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.

The skin is the largest nonreproductive target tissue on which estrogen plays many beneficial and protective roles. Although neither exogenous hormones nor pregnancy represent significant risk factors for melanoma, epidemiological data suggest a higher survival rate in women with metastatic disease versus men and in premenopausal versus postmenopausal patients. Despite the fact that hyperestrogenic signaling has long been implicated in the initiation and progression of several tumors, the role of estrogens in malignant melanoma is still unclear. The cellular effects of estrogens are mediated by two subtypes of estrogen receptors (ERs). Estrogen receptor β (ERβ), the predominant ER in the skin, antagonizes the proliferative action mediated by estrogen receptor α. According to recent immunohistochemical studies, ERβ protein expression decreases progressively with increased Breslow thickness and results in more invasive melanomas; thus, ERβ immunophenotype may distinguish melanomas linked to poor prognosis from those with a favorable course and lead to melanoma unresponsiveness to both estrogen and anti-estrogen treatment. Therefore, if future large-scale immunohistochemical and molecular studies point towards ERβ as an important factor in malignant melanoma progression, they will open up novel and targeted prognostic and therapeutic perspectives.

Background: The dermatological manifestations associated with intestinal diseases are becoming more frequent, especially now when new clinical entities, such as Non-Celiac Gluten Sensitivity (NCGS), are identified. The existence of this new entity is still debated. However, many patients with diagnosed NCGS that present intestinal manifestations have skin lesions that need appropriate characterization. Methods: We involved 17 patients affected by NCGS with non-specific cutaneous manifestations who got much better after a gluten free diet. For a histopathological and immunopathological evaluation, two skin samples from each patient and their clinical data were collected. Results: The median age of the 17 enrolled patients affected by NCGS was 36 years and 76% of them were females. On the extensor surfaces of upper and lower limbs in particular, they all presented very itchy dermatological manifestations morphologically similar to eczema, psoriasis or dermatitis herpetiformis. This similarity was also confirmed histologically, but the immunopathological analysis showed the prevalence of deposits of C3 along the dermo-epidermal junction with a microgranular/granular pattern (82%). Conclusions: The exact characterization of new clinical entities such as Cutaneous Gluten Sensitivity and NCGS is an important objective both for diagnostic and therapeutic purposes, since these are patients who actually benefit from a GFD (Gluten Free Diet) and who do not adopt it only for fashion.

Dermatitis herpetiformis (DH) is a rare autoimmune disease linked to gluten sensitivity with a chronic-relapsing course. It is currently considered to be the specific cutaneous manifestation of celiac disease (CD). Both conditions are mediated by the IgA class of autoantibodies, and the diagnosis of DH is dependent on the detection of granular deposits of IgA in the skin. There is an underlying genetic predisposition to the development of DH, but environmental factors are also important. This paper describes these different factors and discusses the known mechanism that lead to the development of skin lesions.

Purpose of review: Cutaneous vasculitis reflects a spectrum ranging from skin limited to severe systemic forms. To date, there is still no generally acknowledged nomenclature for cutaneous vasculitis. This review aims to summarize the recent advances in the nomenclature of cutaneous vasculitis. Recent findings: The most widely adopted vasculitis classification system is the one of 2012 Revised Chapel Hill Consensus Conference (CHCC) which represent not such a classification but a nomenclature system that name vasculitis on the basis of the size of the vessel affected. The CHCC 2012 did not deal with the special features of cutaneous vasculitis and did not explicitly discuss the presence of skin-limited or skin-dominant forms of vasculitis. Therefore, a consensus group was formed to propose an Addendum to CHCC 2012, focusing on cutaneous vasculitis. The Addendum better clarify the main aspects of some single-organ vasculitis, including IgM/IgG vasculitis, nodular vasculitis, erythema elevatum et diutinum and recurrent macular vasculitis in hypergammaglobulinemia. Moreover, it differentiated normocomplementemic from hypocomplementemic urticarial vasculitis. Finally, it recognized cutaneous polyarteritis nodosa as a distinct subtype of polyarteritis nodosa. Summary: Classification criteria are useful tools to standardize names and definitions for cutaneous vasculitis; however, they do not represent diagnostic criteria. Collaborative efforts are still needed to get a shared classification and valid diagnostic criteria for cutaneous vasculitis.