Clinical Evaluation on the Performance and Safety of a Non-Ablative Fractional 1340 nm Laser for the Treatment of Stretch Marks in Adolescents and Young Adults: A Case Series.

A large part of the world's population suffers from Striae distensae (SD) or stretch marks, which create physical and psychological discomfort in people. We evaluate the SD clinical improvement by using a non-ablative fractional Nd:YAP 1340 nm laser. The research was performed on 25 patients of both sexes, with a mean age of 31 ± 13.09 years. Each patient underwent from a minimum of 3 to a maximum of 4 treatments, with an Nd:YAP (1340 nm) medical device, every four weeks, with 3- and 6-month follow-up, in these areas: back, abdomen, breast, flanks, lower limbs, buttocks, and thighs. Manchester Scar Scale assessed stretch marks improvement. Side effects, patient pain, and SD overall appearance improvement were also recorded for all patients. Digital photographs measured the aesthetic results. Treatment was well-tolerated (pain score 1.08 ± 0.76) by all patients. There were no long-term side effects, and 88% of patients revealed an SD excellent improvement showing good aesthetic results achieved by the treatment. The total mean pretreatment Manchester Scar Scale score decreased from 13.80 (±1.58) to 10.36 (±1.70) after 3 months (p < 0.01) and to 8.36 (±1.07) after 6 months (p < 0.01). An Nd:YAP (1340 nm) laser seems to be a safe and effective treatment, showing a higher security profile with no side effects.

Gliptin-associated bullous pemphigoid shows peculiar features of anti-BP180 and -BP230 humoral response: Results of a multicenter study.

BACKGROUND: Recently, several case-control studies demonstrated an association between gliptins and bullous pemphigoid (BP) occurrence. However, data on the clinical and immunologic features of gliptin-associated bullous pemphigoid (GABP) are controversial. OBJECTIVE: This study aimed to clinically and immunologically characterize a large cohort of GABP patients to get an insight into the pathophysiology of this emerging drug-induced variant of BP. METHODS: Seventy-four GABP patients were prospectively enrolled and characterized from 9 different Italian dermatology units between 2013 and 2020. RESULTS: Our findings demonstrated the following in the GABP patients: (1) a noninflammatory phenotype, which is characterized by low amounts of circulating and skin-infiltrating eosinophils, is frequently found; (2) immunoglobulin (Ig)G, IgE, and IgA humoral responses to BP180 and BP230 antigens are reduced in frequency and titers compared with those in patients with idiopathic BP; (3) IgG reactivity targets multiple BP180 epitopes other than noncollagenous region 16A. LIMITATIONS: A limitation of the study is that the control group did not comprise only type 2 diabetes mellitus patients with BP. CONCLUSION: GABP patients show peculiar features of anti-BP180 and -BP230 humoral responses, laying the foundation for diagnostic improvements and getting novel insights into understanding the mechanism of BP onset.

Case Report: Complete and Fast Recovery From Severe COVID-19 in a Pemphigus Patient Treated With Rituximab.

COVID-19 is characterized by a severe pulmonary disease due to severe acute respiratory syndrome (SARS)-CoV-2 infection. For clinicians involved in the management of patients with chronic autoimmune diseases the risk linked to the conditions itself and to drug-induced immunosuppression during the COVID-19 pandemic is a major topic. Pemphigus is a rare autoimmune blistering disease (AIBD) of the skin and mucous membranes caused by autoantibodies to desmosomal components, desmoglein 1 and 3. Among immunosuppressant therapies, rituximab (RTX) is considered a highly effective treatment with a favorable safety profile, but it induces a prolonged B-cell depletion that can lead to higher susceptibility to infections. For this reason, concerns about its use during the pandemic have been raised. We describe a case of a pemphigus patient in which RTX-induced B cell depletion led to the severe inflammatory phase, whereas corticosteroid treatment allowed a favorable outcome.

Scarce knowledge of systemic photoprotection among skin cancer patients: a cross-sectional survey.

BACKGROUND: The incidence of both melanoma and non-melanoma skin cancers (NMSC) is increasing worldwide and these tumours have become an important health issue. Topical and systemic photoprotection are the cornerstone to decrease the incidence of these tumours. OBJECTIVES: The aim of this study was to collect information about the knowledge of patients with a history of NMSC or melanoma regarding systemic photoprotection. MATERIALS & METHODS: This study was based on a multicentre survey. Standardized, self-administered questionnaires were collected from September 2019 to December 2019 in NMSC and melanoma units, as well as the general dermatology outpatient clinic for the control group. RESULTS: A total of 375 patients were enrolled in two Italian centres. The level of knowledge regarding systemic photoprotection was relatively scarce and was greater in: female patients; patients with normal weight and lighter hair, eye color and skin phototype; patients with a higher educational level; patients with non-cancerous skin conditions; and those who used sunscreens more frequently. CONCLUSIONS: A very low level of knowledge of systemic photoprotection was identified among skin cancer patients.

Pemphigus vulgaris in two pairs of siblings from two unrelated Italian families: Human leukocyte antigen genotypes, ST18 mutation and immunological profile.

Pemphigus vulgaris (PV) is an autoimmune intraepithelial bullous disease. Associations with the class II human leukocyte antigen (HLA) alleles and pemphigus vulgaris have been described. Furthermore, an association between the single nucleotide polymorphism of the ST18 gene and pemphigus vulgaris has been reported. We report two pairs of siblings from two unrelated Italian families affected by pemphigus vulgaris, characterizing their genetic and immunological profile. In order to assess the genetic background, HLA-DQA1, HLA-DQB1, HLA-DRB1 and a relevant ST18 polymorphism were investigated. As for the immunological profiles, anti-desmoglein antibodies were analyzed. In family A, the two pemphigus vulgaris patients had the same HLA genetic profile: HLA-DQA1 *01:04/*03:01, HLA-DQB1 *03:02/*05:03 and HLA-DRB1 *04:02/*14:01. The male patient was heterozygous for the ST18 mutation while the female patient had a wild genotype. In family B, the two pemphigus vulgaris patients were both wild type for the ST18 mutation and showed the same HLA genotype: HLA-DQA1 *03:01/*05:08, HLA-DQB1 *03:01/*03:03 and HLA-DRB1 *04:02/*11:01. Our data show a relevant relationship between the HLA profile and pemphigus vulgaris in our Italian families. In family A, all six alleles are frequently associated with pemphigus vulgaris and were expressed only in the two pemphigus patients; and in family B, two of the six alleles are frequently associated with pemphigus vulgaris. No relevant relationship was found between ST18 polymorphism and pemphigus disease.

[The integrated care pathway for non melanoma skin cancer: the Istituto Dermopatico dell'Immacolata - IRCCS experience in Rome.] / Il percorso diagnostico-terapeutico e assistenziale nella gestione del paziente affetto da tumore cutaneo non melanocitario: l'esperienza dell'IDI - IRCCS di Roma.

The incidence of non-melanoma skin cancers (NMSC) is increasing worldwide and these skin cancers have become an important health issue. An integrated care pathway (ICP) is a multidisciplinary outline of anticipated care, placed in an appropriate timeframe, to help a patient with a specific condition. The aim of this paper is to define the ICP for patients affected by NMSC referring to the Istituto Dermopatico dell'Immacolata - IRCCS of Rome and Villa Paola, Italy. This ICP is multidisciplinary and included various specialists like dermatologist, oncologist, general surgeon, plastic surgeon, anatomopathologist, molecular biologist and epidemiologist. This ICP is based on the most recent acquisitions in the literature, referring in particular to the national (EADO and SIDEMAST) and international guidelines (EDF and NCCN). We firstly valued the current practice for patients affected by NMSC referring to our Institute to define the multidisciplinary process map. This process delineated the activities and the responsibilities performed during delivery of care to the patients and the potential problem areas or opportunities for improvements. Subsequently, we defined the final ICP process. This ICP of NMSC represents an innovative strategy to provide high quality healthcare. This allows to ensure all the necessary procedures for the patient, optimizing the "continuum" of care and the use of health services, and improving the organization of the Institute regarding an important health issue.

Correlation between Depression, Quality of Life and Clinical Severity in Patients with Hidradenitis Suppurativa.

Depression is frequent in patients with hidradenitis suppurativa. However, its relationship with quality of life and clinical severity needs further investigation. In this cross-sectional study, 341 adult, consecutive patients with hidradenitis suppurativa completed the 12-item General Health Questionnaire (GHQ-12), which has been shown to be able to identify cases of major depressive disorder in dermatological patients. The frequency of depression in hidradenitis suppurativa patients was 29.0%. In patients with depression, severity (International Hidradenitis Suppurativa Severity Score System (IHS4)), quality of life (Skindex-17; Dermatology Life Quality Index (DLQI)), and health status (36-item Short Form Health Survey (SF-36)) were significantly worse compared with patients with no depression. The highest linear correlation was observed between GHQ-12 and the psychosocial scale of the Skindex-17 and the SF-36 mental scale. In contrast, correlation between GHQ-12 and clinical severity was poor. Depression is an important comorbidity in hidradenitis suppurativa, which is strongly associated with impairment in quality of life, but not linearly correlated with clinical severity.

Intralesional ultrasound-guided combined treatment with triamcinolone plus lincomycin in hidradenitis suppurativa: A pilot study.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, disease of the hair follicle. Intralesional corticosteroid treatment in HS patients has been reported, and while several data described this route of administration as an efficient delivery system, its efficacy is still debated. The aim of this study was to explore the clinical efficacy and the effect on quality of life (QoL) of an innovative intralesional treatment in HS patients. This was an interventional prospective study. The treatment consisted of two intralesional ultrasound-guided injections of triamcinolone plus lincomycin, at baseline and after 2 weeks. Lesions and QoL were evaluated at baseline and at 4 weeks following intralesional therapy. All clinical variables of 36 HS patients significantly improved after 4 weeks. Mean values of the visual analog scale (VAS) pain decreased from 4.6 to 1.5, P = .027. The Bodily Pain (BP) scale of the Short-Form Health Survey (SF-36) significantly improved from 36.2 at baseline to 53.9 at 4-week follow-up (P < .001). On a scale from 0 to 10, over 90% of the patients gave a satisfaction score of 8 or more. This combination of corticosteroids and antibiotics delivered intralesionally seems to be effective, as it improved both patient- and physician-reported outcomes.

Multiple Sclerosis Treatment and Melanoma Development.

Therapy of multiple sclerosis (MS) with disease-modifying agents such as natalizumab or fingolimod has been associated with the development of cutaneous melanoma. Here we briefly revise literature data and report of a case of a 48-year old woman who developed a melanoma and several atypical naevi after sub sequential treatment with natalizumab (1 year) and fingolimod (7 years). By immunohistochemistry we observed the presence of T cells and leukocyte infiltration as well as of vascular endothelial growth factor (VEGF)-A expression in the patient melanoma biopsy. Then, we analyzed proliferation, migration and VEGF-A expression in three melanoma cell lines and found out that both natalizumab and fingolimod inhibited tumor cell proliferation but promoted or blocked cell migration depending on the cell line examined. VEGF-A secretion was augmented in one melanoma cell line only after fingolimod treatment. In conclusion, our in vitro data do not support the hypothesis of a direct action of natalizumab or fingolimod on melanoma progression but acting on the tumor microenvironment these treatments could indirectly favor melanoma evolution.

Behavioral and demographic factors associated with occurrence of non-melanoma skin cancer in organ transplant recipients.

BACKGROUND: Non-melanoma skin cancers (NMSC) are the most common epithelial malignancies in organ transplantation recipients (OTRs). In Italy, incidence rates of post-transplantation NMSC are approximately 5% after 5 years and 10% after 10 years since organ transplantation. The objective was to describe risk factors associated with NMSC in a cohort of renal and liver transplant recipients, in a single-center longitudinal study. METHODS: Renal and liver transplant patients, who underwent transplantation between June 1985 and December 2015, were visited for the first time or followed-up in a dedicated outpatient clinic every six months until July 2016. RESULTS: We included 356 renal and 76 liver transplant patients. 108 OTRs (25.6%) presented 299 NMSC. 74 patients developed actinic keratosis (17.1%), 36 patients squamous cell carcinoma (8.5%), and 52 patients basal cell carcinoma (12.3%). Time from transplantation and kidney transplant were the main risk factors for NMSC. Higher incidences of all NMSC were observed in patients >60 years, males and smokers, while decreased incidences were detected in individuals with higher educational levels. Multiple logistic regression models confirmed that male gender (RR 3.3, P=0.001), cigarette smoking (RR 2.0, P=0.026), light eye color (RR 2.9, P=0.001) and family history of cancer (RR 1.8, P=0.042) were independently associated with NMSC. CONCLUSIONS: Dermatological follow-up is important in OTRs, due to the higher risk of tumors and mainly NMSC. Clinical and environmental factors, including cigarette smoking, are useful in characterizing OTR with higher risk of NMSC.

Paradoxical psoriasis induced by TNF-α blockade shows immunological features typical of the early phase of psoriasis development.

Immunomodulation with anti-TNF-α is highly effective in the treatment of various immune-mediated inflammatory diseases, including hidradenitis suppurativa (HS). However, this may be responsible for unexpected paradoxical psoriasiform reactions. The pathogenic mechanisms underlying the induction of these events are not clear, even though the involvement of innate immune responses driven by plasmacytoid dendritic cells (pDC) has been described. In addition, the genetic predisposition to psoriasis of patients could be determinant. In this study, we investigated the immunological and genetic profiles of three HS patients without psoriasis who developed paradoxical psoriasiform reactions following anti-TNF-α therapy with adalimumab. We found that paradoxical psoriasiform skin reactions show immunological features common to the early phases of psoriasis development, characterized by cellular players of innate immunity, such as pDC, neutrophils, mast cells, macrophages, and monocytes. In addition, IFN-ß and IFN-α2a, two type I IFNs typical of early psoriasis, were highly expressed in paradoxical skin reactions. Concomitantly, other innate immunity molecules, such as the catheledicin LL37 and lymphotoxin (LT)-α and LT-ß were overproduced. Interestingly, these innate immunity molecules were abundantly expressed by keratinocytes, in addition to the inflammatory infiltrate. In contrast to classical psoriasis, psoriasiform lesions of HS patients showed a reduced number of IFN-γ and TNF-α-releasing T lymphocytes. On the contrary, IL-22 immunoreactivity was significantly augmented together with the IL-36γ staining in leukocytes infiltrating the dermis. Finally, we found that all HS patients with paradoxical reactions carried allelic variants in genes predisposing to psoriasis. Among them, SNPs in ERAP1, NFKBIZ, and TNFAIP genes and in the HLA-C genomic region were found.

Evaluation of cutaneous, oral and intestinal microbiota in patients affected by pemphigus and bullous pemphigoid: A pilot study.

BACKGROUND: Significant alterations of the cutaneous microbiota (CM) have been recently demonstrated in bullous pemphigoid (BP). Microbiome data of both oral cavity (OM) and gut (GM) from patients affected by bullous disease are not available yet and, further consistent studies focused on the role of such microbial populations are still missing. OBJECTIVE: Objective: In this pilot study we characterized and compared GM, OM and CM of patients affected by pemphigus vulgaris (PV) and BP to investigate a distinctive microbiome composition in this two rare dermatological disorders. METHODS: High-throughput sequencing of the V1-V3 hyper-variable regions of 16S rRNA was used to compare the bacterial community composition of stool, skin and oral mucosae swabs in a cohort of PV and BP patients. A dedicated bioinformatics software coupled with in-house pipeline was implemented to analyse and compare diseases dataset. RESULTS: GM samples of both PV and BP patients were principally characterized by Firmicutes and Bacteroidetes phyla. Interestingly, the Firmicutes phylum and Staphylococcus genus were mainly represented in cutaneous samples. The diversity of phyla in oral mucosae was higher than those of gut and skin samples and, Bacteroidetes phylum was significantly underrepresented in all PV samples. CONCLUSION: Firmicutes phylum and Staphilococcus genus were the most represented in OM and CM swabs of PV and BP microbial populations. Moreover, we argue the quantitative imbalance linked to the decrease of Bacteriodetes in the oral cavity of PV patients might be associated to disease typical fetor. To shed light on this peculiar feature further studies are still required.

Role of Nicotinamide in Genomic Stability and Skin Cancer Chemoprevention.

Nicotinamide (NAM) is an amide form of vitamin B3 and the precursor of nicotinamide adenine dinucleotide (NAD+), an essential co-enzyme of redox reactions for adenosine triphosphate (ATP) production and for other metabolic processes. As NAD+ status is critical in maintaining cellular energy, vitamin B3 deficiency mainly affects tissues that need high cellular energy causing pellagra and skin sun sensitivity. In animal models, NAD+ deficiency leads to UV sensitivity of the skin, impairs DNA damage response, and increases genomic instability and cancer incidence. Furthermore, NAD+ depletion is associated with human skin aging and cancer. NAM prevents the UV-induced ATP depletion boosting cellular energy and enhances DNA repair activity in vitro and in vivo. Moreover, NAM reduces skin cancer incidence and prevents the immune-suppressive effects of UV in mice. Thus, NAM is involved in the maintenance of genomic stability and may have beneficial effects against skin aging changes and tumor development. Clinical studies showed that topical use of NAM reduces cutaneous aging. Furthermore, oral NAM administration reduces the level of UV-mediated immunosuppression and lowers the rate of non-melanoma skin cancers in high-risk patients. Therefore, NAM replenishment strategy may be a promising approach for skin cancer chemoprevention.

A comparison between two educational methods in the rehabilitation of the microstomia in systemic sclerosis: a randomized controlled trial.

OBJECTIVE: To test the effectiveness of an educational intervention including "face to face" training, compared to a standard information program, to reduce microstomia in women with systemic sclerosis. DESIGN: Single-blind, two-arm, randomized controlled study with a 12-month follow-up period. SETTING: Hospital wards of a large Italian dermatological reference center. SUBJECTS: Female inpatients with diagnosis of systemic sclerosis. INTERVENTIONS: For both groups an information brochure and an audio-visual DVD were developed specifically for the study. The control group was assigned to educational materials alone (i.e. brochures and DVD), while the experimental group, in addition to the same educational materials, received specific "face-to-face" interventions, repeated at each follow-up visit. MAIN MEASURES: Primary outcome was measurement of the opening of the mouth. Secondary outcomes was the self-reported mouth disability. RESULTS: The intention-to-treat analysis included 63 patients. Compared to the baseline measurement, we observed an increase of the mouth opening of 0.31 cm (95% confidence interval: 0.13-0.49), P = 0.003; in the control group, the increase was 0.13 cm (95% confidence interval: 0.01-0.25), P = 0.06. The difference in improvement between the two groups was not statistically significant (P = 0.10); however, it reached statistical significance in the per-protocol analysis (39 patients, P = 0.02). CONCLUSION: Face-to-face nursing rehabilitation training seems to improve microstomia to a greater extent, when compared to a standard intervention based only on written and audio-visual materials.