[Bullous skin diseases].

This review finds that topical corticosteroids and systemic corticosteroids are the mainstays of initial treatment for bullous pemphigoid and pemphigus diseases. Additional immunomodulatory therapies such as methotrexate, azathioprine and mycophenolatmofetil should be added early during treatment to minimize the adverse effects of chronic corticosteroid therapy and to augment improvement in the disease. Rituximab is a first-line immunomodulatory treatment for moderate to severe pemphigus disease.

[Diagnostic approach of bullous skin disease].

Bullous skin diseases are characterised by a large group of diseases, where the essential clinical feature is fluid-filled skin lesions. Physicians in many different specialities can meet patients with bullous skin diseases, which include a wide range of skin diseases from mild cases to very severe and life-threating diseases. The aim of this review is to provide systematically approach of how make the accurate diagnosis, using important and basic elements of history taking, clinical and paraclinical examination.

Vaccination against PD-L1 with IO103 a Novel Immune Modulatory Vaccine in Basal Cell Carcinoma: A Phase IIa Study.

Antitumor activity of immune checkpoint blocking antibodies against programmed death 1 (PD-1) in basal cell carcinoma (BCC) has been described. IO103 is a peptide vaccine against the major PD-1 ligand PD-L1. A phase IIa study of vaccination with IO103 and Montanide adjuvant was conducted in patients with resectable BCC (NCT03714529). Vaccinations were given six times every 2 weeks (q2w), followed by three vaccines q4w in responders. Primary endpoints were clinical responses of target tumors, change in target tumor size and immune responses to the vaccine. Secondary endpoint was safety. One tumor per patient was designated target tumor and biopsied twice during the course of vaccination. Synchronous non-target BCCs were not biopsied during vaccinations. Ten patients were vaccinated (six patients received six vaccinations and four patients received nine vaccinations). A partial response (PR) was seen in two target tumors. Two complete responses (CR) and one PR were observed in eight non-target tumors in four patients. No tumors progressed. Related adverse events were grade 1 and reversible. Immune responses against IO103 were induced in blood samples from nine of ten and skin-infiltrating lymphocytes from five of the nine patients. The regressions seen in non-target tumors suggest that IO103 may be effective against a subtype of BCC.

Cutaneous adverse reactions to anti-PD-1 treatment-A systematic review.

The use of the humanized monoclonal anti-programmed cell death 1 antibodies pembrolizumab and nivolumab as potent anticancer therapies is rapidly increasing. However, since their approval, numerous cases of cutaneous reactions have been reported. Cutaneous adverse reactions to these agents have yet to be fully characterized and range from nonspecific eruptions to recognizable skin manifestations, which may be localized and vary from mild to life threatening. This systematic review article provides an overview of the various adverse cutaneous reactions to pembrolizumab and nivolumab therapy and offers suggestions for their management.

Photodynamic therapy of necrobiosis lipoidica using methyl aminolevulinate: A retrospective follow-up study.

INTRODUCTION: Necrobiosis lipoidica (NL) is a rare, treatment-resistant, granulomatous skin disease of unknown origin, frequently seen in patients with diabetes. METHODS: In this retrospective study we evaluated the long-term efficacy of methyl aminolaevulinate-based photodynamic therapy (MAL-PDT), including 80 treatments (70 conventional and 10 daylight PDT), on 65 unselected NL patients treated routinely in our clinic. Superficial curettage, avoiding skin oozing or bleeding, was performed prior to MAL application. RESULTS: Conventional MAL-PDT had a 100% cure rate (CR) in 64% (45/70) of the treatment series. With daylight PDT we observed a 100% CR in 80% of the treatment series (8/10), an insignificant difference compared to conventional PDT (p = 0.48). The overall cure rate was 66% (53/80). We observed no correlation between CR and gender, age at first PDT treatment, duration of NL prior to PDT treatment, number of NL elements, or diabetes. New lesions faded, whereas old lesions were clearly visible after inactivation of NL. DISCUSSION: MAL-PDT proved to have full efficacy in 66% of the treatments, with conventional PDT and daylight PDT producing an almost identical result. We observed no correlation between CR and time of follow-up. However, we recommend at least six months to pass before final evaluation of treatment effect.

Epilepsy, anti-epileptic medication use and risk of cancer.

Whether the powerful medications used to treat epilepsy increase the risk of cancer has been debated for decades, but until now no study could disentangle the contributions of anti-epileptic medications and epilepsy itself to cancer risk. Using a cohort comprising all Danish residents ≥ 16 years old at some point during the period 1996-2010 (>56 million person-years of follow-up) and information from national health registers, we examined associations between anti-epileptic medication use and cancer rates in persons with and without epilepsy, and between epilepsy and cancer rates in treated and untreated individuals. Associations were expressed as incidence rate ratios (IRRs) estimated using Poisson regression. Among persons without epilepsy, use of anti-epileptic medication increased the rates of most cancers little or not at all, although we observed moderately increased rates of liver, mouth and throat, and respiratory tract cancers (IRRs 1.40-1.59). In contrast, we observed strong associations between epilepsy and the rates of central nervous system and mouth and throat cancers (IRRs 2.00-3.91), and a modest association between epilepsy and the rate of respiratory tract cancers (IRRs 1.30-1.35), independent of anti-epileptic medication use. Our finding of only modest increases in cancer risk directly attributable to anti-epileptic medication use suggests that these medications may not be as strongly carcinogenic as has been feared, and that it is not primarily anti-epileptic medications that are responsible for the increased cancer risk among epileptics but another aspect of epilepsy diagnosis or treatment or an etiologic factor common to the two conditions.

The hands in health and disease of individuals with filaggrin loss-of-function mutations: clinical reflections on the hand eczema phenotype.

During the last 2 years, we have performed filaggrin genotyping in patients with eczema seen in our hand eczema clinic. We present pictures of healthy and diseased hands from individuals with filaggrin gene (FLG) mutations to describe a clinical entity of hand eczema. We show that xerosis and hyperkeratosis on the dorsal aspects of the hands and fingers, as well as palmar hyperlinearity, should alert the clinician about a possible inherited barrier abnormality of the skin resulting from FLG mutations. The series of photographs range from the hands of an individual with FLG mutations but no history of eczema, to the hands of individuals with typical and atypical filaggrin hand eczema, and finally to the hands of an individual with FLG mutations and hand eczema caused by exposure to irritants and allergens. We briefly discuss this possible subtype of hand eczema, present pathomechanisms, and indicate the signs that should alert the clinicians about a possible inherited skin barrier defect.

Photosensitizing medication use and risk of skin cancer.

BACKGROUND: Many commonly used medications, including both medications for long-term (daily) use and short-term use (treatment courses of finite duration), have photosensitizing properties. Whether use of these medications affects skin cancer risk, however, is unclear. METHODS: Using a cohort of all Danish residents ≥15 years old in 1995 to 2006 (n = 4,761,749) and information from Danish national registers, we examined associations between use of photosensitizing medications and risk of basal cell carcinoma, cutaneous malignant melanoma, Merkel cell carcinoma, and squamous cell carcinoma. RESULTS: Users of only 2 of 19 medications for long-term use (methyldopa and furosemide) had both a ≥20% increased risk of skin cancer (compared with nonusers) and an increase in risk with increasing duration of use; these effects were limited to basal cell carcinoma and squamous cell carcinoma, respectively. In contrast, 8 of 10 medications for short-term use were associated with both a ≥20% increased risk of skin cancer and an increase in risk with increasing use for at least one of the four cancers. CONCLUSION: We found little evidence of an increased risk of skin cancer among users of photosensitizing medications for long-term daily use, but could not rule out the possibility that users of some photosensitizing medications for short-term use may have an increased risk of skin cancer. IMPACT: Previous studies have been limited to specific medication types (e.g., antidiuretics). Our study examined the effect of a wide range of photosensitizing medications on skin cancer risk and suggests that future work should focus on photosensitizing medications for short-term use.

Merkel cell carcinoma: incidence, mortality, and risk of other cancers.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare skin cancer that was recently found to be associated with a polyomavirus and with immunosuppression, provoking new interest in its epidemiology. We conducted a nationwide study in Denmark to describe MCC incidence and mortality and the association between MCC and other cancers. METHODS: We used data from Danish national health and population registers on MCC diagnoses, deaths, and population counts during the study period (1978-2006) to calculate MCC incidence rates, cumulative risks of MCC at age 100 years, and MCC mortality rates by tumor stage. We used Poisson regression to estimate the excess mortality rate ratio attributable to MCC and examined associations between MCC and other cancers diagnosed before and after the MCC diagnosis using standardized incidence rate ratios (SIRs). All statistical tests were two-sided. RESULTS: Between January 1, 1978, and December 31, 2006, 185 persons were diagnosed with MCC in Denmark. MCC incidence between 1995 and 2006 was 2.2 cases per million person-years. In the first year after MCC diagnosis, 22% of persons with localized disease died compared with 54% of patients with nonlocalized disease; by 5 years after diagnosis, the proportions of MCC patients who had died increased to 55% and 84%, respectively. MCC incidence was statistically significantly increased more than 1 year after a diagnosis of squamous cell carcinoma of the skin (SIR = 14.6, 95% confidence interval [CI] = 8.4 to 25.6), basal cell carcinoma (SIR = 4.3, 95% CI = 2.7 to 6.6), malignant melanoma (SIR = 3.3, 95% CI = 1.1 to 10.3), chronic lymphocytic leukemia (SIR = 12.0, 95% CI = 3.8 to 37.8), Hodgkin lymphoma (SIR = 17.6, 95% CI = 2.5 to 126), and non-Hodgkin lymphoma (SIR = 5.6, 95% CI = 1.4 to 22.4). Squamous cell carcinoma (SIR = 12.1, 95% CI = 5.1 to 29.1) and chronic lymphocytic leukemia (SIR = 14.7, 95% CI = 3.7 to 58.8) occurred in statistically significant excess more than 1 year after MCC diagnosis. CONCLUSIONS: These results support the existence of shared risk factors for MCC and other cancers. Heightened awareness of the association between MCC and other cancers, particularly squamous cell carcinoma and chronic lymphocytic leukemia, may facilitate earlier clinical detection and treatment of MCC, thereby improving patient survival.

Immediate whealing urticaria in red light exposed areas during photodynamic therapy.

One of the recommended first-line treatments for basal cell carcinomas, actinic keratoses and Bowen's disease is photodynamic therapy. Commonly associated side- effects include pain and phototoxicity. Histamine release is a part of this reaction, but whealing urticaria follow noting photodynamic therapy has only been reported by the manufacturer. The aim of this study was to investigate the prevalence of immediate whealing urticaria in exposed areas during photodynamic therapy with topical methylester aminolevulinate and red light. Patients who developed immediate whealing urticaria during photodynamic therapy were prospectively registered in the period from 1 March 2002 to 14 May 2007. Twelve out of 1353 patients (0.9%) treated with photodynamic therapy developed immediate whealing urticaria and itch during red light illumination, which had not been experienced during previous sessions. Urticaria occurred in 3.8% of patients who had received more than 7 sessions of photodynamic therapy. Prophylactic use of systemic antihistamines reduced itch and whealing, permitting photodynamic therapy sessions to be continued.

The impact of autoimmune diseases on the incidence and prognosis of cutaneous malignant melanoma.

BACKGROUND: Persons being treated with IFNalpha-2b for advanced cutaneous malignant melanoma (CMM) have been reported to have a greatly improved prognosis if they develop autoantibodies or clinical signs of autoimmunity during therapy. Consequently, we examined whether autoimmune diseases might also be associated with lower CMM incidence and better prognosis. METHODS: We established a study cohort based on the entire Danish population, obtaining information on CMM and autoimmune diseases from the Danish national registers. Using log-linear regression models adjusting for age, period, and sex, we compared CMM incidence and CMM-specific mortality rates in persons with and without a history of autoimmune disease. RESULTS: Between 1977 and 2003, 20,482 cases of CMM were registered in the Danish Cancer Register. Previously diagnosed autoimmune diseases did not affect the incidence of CMM (incidence rate ratio, 1.0; 95% confidence interval, 0.9-1.1). In the first 5 years after CMM diagnosis, we observed 8,957 deaths in individuals with CMM (5,181 expected). CMM-specific mortality rates 1 to 5 years after diagnosis were similar in CMM patients with and without autoimmune diseases (mortality rate ratio, 0.9; 95% confidence interval, 0.7-1.2). CONCLUSIONS: Autoimmune conditions were not associated with CMM incidence or prognosis. The better CMM prognosis previously observed when autoantibodies or clinical signs of autoimmunity developed during IFNalpha-2b therapy may have been related to variation in individual responses to this therapy, with individuals sensitive to treatment exhibiting more signs of autoimmunity but also (independently) experiencing greater antitumor responses as a result of treatment.

Reproductive history and cutaneous malignant melanoma: a comparison between women and men.

To evaluate whether previously observed associations between parity and cutaneous malignant melanoma (CMM) risk in women reflected a biologic mechanism or resulted from uncontrolled confounding by lifestyle factors associated with parity (e.g., patterns of sun exposure), the authors investigated the effect of reproductive history (parenthood) on CMM risk in both women and men. Using information from Danish national registers (1968-2003), the authors established a population-based cohort of more than 3,500,000 persons with information on parenthood and CMM. Relative risks were estimated using Poisson regression models. Overall, number of children was significantly associated with a woman's risk of CMM (p = 0.004), with the lowest risk being seen among women with many births. Women aged 25 years or older at their first birth had a 24% (95% confidence interval: 16, 33) higher risk of CMM than younger women. Ten or more years after the birth of her youngest child, a woman had a 15% (95% confidence interval: 5, 27) higher risk of CMM than she did in the first 10 years. Similar results were observed in men. The similarity of effects for men and women suggests that lifestyle factors, rather than exposure to pregnancy hormones, may be responsible for the observed associations between reproductive history and CMM risk in women.