Showing papers in "JAMA Dermatology in 2015"

Incidence Estimate of Nonmelanoma Skin Cancer (Keratinocyte Carcinomas) in the US Population, 2012

Abstract: Importance Understanding skin cancer incidence is critical for planning prevention and treatment strategies and allocating medical resources. However, owing to lack of national reporting and previously nonspecific diagnosis classification, accurate measurement of the US incidence of nonmelanoma skin cancer (NMSC) has been difficult. Objective To estimate the incidence of NMSC (keratinocyte carcinomas) in the US population in 2012 and the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in the 2012 Medicare fee-for-service population. Design, Setting, and Participants This study analyzes US government administrative data including the Centers for Medicare & Medicaid Services Physicians Claims databases to calculate totals of skin cancer procedures performed for Medicare beneficiaries from 2006 through 2012 and related parameters. The population-based National Ambulatory Medical Care Survey database was used to estimate NMSC-related office visits for 2012. We combined these analyses to estimate totals of new skin cancer diagnoses and affected individuals in the overall US population. Main Outcomes and Measures Incidence of NMSC in the US population in 2012 and BCC and SCC in the 2012 Medicare fee-for-service population. Results The total number of procedures for skin cancer in the Medicare fee-for-service population increased by 13% from 2 048 517 in 2006 to 2 321 058 in 2012. The age-adjusted skin cancer procedure rate per 100 000 beneficiaries increased from 6075 in 2006 to 7320 in 2012. The number of procedures in Medicare beneficiaries specific for NMSC increased by 14% from 1 918 340 in 2006 to 2 191 100 in 2012. The number of persons with at least 1 procedure for NMSC increased by 14% (from 1 177 618 to 1 336 800) from 2006 through 2012. In the 2012 Medicare fee-for-service population, the age-adjusted procedure rate for BCC and SCC were 3280 and 3278 per 100 000 beneficiaries, respectively. The ratio of BCC to SCC treated in Medicare beneficiaries was 1.0. We estimate the total number of NMSCs in the US population in 2012 at 5 434 193 and the total number of persons in the United States treated for NMSC at 3 315 554. Conclusions and Relevance This study is a thorough nationwide estimate of the incidence of NMSC and provides evidence of continued increases in numbers of skin cancer diagnoses and affected patients in the United States. This study also demonstrates equal incidence rates for BCC and SCC in the Medicare population.

Pembrolizumab Cutaneous Adverse Events and Their Association With Disease Progression

Abstract: Importance Immunomodulatory anticancer drugs, such as the anti–programmed death-1 drug pembrolizumab, have shown promising results in trials, and more patients will receive such treatments. Little is known about cutaneous adverse events (AEs) caused by these drugs and their possible correlation with treatment response. Objective To describe the frequency and spectrum of cutaneous AEs linked with pembrolizumab and their possible correlation with treatment response. Design, Setting, and Participants A single-institution, retrospective medical record review was conducted of patients with cancer who were treated with pembrolizumab from March 1, 2011, to May 28, 2014. The review comprised 83 consecutive patients who were enrolled in 2 clinical trials, received at least 1 dose of pembrolizumab, and had at least 1 follow-up visit. Patients were grouped according to the following therapeutic regimen for pembrolizumab: 43 received 10 mg/kg every 3 weeks, 24 received 10 mg/kg every 2 weeks, and 16 received 2 mg/kg every 3 weeks. Sixty-six patients were treated for melanoma, 15 patients for lung cancer, 1 patient for prostate cancer, and 1 patient for Merkel cell carcinoma. Median follow-up was 15 weeks (range, 2-105 weeks). The analysis was conducted from March 1 to September 30, 2014. Main Outcomes and Measures Occurrence, severity, and type of cutaneous AEs, as well as disease progression and response to pembrolizumab treatment. Results Thirty-five patients (42%) developed cutaneous AEs attributed to pembrolizumab. The most common cutaneous AEs were macular papular eruption (24 [29%]), pruritus (10 [12%]), and hypopigmentation (7 [8%]). All 7 patients who developed hypopigmentation were treated for melanoma. Survival analyses showed that patients who developed cutaneous AEs had significantly longer progression-free intervals in all 3 groups (pembrolizumab, 10 mg/kg, every 3 weeks,P = .001; pembrolizumab, 10 mg/kg, every 2 weeks,P = .003; pembrolizumab, 2 mg/kg, every 3 weeks,P = .009) compared with patients who did not develop cutaneous AEs. Conclusions and Relevance Pembrolizumab therapy was associated with cutaneous AEs in 42% of patients. The development of cutaneous AEs, especially of hypopigmentation in patients with melanoma, could point toward better treatment response.

Risk of Serious Infection With Biologic and Systemic Treatment of Psoriasis: Results From the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

Abstract: Importance The efficacy of treatment for psoriasis must be balanced against potential adverse events. Objective To determine the effect of treatment on the risk of serious infections in patients with psoriasis. Design, Setting, and Participants A multicenter, longitudinal, disease-based registry (Psoriasis Longitudinal Assessment and Registry [PSOLAR]) at dermatology centers. Participants were adult patients with psoriasis who were receiving or were eligible to receive conventional systemic or biologic agents. The registry opened on June 20, 2007, and data included herein were collected through August 23, 2013. Exposures Patients were prescribed psoriasis therapies as in standard clinical practice. Patients will be followed for up to 8 years. Data were collected and serious adverse events (including serious infections) were assessed at regular intervals. Main Outcomes and Measures Cohort characteristics are described based on evaluation at entry into the registry. The cumulative incidence rates of serious infections are reported across treatment cohorts, including ustekinumab, infliximab, adalimumab, etanercept, and nonbiologics (with or without methotrexate). A multivariate analysis using a Cox proportional hazards regression model was used to identify predictors of the time to the first serious infection using the nonmethotrexate/nonbiologics cohort as the reference. Results Data were analyzed from 11 466 patients with psoriasis (22 311 patient-years). Differences in patient characteristics were found between the biologics and nonmethotrexate/nonbiologics cohorts (eg, age, sex, body mass index, and disease characteristics), as well as among the individual biologic groups (eg, a higher prevalence of psoriatic arthritis in the infliximab cohort). The cumulative incidence rate of serious infections was 1.45 per 100 patient-years (n = 323) across treatment cohorts, and the rates were 0.83, 1.47, 1.97, and 2.49 per 100 patient-years in the ustekinumab, etanercept, adalimumab, and infliximab cohorts, respectively, and 1.05 and 1.28 per 100 patient-years in the nonmethotrexate/nonbiologics and methotrexate/nonbiologics cohorts, respectively. The most commonly reported types of serious infections across the registry were pneumonia and cellulitis. Increasing age, diabetes mellitus, smoking, significant infection history, infliximab exposure, and adalimumab exposure were each associated with an increased risk of serious infection. Conclusions and Relevance Results from PSOLAR suggest a higher risk of serious infections with adalimumab and infliximab compared with nonmethotrexate and nonbiologic therapies. No increased risk was observed with ustekinumab or etanercept. Trial Registration clinicaltrials.gov Identifier:NCT00508547

Long-term Management of Adult Vulvar Lichen Sclerosus A Prospective Cohort Study of 507 Women

Abstract: Importance Adult vulvar lichen sclerosis (VLS) may be complicated by loss of vulvar structure and vulvar carcinoma. There is a lack of evidence as to the ideal method to maintain long-term remission and prevent complications. Objectives To determine whether long-term preventive topical corticosteroid (TCS) treatment of VLS, with a target outcome of induction and maintenance of normal skin texture and color, reduces the risk of vulvar carcinoma, relieves symptoms, improves function, and preserves vulvar architecture, and to evaluate the adverse effects of treatment. Design, Setting, and Participants A prospective longitudinal cohort study was conducted in 507 women with biopsy-proved VLS from January 2, 2008, through September 26, 2014, in the private practice of a dermatologist and a gynecologist in Sydney, Australia. Interventions Preventive treatment using TCSs of various potencies, adjusted to meet a target outcome of normal skin color and texture, with regular long-term follow-up by a dermatologist or gynecologist. Main Outcomes and Measures Symptoms or signs of VLS, scarring, development of malignant neoplasms, and adverse effects. Results The mean age at presentation was 55.4 years (range, 18-86 years); duration of symptoms at presentation, 5.0 years (range, 0.1-40.0 years); and duration of follow-up, 4.7 years (range, 2.0-6.8 years). Remission was induced with a potent TCS, followed by regular preventive TCS treatment of a potency titrated to achieve the target outcome. Patients were followed up at least annually. A total of 150 patients (29.6%) did not carry out the advised treatment and were considered partially compliant. A total of 357 patients (70.4%) adhered to treatment instructions and were considered compliant. Biopsy-proved squamous cell carcinoma or vulvar intraepithelial neoplasia occurred during follow-up in 0 of the compliant patients vs 7 (4.7%) of the partially compliant patients ( P P P Conclusions and Relevance This prospective, single-center, longitudinal cohort study of adult patients with VLS suggests that individualized preventive TCS regimens that achieve objective normality of skin color and texture and are used by compliant patients who attend regular long-term follow-up visits may modify the course of the disease. There was a significant difference in symptom control, scarring, and occurrence of vulvar carcinoma between compliant and partially compliant patients. The adverse effects of TCSs were minimal.

Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy

Abstract: Importance Vitiligo is a common condition that is often emotionally devastating for patients. At present, no reliably effective treatments are available. Observations Recent advances in the understanding of the pathogenesis of vitiligo suggest that Janus kinase inhibitors may be a therapeutic option. We report a case of generalized vitiligo for which treatment with tofacitinib citrate, an oral Janus kinase 1/3 inhibitor, resulted in significant repigmentation. Conclusions and Relevance The results suggest that tofacitinib and other Janus kinase inhibitors may be effective in the treatment of vitiligo. Additional studies will be needed to confirm their efficacy and to explore their safety.

Economic Burden of Psoriasis in the United States: A Systematic Review

Abstract: Importance The total cost of psoriasis in the United States is unknown. Defining the US economic burden of psoriasis is needed because it provides the foundation for research, advocacy, and educational efforts. Objective To determine the US economic burden of psoriasis from a societal perspective. Evidence Review PubMed and MEDLINE databases were searched between January 1, 2008, and September 20, 2013, for economic investigations on the direct, indirect, intangible, and comorbidity costs of adult psoriasis in the United States. The base year costs were adjusted to 2013 US dollars using the Consumer Price Index for All Urban Consumers and multiplied by the estimated number of US patients with psoriasis in 2013 to determine the 2013 psoriasis cost burden. Findings Among 100 identified articles, 22 studies were included in the systematic review. The direct psoriasis costs ranged from $51.7 billion to $63.2 billion, the indirect costs ranged from $23.9 billion to $35.4 billion, and medical comorbidities were estimated to contribute $36.4 billion annually in 2013 US dollars. Patients with psoriasis would pay a lifetime cost of $11 498 for relief of physical symptoms and emotional health; however, intangible cost data are limited. The annual US cost of psoriasis amounted to approximately $112 billion in 2013. Conclusions and Relevance The economic burden of psoriasis is substantial and significant in the United States.

Association of Vitiligo and Alopecia Areata With Atopic Dermatitis: A Systematic Review and Meta-analysis

Abstract: Importance Previous studies found conflicting results as to whether atopic dermatitis (AD) is increased in patients with vitiligo and alopecia areata (AA). Objective To compare the prevalence of AD between patients with either vitiligo or AA and those without these disorders by performing a meta-analysis of observational studies. Data Sources MEDLINE, EMBASE, Cochrane Library, Google Scholar, and a manual search of 12 additional journals between 1946 and April 5, 2014. Study Selection Observational studies published in any language that compared the prevalence of AD among patients with and without either vitiligo or AA. Data Extraction and Synthesis Data were extracted by 2 independent investigators. Quality of evidence was assessed using the Newcastle-Ottawa Scale and Methodological Evaluation of Observational Research checklist. A meta-analysis of studies assessing AD, vitiligo, and/or AA was performed using a fixed-effects model to estimate pooled odds ratios (ORs). Subset analyses were performed for childhood vs adult-onset vitiligo and alopecia totalis or alopecia universalis vs patchy alopecia. Main Outcomes and Measures Self-reported and/or physician-diagnosed AD, vitiligo, and AA. Results In total, 16 studies of vitiligo and 17 studies of AA were included in the review. In the pooled analysis of the studies that included control patients without vitiligo (n = 2) and control patients without AA (n = 3), patients with vitiligo (Cochran-Mantel-Haenszel OR, 7.82; 95% CI, 3.06-20.00, P P P P = .04). Conclusions and Relevance Patients with either vitiligo, especially early-onset disease, or AA, especially alopecia totalis or alopecia universalis, have significantly increased risk for AD.

Drug-Associated Dermatomyositis Following Ipilimumab Therapy: A Novel Immune-Mediated Adverse Event Associated With Cytotoxic T-Lymphocyte Antigen 4 Blockade

Abstract: Importance Ipilimumab, a human monoclonal antibody targeted against cytotoxic T-lymphocyte antigen 4, has shown promise in the treatment of metastatic melanoma. However, given its mechanism of action, immune-related adverse effects have been reported with this therapy. Despite increasing reports of immune-related adverse effects related to ipilimumab therapy, dermatomyositis associated with this agent has not previously been reported. Observations We describe a woman undergoing treatment with ipilimumab for metastatic melanoma who developed classic cutaneous findings of dermatomyositis along with proximal muscle weakness and elevated muscle enzymes. Conclusions and Relevance This case adds to the expanding literature regarding immune-related adverse events associated with ipilimumab. To our knowledge, drug-induced dermatomyositis from ipilimumab has not previously been reported. Physicians should be aware of these potential immune-related adverse events and consider drug-associated dermatomyositis in the differential diagnosis in patients receiving ipilimumab who present with a cutaneous eruption or muscle weakness.

Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma.

Abstract: Importance The cutaneous adverse effects of the BRAF inhibitors vemurafenib and dabrafenib mesylate in the treatment of metastatic melanoma have been well reported. The addition of a MEK inhibitor to a BRAF inhibitor improves the blockade of the mitogen-activated protein kinase pathway. The combination of dabrafenib with the MEK inhibitor trametinib dimethyl sulfoxide (CombiDT therapy) increases response rate and survival compared with a BRAF inhibitor alone. Clinical trials have suggested that CombiDT therapy induces fewer cutaneous toxic effects than a single-agent BRAF inhibitor. To our knowledge, a direct comparison has not been performed before. Objective To compare the cutaneous toxic effects of BRAF inhibitor monotherapy and CombiDT therapy in a large cohort of patients. Design, Setting, and Participants We performed a retrospective cohort study from September 1, 2009, through November 30, 2013. The study population included 185 Australian patients with unresectable stages IIIC and IV melanoma referred from Crown Princess Mary Cancer Care Centre who underwent review at the Department of Dermatology, Westmead Hospital. Of these, 119 patients received dabrafenib; 36, vemurafenib; and 30, CombiDT therapy. Data analysis were performed in December 2013. Main Outcomes and Measures Multiple cutaneous adverse effects between BRAF inhibitor monotherapy and CombiDT therapy were identified and compared in a cohort of patients who underwent the same dermatologic assessment. Results The most common cutaneous adverse effects seen in patients receiving the single-agent BRAF inhibitor dabrafenib or vemurafenib included Grover disease (51 patients [42.9%] and 14 [38.9%], respectively [ P = .67]), plantar hyperkeratosis (47 [39.5%] and 14 [38.9%], respectively [ P = .95]), verrucal keratosis (79 [66.4%] and 26 [72.2%], respectively [ P = .51]), and cutaneous squamous cell carcinoma (31 [26.1%] and 13 [36.1%], respectively [ P = .54]). Photosensitivity was more common with vemurafenib (14 patients [38.9%]) compared with dabrafenib (1 [0.8%]; P P P P P Conclusions and Relevance This study confirms that the prevalence of cutaneous toxic effects differs among vemurafenib, dabrafenib, and CombiDT therapies. Cutaneous squamous cell carcinoma is the most concerning cutaneous toxic effect related to BRAF inhibitor monotherapy that did not appear with CombiDT therapy. Although CombiDT therapy has an improved profile of cutaneous toxic effects, continuous dermatologic assessments should be provided for all patients when receiving these treatments.

Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial

Abstract: Importance Narrowband UV-B (NB–UV-B) phototherapy is used extensively to treat vitiligo. Afamelanotide, an analogue of α–melanocyte-stimulating hormone, is known to induce tanning of the skin. Objective To evaluate the efficacy and safety of combination therapy for generalized vitiligo consisting of afamelanotide implant and NB–UV-B phototherapy. Design, Setting, and Participants This study was performed in 2 academic outpatient dermatology centers and 1 private dermatology practice. We enrolled men and women 18 years or older with Fitzpatrick skin phototypes (SPTs) III to VI and a confirmed diagnosis of nonsegmental vitiligo that involved 15% to 50% of total body surface area. Vitiligo was stable or slowly progressive for 3 months. Patients were randomized to combination therapy (n = 28) vs NB–UV-B monotherapy (n = 27). After 1 month of NB–UV-B phototherapy, 16 mg of afamelanotide was administered subcutaneously to the combination therapy group monthly for 4 months while NB–UV-B phototherapy continued; the other group continued to receive NB–UV-B monotherapy. Interventions Narrowband UV-B monotherapy vs combined NB–UV-B phototherapy and afamelanotide. Main Outcomes and Measures Response on the Vitiligo Area Scoring Index and Vitiligo European Task Force scoring system. Results Response in the combination therapy group was superior to that in the NB–UV-B monotherapy group ( P P = .001]; upper extremities, 46.0 vs 69.0 days [ P = .003]). In the combination therapy group, repigmentation was 48.64% (95% CI, 39.49%-57.80%) at day 168 vs 33.26% (95% CI, 24.18%-42.33%) in the NB–UV-B monotherapy group. Notable adverse events included erythema in both groups and minor infections and nausea in the combination therapy group. Comparison between Fitzpatrick SPTs showed patients with SPTs IV to VI in the combination therapy group had improvement in the Vitiligo Area Scoring Index at days 56 and 84 ( P Conclusions and Relevance A combination of afamelanotide implant and NB–UV-B phototherapy resulted in clinically apparent, statistically significant superior and faster repigmentation compared with NB–UV-B monotherapy. The response was more noticeable in patients with SPTs IV to VI. Trial Registration clinicaltrials.gov Identifier:NCT01430195

Trends in Basal Cell Carcinoma Incidence and Identification of High-Risk Subgroups, 1998-2012

Abstract: Importance The incidence of basal cell carcinomas (BCCs) is increasing globally, but incidence rates in the United States are difficult to quantify because BCCs are not reportable tumors. Objective To estimate annual BCC incidence rates by age, sex, and race/ethnicity to identify demographically distinct high-risk subgroups and to assess changes in rates over time. Design, Setting, and Participants In this retrospective cohort study (January 1, 1998, through December 31, 2012), we studied 147 093 patients with BCC from Kaiser Permanente Northern California, a large, integrated health care provision system, identified using a previously validated BCC registry. Main Outcomes and Measures We estimated annual BCC incidence rates by age, sex, and race/ethnicity and assessed changes in rates over time. The BCC incidence rates were standardized to the age, sex, and race/ethnicity distribution of the 2010 US Census population. Results In models adjusting for age, sex, and race, male patients had higher rates than female patients (incidence rate ratio [IRR], 1.65; 95% CI, 1.60-1.70). Persons 65 through 79 years of age and those 80 years and older had higher rates than persons 40 through 64 years of age (IRR, 2.96; 95% CI, 2.86-3.06; and IRR, 5.14; 95% CI, 4.94-5.35, respectively). Whites had higher rates than multiracial persons (IRR, 1.96; 95% CI, 1.80-2.13), Hispanics (IRR, 8.56; 95% CI, 7.79-9.41), Asians (IRR, 33.13; 95% CI, 27.84-39.42), and blacks (IRR, 72.98; 95% CI, 49.21-108.22). Conclusions and Relevance We estimate that BCCs occur in approximately 2 million Americans annually. Our findings provide an updated estimate of the incidence of BCCs, highlight the changing epidemiologic findings, and better identify demographically distinct high-risk subgroups.

Use of a Picosecond Pulse Duration Laser With Specialized Optic for Treatment of Facial Acne Scarring

Abstract: Importance Fractional laser technology is routinely used in the treatment of acne scarring, with thermal injury resulting in collagen synthesis and remodeling. Use of a picosecond pulse duration with a diffractive lens array may be a new technologic advancement in the treatment of acne scarring. Objective To investigate the safety and efficacy of a 755-nm alexandrite picosecond pulse duration laser with diffractive lens array for the treatment of facial acne scarring. Design, Setting, and Participants This single-center, prospective study performed in a private practice with a dedicated research department included patients with clinically diagnosed scarring secondary to inflammatory or cystic acne. Interventions Patients received 6 treatments with a 755-nm picosecond laser with a spot size of 6 mm, fluence of 0.71 J/cm 2 , repetition rate of 5 Hz, and pulse width of 750 picoseconds in combination with a diffractive lens array, allowing for greater surface area and pattern density per pulse. Main Outcomes and Measures The pain and satisfaction scores for overall appearance and texture were recorded. Masked assessment of clinical photographs and analysis of 3-dimensional volumetric data were performed. Biopsy specimens were obtained for independent histologic evaluation by 2 investigators at baseline and at 3 months after last treatment. Results Fifteen women and 5 men (mean age, 44 years; age range, 27-61 years) with Fitzpatrick skin types I through V and facial acne scarring were enrolled. The mean pain score was 2.83 of 10. Patients were satisfied to extremely satisfied with improvement in appearance and texture at their final treatment and follow-up visits. The masked assessment scores of 17 patients were 1.5 of 3 and 1.4 of 3 at 1 and 3 months, respectively (a score of 0 indicates 0%-25% improvement and a score of 3 indicates >75% improvement). A 3-dimensional analysis revealed a mean 24.3% improvement in scar volume, maintained at 1 (24.0%) and 3 (27.2%) months after treatment. Histologic analysis revealed elongation and increased density of elastic fibers, with an increase in dermal collagen and mucin. Conclusions and Relevance Treatment of facial acne scars with a diffractive lens array and 755-nm picosecond laser produced improvement in appearance and texture at 3 months after the last treatment, with objective findings similar to those published for a series of fractional ablative laser treatments. Histologic findings suggest that improvement in scarring from this treatment goes beyond remodeling of collagen.

Association Between Malignancy and Topical Use of Pimecrolimus.

Abstract: Importance A black box warning describes a potential risk of malignancy associated with topical use of pimecrolimus to treat atopic dermatitis due to its similarity to oral calcineurin inhibitors used in solid-organ transplantation and spontaneous reporting of malignancies, including lymphomas and cutaneous malignancies. Objective To evaluate the risk of malignancy in a postmarketing study of children exposed to pimecrolimus. Design, Setting, and Participants A longitudinal cohort study among a nationwide ongoing long-term cohort of children enrolled in the Pediatric Eczema Elective Registry (PEER) who had a history of atopic dermatitis and pimecrolimus use with data available up through May 2014. Main Outcomes and Measures Reports of malignancy among those in the PEER compared with expected rates from the Surveillance, Epidemiology, and End Results (SEER) program. Results Overall, 7457 children were enrolled in the PEER, for a total of 26 792 person-years. Children used a mean (SD) of 793 (1356) g of pimecrolimus when enrolled in the study. As of May 2014, five malignancies had been reported. These include 2 leukemias, 1 osteosarcoma, and 2 lymphomas. No skin cancers were reported. The standardized incidence ratio for all malignancies (primary outcome) based on the age-standardized SEER population was 1.2 (95% CI, 0.5-2.8). As secondary analyses, the standardized incidence ratios (based on 2 cases for each) were 2.9 (95% CI, 0.7-11.7) for lymphoma and 2.0 (95% CI, 0.5-8.2) for leukemia. None of these findings were statistically significant. Conclusions and Relevance Based on more than 25 000 person-years of follow-up, it seems unlikely that topical pimecrolimus as it was used in the PEER cohort to treat atopic dermatitis is associated with an increased risk of malignancy.

Treatment of Nail Psoriasis: Best Practice Recommendations From the Medical Board of the National Psoriasis Foundation

Abstract: Importance Nail psoriasis can be difficult to treat and has a significant effect on quality of life. Relatively few controlled trials evaluating treatments for nail psoriasis have been published. There is an unmet need for treatment recommendations to guide therapeutic decisions. Objective To develop treatment recommendations for nail psoriasis from the Medical Board of the National Psoriasis Foundation. Evidence Review A PubMed search for publications on nail psoriasis treatments was performed from January 1, 1947, through May 11, 2014, without language restrictions. Findings Treatment recommendations for 4 clinical nail psoriasis scenarios were developed based on the evidence reviewed in this study and expert opinion of the Medical Board of the National Psoriasis Foundation. Treatment of nail psoriasis should balance consideration of the extent of skin disease, psoriatic arthritis, and severity of nail disease with concomitant impairment of quality of life. All patients should be evaluated for onychomycosis because this may complicate psoriatic nail disease. For disease limited to the nails, high-potency topical corticosteroids with or without calcipotriol are initial options. For patients with significant nail disease for whom topical therapy has failed, treatment with adalimumab, etanercept, intralesional corticosteroids, ustekinumab, methotrexate sodium, and acitretin are recommended. For patients with significant skin and nail disease, adalimumab, etanercept, and ustekinumab are strongly recommended, and methotrexate, acitretin, infliximab, and apremilast are recommended. Finally, for a patient with significant nail, skin, and joint disease, adalimumab, etanercept, ustekinumab, infliximab, methotrexate, apremilast, and golimumab are recommended. Conclusions and Relevance Treatment of nail psoriasis poses a clinical challenge. Clinical trial data are limited, and results are reported inconsistently, making comparisons among treatment options difficult. The treatment recommendations from the Medical Board of the National Psoriasis Foundation will help guide treatment decisions for clinicians who are treating patients with nail psoriasis.

In Vivo Multiphoton Microscopy of Basal Cell Carcinoma

Abstract: RESULTS The main MPM feature associated with the BCC lesions involved nests of basaloid cells present in the papillary and reticular dermis. This feature correlated well with histopathologic examination. Other MPM features included elongated tumor cells in the epidermis aligned in 1 direction and parallel collagen and elastin bundles surrounding the tumors.

Stimulator of Interferon Genes-Associated Vasculopathy With Onset in Infancy A Mimic of Childhood Granulomatosis With Polyangiitis

Abstract: Importance The type I interferonopathies comprise a recently recognized group of mendelian diseases characterized by an upregulation of type I interferon signaling. These monogenic phenotypes include classic Aicardi-Goutieres syndrome and syndromic forms of systemic lupus erythematosus, including familial chilblain lupus and spondyloenchondrodysplasia. Dermatologic features provide a major diagnostic clue to this disease grouping, as exemplified by the recently described stimulator of interferon genes–associated vasculopathy with onset in infancy (SAVI) caused by gain-of-function mutations in TMEM173 . Observations We describe a male child who, from the age of 2 months, had significant cutaneous disease that manifested as red violaceous plaques of the cheeks, nose, ears, fingers, and toes that progressed to gangrenous necrosis. In addition to his severe cutaneous vasculopathy, he experienced recurrent fevers, interstitial lung disease, and failure to thrive. His clinical syndrome was refractory to multiple immunosuppressive therapies. Evidence of marked upregulation of type I interferon signaling was observed in peripheral blood, and genetic testing identified a de novo germline mutation in TMEM173 , confirming a diagnosis of SAVI 7 years after the onset of his disease. Conclusions and Relevance This observational report describes a new case of SAVI, a recently defined monogenic inflammatory phenotype, that exemplifies an emerging group of disorders related to primary upregulation of type I interferon signaling.

Genetic vs Environmental Factors That Correlate With Rosacea: A Cohort-Based Survey of Twins

Abstract: Importance To our knowledge, this is the first study on rosacea to formally define genetic and environmental contributions. Objectives To study a cohort of identical and fraternal twins to determine whether genetic factors contribute to rosacea development and, if genetic factors are present, quantitatively estimate the genetic contribution, as well as to identify environmental factors that correlate with rosacea by controlling for genetic susceptibility. Design, Setting, and Participants Identical and fraternal twins were surveyed regarding risk factors implicated in rosacea. Faculty dermatologists determined a rosacea score for each twin participant according to the National Rosacea Society (NRS) grading system. Data were collected at the annual Twins Days Festival in Twinsburg, Ohio, on August 4-5, 2012, and August 2-3, 2013. Analysis was conducted for several months after each meeting. A cohort of 550 twin individuals, with most from Ohio, Pennsylvania, and the northeastern United States, participated. Main Outcomes and Measures The NRS score and rosacea subtype were assessed using the NRS grading system and physical examination by board-certified dermatologists. Results Among the 275 twin pairs (550 individuals), there were 233 identical twin pairs with a mean rosacea score of 2.46 and 42 fraternal twin pairs with a mean rosacea score of 0.75. We observed a higher association of NRS scores between identical vs fraternal twins ( r = 0.69 vs r = 0.46; P = .04), demonstrating a genetic contribution. Using the ACE model (proportion of variance in a trait heritable secondary to additive genetics [A] vs the proportions due to a common environment [C] and unique environment [E]), we calculated this genetic contribution to be 46%. A higher NRS score was also significantly associated with the following factors: age ( r = 0.38; P r = 0.26; P r = 0.21; P r = 0.10; P r = 0.11; P = .01), cardiovascular comorbidity ( r = 0.17; P r = 0.19; P Conclusions and Relevance The study of twins allows us to separate genetic susceptibility and the influence of environmental factors affecting rosacea. We found that approximately half of the contribution to the NRS score could be accounted for by genetics and the other half by environment. We identified correlations between rosacea and UV radiation exposure, alcohol, smoking, skin cancer history, cardiac comorbidity, and age. These findings may help improve current management and expectations of individuals affected by rosacea.

The risk of melanoma in airline pilots and cabin crew: a meta-analysis.

Abstract: Importance Airline pilots and cabin crew are occupationally exposed to higher levels of cosmic and UV radiation than the general population, but their risk of developing melanoma is not yet established. Objective To assess the risk of melanoma in pilots and airline crew. Data Sources PubMed (1966 to October 30, 2013), Web of Science (1898 to January 27, 2014), and Scopus (1823 to January 27, 2014). Study Selection All studies were included that reported a standardized incidence ratio (SIR), standardized mortality ratio (SMR), or data on expected and observed cases of melanoma or death caused by melanoma that could be used to calculate an SIR or SMR in any flight-based occupation. Data Extraction and Synthesis Primary random-effect meta-analyses were used to summarize SIR and SMR for melanoma in any flight-based occupation. Heterogeneity was assessed using the χ 2 test and I 2 statistic. To assess the potential bias of small studies, we used funnel plots, the Begg rank correlation test, and the Egger weighted linear regression test. Main Outcomes and Measures Summary SIR and SMR of melanoma in pilots and cabin crew. Results Of the 3527 citations retrieved, 19 studies were included, with more than 266 431 participants. The overall summary SIR of participants in any flight-based occupation was 2.21 (95% CI, 1.76-2.77; P P = .001; 12 records). The summary SIR for cabin crew was 2.09 (95% CI, 1.67-2.62; P = .45; 2 records). The overall summary SMR of participants in any flight-based occupation was 1.42 (95% CI, 0.89-2.26; P = .002; 6 records). The summary SMR for pilots was 1.83 (95% CI, 1.27-2.63, P = .33; 4 records). The summary SMR for cabin crew was 0.90 (95% CI, 0.80-1.01; P = .97; 2 records). Conclusions and Relevance Pilots and cabin crew have approximately twice the incidence of melanoma compared with the general population. Further research on mechanisms and optimal occupational protection is needed.

Central Obesity and High Blood Pressure in Pediatric Patients With Atopic Dermatitis

Abstract: Importance Atopic dermatitis (AD) is associated with multiple potential risk factors for obesity and high blood pressure (BP), including chronic inflammation, sleep disturbance, and mental health comorbidity. Previous studies found associations between general obesity and AD. However, it is unknown whether AD is associated with central obesity and/or high BP. Objectives To determine whether central obesity and high BP are increased in pediatric AD. Design, Setting, and Participants This case-control study performed in multicenter pediatric dermatology practices in the United States recruited 132 children (age range, 4-17 years) with active moderate to severe AD and 143 healthy controls from April 1, 2009, through December 31, 2012. Exposures Diagnosis and severity of AD assessed by a pediatric dermatologist. Main Outcomes and Measures Body mass index, waist circumference, waist to height ratio, systolic BP, and diastolic BP. Results Moderate to severe AD was associated with body mass index for age and sex of 97th percentile or greater (logistic regression; odds ratio [OR], 2.64; 95% CI, 1.15-6.06), International Obesity Task Force obesity cutoffs (OR, 2.38; 95% CI, 1.06-5.34), waist circumference in the 85th percentile or greater (OR, 3.92; 95% CI, 1.50-10.26), and waist to height ratio of 0.5 or greater (OR, 2.22; 95% CI, 1.10-4.50). Atopic dermatitis was associated with higher BP for age, sex, and height percentiles (systolic BP: OR, 2.94; 95% CI, 1.04-8.36; diastolic BP: OR, 3.68; 95% CI, 1.19-11.37), particularly a systolic BP in the 90th percentile or higher (OR, 2.06; 95% CI, 1.09-3.90), in multivariate models that controlled for demographics, body mass index and waist circumference percentiles, and history of using prednisone or cyclosporine. Atopic dermatitis was associated with higher systolic BP in Hispanics/Latinos (general linear model; β, .23; 95% CI, .04-.43) and Asians (β, .16; 95% CI, .03-.30). Severe to very severe AD was associated with systolic BP in the 90th percentile or higher (adjusted OR, 3.14; 95% CI, 1.13-8.70). Atopic dermatitis was associated with a family history of hypertension (adjusted OR, 1.88; 95% CI, 1.14-3.10) and type 2 diabetes mellitus (adjusted OR, 1.64; 95% CI, 1.02-2.68) but not obesity or hyperlipidemia. Conclusions and Relevance Moderate to severe pediatric AD may be associated with central obesity and increased systolic BP.

Low Usefulness of Potassium Monitoring Among Healthy Young Women Taking Spironolactone for Acne.

Abstract: Importance Spironolactone has been shown to be an effective treatment option for hormonally mediated acne but can cause hyperkalemia The prevalence of hyperkalemia among healthy young women taking spironolactone for acne is unclear Objective To measure the rate of hyperkalemia in healthy young women taking spironolactone for acne or for an endocrine disorder with associated acne Design, Setting, and Participants Retrospective study of healthy young women taking spironolactone for acne Data from December 1, 2000, through March 31, 2014, were obtained from a clinical data repository Outpatient data were collected from 2 tertiary care centers in the United States We analyzed rates of hyperkalemia in 974 healthy young women taking spironolactone for acne We also analyzed 1165 healthy young women taking and not taking spironolactone to obtain a profile for the baseline rate of hyperkalemia in this population Exclusion criteria were cardiovascular disease, renal failure, and the use of medications that affect the renin-angiotensin-aldosterone system Main Outcomes and Measures The rate of hyperkalemia in healthy young women taking spironolactone for acne was calculated Secondary measures included spironolactone prescriber profiles and potassium monitoring practices Results There were 13 abnormal serum potassium measurements in 1802 measurements obtained among young women receiving spironolactone therapy, yielding a hyperkalemia rate of 072%, equivalent to the 076% baseline rate of hyperkalemia in this population Repeat testing in 6 of 13 patients demonstrated normal values, suggesting that these measurements may have been erroneous In the remaining 7 patients, no action was taken Conclusions and Relevance The rate of hyperkalemia in healthy young women taking spironolactone for acne is equivalent to the baseline rate of hyperkalemia in this population Routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne

Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial

Abstract: Importance Topical fluorouracil was demonstrated to be effective in reducing the number of actinic keratoses (AKs) for up to 6 months, but no randomized trials studied its long-term efficacy. Objective To evaluate the long-term efficacy of a single course of fluorouracil cream, 5%, for AK treatment. Design, Setting, and Participants The Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) trial was a randomized, double-blinded, placebo-controlled trial with patients from dermatology clinics at 12 VA medical centers recruited from 2009 to 2011 and followed up until 2013. Our study population comprised 932 veterans with 2 or more keratinocyte carcinomas in the 5 years prior to enrollment. The mean follow-up duration was 2.6 years in both treatment and control groups. Interventions Participants applied either topical fluorouracil cream, 5% (n = 468), or vehicle control cream (n = 464) to the face and ears twice daily for up to 4 weeks. Main Outcomes and Measures This study reports on AK counts and treatments, which were secondary outcomes of the VAKCC trial. Actinic keratoses on the face and ears were counted by study dermatologists at enrollment and at study visits every 6 months. The number of spot treatments for AKs on the face and ears at semiannual study visits and in between study visits was recorded. Results The number of AKs on the face and ears per participant was not different between the fluorouracil and control groups at randomization (11.1 vs 10.6, P > .10). After randomization, the fluorouracil group had fewer AKs compared with the control group at 6 months (3.0 vs 8.1, P P P P = .60), although there were fewer hypertrophic AKs in the fluorouracil group at 6 months (0.23 vs 0.41) ( P = .05). Conclusions and Relevance Our results indicate that a single course of fluorouracil cream, 5%, effectively reduces AK counts and the need for spot treatments for longer than 2 years. Trial Registration clinicaltrials.gov Identifier:NCT00847912

Effect of Psoriasis Severity on Hypertension Control: A Population-Based Study in the United Kingdom

Abstract: Importance Hypertension is prevalent among patients with psoriasis. The effect of psoriasis and its severity on hypertension control is unknown. Objective To determine the association between uncontrolled blood pressure and psoriasis, both overall and according to objectively measured psoriasis severity, among patients with diagnosed hypertension. Design, Setting, and Participants Population-based cross-sectional study nested in a prospective cohort drawn from The Health Improvement Network (THIN), an electronic medical records database broadly representative of the general population in the United Kingdom. The study population included a random sample of patients with psoriasis (n = 1322) between the ages of 25 and 64 years in THIN who were included in the Incident Health Outcomes and Psoriasis Events prospective cohort and their age- and practice-matched controls without psoriasis (n = 11 977). All included patients had a diagnosis of hypertension; their psoriasis diagnosis was confirmed and disease severity was classified by their general practitioners. Main Outcomes and Measures Uncontrolled hypertension was defined as a systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher based on the blood pressure recorded closest in time to the assessment of psoriasis severity. Results There was a significant positive dose-response relationship between uncontrolled hypertension and psoriasis severity as objectively determined by the affected body surface area in both unadjusted and adjusted analyses that controlled for age, sex, body mass index, smoking and alcohol use status, presence of comorbid conditions, and current use of antihypertensive medications and nonsteroidal anti-inflammatory drugs (adjusted odds ratio [aOR], 0.97; 95% CI, 0.82-1.14 for mild psoriasis; aOR, 1.20; 95% CI, 0.99-1.45 for moderate psoriasis; and aOR, 1.48; 95% CI, 1.08-2.04 for severe psoriasis; P = .01 for trend). The likelihood of uncontrolled hypertension among psoriasis overall was also increased, although not statistically significantly so (aOR, 1.10; 95% CI, 0.98-1.24). Conclusions and Relevance Among patients with hypertension, psoriasis was associated with a greater likelihood of uncontrolled hypertension in a dose-dependent manner, with the greatest likelihood observed among those with moderate to severe psoriasis defined by 3% or more of the body surface area affected. Our data suggest a need for more effective blood pressure management, particularly among patients with more severe psoriasis.

Occurrence of Psoriasiform Eruption During Nivolumab Therapy for Primary Oral Mucosal Melanoma.

Abstract: described in the Japanese population, several PP cases have also been reported in Western countries and, recently, in the Middle East.2,3 The pathogenesis of PP is not completely clear. In addition to being associated with several factors including exogenous (physical trauma, friction) and hormonal (pregnancy, menstruation), PP has classically been reported in association with metabolic derangements, especially ketotic states (dieting, fasting, diabetes mellitus).2,3 Actually, several studies have detected elevated urine and/or blood ketone levels in patients with PP.2,3 In such circumstances, it is believed that ketone bodies may distribute around blood vessels leading to perivascular inflammation or enter into cells modifying their intracytoplasmic processes. The inflammation is believed to be mainly mediated by neutrophils: PP usually responds well to medications with antineutrophil effect, such as dapsone and tetracyclines, which would support this neutrophil-mediated theory. A role for decreased insulin levels, which is reported to occur after bariatric surgery,4 has also been hypothesized as cause of PP.2 In addition to its effect in changing the course of many skin diseases such as psoriasis, bariatric surgery has been associated with several dermatoses including bowel-associated dermatosis–arthritis syndrome, nutritional deficiency dermatoses, and alopecia.5 However, PP has never been reported after bariatric surgery. Given that such surgery may easily replicate the metabolic disturbance associated with other ketotic states such as dieting or fasting,5,6 we believe that the association between PP and bariatric surgery may be underdiagnosed or underreported. In conclusion, to our knowledge, this report is the first to describe PP developing after bariatric surgery, adding PP to the cutaneous complications of such procedures. Increased awareness of this rare entity and this association is important because bariatric surgery is a common procedure nowadays, and the metabolic abnormalities accompanying it mimic those that occur with other ketotic states.

Trends in indoor tanning among US high school students, 2009-2013.

Abstract: Indoor tanning increases the risk of skin cancer, particularly among frequent users and those initiating use at a young age.1,2 While previous research has demonstrated that indoor tanning is common among youth,3 to our knowledge, this study provides the first national estimates of indoor tanning trends among this population.

Skin Cancer Diagnosis With Reflectance Confocal Microscopy: Reproducibility of Feature Recognition and Accuracy of Diagnosis

Abstract: Importance Reflectance confocal microscopy (RCM) studies have been performed to identify criteria for diagnosis of skin neoplasms. However, RCM-based diagnosis is operator dependent. Hence, reproducibility of RCM criteria needs to be tested. Objective To test interobserver reproducibility of recognition of previously published RCM descriptors and accuracy of RCM-based skin cancer diagnosis. Design, Setting, and Participants Observational retrospective web-based study of a set of RCM images collected at a tertiary academic medical center. Nine dermatologists (6 of whom had ≥3 years of RCM experience) from 6 countries evaluated an RCM study set from 100 biopsy-proven lesions, including 55 melanocytic nevi, 20 melanomas, 15 basal cell carcinomas, 7 solar lentigines or seborrheic keratoses, and 3 actinic keratoses. Between June 15, 2010, and October 21, 2010, participanting dermatologists, blinded to histopathological diagnosis, evaluated 3 RCM mosaic images per lesion for the presence of predefined RCM descriptors. Main Outcomes and Measures The main outcome was identification of RCM descriptors with fair to good interrater agreement (κ statistic, ≥0.3) and independent correlation with malignant vs benign diagnosis on discriminant analysis. Additional measures included sensitivity and specificity for diagnosis of malignant vs benign for each evaluator, for majority diagnosis (rendered by ≥5 of 9 evaluators), and for experienced vs recent RCM users. Results Eight RCM descriptors showed fair to good reproducibility and were independently associated with a specific diagnosis. Of these, the presence of pagetoid cells, atypical cells at the dermal-epidermal junction, and irregular epidermal architecture were associated with melanoma. Aspecific junctional pattern, basaloid cords, and ulceration were associated with basal cell carcinomas. Ringed junctional pattern and dermal nests were associated with nevi. The mean sensitivity for the group of evaluators was 88.9% (range, 82.9%-100%), and the mean specificity was 79.3% (range, 69.2%-90.8%). Majority diagnosis showed sensitivity of 100% and specificity of 80.0%. Sensitivity was higher for experienced vs recent RCM users (91.0% vs 84.8%), but specificity was similar (80.0% vs 77.9%). Conclusions and Relevance The study highlights key RCM diagnostic criteria for melanoma and basal cell carcinoma that are reproducibly recognized among RCM users. Diagnostic accuracy increases with experience. The higher accuracy of majority diagnosis suggests that there is intrinsically more diagnostic information in RCM images than is currently used by individual evaluators.

Health Care Utilization, Patient Costs, and Access to Care in US Adults With Eczema: A Population-Based Study.

Abstract: Importance Little is known about the health burden of adult eczema in the United States. Objective To study the out-of-pocket costs, health care access and utilization in adult eczema in the United States. Design, Setting, and Participants Two US population-based studies, the 2010 and 2012 National Health Interview Surveys, surveyed 27 157 and 34 613 adults (ages 18-85 years). Exposures History of eczema. Main Outcomes and Measures The out-of-pocket costs, lost workdays, days in bed, and access to care. Results Adults with eczema had $371 to $489 higher out-of-pocket costs per person-year compared with those without eczema, with higher odds of increased out-of-pocket costs (survey multinomial logistic regression, adjusted odds ratios [ORs] [95% CIs] for NHIS 2012, P Conclusions and Relevance This study demonstrates a large health burden of eczema in adults and suggests substantial out-of-pocket costs, indirect costs from lost workdays and sick days, and increased health care utilization.

Growth Attenuation of Cutaneous Angiosarcoma With Propranolol-Mediated β-Blockade

Abstract: IMPORTANCE Patients with stage T2 multilesion angiosarcomas of the scalp and face that are larger than 10 cm demonstrate a 2-year survival rate of 0%. To our knowledge, major therapeutic advances against this disease have not been reported for decades. Preclinical data indicate that blocking β-adrenergic signaling with propranolol hydrochloride disrupts angiosarcoma cell survival and xenograft angiosarcoma progression. OBSERVATIONS A patient presented with a β-adrenergic–positive multifocal stage T2 cutaneous angiosarcoma (20 cm) involving 80% of the scalp, left forehead, and left cheek, with no evidence of metastasis. The patient was immediately administered propranolol hydrochloride, 40 mg twice a day, as his workup progressed and treatment options were elucidated. Evaluation of the proliferative index of the tumor before and after only 1 week of propranolol monotherapy revealed a reduction in the proliferative index of the tumor by approximately 34%. A combination of propranolol hydrochloride, 40 mg 3 times a day, paclitaxel, 2 mg/m 2 infused weekly, and radiotherapy during the subsequent 8 months resulted in extensive tumor regression with no detectable metastases. CONCLUSIONS AND RELEVANCE Our data suggest that β-blockade alone substantially reduced angiosarcoma proliferation and, in combination with standard therapy, is effective for reducing the size of the tumor and preventing metastases. If successful, β-blockade could be the first major advancement in the treatment of angiosarcoma in decades.

Developing a Therapeutic Range of Adalimumab Serum Concentrations in Management of Psoriasis: A Step Toward Personalized Treatment.

Abstract: Importance Adalimumab has proven to be effective in suppressing psoriasis disease activity and is administered in a standard dose. Objective To establish a therapeutic range for adalimumab trough levels in the treatment of plaque-type psoriasis, leading to a more personalized treatment. Design, Setting, and Participants A multicenter, prospective, observational, daily practice cohort study conducted at an academic hospital with affiliated secondary care hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2). Both cohorts included adult patients treated with adalimumab for plaque-type psoriasis. Cohort 1 comprised 73 patients who were being treated with adalimumab for more than 24 weeks until 401 weeks. In cohort 2 (n = 62), serum samples were obtained between weeks 24 and 52 of treatment. Interventions Before the start of adalimumab therapy and at time of serum sampling, Psoriasis Area and Severity Index (PASI) scores were determined. Main Outcomes and Measures Adalimumab trough level and PASI score at the time of serum sampling to determine the receiver-operator characteristics analyses and concentration effect curve. Results By means of receiver-operator characteristics analyses with an area under the curve of 0.756 (SD, 0.046; 95% CI, 0.666-0.847) and a sensitivity of 78% and a specificity of 70%, 3.51 mg/L was established as the lower margin for the therapeutic range. By means of a concentration effect curve, 7 mg/L was established as the upper margin. One-third of patients had an adalimumab trough concentration exceeding 7 mg/L. Conclusions and Relevance A therapeutic range of adalimumab trough levels of 3.51 mg/L to 7.00 mg/L, which corresponds to an optimal clinical effect, was identified. In one-third of patients, it was observed that trough concentrations exceeded the therapeutic window. Based on the established range, a therapeutic algorithm for adalimumab treatment for patients with psoriasis can be developed and validated in a prospective patient cohort. By identifying this range, a step has been taken toward a more rational use of biological therapy in psoriasis. Developing a therapeutic algorithm may lead to less overtreatment of patients and cost savings.

Dermatologic Features of ADA2 Deficiency in Cutaneous Polyarteritis Nodosa

Abstract: Importance Mutations in the CERC1 gene associated with deficiency in the ADA2 protein (DADA2) have been implicated in the pathogenesis of cutaneous polyarteritis nodosa (cPAN) and early-onset vasculopathy. DADA2 is not only limited to cPAN and vasculopathy but also includes immunodeficiency that affects several cellular compartments, including B cells; however, some patients appear to have a more indolent, skin-limited disease. Observations In this report, we describe 2 white siblings (female and male) with a history of cPAN with DADA2 as a result of novel compound heterozygous mutations inherited in trans in the CECR1 gene (c.37_39del [p.K13del] and c.984C>A [p.N328K]). The onset of disease was earlier in the female sibling than the male sibling although both were diagnosed as having cPAN in early childhood. The disease is associated with a more significant immunodeficiency and other systemic symptoms in the female than the male sibling. Conclusions and Relevance These findings suggest a genetic cause of cPAN in some patients. Therefore, DADA2 should be considered in patients with cPAN, specifically in those whose conditions are diagnosed at an early age, regardless of their ethnicity, presence or absence of systemic symptoms, or a family history of the disease.

Systemic Therapy for Psoriasis and the Risk of Herpes Zoster: A 500,000 Person-year Study.

Abstract: Importance The risk for herpes zoster (HZ) in patients with psoriasis treated with biologic medications or other systemic treatments has been given little attention to date. Objective To describe the risk for HZ in patients with psoriasis and its relation to treatment. Design, Setting, and Participants A cohort study was performed using the administrative database of Clalit Health Services, the largest public health care provider organization in Israel, in the setting of general community clinics, primary care and referral centers, and ambulatory and hospitalized care. We extracted information for all patients who received a psoriasis diagnosis from January 2002 to June 2013. Follow-up was conducted until the end of July 2013. The study included 95 941 patients with psoriasis in the analysis, with 522 616 person-years of follow-up. Incidence of HZ events was calculated for each systemic antipsoriatic medication provided, during a follow-up period of 11 years and 7 months. We used a generalized estimating equation Poisson regression model to examine the effect of each systemic treatment for psoriasis on HZ incidence, adjusting for age, sex, psoriasis severity, Charlson comorbidity index, steroid treatment, and socioeconomic status. Main Outcomes and Measures Incidence of HZ associated with systemic therapies. Results In a multivariate analysis, it was observed that treatment with phototherapy (rate ratio [RR], 1.09 [95% CI, 0.62-1.93]; P = .99), methotrexate (RR, 0.98 [95% CI, 0.78-1.23]; P = .83), cyclosporine (RR, 1.16 [95% CI, 0.48-2.80]; P = .49), and biologic medications as a single agent (RR, 2.67 [95% CI, 0.69-10.3]; P = .14) was not associated with HZ. The use of combination treatment with biologic medications and methotrexate was significantly associated with an increased incidence of HZ (RR, 1.66 [95% CI, 1.08-2.57]; P = .02). The use of acitritin was associated with decreased incidence of HZ (RR, 0.69 [95% CI, 0.49-0.97]; P = .004). Conclusions and Relevance Physicians may need to consider offering an HZ preventive vaccine to patients receiving combination treatment with biologic medications and methotrexate, particularly if they have additional risk factors for HZ.