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Laminin-332 pemphigoid is a rare and severe autoimmune blistering disease, caused by IgG autoantibodies targeting laminin-332 in the dermal-epidermal basement zone. Laminin-332 pemphigoid is characterized by variable inflammatory infiltrate and the predominance of non-complement-fixing antibodies. Given these findings, we hypothesized that IgG autoantibodies to laminin-332 directly resulted in keratinocyte expression of inflammatory factors. We performed RNA-seq on primary human keratinocytes treated with IgG from patients with laminin-332 pemphigoid. Genes for numerous cytokines and chemokines were upregulated, including CSF2, CSF3, CXCL1, CXCL5, CXCL3, CXCL8, CXCL10, CXCL1, IL6, IL7, IL15, IL23, IL32, IL37, TGFB2 as well as metalloproteases. Considering the pro-inflammatory and proteolytic effect of autoantibodies from patients with laminin-332 pemphigoid identified in our initial experiment, we next questioned whether the reactivity against specific laminin subunits dictates the inflammatory and proteolytic keratinocyte response. Then, we treated keratinocytes with IgG from a separate cohort of patients with reactivity against individual subunits of laminin-332. We identified upregulation of IL-1α, IL-6, IL-8, CXCL1, MMP9, TSLP, and GM-CSF at the protein level, most notably in keratinocytes treated with IgG from laminin β3-reactive patients. We for the first time demonstrated a pro-inflammatory response, similar to that described in keratinocytes treated with IgG autoantibodies from patients with bullous pemphigoid, providing novel insight into the pathogenesis of laminin-332 pemphigoid and laminin-332 biology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bao, Li, Solimani, Didona, Patel, Li, Qian, Ishii, Hashimoto, Hertl and Amber.)

Background: T H 2 cells were thought to be a pivotal factor for initiation of the autoimmune blistering disease pemphigus. However, the role of other T-cell subsets in pemphigus pathogenesis remained unclear., Objective: We aimed to characterize the exact phenotype of T cells responsible for the development of pemphigus., Methods: Whole transcriptome shotgun sequencing was performed to determine differential gene expression in pemphigus lesions and skin of healthy individuals. The cutaneous cytokine signature was further evaluated by real-time quantitative PCR. In peripheral blood, the distribution of T H cell and folliclular helper (T FH ) cell subsets was analyzed by flow cytometry. Finally, the capacity of T H and T FH cell subsets to induce desmoglein (Dsg)-specific autoantibodies by memory B cells was evaluated in coculture experiments., Results: Transcriptome analysis of skin samples identified an IL-17A-dominated immune signature in patients with pemphigus, and Kyoto Encyclopedia of Genes and Genomes pathway analysis confirmed the dominance of the IL-17A signaling pathway. Increased expression of IL17A and associated cytokines was also detected by real-time quantitative PCR comparing lesional with perilesional or healthy skin. Interestingly, utilization of flow cytometry showed that patients with active pemphigus had elevated levels of circulating IL-17 + , T H 17, T FH 17, and T FH 17.1 cells. Notably, levels of T H 17 and T FH 17 cells correlated with levels of Dsg-specific CD19 + CD27 + memory B cells, and patients with acute pemphigus showed higher levels of Dsg3-autoreactive T FH 17 cells. Coculture experiments revealed T FH 17 cells as primarily responsible for inducing Dsg-specific autoantibody production by B cells., Conclusion: Our findings show that T FH 17 cells are critically involved in the pathogenesis of pemphigus and offer novel targets for therapeutic intervention., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Originally described by Anhalt as paraneoplastic pemphigus in 1990, paraneoplastic autoimmune multiorgan syndrome (PAMS) is a potentially lethal blistering disease, characterized by polymorphous clinical features, including mucocutaneous erosions, blisters, lichenoid papules, and erythemas. Several autoantibodies have been detected in serum of PAMS patients, including antiplakins, anti-alpha-2-macroglobulin like 1, and antidesmogleins autoantibodies. The mortality rate of PAMS is up to 90%. This is due on the one hand to the poor response to treatments and on the other hand to the delay in the diagnosis and to the prognosis of the underlying neoplasia.

Introduction: Immunotherapy has changed the management of patients with various types of malignancies (melanoma, renal, lung, and bladder cancers) but immune checkpoint inhibitors may be associated with several adverse events. Up to 20% of patients treated with immune checkpoint inhibitors may develop dermatological immune-related adverse events, mostly rashes and pruritus but rarely even bullous pemphigoid., Case Report: We report a case of an elderly patient with advanced non-small cell lung cancer in therapy with pembrolizumab, 200 mg/body every three weeks. After 26 cycles of therapy, the patient developed widespread itching and then after 28 cycles she developed strained blisters filled with serous fluids on predominantly erythematous skin with suspicious of bullous pemphigoid. Management and outcome: Skin biopsy confirms bullous pemphigoid, so we decided to permanently discontinue therapy with pembrolizumab and the patient is currently on therapy with doxycycline, nicotinamide, and clobetasol propionate with good regression of symptoms and cutaneous lesions., Discussion: In the literature, the first case of bullous pemphigoid induced by pembrolizumab has been described in 2015. On Pubmed, from 2015 to date, we have found 19 cases of bullous pemphigoid during pembrolizumab therapy but only three of them are related to non-small cell lung cancer, adding our patient we reach a total of 20 cases. It could be interesting to investigate if there is a specific relationship between the appearance of itching and the development of bullous pemphigoid.

Bullous pemphigoid (BP) is a prototypic autoimmune disorder of the elderly, characterized by serum IgG autoantibodies, namely anti-BP180 and anti-BP230, directed against components of the basal membrane zone that lead to sub-epidermal loss of adhesion. Pruritus may be indicative of a pre-clinical stage of BP, since a subset of these patients shows serum IgG autoantibodies against BP230 and/or BP180 while chronic pruritus is increasingly common in the elderly population and is associated with a variety of dermatoses. Clinical and experimental evidence further suggests that pruritus of the elderly may be linked to autoimmunity with loss of self-tolerance against cutaneous autoantigens. Thus, the objective of this study was to determine autoreactive T cell responses against BP180 in elderly patients in comparison to patients with BP. A total of 22 elderly patients with pruritic disorders, 34 patients with bullous or non-bullous BP and 34 age-matched healthy controls were included in this study. The level of anti-BP180 and anti-BP230 IgG serum autoantibodies, Bullous Pemphigoid Disease Area Index (BPDAI), and pruritus severity were assessed for all patients and controls. For characterization of the autoreactive T cell response, peripheral blood mononuclear cells were stimulated ex vivo with recombinant BP180 proteins (NH 2 - and COOH-terminal domains) and the frequencies of BP180-specific T cells producing interferon-γ, interleukin (IL)-5 or IL-17 were subsequently determined by ELISpot assay. Patients with BP showed a mixed Th1/Th2 response against BP180 while autoreactive Th1 cells were identified in a minor subset of elderly patients with pruritic disorders. Furthermore, our T cell characterization revealed that therapeutic application of topical clobetasol propionate ointment in BP patients significantly reduced peripheral blood BP180-specific T cells, along with clinically improved symptoms, strongly suggesting a systemic immunosuppressive effect of this treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Didona, Scarsella, Fehresti, Solimani, Juratli, Göbel, Mühlenbein, Holiangu, Pieper, Korff, Schmidt, Sitaru, Eming, Hertl and Pollmann.)

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen's disease) or an invasive form. A significant cSCC risk factor is advanced age, together with cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses. Although most cSCCs can be treated by surgery, a fraction of them recur and metastasize, leading to death. cSCC could arise de novo or be the result of a progression of the actinic keratosis, an in situ carcinoma. The multistage process of cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes. Thus, cSCC development is a gradual process with several histological- and pathological-defined stages. Dermoscopy and reflectance confocal microscopy enhanced the diagnostic accuracy of cSCC. Surgical excision is the first-line treatment for invasive cSCC. Moreover, radiotherapy may be considered as a primary treatment in patients not candidates for surgery. Extensive studies of cSCC pathogenic mechanisms identified several pharmaceutical targets and allowed the development of new systemic therapies, including immunotherapy with immune checkpoint inhibitors, such as Cemiplimab, and epidermal growth factor receptor inhibitors for metastatic and locally advanced cSCC. Furthermore, the implementation of prevention measures has been useful in patient management.

Lentigo maligna (LM) is usually diagnosed in sun-damaged skin of elderly patients and a correct excision of the lesion determines a complete healing from the disease. LM is very rare in young patients and, for this reason, it can be commonly misdiagnosed. We describe the case of a locally recurrent LM in a 19-year-old male patient, which initially arose at the age of 17 years. In order to avoid diagnostic pitfalls, clinicians have to put more emphasis on diseases which previously were prerogative only of elderly patients and that now could begin to engage a younger age, according to climate and behavior changes.

Background: Amelanotic and hypomelanotic melanoma (AHM) has a higher risk of delayed diagnosis and a significant lower 5-year melanoma-specific survival compared to pigmented melanoma. Our aim was the evaluation of the clinicopathological/dermoscopic features of amelanotic melanoma (AM) and hypomelanotic melanoma (HM)., Methods: All participants had a personal history of AHM. We defined HM as showing clinical/dermoscopic pigmentation in < 25% of the lesion's surface and histopathological focal pigmentation, while AM as melanomas with clinical/dermoscopic and histopathological absence of pigmentation., Results: The most common phenotypic traits among the 145 AHM patients were as follows: phototype II, blue-grey eyes, and dark brown hair. Red hair was present in 23.8% AHM cases (AM = 22.60%; HM = 25.80%). The most affected area was the back (29.5%). A total of 67.1% were classified as AM and 32.9% as HM. The most represented hair colors in AM and HM were, respectively, blonde and dark brown hair. Median Breslow thickness was 1.7 mm, superficial spreading melanoma (SSM) and nodular melanoma (NM) were the most represented histotypes, and mitotic rate > 1 × mm 2 was reported in 73.3% cases, and regression was significantly more present in HM. Dermoscopy showed high prevalence of white structureless zones (63.4%), linear looped vessels (58.8%), linear irregular vessels (50.0%), and arborizing vessels (47.2%). Multivariate logistic regression confirmed the association between the presence of pigmentation and the following: histological regression, dermoscopic globules, and arborizing vessels., Conclusions: Predominance of red hair in AHM patients was not confirmed. AHM affects mostly intermittent sun-exposed body areas. The deeper median Breslow thickness (versus pigmented melanoma), the association of AM with the nodular histotype, and the high mitotic rate highlight the AHM's aggressiveness. HM's higher levels of regression can be explained by the presence of pigmentation, driving the underlying immune response. AHM showed a polymorphous vascular pattern and significant presence of arborizing vessels (especially HM)., (© 2020 the International Society of Dermatology.)

Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhibitors, such as vismodegib and sonidegib, are successfully used as targeted treatment for advanced or metastatic BCC. Furthermore, the implementation of prevention measures has demonstrated to be useful in the patient management.

Background: Toxic epidermal necrolysis (TEN) is a severe, potentially lethal drug reaction for which no standard treatment is available., Objective: To describe 17 consecutive TEN patients treated with a single dose of etanercept, a TNF-alpha inhibitor., Materials & Methods: Comorbidities and any drug treatment initiated within the previous month were recorded on admission. Patients received 50 mg etanercept in a single subcutaneous injection. The clinical severity of the disease was computed using the SCORTEN scale. The expected number of deaths was calculated based on the probability of death associated with each SCORTEN score level. Healing was defined as complete re-epithelialization. Time to healing was analysed using the Kaplan-Meier estimator., Results: The lowest SCORTEN score was 2, and seven patients scored in the most severe risk category (i.e., =>5). A comparison between observed (2/17) vs. expected deaths (10/17) was statistically significant (p=0.012). Fifteen patients promptly responded to treatment and achieved complete re-epithelization (median time to healing: 8.5 days), without complications or side effects. The two observed deaths were due to other causes, although re-epithelization had initiated in both patients., Conclusion: These preliminary results add to our initial observations indicating that etanercept may effectively control TEN, a potentially lethal skin condition for which there is currently no effective cure. Where funding is available, randomized controlled trials on etanercept for TEN should be conducted.

Dermatomyositis belongs to a group of rare autoimmune diseases characterized by a variable degree of skin symptoms and myopathy. The clinically diagnostic hallmarks of dermatomyositis are heliotrope rash, Gottron's papules and weakness of the proximal muscles. Along with pathognomonic, characteristic, and compatible cutaneous features, several uncommon and rare skin manifestations have been reported. In addition, new skin lesions have been described in dermatomyositis patients. Furthermore, rare clinical subtypes of dermatomyositis have been reported in the literature, including Wong-type dermatomyositis, characterised by the coexistence of dermatomyositis and pityriasis rubra pilaris with hyperkeratotic, erythematous, follicular confluent papules on the back of the hands along the bony prominences. In addition, plenty of autoantibody subsets have been recently described that are related to distinct clinical features and systemic involvement, such as anti-MDA5 autoantibodies. We reviewed the English- and German-language scientific literature using the key words "dermatomyositis", "autoantibodies", and "clinical features", alone or in combination, focusing on particular cutaneous symptoms and their association with defined autoantibody profiles. Furthermore, we focused on rare subtypes of dermatomyositis, unusual clinical features, and recently described skin lesions.

Dermatomyositis (DM) is a group of autoimmune diseases characterized by a variable degree of skin symptoms and myopathy. An amyopathic form of DM (ADM) has been described, and more recently, an anti-TIF-1 gamma-positive subtype, characterized by poikiloderma and associated with a relatively high risk of cancer. To characterise a cohort of DM patients. A cohort of 29 DM patients was followed between January 2004 and March 2019, and investigated for clinical characteristics, pathological features based on electromyography and MRI, laboratory data, and auto-antibody profile. Based on the investigations, DM was shown to be heterogeneous. However, we identified a subgroup of anti-TIF-1 gamma-positive patients who all shared heliotrope erythema. Furthermore, we observed a positive correlation between serum glutamicoxaloacetic transaminase (GOT) and creatine kinase (CK) concentrations in patients with anti-TIF-1 gamma antibodies, which is not found in patients with anti-MDA-5 antibodies. Based on the findings of this study, we propose an update of the Sontheimer et al. diagnostic criteria to improve the sensitivity of diagnosis for ADM. In addition, we describe a significant association between serum GOT and CK levels in DM patients with anti-TIF-1 gamma antibodies, and further highlight the significance of heliotrope rash as a clinical hallmark for this particular subset of patients.

Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform an early diagnosis of the underlying neoplasm. Lack of familiarity with cutaneous clues of internal malignancy may delay diagnosis and treatment of cancer. In this review, we described several paraneoplastic dermatoses and discussed extensively two paradigmatic ones, namely paraneoplastic pemphigus and paraneoplastic dermatomyositis.

Background: Head and neck melanoma is a clinical challenge. Indeed, cutaneous head and neck melanoma shows a worse prognosis in comparison to melanomas of other body sites. Although the emphasis on facial cosmetic preservation plays a pivotal role in comparison to other body areas, specific Facial Aesthetic Units (FAU) could also play a key role in the prognostic evaluation of the malignancy., Methods: The aim of the current study was to evaluate the general outcome and clinicopathological features of head and neck melanoma and to detect prognostic differences according to each FAU. The Kaplan-Meier product was used to calculate survival curves, while Cox proportional-hazard regression was performed to evaluate the predictive value of each FAU., Results: A total of 221 head and neck melanoma patients was included in our analysis. In the nasal FAU, we found a high rate of local recurrence, which affected significantly disease-free survival. The worse prognosis was observed in melanoma of the scalp, which showed a greater tendency to skip metastases in internal organs. Moreover, we found that scalp showed a low incidence of non-melanoma skin cancers, if compared to other FAU, highlighting that the scalp local milieu might play a more prominent role in melanoma biology than chronic UV exposition., Conclusions: Although FAUs have an aesthetic function, they could also play a role in the evaluation and follow-up of melanoma.

Current evidences suggest that mast cells contribute to the proliferation and differentiation of skin melanocytes. According to these findings, we carried out an observational cross-sectional study to investigate the correlation between the total number of nevi (TN), Breslow thickness (BT), and serum tryptase (ST) levels in a cohort of 35 melanoma (MM) patients. A Mann-Whitney test was performed to compare ST values within each variable. Subsequently, the independent predictive factors were assessed by multiple logistic regression. Pearson's χ-test was chosen to detect statistically significant findings on the TN and the histopatological variables (Breslow, ulceration, and mitotic index). The TN was assessed using a dichotomous scale (≤ 10 or > 10). Patients with TN of 10 or less (3.48 vs. 6.05 ng/ml; P = 0.045), patients with a Breslow thickness of at least 1.01 mm (2.99 vs. 5.67 ng/ml; P = 0.1), and ulcerated MM (2.37 vs. 6.05 ng/ml; P < 0.001) showed lower median ST levels. Similarly, MM with mitotic index of at least 1/mm had median ST levels lower than MM with mitotic index less than 1/mm (P = 0.005). Multiple logistic regression confirmed the statistical significance for the variables ulceration, TN, and mitotic index. Pearson's χ-test showed a statistically significantly (P = 0.003) increased prevalence of MMs with a BT of at least 1.01 mm in patients with a TN of 10 or less. Patients with a TN of 10 or less also showed a higher prevalence of ulceration and mitotic index of at least 1/mm in comparison with the rest of the cohort. Our study highlights lower median ST levels in patients whose MM thickness is at least 1.01 mm; this may encourage new studies on the role of ST in MM also according to the number of nevi.

Mast cells (MCs) are a potent proangiogenic factor in tumors, they product several pro-angiogenic factors such as fibroblast growth factor 2 (FGF-2), vascular epithelial growth factor (VEGF), tryptase and chymase. Tryptase is a serine protease classified as α-tryptase and β-tryptase, both produced by MCs. Tryptase degrades the tissues, playing an important role in angiogenesis and in the development of metastases. Serum tryptase increases with age, with increased damage to cells and risk of developing a malignancy and it could be considered the expression of a fundamental role of MCs in tumor growth or, on the contrary, in the antitumor response. Many biomarkers have been developed in clinical practice for improving diagnosis and prognosis of some neoplasms. Elevated tryptase levels are found in subgroups of patients with haematologic and solid cancers. In the current review, we want to update the perspectives of tryptase as a potential biomarker in daily practice in different neoplasms.

Pemphigus encompasses a heterogeneous group of autoimmune blistering diseases, which affect both mucous membranes and the skin. The disease usually runs a chronic-relapsing course, with a potentially devastating impact on the patients' quality of life. Pemphigus pathogenesis is related to IgG autoantibodies targeting various adhesion molecules in the epidermis, including desmoglein (Dsg) 1 and 3, major components of desmosomes. The pathogenic relevance of such autoantibodies has been largely demonstrated experimentally. IgG autoantibody binding to Dsg results in loss of epidermal keratinocyte adhesion, a phenomenon referred to as acantholysis. This in turn causes intra-epidermal blistering and the clinical appearance of flaccid blisters and erosions at involved sites. Since the advent of glucocorticoids, the overall prognosis of pemphigus has largely improved. However, mortality persists elevated, since long-term use of high dose corticosteroids and adjuvant steroid-sparing immunosuppressants portend a high risk of serious adverse events, especially infections. Recently, rituximab, a chimeric anti CD20 monoclonal antibody which induces B-cell depletion, has been shown to improve patients' survival, as early rituximab use results in higher disease remission rates, long term clinical response and faster prednisone tapering compared to conventional immunosuppressive therapies, leading to its approval as a first line therapy in pemphigus. Other anti B-cell therapies targeting B-cell receptor or downstream molecules are currently tried in clinical studies. More intriguingly, a preliminary study in a preclinical mouse model of pemphigus has shown promise regarding future therapeutic application of Chimeric Autoantibody Receptor T-cells engineered using Dsg domains to selectively target autoreactive B-cells. Conversely, previous studies from our group have demonstrated that B-cell depletion in pemphigus resulted in secondary impairment of T-cell function; this may account for the observed long-term remission following B-cell recovery in rituximab treated patients. Likewise, our data support the critical role of Dsg-specific T-cell clones in orchestrating the inflammatory response and B-cell activation in pemphigus. Monitoring autoreactive T-cells in patients may indeed provide further information on the role of these cells, and would be the starting point for designating therapies aimed at restoring the lost immune tolerance against Dsg. The present review focuses on current advances, unmet challenges and future perspectives of pemphigus management.

Despite the presence of several studies in literature, the real connection between vitamin D serological levels, vitamin D receptor and melanoma remains unclear, probably because of the complex correlation between vitamin D and melanoma. Indeed, UV radiations are not reported as the main risk factor for melanoma in non-sun-exposed, while systemic immunosuppression, anatomical and physiological features may contribute to malignancy. Therefore, the correlation between melanoma cells in sun-exposed areas and vitamin D, as well as vitamin D receptor could be different from the one in melanoma of sun-shielded sites. These differences may also explain the controversial results reported in the literature regarding the correlation between melanoma and vitamin D, as well as the different outcomes in melanoma patients treated with vitamin D as adjuvant therapy. The aim of this review is to highlight the most recent findings about vitamin D and melanoma, focusing on the anatomic site of the primary tumor as well as on the possible therapeutic uses of vitamin D in melanoma patients.

Background: Serum tryptase results from the constant release of the enzyme from mast cells and serum tryptase levels are commonly considered to be related to the total number of mast cells. They are increased in several malignancies, as pancreatic carcinoma, angiosarcoma, hepatic carcinoma and proliferative and/or non-proliferative hematological disorders. Contrariwise, it has been reported that the number of tryptase- and chymase-positive mast cells was lower in deeply invasive melanoma compared to in-situ melanoma and dysplastic nevi. Considering the underlying pathophysiological linkages between mast cells and melanocytes and that serum tryptase is related to angiogenesis, tissue-degrading proprieties and metastatization, we have decided to evaluate serum tryptase levels in melanoma patients and in a healthy control., Methods: We performed a case-control study evaluating serum tryptase in melanoma and in healthy group. Starting from an initial general analysis, we have performed a sub-analysis for each sample., Results: In general population serum tryptase was statistically higher in elderly patients. Generally, in melanoma patients, median serum tryptase was in lower normal range. We found a decreasing of serum tryptase levels from the healthy control to thin (≤1.00 mm Breslow thickness), reaching the lowest levels in thicker melanoma (≥1.01 mm Breslow thickness), in ulcerated and metastatic melanoma., Conclusions: Tryptase may have a protective role in melanoma or in the early stage of the tumorigenesis. Serum tryptase is an easy and useful biomarker to better investigate melanoma biology.

The clinical features of bullous pemphigoid are extremely polymorphous. Several atypical forms of bullous pemphigoid have been described, and the diagnosis critically relies on immunopathological findings. We describe three bullous pemphigoid patients characterized by palmoplantar keratoderma, diffused hyperkeratotic cutaneous lesions and extremely high levels of immunoglobulin E serum. The diagnosis of bullous pemphigoid should be taken into account in patients presenting diffused hyperkeratotic cutaneous lesions and palmoplantar keratoderma, even in the absence of blisters. Alteration of the keratinization process, that could occur in patients with genetic mutations in desmosomal and hemidesmosomal genes, may also be due to circulating autoantibodies against hemidesmosomal proteins in these bullous pemphigoid patients., (© 2018 Japanese Dermatological Association.)

Background: Dermatofibrosarcoma protuberans is a malignant tumor that affects exclusively the skin. It is a low-grade malignant tumor of subcutaneous tissues, characterized by a local recurrence but it seldom metastasizes. This study aimed to evaluate the impact of different clinical parameters on disease free survival and overall survival of dermatofibrosarcoma protuberans patients., Methods: A retrospective study of data including seventeen cases of dermatofibrosarcoma protuberans (eleven male, six female) retrieved from the files of the Dermatology Clinics of La Sapienza University, Rome. We evaluated three clinical parameters (age, sex and anatomic site of the primary tumor) using the Kaplan-Meier product and the Log-Rank Test., Results: The results highlighted that patients with an age ≤49 years showed a median disease free survival of 36 months, while patients with an age ≥50 years of 4 months (P<0.0003). In addition, performing Rank-correlation, only the variable age (P<0.0001) reached the statistical significance. Regarding overall survival, performing Rank-correlation only the variable age reached the statistical significance (P=0.02)., Conclusions: Our data suggests that age has a statistically significant role on disease free survival and overall survival of dermatofibrosarcoma protuberans patients.

Autoimmune blistering diseases are characterized by autoantibodies against structural adhesion proteins of the skin and mucous membranes. Extensive characterization of their autoantibody targets has improved understanding of pathogenesis and laid the basis for the study of antigens/epitopes diversification, a process termed epitope spreading (ES). In this review, we have reported and discussed ES phenomena in autoimmune bullous diseases and underlined their functional role in disease pathogenesis. A functional ES has been proposed: (1) in bullous pemphigoid patients and correlates with the initial phase of the disease, (2) in pemphigus vulgaris patients with mucosal involvement during the clinical transition to a mucocutaneous form, (3) in endemic pemphigus foliaceus, underlining its role in disease pathogenesis, and (4) in numerous cases of disease transition associated with an intermolecular diversification of immune response. All these findings could give useful information to better understand autoimmune disease pathogenesis and to design antigen/epitope specific therapeutic approaches.

Pityriasis rubra pilaris (PRP) is a rare, chronic, inflammatory skin disease of unknown etiology. Patients refractory to conventional therapies have been treated successfully with biologic drugs such as anti-tumor necrosis factor agents. Recently, a role of the interleukin-23/T-helper 17 axis in PRP has been described. Our objective was to assess the effectiveness of ustekinumab in five patients with adult-onset PRP refractory to conventional therapies. In the present study, four patients had type I and one patient type II adult-onset PRP. They were treated with three s.c. doses of ustekinumab at weeks 0, 4 and 16. Clinical response was evaluated monthly during treatment up to a 15-month follow-up period. All patients promptly showed a decrease in erythema, follicular hyperkeratosis and scaling. After three injections, complete remission of skin lesions was achieved in four out of five cases and a significant clinical improvement was shown in one case. To the best of our knowledge, this is the largest case series reported on ustekinumab treatment in PRP. Our results, in addition to previous studies from other groups, suggest that ustekinumab may be a possible first-line treatment for PRP patients refractory to conventional therapies., (© 2017 Japanese Dermatological Association.)

(1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer., Competing Interests: The authors declare no conflict of interest.