E. Cozzani

Bullous pemphigoid in Liguria: A 2‐year survey

The epidemiology of bullous pemphigoid (BP) is not clear because of the heterogeneity of the disease, and its possible association with internal malignancies has been under debate for many years. We report the findings of a 2‐year study on incident BP cases in the Liguria region of Italy.

Scar sarcoidosis after hyaluronic acid injection

A 54‐year‐old woman presented with a 5‐month history of tender nodules in both nasolabial folds that had developed 4 months after the injection of hyaluronic acid (HA) (Restylane®) for wrinkles. The patient was treated with 1.5 mg/day betamethasone for 6 days and her lesions disappeared within 1 week. About 8 days after stopping therapy, however, new nodules developed at the same site, on previously healthy buttocks, and on old scars.

HLA‐DQB1 alleles in Italian patients with mucous membrane pemphigoid predominantly affecting the oral cavity

Background Mucous membrane pemphigoid (MMP) used to be considered as a single entity but it is now evident that a range of variants exists. Among them, pure ocular cicatricial pemphigoid (OCP) and pure oral pemphigoid (OP) appear to be very different subsets. Previous immunogenetics studies have found increased occurrence of the DQB1*0301 allele mainly in patients with OCP whereas in patients with OP the data are more open to doubt.

Urban legends: pemphigus vulgaris

Pemphigus vulgaris (PV) is the most common type of pemphigus. PV pathogenesis is still debated, and treatment remains challenging. We investigated five controversial topics: (1) What are the target antigens in PV? (2) Do desmogleins adequately address PV pathophysiology? (3) How does acantholysis occur in PV? (4) Is PV still a lethal disease? (5) What is the role of rituximab (RTX) in PV treatment? Results from extensive literature searches suggested the following: (1) Target antigens of PV include a variety of molecules and receptors that are not physically compartmentalized within the epidermis. (2) PV is caused by a variety of autoantibodies to keratinocyte self-antigens, which concur to cause blistering by acting synergistically. (3) The concept of apoptolysis distinguishes the unique mechanism of autoantibody-induced keratinocyte damage in PV from other known forms of cell death. (4) PV remains potentially life-threatening largely because of treatment side effects, but it is uncertain which therapies carry the highest likelihood of lethal risk. (5) RTX is a very promising treatment option in patients with widespread recalcitrant or life-threatening PV. RTXs cost is an issue, its long-term side effects are still unknown, and randomized controlled trials are needed to establish the optimal dosing regimen.

Antidesmoplakin antibodies in pemphigus vulgaris

Background  Besides being present in paraneoplastic pemphigus (PNP), circulating antidesmoplakin (DP) antibodies have been found anecdotally in other bullous diseases, including pemphigus foliaceus and pemphigus vulgaris.

Paraneoplastic pemphigus. A report of two cases associated with chronic B-cell lymphocytic leukaemia

Paraneoplastic pemphigus (PNP) is an autoimmune blistering and erosive mucocutaneous disease associated with neoplasia. Clinical manifestations are polymorphous, and include erythema, bullae, erythema multiforme‐like lesions and severe mucous membrane involvement. PNP manifesting as lichenoid dermatitis has recently been observed. We describe two Italian men with fatal PNP featuring typical PNP autoantigens associated with chronic B‐cell lymphocytic leukaemia. The first patient presented with an extensive blistering eruption, several erythema multiforme‐like lesions and severe mucosal involvement. The second patient presented with a lichenoid dermatitis, then developed bullae, and died with an erythrodermic and exfoliative dermatosis resembling pemphigus foliaceus. Our patients represent two Italian cases of well‐documented PNP. In patient 2, the sequence of clinical presentations was unique, and strongly supports the hypothesis of epitope spreading through chronic lichenoid inflammation of the dermo‐epidermal junction exposing new self antigens, leading to the humoral response characteristic of PNP.

Diagnosis and disease severity assessment of epidermolysis bullosa acquisita by ELISA for anti-type VII collagen autoantibodies: an Italian multicentre study

Background  Epidermolysis bullosa acquisita (EBA) is a rare autoimmune mucocutaneous bullous disease caused by autoantibodies against type VII collagen, a component of anchoring fibrils that stabilizes dermoepidermal adherence. Type VII collagen is composed of a collagenous domain linked by the noncollagenous (NC)1 and NC2 domains.

Contact dermatitis from para-phenylenediamine used as a skin paint : A further case

Case Report A 26-year-old woman had a design painted on her right shoulder with what she believed to be henna dye. She had never previously used any kind of skin paints or hair dyes. 2 weeks later, she developed an itchy erythematooedematous reaction that exactly reproduced the original design (Fig. 1). The eruption resolved on treatment with topical corticosteroids leaving slight post-inflammatory pigmentation. Patch testing to the GIRDCA standard series and to the ‘‘henna’’ powder brought by the patient showed the following unexpected results:

Pemphigus herpetiformis associated with prostate cancer.

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Gene Expression Profiling in Dermatitis Herpetiformis Skin Lesions

Dermatitis herpetiformis (DH) is an autoimmune blistering skin disease associated with gluten-sensitive enteropathy (CD). In order to investigate the pathogenesis of skin lesions at molecular level, we analysed the gene expression profiles in skin biopsies from 6 CD patients with DH and 6 healthy controls using Affymetrix HG-U133A 2.0 arrays. 486 genes were differentially expressed in DH skin compared to normal skin: 225 were upregulated and 261 were downregulated. Consistently with the autoimmune origin of DH, functional classification of the differentially expressed genes (DEGs) indicates a B- and T-cell immune response (LAG3, TRAF5, DPP4, and NT5E). In addition, gene modulation provides evidence for a local inflammatory response (IL8, PTGFR, FSTL1, IFI16, BDKRD2, and NAMPT) with concomitant leukocyte recruitment (CCL5, ENPP2), endothelial cell activation, and neutrophil extravasation (SELL, SELE). DEGs also indicate overproduction of matrix proteases (MMP9, ADAM9, and ADAM19) and proteolytic enzymes (CTSG, ELA2, CPA3, TPSB2, and CMA1) that may contribute to epidermal splitting and blister formation. Finally, we observed modulation of genes involved in cell growth inhibition (CGREF1, PA2G4, and PPP2R1B), increased apoptosis (FAS, TNFSF10, and BASP1), and reduced adhesion at the dermal epidermal junction (PLEC1, ITGB4, and LAMA5). In conclusion, our results identify genes that are involved in the pathogenesis of DH skin lesions.