles on the elbows, knees, and buttocks with granular IgA deposits of IgA by DIF (5). In this study, we report a Japanese case of a patient who showed possible concurrence of DH and LAGBD based on clinical, histological, and immunological findings. A 72-year-old Japanese man who had a past history of dyslipidemia and resected lung cancer but was not taking any medicines, presented with a one-year history of blistering skin lesions. Physical examination revealed erythemas and peripherally arranged vesicles and erosions on the bilateral elbows, knees, and the buttock (Figure 1, a-c). Mucous membranes were not involved. The results of all laboratory tests were within normal ranges, except for increased serum IgA level 351 mg/dL (normal ranges; 46-260 mg/dL). Skin biopsy histopathologically showed subepidermal blisters infiltrated with neutrophils and eosinophils (Figure 1, d). DIF showed deposits of IgG, IgA, and complement component 3 along the BMZ mainly in granular but partially in a linear pattern (Figure 1, e-g). Circulating IgG (Figure 1, h) and IgA (Figure 1, i) autoantibodies were not detected by indirect immunofluorescence (IIF) of normal skin, however, circulating IgA (Figure 1, j) but not IgG (Figure 1, k) antibodies were bound to both the epidermal and dermal sides by IIF of 1M NaCl-split normal skin. Commercially available enzyme-linked immunosorbent assays (ELISAs) for BP180 NC16a domain, BP230, and type Vll collagen (MBL, Nagoya, Japan), showed negative results for both IgG and IgA antibodies. IgG in-house ELISA for full length BP180 was also negative. IgG and IgA immunoblotting analyses of different antigen sources, including normal human epidermal and dermal extracts, recombinant proteins of NC16a, and C-terminal domains of BP180 region, BP230, purified laminin 332, and concentrated culture supernatant of HaCaT cells for LAD-1, were all negative. IgA ELISAs of tissue- and epidermal-transglutaminases were negative (1.92 AU/mL and 20.98 AU/mL, respectively; normal range <22.0 AU/mL). The patient was successfully treated with only topical corticosteroids with occasional mild local relapses. Japanese DH is different from European DH in some respects, i.e., DH is very rare in Japan due to genetic/HLA difference, absence of celiac disease, and frequent fibrillar IgA deposition in DIF. Therefore, we believe that this case is interesting as a rare Japanese DH case with complicated conditions. The clinical and immunochemical characteristics in the present case were compatible for both DH and LAGBD. Clinical features of vesicles on erythemas on the knees and buttock suggested DH, while histopathological features were compatible with LAGBD but also with DH, DIF results suggested both LAGBD and DH, and the results of IIF of 1M NaCl-split skin suggested LAGBD. All biochemical studies for autoantigens were negative, which suggested DH. However, autoantigens are not clearly detected in many LAGBD cases, either. IgA anti-epidermal transglutaminase antibody, a DH marker, was negative, but the titer was relatively high but within normal range. Therefore, we considered that this case might have developed DH and LAGBD concurrently. However, there may be two other possibilities: [1] this case was DH and non-pathogenic circulating autoantibodies were secondary production, and [2] LAGBD cases may sometimes show granular-linear BMZ deposition of IgG and IgA. Future studies on similar cases are needed to clarify our speculations.

Persistent Skin Symptoms after Diagnosis and on a Long-term Gluten-free Diet in Dermatitis Herpetiformis.

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.