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Background: Nearly 10% of all cases of cutaneous melanoma (CM) occur in patients with a personal or family history of the disease., Objectives: To obtain information about genetic predisposition to CM in Ticino, the southern region of Switzerland, a zone with moderate-to-high CM incidence., Methods: We identified germline mutations in highly CM-associated genes (CDKN2A and CDK4) and low/medium-penetrance variants (MC1R and MITF) in patients with multiple primary CMs or individuals with one or more CM and a positive family history for CM or pancreatic cancer among first- or second-degree relatives. Healthy blood donors (n = 146) were included as a control group., Results: From July 2010 to July 2012, 57 patients (41 pedigrees) were included. Twenty-six were melanoma-prone families (with at least two cases) and 15 had multiple CMs. Pancreatic cancer was found in six families. The CDKN2A mutation p.V126D was identified in seven patients (four families) with a founder effect, whereas CDKN2A A148T was detected in seven cases (five families) and seven healthy donors (odds ratio 2·76, 95% confidence interval 0·83-9·20). At least one MC1R melanoma-associated polymorphism was detected in 32 patients (78%) and 97 healthy donors (66%), with more than one polymorphism in 12 patients (29%) and 25 healthy donors (17%). The MITF variant p.E318K was identified in four patients from three additional pedigrees (7%) and one healthy control (0·7%)., Conclusions: Inclusion criteria for the Ticino population for genetic assessment should follow the rule of two (two affected individuals in a family or a patient with multiple CMs), as we detected a CDKN2A mutation in almost 10% of our pedigrees (four of 41), MITF p.E318K in 7% (three of 41) and a higher number of MC1R variants than in the control population., (© 2016 British Association of Dermatologists.)

Background: Prospective systematic analyses of the clinical presentation of bullous pemphigoid (BP) are lacking. Little is known about the time required for its diagnosis. Knowledge of the disease spectrum is important for diagnosis, management and inclusion of patients in therapeutic trials., Objectives: The primary aims of the study were: (i) to characterize the clinical features of BP at time of diagnosis; and (ii) to assess the diagnostic delay in BP and its impact on prognosis, Methods: All new cases of BP diagnosed in Switzerland between 1 January 2001 and 31 December 2002 were prospectively registered by means of a standardized data collection form., Results: One hundred-seventeen patients with BP were included in the study. 97cases (82.9%) had typical features with vesicles, blisters and/or erosions at time of diagnosis, while in the remaining cases (17.1%) only excoriations, eczematous and/or urticarial infiltrated lesions were observed. Head/neck as well as palmo-plantar involvement were found in up to 20% of patients, while mucosal lesions were present in 14.5% of the cases. Diagnosis was made after a mean of 6.1 months after the first symptoms. In patients, in whom the diagnostic delay was 4 months or more (defined as late diagnosis group), lesions were more often limited to one body area. The type of lesions did not affect the diagnostic delay. Diagnosis was made more rapidly in patients with limb involvement compared to those without. The calculated mortality rate in the early and late diagnosis group was 18.9% and 17.9%, respectively, without significant difference., Conclusion: BP often presents with bullous lesions at time of diagnosis after a mean diagnostic delay of 6 months. Nevertheless, up to 20% of patients lack obvious blistering and postbullous erosions, mimicking thus a variety of inflammatory dermatoses. Localized disease is associated with an increased diagnostic delay, which has however no impact on prognosis., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Background: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and has been associated with a significant morbidity and an increased mortality rate., Objectives: Our aims were: (i) to evaluate the mortality rate of BP in Swiss patients during the first 3 years after the diagnosis of BP, as the primary endpoint; and (ii) to compare this mortality rate with that of the general Swiss population and determine prognostics factors, as secondary endpoints., Methods: All new cases of BP diagnosed in Switzerland between 1 January 2001 and 31 December 2002 were collected prospectively by means of a standardized data collection form. After collection of the data, the treating physicians were asked to specify the course and evolution of the disease. In total, 115 patients were included in our study., Results: The 1-, 2- and 3-year probability of death were 20·9%, 28·0% and 38·8%, respectively. The mortality rate of patients with BP was three times higher than that of age- and sex-matched members of the general Swiss population. Besides age, the presence of neurological diseases at diagnosis was associated with increased mortality in multivariate analysis., Conclusion: This is the first prospective study analysing the mortality rate of BP in an entire country. The calculated mortalities are in the lower range of those reported in previous European studies. However, in line with the latter, our findings confirm a high case-fatality rate for BP, with an increased 1-year mortality rate compared with the expected mortality rate for age- and sex-adjusted general population., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.)

Background: Antitumour necrosis factor (anti-TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon-gamma release assays (IGRA) have been shown to be more sensitive and specific than TST., Objective: To compare the TST and the T-SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti-TNF treatment., Methods: A retrospective study was carried out over a 4-year period on patients with psoriasis requiring anti-TNF treatment. All were subjected to the TST, T-SPOT.TB and chest X-ray. Risk factors for LTBI and history of bacillus Calmette-Guérin (BCG) vaccination were recorded. The association of T-SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti-TNF therapy when indicated., Results: Fifty patients were included; 90% had prior BCG vaccination. A positive T-SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7.43; 95% confidence interval 1.38-39.9), which was not the case for the TST. Agreement between the T-SPOT.TB and TST was poor, kappa = 0.33 (SD 0.13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T-SPOT.TB. All patients received an anti-TNF agent for a median of 56 weeks (range 20-188); among patients with a positive TST/negative T-SPOT.TB, no tuberculosis was detected with a median follow-up of 64 weeks (44-188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin., Conclusion: This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti-TNF therapy, even if LTBI is correctly diagnosed and treated.

Background: Bullous pemphigoid (BP), pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune bullous diseases characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Although rare, these diseases run a chronic course and are associated with significant morbidity and mortality. There are few prospective data on gender- and age-specific incidence of these disorders., Objectives: Our aims were: (i) to evaluate the incidence of BP and PV/PF in Swiss patients, as the primary endpoint; and (ii) to assess the profile of the patients, particularly for comorbidities and medications, as the secondary endpoint., Methods: The protocol of the study was distributed to all dermatology clinics, immunopathology laboratories and practising dermatologists in Switzerland. All newly diagnosed cases of BP and pemphigus occurring between 1 January 2001 and 31 December 2002 were collected. In total, 168 patients (73 men and 95 women) with these autoimmune bullous diseases, with a diagnosis based on clinical, histological and immunopathological criteria, were finally included., Results: BP showed a mean incidence of 12.1 new cases per million people per year. Its incidence increased significantly after the age of 70 years, with a maximal value after the age of 90 years. The female/male ratio was 1.3. The age-standardized incidence of BP using the European population as reference was, however, lower, with 6.8 new cases per million people per year, reflecting the ageing of the Swiss population. In contrast, both PV and PF were less frequent. Their combined mean incidence was 0.6 new cases per million people per year. CONCLUSIONS; This is the first comprehensive prospective study analysing the incidence of autoimmune bullous diseases in an entire country. Our patient cohort is large enough to establish BP as the most frequent autoimmune bullous disease. Its incidence rate appears higher compared with other previous studies, most likely because of the demographic characteristics of the Swiss population. Nevertheless, based on its potentially misleading presentations, it is possible that the real incidence rate of BP is still underestimated. Based on its significant incidence in the elderly population, BP should deserve more public health concern.

Psoriasis is a chronic inflammatory skin disorder that can cause substantial disability. The recognition of psoriasis as an immunologically mediated disease led to the development of agents that specifically target key steps in the pathological process. In this review, we focus on the mechanism of action, the efficacy and the safety data of the new biological treatments: alefacept, efalizumab, etanercept, infliximab and adalimumab.

Hallopeau's acrodermatitis is characterized by the presence of aseptic pustules on an inflammatory basis of the periungual or subungual region. The cyclic recurrences induce important physical and psychological morbidity. By analogy to the efficacy of TNF-alpha antagonists in the treatment of generalized pustular psoriasis, our patient illustrates the long-term efficacy and safety of etanercept (Enbrel) in the treatment of Hallopeau's acrodermatitis refractory to infliximab (Remicade). This treatment alternative should in consequence be considered in patients with a recalcitrant form of a potentially debilitating disease., ((c) 2008 S. Karger AG, Basel.)

The growing emergency of infections with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) secreting the Panton-Valentine toxin (PVL) has become a serious health problem with epidemic proportions. These bacteria are responsible of severe skin and soft tissue infections, with frequently necrotic lesions, and severe necrotizing pneumonias. CA-MRSA, the spreading of which is particularly observed in certain risk populations (such as schoolchildren, prison inmates, exposure to healthcare establishment) is now also implicated in nosocomial infections. Besides adequate antibiotic treatment, surgical drainage and incision of the skin lesions are important. It is therefore essential to respect elementary hygiene rules in order to prevent the acquisition and transmission of CA-MRSA.

There has been a considerable progress in the understanding of the physiopathology of BP during the past 2 decades. The insights into the humoral and cellular immune response against BP180 and BP230 have increased significantly. Nevertheless, the factors underlying the initiation of the disease leading to a disruption of self-tolerance remain unclear. Clinically, the disease shows protean presentations, and diagnostic delay is common. A practical, relevant, and unresolved question is how to identify patients suffering from BP at an early stage of the disease, when direct immunofluorescence microscopy findings still may be negative. The characterization of markers allowing the differentiation of BP from other pruritic eruptions occurring in the elderly population would be extremely helpful in daily practice. Finally, despite the knowledge that potent topical steroids are efficient in controlling the disease, management of BP sometimes remains difficult and requires systemic therapies. It is hoped that a better knowledge of the regulation of the autoimmune response in BP also will facilitate the design of novel immunomodulatory therapeutic approaches devoid of the severe side effects of current immunosuppressive treatments.

Background: Muir-Torre syndrome (MTS) is an autosomal dominant genodermatosis characterized by the association of at least 1 cutaneous sebaceous tumor and 1 internal malignancy, often arising in the gastrointestinal tract. It is secondary to germline mutations in DNA mismatch repair genes, mainly MLH-1 and MSH-2., Observations: We report the case of a 54-year-old man with a 2-year history of skin-colored papules clinically reminiscent of large sebaceous hyperplasias on the nose and back, but histologically diagnosed as sebaceous adenomas and epitheliomas. His family history was positive for colon cancer in the mother and 2 brothers. A colonoscopy done during the hospitalization revealed 2 sessile polyps in the left colon, both showing a low-grade dysplasia on the biopsy specimen. Immunohistochemical staining performed on the cutaneous and colic biopsy specimens revealed a lack of expression of MSH-2 and MSH-6. Genetic testing revealed microsatellite instability in the colon and cutaneous tumors., Conclusion: The immunohistochemical testing for MSH-2, MSH-6, and MLH-1 is useful for rapid identification of an underlying mismatch repair defect and early diagnosis of MTS.

Fulminant herpetic sycosis is a rare but well-known manifestation of herpes simplex virus (HSV) infection occurring in the context of viral recurrence in immunodepressed patients. We present here the case of a 32-year-old male patient, without notable medical history, who developed papulovesicular lesions of the beard accompanied by fever, painful cervical lymphadenopathy and odynophagia, with a clinical evolution that was initially unfavourable under antibiotic treatment. The diagnosis of herpetic sycosis was established by means of direct immunofluorescence and culture which confirmed positivity for HSV-1 and serologies compatible with a primary viral infection. No sign for a latent immune deficit was found at the time of investigations. The clinical evolution was rapidly favourable with administration of intravenous aciclovir for 1 week. To our knowledge, herpetic sycosis as a presentation of primary viral infection has not been reported previously. The possibility of a herpetic sycosis of the beard must be considered in the case of non-response to antibiotic or antifungal treatment., (Copyright 2004 S. Karger AG, Basel)