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.

THE MANAGEMENT OF DERMATITIS HERPETIFORMIS BY THE GASTROENTEROLOGIST. A SERIES OF CASES.

BACKGROUND: Dermatitis herpetiformis (DH) is considered a skin celiac disease (CD). The individuals can be seen by primary care professionals or by dermatologists that could refer the patient to a gastroenterologist. OBJECTIVE: The study aimed to investigate the clinical profile of patients diagnosed with DH and referred to a gastroenterologist and evaluate the treatment response. METHODS: We retrospectively studied patients with DH referred to the same gastroenterologist at a private office in Curitiba, Brazil, between January 2010 to December 2019. We included adult patients with a confirmed DH diagnosis. Symptoms, clinical signs, laboratory and histological data, as well as treatment response, were collected. RESULTS: Thirty-three patients were studied (60.6% women, mean age at diagnosis 40.8±12.61 years). The median delay for DH diagnosis was four years. Skin involvement was mild in 33.3%, moderate in 18.2%, and severe in 48.5%. The more frequent gastrointestinal complaints were abdominal distension (78.8%), flatulence (75.7%), and gastroesophageal reflux (51.5%). Depression and anxiety were observed in 81.8% and anemia in 51.1%. A higher prevalence of bone disorders was associated with higher age at DH diagnosis (P=0.035). Duodenal biopsy showed changes in all patients. Improvement after treatment only with a gluten-free diet (GFD) plus dapsone was verified in 81.2%. CONCLUSION: Patients with DH referred to a gastroenterologist showed a high frequency of gluten intolerance and systemic complaints. Duodenal histological alterations were found in all the cases. The treatment based on GFD plus dapsone was effective in most patients.

Dermatitis Herpetiformis: An Update on Diagnosis, Disease Monitoring, and Management.

Dermatitis herpetiformis (DH), Duhring disease, is caused by gluten sensitivity and affects 11.2 to 75.3 per 100,000 people in the United States and Europe with an incidence of 0.4 to 3.5 per 100,000 people per year. DH is characterized by a symmetrical blistering rash on the extensor surfaces with severe pruritus. The diagnosis continues to be made primarily by pathognomonic findings on histopathology, especially direct immunofluorescence (DIF). Recently, anti-epidermal transglutaminase (TG3) antibodies have shown to be a primary diagnostic serology, while anti-tissue transglutaminase (TG2) and other autoantibodies may be used to support the diagnosis and for disease monitoring. Newly diagnosed patients with DH should be screened and assessed for associated diseases and complications. A gluten-free diet (GFD) and dapsone are still mainstays of treatment, but other medications may be necessary for recalcitrant cases. Well-controlled DH patients, managed by a dermatologist, a gastroenterologist, and a dietician, have an excellent prognosis. Our review comprehensively details the current diagnostic methods, as well as methods used to monitor its disease course. We also describe both the traditional and novel management options reported in the literature.

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.

Update on the use of dapsone in dermatology.

Dapsone (4,4'-diaminodiphenylsulfone) is the only remaining sulfone used in anthropoid therapeutics and is commercially available as an oral formulation, an inhaled preparation, and a 5% or 7.5% cream. Dapsone has antimicrobial effects stemming from its sulfonamide-like ability to inhibit the synthesis of dihydrofolic acid. It also has anti-inflammatory properties such as inhibiting the production of reactive oxygen species, reducing the effect of eosinophil peroxidase on mast cells and down-regulating neutrophil-mediated inflammatory responses. This allows for its use in the treatment of a wide variety of inflammatory and infectious skin conditions. Currently in dermatology, the US Food and Drug Administration (FDA)-approved indications for dapsone are leprosy, dermatitis herpetiformis, and acne vulgaris. However, it proved itself as an adjunctive therapeutic agent to many other skin disorders. In this review, we discuss existing evidence on the mechanisms of action of dapsone, its FDA-approved indications, off-label uses, and side effects.

Sulfasalazine-induced generalized vitiligo in a patient with dermatitis herpetiformis and celiac disease.

Vitiligo is an acquired idiopathic pigmentary skin disorder characterized by the development of white macules and patches due to the loss of functioning melanocytes. In this report, we describe a case of a patient with a longstanding history of dermatitis herpetiformis (DH) and celiac disease that developed rapidly progressing, biopsy-confirmed generalized vitiligo after 11 months of treatment with anti-inflammatory medication sulfasalazine, prescribed for the patient's DH. To the best of our knowledge, this is the first case report which has demonstrated the possible biochemical pathways, triggered by sulfasalazine, in the development of vitiligo.

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.

Dermatitis Herpetiformis and Celiac Disease Increase the Risk of Bullous Pemphigoid.

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are autoimmune bullous skin diseases. DH has been described to evolve into BP and the two diseases can have overlapping clinical appearances and diagnostic findings, but the association between DH and BP has not previously been studied in a large population. To evaluate DH and celiac disease as risk factors for BP, we conducted a retrospective case-control study of patients with BP and matched controls with basal cell carcinoma diagnosed in Finland between 1997 and 2013. A total of 3,397 patients with BP and 12,941 controls were included in the study. Forty-one (1.2%) BP patients and 7 (0.1%) controls had preceding DH. Diagnosed DH increased the risk of BP 22-fold (odds ratio = 22.30; 95% confidence interval = 9.99-49.70) and celiac disease 2-fold (odds ratio = 2.54; 95% confidence interval = 1.64-3.92) compared to controls. Eighteen (43.9%) of the patients who had DH and subsequent BP had bought dapsone during the 2 years prior to their BP diagnosis. Mean time between diagnosed DH and BP was 3 years. We conclude that diagnosis of DH is associated with a striking increase in the risk for BP.

Two Cases of Dermatitis Herpetiformis Successfully Treated with Tetracycline and Niacinamide.

Dear Editor, Dermatitis herpetiformis (DH) is a chronic, polymorphic, pruritic autoimmune blistering skin disease characterized by subepidermal blisters, neutrophilic microabscesses, and granular IgA deposition within the dermal papillae. DH is classified as a cutaneous manifestation of coeliac disease, a type of gluten-sensitive enteropathy (1). The treatment of DH includes dapsone and a gluten-free diet (GFD). Other therapies should be considered in patients who are unable to tolerate dapsone, including sulfapyridine and glucocorticoids. Herein we present two cases of DH with good responses to tetracycline and niacinamide combination therapy. Case 1 was a 42-year-old man who was admitted to our hospital with a 3-year history of recurrent pruritic papules and bullous lesions involving the trunk and upper limbs. On examination, the patient showed disseminated erythematous papules on the upper limbs and back as well as vesicles. Nikolsky's sign for vesicles was negative (Figure 1, a-c). The results of routine blood examinations were within normal ranges. He did not have a history of chronic diarrhea. The histologic examination showed subepidermal blisters and accumulation of neutrophils at the papillary dermis of the involved ski. Direct immunofluorescence revealed fibrillar deposition of IgA on the dermal papillae (Figure 1. g, h). Case 2 was a 34-year-old woman who had a history of skin rash and pruritic lesions predominantly involving the arms and legs, which had been present for 10 months. She had been treated with prednisone (30 mg daily) with improvement; however, the lesions reappeared when the prednisone was discontinued. She had a history of constipation. On physical examination, the skin lesions manifested as erythematous papules, vesicles, and scabs on the limbs (Figure 2. a-c). She felt apparently pruritic. The histologic examination of the biopsy identified subepidermal blisters with a neutrophil infiltrate in the upper dermis. Direct immunofluorescence revealed granular deposition of IgA on the dermal papillae (Figure 2. e, f). The results of routine blood examinations were within normal ranges, with the exception of elevated IgE concentration (222.5 ku/L (normal range, 0-100 ku/L)). The clinical manifestations and histologic and immunofluorescence examinations of the two cases confirmed the diagnosis of DH. The two patients were subsequently started on a strict GFD. At that time, dapsone was not available in the hospital. The patients were treated with oral tetracycline (500 mg four times daily) and nicotinamide (500 mg three times daily). The rash affecting case 1 resolved entirely in 2 weeks. The patient discontinued the medications after 6 months, and occasionally presented with a few pruritic papules and vesicles, but the lesions resolved within 1 week. The lesions affecting case 2 completely healed within 1 month. The patient continued taking those medications and no recurrence of the skin lesions occurred during 2 years of follow-up. Dapsone is considered first-line therapy for patients with DH (2). Recent findings have shown dapsone and lower dosages of sulfasalazine combination therapy in DH are effective and well-tolerated (3). Alternative monotherapeutic agents in mild autoimmune bullous diseases such as DH include a tetracycline group of antibiotics with niacinamide or its derivatives as well as sulfasalazine. Because dapsone is difficult to obtain in China except for patients with leprosy, we treated the patients with tetracycline and nicotinamide. To our knowledge, only a few cases of DH have been successfully treated with oral tetracycline and niacinamide (2,4). One of the patients was also prescribed heparin (4). Tetracycline has anti-inflammatory properties due to the inhibition of metalloproteinase activity and mast cell activation (5). Nicotinamide is a potent modulator of several pro-inflammatory cytokines. Nicotinamide can inhibit cytokine release (IL-1, IL-6, IL-8, and TNF-α) from immune cells, inhibit chemotaxis and degranulation of immune cells, inhibit lymphocyte blast transformation, and suppress T-cell activity (6). The non-antibiotic properties of tetracycline in combination with nicotinamide may participate in inhibition of antibody formation, modulation of pro-inflammatory cytokines, inflammatory cell accumulation, lymphocyte transformation, and T-cell activation. In summary, we reported two typical cases of DH that were successfully treated with oral tetracycline and niacinamide, which completely healed the rash and relieved the symptoms within 1 month. The combination of tetracycline and nicotinamide can be recommended as a useful therapy for patients where dapsone is not available or for patients who do not tolerate dapsone.