Cross-Sectional Study on Autosomal Recessive Congenital Ichthyoses: Association of Genotype with Disease Severity, Phenotypic, and Ultrastructural Features in 74 Italian Patients.

BACKGROUND: Autosomal recessive congenital ichthyoses (ARCIs) are a clinically heterogeneous group of keratinization disorders characterized by generalized skin scaling due to mutations in at least 12 genes. The aim of our study was to assess disease severity, phenotypic, and ultrastructural features and to evaluate their association with genetic findings in ARCI patients. METHODS: Clinical signs and symptoms, and disease severity were scored in a single-center series of patients with a genetic diagnosis of ARCI. Skin ultrastructural findings were reviewed. RESULTS: Seventy-four consecutive patients (mean age 11.0 years, range 0.1-48.8) affected with lamellar ichthyosis (50/74, 67.5%), congenital ichthyosiform erythroderma (18/74, 24.3%), harlequin ichthyosis (two/74, 2.7%), and other minor ARCI subtypes (four/74, 5.4%) were enrolled. Mutated genes were as follows: TGM1 in 18/74 (24.3%) patients, ALOX12B in 18/74 (24.3%), CYP4F22 in 12/74 (16.2%), ABCA12 in nine/74 (12.2%), ALOXE3 in seven/74 (9.5%), NIPAL4 in seven/74 (9.5%), and CERS3, PNPLA1, and SDR9C7 in 1 patient each (1.4%). Twenty-five previously undescribed mutations in the different ARCI causative genes, as well as two microduplications in TGM1, and two microdeletions in CYP4F22 and NIPAL4 were identified. The mean ichthyosis severity score in TGM1- and ABCA12-mutated patients was significantly higher than in all other mutated genes, while the lowest score was observed in CYP4F22-mutated patients. Alopecia, ectropion, and eclabium were significantly associated with TGM1 and ABCA12 mutations, and large, thick, and brownish scales with TGM1 mutations. Among specific phenotypic features, psoriasis-like lesions as well as a trunk reticulate scale pattern and striated keratoderma were present in NIPAL4-mutated patients. Ultrastructural data available for 56 patients showed a 100% specificity of cholesterol clefts for TGM1-mutated cases and revealed abnormal lamellar bodies in SDR9C7 and CERS3 patients. CONCLUSION: Our study expands the phenotypic and genetic characterization of ARCI by the description of statistically significant associations between disease severity, specific clinical signs, and different mutated genes. Finally, we highlighted the presence of psoriasis-like lesions in NIPAL4-ARCI patients as a novel phenotypic feature with diagnostic and possible therapeutic implications.

Quality of life measurement in vitiligo. Position statement of the European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes with external experts.

Members of the European Academy of Dermatology and Venereology (EADV) Task Force on Quality of Life (QoL) and Patient Oriented Outcomes reviewed the instruments available for health-related (HR) QoL assessment in vitiligo and together with external vitiligo experts (including representatives of the EADV Vitiligo Task Force) have made practical recommendations concerning the assessment of QoL in vitiligo patients. The Dermatology Life Quality Index (DLQI) was the most frequently used HRQoL instrument, making comparison of results between different countries possible. Several vitiligo-specific instruments were identified. The vitiligo Impact Scale (VIS) is an extensively validated vitiligo-specific HRQoL instrument with proposed minimal important change and clinical interpretation for VIS-22 scores. VIS-22 was developed for use in India, where there are some specific cultural beliefs concerning vitiligo. The EADV Task Force on QoL and Patient Oriented Outcomes recommends use of the DLQI and the Children's Dermatology Life Quality Index (CDLQI) as dermatology-specific instruments in vitiligo. There is a strong need for a valid (including cross-cultural validation) vitiligo-specific instrument that can be either a new instrument or the improvement of existing instruments. This validation must include the proof of responsiveness.

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.

Pediatric Hidradenitis Suppurativa: A Cross-Sectional Study on Clinical Features and Treatment Approaches.

BACKGROUND: Hidradenitis suppurativa is uncommon in patients of pediatric age, and differentiation with adult-onset disease is controversial. Treatment of pediatric hidradenitis suppurativa is scarcely standardized, and specific guidelines are lacking. OBJECTIVE: We report the clinical features, relevant risk-factors, comorbidity profile, and treatment patterns of a hospital-based cohort of pediatric hidradenitis suppurativa. METHODS: In a cross-sectional study data on patients' demographics, disease-specific characteristics, early/pre-pubertal onset of disease, comorbidities, and treatment management were retrieved. Reference population data and clinical data from the national hidradenitis suppurativa disease registry were used for comparison. RESULTS: From a database of 870 patients with hidradenitis, 71 (15 males and 56 females) patients aged <18 years (mean age: 15.3 years; range 8-17 years), with mild (Hurley I, 45.1%) and moderate-severe disease (Hurley II-III, 54.9%), were retrieved. Smoking (23.9%) and overweight/obese frequencies (59.2%) were higher than reference population standards. Patient's older age at baseline (OR 1.43, 95% CI: 1.01 to 2.02) and higher BMI (OR 1.26, 95% CI: 1.07-1.48) were the only factors associated with moderate-severe disease. Family history and early/pre-pubertal onset of disease were not associated with severity or extent of disease. Sebaceous-follicular comorbid conditions were associated with cigarette smoking (P = .002). Among 81 treatment courses, clindamycin-based and zinc-sulphate-based combination regimens were most frequently used (59.3%). Female preponderance, family history of disease and extensive involvement were significantly different from the general hidradenitis suppurativa population. CONCLUSIONS: Pediatric hidradenitis suppurativa presents a clinical spectrum comparable to adult-onset disease. Increased preventive measures should target obesity and smoking in this population.

Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets.

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD have increased in recent years. The onset of AD mostly occurs in childhood, although in some cases AD may persist in adult life or even manifest in middle age (adult-onset AD). AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, as well as itch contribute to disease development, progression, and chronicization. One of the most important features of AD is skin dehydration, which is mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, and antigen penetration. In accordance with the "outside-inside" theory of AD pathogenesis, in a context of an altered epidermal barrier, antigens encounter epidermal antigen presentation cells (APCs), such as epidermal Langerhans cells and inflammatory epidermal dendritic cells, leading to their maturation and Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), which induce IgE-mediated sensitizations as part of pathogenic mechanisms leading to AD. In this review, we discuss the role of cytokines in the pathogenesis of AD, considering patients with various clinical AD phenotypes. Moreover, we describe the cytokine patterns in patients with AD at different phases of the disease evolution, as well as in relation to different phenotypes/endotypes, including age, race, and intrinsic/extrinsic subtypes. We also discuss the outcomes of current biologics for AD, which corroborate the presence of multiple cytokine axes involved in the background of AD. A deep insight into the correlation between cytokine patterns and the related clinical forms of AD is a crucial step towards increasingly personalized, and therefore more efficient therapy.

Skin signs in eating disorders: a literature review.

PURPOSE: To summarize and describe the available knowledge on dermatological manifestation of eating disorders: anorexia nervosa, bulimia nervosa, binge eating disorder and eating disorder not otherwise specified, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders IV-TR and 5th edition. METHODS: We searched in PubMed, Scopus and Web of Science databases from January 1, 1980 through May 1, 2020 for papers in English language on the skin manifestation of eating disorders. Results were screened using the PRISMA tool. RESULTS: The study yielded 207 results. According with PRISMA guidelines, 26 papers were included in the review. More than 73% of screened papers (19/26) were case reports. Cross-sectional studies represented the 19.2% of screened papers (5/26). Each eligible study has been screened and analyzed. CONCLUSION: Huge heterogeneity of skin signs of eating disorders were identified. The number of controlled studies available is very limited, and most papers of interest are case reports or narrative review articles. Larger, more methodologically rigorous studies to evaluate the presence of dermatological issue in eating disorder patients are needed. LEVEL OF EVIDENCE: Level IV. Evidence obtained from multiple time series analysis such as case studies.

A qualitative and quantitative comparison of IgE antibody profiles with two multiplex platforms for component-resolved diagnostics in allergic patients.

BACKGROUND: Clinically complex phenotypes require more and more sophisticated and comprehensive diagnostic approaches, able to discriminate genuine sensitizations from cross-reactivity. Interpretative complexity of multiplex diagnostic arrays has somewhat limited their diffusion. This study compares two currently available methods, namely ISAC® test and ALEX2® test. METHODS: In total, 140 allergic individuals, with a history of atopic dermatitis, adverse food reactions, allergic rhinitis and/or bronchial asthma were studied by Allergy Explorer-ALEX2® macroarray and ImmunoCAP ISAC112® . Lin's concordance correlation coefficient, intraclass correlation coefficient and Bland-Altman plots were used to verify the agreement between continuous values. Cohen's kappa coefficient (k) was assessed for the molecules available in both tests. The degree of relationship was analysed using Spearman's correlation (quantitative variables) and Pearson's χ2 or Fisher's exact test (categorical variables). RESULTS: A substantial agreement (κ = 0.795) was observed between the two methods with 94,3% concordant results when results were dichotomized as negative or positive, but if double-negative results were discarded, the agreement dropped to 71%. Conversely, little or no concordance was observed comparing raw data. Considering the 102 molecules shared by both systems, 28/102 (27%) showed an almost perfect agreement (k > 0.81), and concordance was good (k > 0.61) in a further 32 (31%) cases. A perfect to substantial agreement was observed by comparing species-specific aeroallergens. Heterogeneous results emerged comparing panallergens (co-recognition ranging from 30% for tropomyosin/serum albumins to 70% for PR-10/profilin). The correlation among LTP, profilin and PR-10 assayed with ISAC® was better than ALEX2® , but the latter identified more positive cases due to the wider number of molecules available. The CCD blocker provided by ALEX® test abolishes the carbohydrate determinants signal in 60% of the 33 cases reactive to MUXF3 on the ISAC® test. CONCLUSION: Despite the excellent concordance of the species-specific markers, the analysis of the panallergens provided in both methods suggests a better performance of the ISAC® test on those components, while the ALEX2® test, which includes a larger number of allergens, allowing a broader molecular detection.

Alexithymia, Psychological Distress, and Social Impairment in Patients with Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a rare, chronic, inflammatory skin disease characterized by deep-seated nodules, abscesses, and draining fistulas. HS has a substantial adverse impact on patients' lives. Only a few studies investigated the relationship between health-related quality of life, psychological distress, and emotional dysregulation in patients with HS. Alexithymia, namely the difficulty in describing or recognizing emotions, has been associated with various psychological disorders, such as anxiety, depression, and psychological distress. OBJECTIVE: The aim of this study was to examine the prevalence of alexithymia in patients with HS and its association with demographic and clinical variables, quality of life indices, and psychological distress. METHODS: Ninety outpatients with HS completed the 20-item Toronto Alexithymia Scale, the 12-item General Health Questionnaire (GHQ-12), the Dermatology Life Quality Index, the Skindex-17, and the 36-Item Short-Form Health Survey. Information on sociodemographic and clinical variables was retrieved from clinical records. RESULTS: Alexithymia or borderline alexithymia was observed in 44.4% of patients with HS, with a higher prevalence of the alexithymic trait in women than in men (51.7 vs. 31.2%). We did not find any association between alexithymia and clinical variables. Of the entire sample analyzed, 46.1% reported high psychological distress; among them, 78% reported alexithymia or borderline alexithymia compared to 16.7% among GHQ noncases. Furthermore, HS patients with alexithymia or borderline alexithymia showed significantly higher scores on the Skindex-17 psychosocial scale and the Dermatology Life Quality Index, and a lower score on the mental component of the 36-item Short-Form Health Survey, than nonalexithymic patients. CONCLUSIONS: Dermatologists should consider alexithymia in the diagnosis and treatment of HS patients, given its important role in psychological and psychosocial distress.

Sex Differences in Health-related Quality of Life in Patients with Keratinocyte Carcinomas.

The difference between men and women in the impact of keratinocyte carcinomas on quality of life has not been widely studied. This study of 364 patients with keratinocyte carcinoma, measured quality of life using the self-administered 12-item Short Form Health Survey (SF-12) and Skindex-29. Results for both the physical and the mental components of SF-12 were worse in women than in men. For the mental component, women had significantly lower scores compared with men in almost all subgroups, based on demographic and clinical variables. The Skindex-29 emotions mean score was worse in women than in men. Women reported significantly higher level of worry that the disease could get worse and of developing scars, and more depression. On the other hand, men reported lower quality of sleep. The impact of keratinocyte carcinomas on quality of life is generally higher in women than in men. Such data may be important for tailored management of the disease in different categories of patients.

The Burden of Autosomal Recessive Congenital Ichthyoses on Patients and their Families: An Italian Multicentre Study.

Autosomal recessive congenital ichthyoses (ARCI) are characterized by generalized skin scaling, hyperkeratosis, erythroderma, and disabling features affecting the skin (palmoplantar keratoderma, fissures, pain, itch), eyes, ears, and joints. Disease severity and chronicity, patient disfigurement, and time and costs required for care impose a major burden on quality of life. This multicentre cross-sectional study investigated the impact of ARCI on quality of life of patients and families, using the Dermatology Life Quality Index (DLQI), the Children DLQI (CDLQI) and Family Burden of Ichthyosis (FBI) questionnaires. Disease severity was assessed by a dermatologist. A total of 94 patients were recruited, of whom 52 (55.3%) children. Mean age was 20.1 (median 13.5) years. The mean CDLQI/DLQI score was 7.8, and 21 patients scored >10, indicating a major impairment in quality of life: symptoms, feelings and treatment problems were the most affected domains of quality of life. FBI showed a major repercussion on psychological factors and work. The results of this study highlight the impact of ARCI on specific aspects of patient and family life, underlining the need for psychological support.

ß-1,3-glucanase rOle e 9 and MnSOD rAsp f 6 IgE reactivity are the signature of atopic dermatitis in the Mediterranean area.

BACKGROUND: Atopic dermatitis (AD) represents a chronic skin disorder seriously affecting patients' QoL and is often associated with immunological imbalance, disorders of the skin barrier function and environmental factors. OBJECTIVE: We extensively studied the proteomic IgE sensitization profile in a large AD Mediterranean cohort. METHODS: A total of 588 individuals with moderate-severe (70.6%) or mild and/or history of (29.4%) AD were evaluated in comparison to 1285 unselected atopic controls (AC) with a history of adverse reactions to foods, allergic rhinitis and/or bronchial asthma by means of ImmunoCAP ISAC112 ® and Allergy Explorer-ALEX® microarray analysis. RESULTS: The olive tree pollen ß-1,3-glucanase rOle e 9 and the manganese superoxide dismutase from Aspergillus rAsp f 6 were the molecules most significantly associated with AD occurrence and allowed to discriminate among the moderate and severe forms of disease. An IgE hyper-reactivity to cypress, grasses, olive tree, house dust mites (including rDer p 11), and to all cross-reactive components except profilin and polcalcin was observed. About 60% of adults with severe AD were sensitized to nsLTPs. Cross-reactive carbohydrate determinants (CCDs) IgE was found in about one-third of AD participants. Hen eggs nGal d 1 IgE sensitization was more prevalent in the paediatric population, whilst rAsp f 6 and rOle e 9 reactivity was found particularly in older patients. Despite the status of widespread IgE sensitization to both environmental and food allergens, a reduced frequency of patient-reported severe reactions to food or of asthma was observed in AD patients compared to AC, particularly in case of concomitant Ole e 9 reactivity. CONCLUSION AND CLINICAL RELEVANCE: Testing IgE reactivity to a large panel of molecular components unveils important associations between IgE reactivity profiles and AD clinical presentation, highlights the allergens useful for a precise AD signature and allows the detection of interesting sensitisations patterns.

Disease-Specific Molecular Profiles Highlighted by Radar Graphic Display.

BACKGROUND: Management of hundreds of analytes obtained from the molecular multiplex techniques currently available may represent a challenge for clinicians in daily clinical practice. OBJECTIVES: The aim of the study was to describe a comprehensive and simple approach to assess such complex molecular results, to display relevant disease-specific signatures at a glance, and to facilitate their interpretation. METHOD: A total of 6,332 consecutive allergic patients, categorized based on clinical symptoms reported at the time of the first visit before IgE testing, were evaluated through ImmunoCAP ISAC112®. RESULTS AND CONCLUSIONS: The occurrence of bronchial asthma is associated with polcalcin, serum albumin, or lipocalin reactivity. Higher risk of severe reaction to food is linked to tropomyosin or nonspecific lipid transfer protein reactivity (in the absence of plant pathogenesis-related proteins [PR-10] or profilin sensitization). We used radar graphic display to highlight, at a glance, the molecular reactivity profiles associated with relevant disease-specific patterns.

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.

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.

Exploring the EQ-5D Dimension of Pain/Discomfort in Dermatology Outpatients from a Multicentre Study in 13 European Countries.

Pain and discomfort are important symptoms in dermatology. The aim of this cross-sectional, multicentre study was to describe the prevalence of pain/discomfort and its associations in patients with several dermatological conditions across 13 European countries. The outcome was the prevalence of pain/discomfort according to a question of the EQ-5D questionnaire. Data collected from November 2011 to February 2013 were complete for 3,509 consecutive outpatients. Moderate or extreme pain/discomfort was reported by 55.5% of patients and 31.5% of controls with no skin conditions. The highest proportions were reported by patients with hidradenitis suppurativa (92.9%), leg ulcer (81.4%), prurigo (80%) and lichen planus (75.6%). Pain/discomfort was associated with older age, low educational level, clinical severity, flare on scalp or hands, itch, depression, anxiety, low quality of life, and thoughts of suicide. It is important to enquire specifically about pain/discomfort during clinical consultations and to address it when planning a patient's care.

Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies.

BACKGROUND: Lacking protective antibodies, patients with primary antibody deficiencies (PADs) experience frequent respiratory tract infections, leading to chronic pulmonary damage. Macrolide prophylaxis has proved effective in patients with chronic respiratory diseases. OBJECTIVE: We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in patients with PADs. METHODS: We designed a 3-year, double-blind, placebo-controlled, randomized clinical trial to test whether oral azithromycin (250 mg administered once daily 3 times a week for 2 years) would reduce respiratory exacerbations in patients with PADs and chronic infection-related pulmonary diseases. The primary end point was the number of annual respiratory exacerbations. Secondary end points included time to first exacerbation, additional antibiotic courses, number of hospitalizations, and safety. RESULTS: Eighty-nine patients received azithromycin (n = 44) or placebo (n = 45). The number of exacerbations was 3.6 (95% CI, 2.5-4.7) per patient-year in the azithromycin arm and 5.2 (95% CI, 4.1-6.4) per patient-year in the placebo arm (P = .02). In the azithromycin group the hazard risk for having an acute exacerbation was 0.5 (95% CI, 0.3-0.9; P = .03), and the hazard risk for hospitalization was 0.5 (95% CI, 0.2-1.1; P = .04). The rate of additional antibiotic treatment per patient-year was 2.3 (95% CI, 2.1-3.4) in the intervention group and 3.6 (95% CI, 2.9-4.3) in the placebo group (P = .004). Haemophilus influenzae and Streptococcus pneumoniae were the prevalent isolates, and they were not susceptible to macrolides in 25% of patients of both arms. Azithromycin's safety profile was comparable with that of placebo. CONCLUSION: The study reached the main outcome centered on the reduction of exacerbation episodes per patient-year, with a consequent reduction in additional courses of antibiotics and risk of hospitalization.

The Broad-Spectrum Impact of Hidradenitis Suppurativa on Quality of Life: A Comparison with Psoriasis.

BACKGROUND/AIM: Hidradenitis suppurativa (HS) is a chronic skin disease with a heavy impact on patients' quality of life (QoL). The aim of this study was to evaluate in detail the QoL impact of HS comparing it with other skin conditions, and in particular with psoriasis. METHODS: Patients with a diagnosis of HS were recruited. QoL was measured using the Skindex-17 questionnaire. RESULTS: Data were available for 69 HS patients. HS had the worst QoL among several skin conditions. Compared to psoriasis the mean symptom score was 69.4 versus 53.7, and the mean psychosocial score was 56.1 versus 32.7. Overall, the scores of patients with HS were higher than those of psoriasis patients on 16 of the 17 items of the Skindex-17. CONCLUSIONS: When compared to many different skin conditions, and in particular to psoriasis, HS was the most impairing condition, even at low levels of clinical severity.

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.

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.