Melasma: systematic review of the systemic treatments.

Currently available treatment options for melasma include prevention of UV radiation, topical lightening agents, chemical peels, and light-based and laser therapies. However, none have shown effective and sustained results, with incomplete clearance and frequent recurrences. There has been increasing interest recently in oral medications and dietary supplements in improving melasma. We sought to evaluate the efficacy and safety/tolerability of oral medications and dietary supplements for the treatment of melasma. Multiple databases were systematically searched for randomized clinical trials (RCTs) evaluating the use of oral medication for treatment of melasma alone or in combination with other treatments. A total of eight RCTs met inclusion criteria. Oral medications and dietary supplements evaluated include tranexamic acid, Polypodium leucotomos extract, beta-carotenoid, melatonin, and procyanidin. These agents appear to have a beneficial effect on melasma improvement. In conclusion, oral medications have a role in melasma treatment and have been shown to be efficacious and tolerable with a minimal number and severity of adverse events. Therefore, dermatologists should keep oral medications and dietary supplements in their armamentarium for the treatment of melasma.

Risk of Malignancy in Dermatomyositis and Polymyositis.

BACKGROUND: There is variation in the risk of malignancy in dermatomyositis (DM) and polymyositis (PM) in the existing literature. OBJECTIVE: To conduct a meta-analysis to estimate the risk of malignancy in DM and PM as compared with the general population. METHODS: Medline and Embase Database abstracts were searched through August 2014 using the search terms myositis, neoplasms, and paraneoplastic syndromes. Population-based, observational studies in English were included. Meta-analyses were conducted using random-effects models. RESULTS: A total of 5 studies with 4538 DM or PM patients were included in the analysis. The overall relative risk was 4.66 for DM and 1.75 for PM. By gender, the standardized incidence ratio (SIR) of malignancy among DM patients was 5.29 for males and 4.56 for females; the SIR of malignancy among PM patients was 1.62 for males and 2.02 for females. By time since diagnosis, the SIR of malignancy among DM patients was 17.29 in the first year, 2.7 between 1 and 5 years, and 1.37 after 5 years. By age group, the SIR among DM patients was 2.79 for patients between 15 and 44 years and 3.13 beyond 45 years. CONCLUSIONS: Both DM and PM are associated with increased risk of malignancy, but the risk is higher in DM. The risk of malignancy is present in both genders and all age groups and is highest in the first year after diagnosis but persists beyond the fifth year in DM. Adults should be evaluated for malignancy at diagnosis, followed by long-term surveillance.

Canadian Clinical Practice Guidelines for Rosacea.

Rosacea is a chronic facial inflammatory dermatosis characterized by background facial erythema and flushing and may be accompanied by inflammatory papules and pustules, cutaneous fibrosis and hyperplasia known as phyma, and ocular involvement. These features can have adverse impact on quality of life, and ocular involvement can lead to visual dysfunction. The past decade has witnessed increased research into pathogenic pathways involved in rosacea and the introduction of novel treatment innovations. The objective of these guidelines is to offer evidence-based recommendations to assist Canadian health care providers in the diagnosis and management of rosacea. These guidelines were developed by an expert panel of Canadian dermatologists taking into consideration the balance of desirable and undesirable outcomes, the quality of supporting evidence, the values and preferences of patients, and the costs of treatment. The 2015 Cochrane review "Interventions in Rosacea" was used as a source of clinical trial evidence on which to base the recommendations.

Hospitalizations for cellulitis in Canada: a database study.

BACKGROUND: Cellulitis is the skin disease most commonly responsible for emergency department visits and inpatient admissions. OBJECTIVE: To determine factors associated with prolonged admissions and mortality in inpatients with cellulitis. METHODS: Data on patients with an admission diagnosis of cellulitis from 2004 to 2008 in the Canadian Discharge Abstract Database were analyzed. Factors associated with mortality and prolonged hospital stay (> 7 days) were analyzed in univariate and multivariate analysis through logistic regression. RESULTS: During the study period, 65,454 patients were hospitalized for cellulitis. Factors associated with prolonged admission included admission to or consultation by a surgical service (OR 2.30, 95% CI 2.17-2.43) and dermatology consultation (OR 4.50, 95% CI 3.92-5.17). Factors associated with mortality included surgical (OR 1.35, 95% CI 1.03-1.76) or infectious disease (OR 1.75, 95% CI 1.39-2.21) consultation. CONCLUSION: Misdiagnosis of cellulitis, suggested by the use of consulting services, may play a role in the morbidity and mortality of cellulitis patients.

Lichen planopilaris: update on pathogenesis and treatment.

Lichen planopilaris (LPP) is considered to be a follicular variant of lichen planus. Clinical variants include classic LPP, frontal fibrosing alopecia, and the Graham-Little-Piccardi-Lassueur syndrome. The pathogenesis of LPP remains to be fully elucidated, but like other cicatricial alopecias involves the irreversible destruction of hair follicle stem cells and loss of a hair follicle's capacity to regenerate itself In the early stages of LPP, patients may have scalp pruritus, burning, tenderness, and increased hair shedding. A scalp biopsy shows a lymphocytic infiltrate involving the isthmus and infundibulum. Apoptotic cells present in the external root sheath and concentric fibrosis surrounds the hair follicle. Treatment is prescribed with the goal to alleviate patient symptoms and to halt the progression of hair loss. Treatment involves use of potent topical corticosteroids and/or intralesional corticosteroids. Options for systemic treatment include anti-inflammatory agents such as hydroxychloroquine, tetracyclines, pioglitazones, and immunosuppressive medications such as cyclosporine, mycophenolate mofetil, or systemic corticosteroids. Hair transplantation may also be an option if the disease has been in clinical remission. The management of LPP can sometimes be challenging and additional research is needed to improve outcomes for patients.

Update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment options.

Necrobiosis lipoidica (NL) is a rare chronic granulomatous disease that has historically been associated with diabetes mellitus. Debate exists regarding the etiology and pathogenesis of NL with a widely accepted theory that microangiopathy plays a significant role. NL typically presents clinically as erythematous papules on the front of the lower extremities that can coalesce to form atrophic telangiectatic plaques. NL is usually a clinical diagnosis, but if the clinical suspicion is uncertain, skin biopsy specimen can help differentiate it from sarcoidosis, necrobiotic xanthogranuloma, and granuloma annulare. NL is a difficult disease to manage despite a large armamentarium of treatment options that include topical and intralesional corticosteroids, immunomodulators, biologics, platelet inhibitors, phototherapy, and surgery. Randomized control trials are lacking to evaluate the many treatment methods and establish a standard regimen of care. Disease complications such as ulceration are common, and lesions should also be monitored for transition to squamous cell carcinoma, a less common sequelae.

Mortality from acquired bullous diseases of skin in Canadian adults 2000-2007.

BACKGROUND: Bullous skin diseases are known to be associated with significant morbidity and mortality. There have been no studies on mortality from severe bullous skin diseases in Canada. METHODS: We used mortality data from the Statistics Canada website from 2000 to 2007 for three major bullous skin diseases: bullous pemphigoid; pemphigus; and toxic epidermal necrolysis (TEN). Crude and age-standardized mortality rates were calculated and compared with the corresponding US mortality rates. Linear regression was used to assess time trend and effect of gender and age on mortality rates. RESULTS: During the period of eight years, there were 115 deaths attributed to pemphigoid, 84 to pemphigus, and 44 to TEN. The crude annual mortality rate was the highest for pemphigoid (0.045 per 100,000), followed by pemphigus (0.033), and TEN (0.017). None of these conditions demonstrated significant time trends in mortality rates over the eight-year period, although a trend towards decreasing pemphigus mortality was observed (P = 0.07). No gender difference in mortality was observed, but advanced age was associated with mortality in all three conditions. CONCLUSION: Among bullous skin diseases, pemphigoid is the leading cause of mortality in Canada. This is in contrast to the USA, where TEN is the leading cause of mortality from bullous skin diseases. It is not clear whether differences in healthcare systems explain these findings.

Narrowband UVB as an effective substitute for psoralen plus UVA: lessons from a psoralen shortage.

From March to August 2010, there was a shortage of encapsulated liquid 8-methoxypsoralen (8-MOP), the psoralen used for bath psoralen plus UVA (PUVA) in Toronto, Canada. Patients were forced to discontinue bath PUVA treatment and were transitioned to other therapeutic modalities, including narrowband UVB (nbUVB). A retrospective chart review was conducted of all patients who discontinued bath PUVA due to the unavailability of 8-MOP, with a focus on those who were switched to nbUVB. Sixty-three patients discontinued PUVA, 39 of whom were switched to nbUVB. Fifteen of 17 patients with mycosis fungoides (MF) who were switched to nbUVB improved, and patients with earlier-stage disease were more likely to improve. Ten of 13 (77%) psoriasis patients improved with nbUVB, including two patients whose psoriasis cleared completely. All three small-plaque parapsoriasis patients who switched to nbUVB had complete clearance of their lesions. In conclusion, nbUVB may be a suitable alternative for patients with MF, small-plaque parapsoriasis and psoriasis who cannot access PUVA therapy.

Prospective registration and outcome-reporting bias in randomized controlled trials of eczema treatments: a systematic review.

We assessed completeness of trial registration and the extent of outcome-reporting bias in published randomized controlled trials (RCTs) of eczema (atopic dermatitis) treatments by surveying all relevant RCTs published from January 2007 to July 2011 located in a database called the Global Resource of Eczema Trials (GREAT). The GREAT database is compiled by searching six bibliographic databases, including EMBASE and MEDLINE. Out of 109 identified RCTs, only 37 (34%) had been registered on an approved trial register. Only 18 out of 109 trials (17%) had been registered "properly" in terms of submitting the registration before the trial end date and nominating a primary outcome. The proportion of "any registered" and "properly registered" RCTs increased from 19% and 10% in 2007 to 57% and 36% in 2011, respectively. Assessment of selective outcome-reporting bias was difficult even among the properly registered trials owing to unclear primary outcome description especially with regard to timing. Only 5 out of the 109 trials (5%) provided enough information for us to be confident that the outcomes reported in the published trial were consistent with the original registration. Adequate trial registration and description of primary outcomes for eczema RCTs is currently poor.

Use of pioglitazone in patients with lichen planopilaris.

BACKGROUND: Recent basic science research has revealed a decreased tissue expression of peroxisome proliferator-activated receptor (PPAR) γ in lichen planopilaris (LPP). Therefore, thiazolidinediones, being PPARγ agonists, could be used to treat LPP. METHODS: We followed 24 patients with LPP who were treated with oral pioglitazone hydrochloride. Improvement in LPP was defined as a decrease in or disappearance of symptoms and perifollicular erythema in the context of halted spread of old patches. RESULTS: Twenty of 24 patients were females. The average age was 52.5 years, and ages ranged from 22 to 70 years. Five of 24 patients have achieved remission; improvement was noted in half of the patients; there was no change in 3 patients; and 4 patients discontinued treatment due to side effects. Side effects were mild and included left calf pain, lightheadedness and nausea, dizziness, and hives. CONCLUSION: Use of thiazolidinediones might be a new promising venue of LPP treatment.

Techniques to minimize the pain of injected local anesthetic.

The process of injecting local anesthetic still often remains the most uncomfortable part of dermatologic surgery for patients. This review discusses strategies that may be used to reduce this discomfort.

Socioeconomic status, hospital volume, and stroke fatality in Canada.

BACKGROUND AND PURPOSE: Low socioeconomic status is associated with stroke fatality; however, the mechanism behind this association is uncertain. We sought to determine whether residence in a low-income neighborhood was associated with admission to low-volume facilities and whether this contributed to differences in fatality after stroke. METHODS: All hospitalizations for ischemic stroke from April 2003 to March 2004 were identified from a national administrative database containing patient-level sociodemographic, diagnostic, procedural, and administrative information. Patients were assigned to income quintiles based on the median income of their primary neighborhood of residence and then categorized as low income (quintiles 1 and 2) or high income (quintiles 3 through 5). Hospitals were categorized as low or high volume on the basis of their annual number of stroke admissions. Multivariable analyses were performed to compare stroke fatality at 7 days and at discharge in patients in low- and high-income groups seen at low- and high-volume facilities. RESULTS: Overall, 25,228 patients with ischemic stroke were included in the analysis. Those from high-income areas were more likely to be admitted to high-volume hospitals. Fatality at 7 days was 8.4%, 8.2%, 7.7%, 7.1, and 6.6% (chi(2)=0.002) for income quintiles 1 (lowest) to 5 (highest), respectively. Low-income patients admitted to low-volume hospitals had the highest risk-adjusted stroke fatality. CONCLUSIONS: Patients from low-income areas presenting with acute stroke are more likely to be seen in low-volume facilities. This subgroup of patients had a higher risk-adjusted fatality than those from high-income areas seen at high-volume facilities. Understanding the pathways through which socioeconomic status affects health care may lead to strategies for quality improvement.

A comparison of the cost-effectiveness of in vitro fertilization strategies and stimulated intrauterine insemination in a Canadian health economic model.

BACKGROUND: In vitro fertilization (IVF) with single embryo transfer (SET) has been proposed as a means of reducing multiple pregnancies associated with infertility treatment. All existing cost-effectiveness studies of IVF-SET have compared it with IVF with multiple embryo transfer but not with intrauterine insemination with gonadotropin stimulation (sIUI). METHODS: We conducted a systematic review of studies of cost-effectiveness of IVF-SET versus IVF with double embryo transfer (DET). Further, we developed a health economy model that compared three strategies: (1) IVF-SET, (2) IVF-DET, and (3) sIUI. The decision analysis considered three cycles for each treatment option. IVF treatment was assumed to be a combination of cycles with transfer of fresh and frozen-thawed embryos. Probabilities used to populate the model were taken from published randomized clinical trials and observational studies. Cost estimates were based on average costs of associated procedures in Canada. RESULTS: The results of published studies on the cost-effectiveness of IVF-SET versus IVF-DET were not consistent. In our analysis, IVF-DET proved to be the most cost-effective strategy at $35,144/live birth, followed by sIUI at $66,960/live birth, and IVF-SET at $109,358/live birth. The results were sensitive both to the cost of IVF cycles and to the probability of live birth. CONCLUSION: This economic analysis showed that IVF-DET was the most cost-effective strategy of the options, and IVF-SET was the least cost-effective. The results in this model were insensitive to various probability inputs and to the costs associated with sIUI and IVF procedures.

Weekends: a dangerous time for having a stroke?

BACKGROUND AND PURPOSE: Weekend admissions are associated with higher in-hospital mortality. However, limited information is available concerning the "weekend effect" on stroke mortality. Our aim was to evaluate the impact of weekend admissions on stroke mortality in different settings. METHODS: We analyzed all hospital admissions for ischemic stroke from April 2003 to March 2004 through the Hospital Morbidity Database. The Hospital Morbidity Database is a national database that contains patient-level sociodemographic, diagnostic, procedural, and administrative information including all acute care facilities across Canada. The major inclusion criterion was admission to an acute care facility with a principal diagnosis of ischemic stroke. Clinical variables and facility characteristics were included in the analysis. RESULTS: Overall, 26,676 patients were admitted to 606 hospitals for ischemic stroke. Weekend admissions comprised 6629 (24.8%) of all admissions. Seven-day stroke mortality was 7.6%. Weekend admissions were associated with a higher stroke mortality than weekday admissions (8.5% vs 7.4%; odds ratio, 1.17; 95% CI, 1.06 to 1.29). Mortality was similarly affected among patients admitted to rural versus urban hospitals or when the most responsible physician was a general practitioner versus specialist. In the multivariable analysis, weekend admissions were associated with higher early mortality (odds ratio, 1.14; 95% CI, 1.02 to 1.26) after adjusting for age, sex, comorbidities, and medical complications. CONCLUSIONS: Stroke patients admitted on weekends had a higher risk-adjusted mortality than did patients admitted on weekdays. Disparities in resources, expertise, and healthcare providers working during weekends may explain the observed differences in weekend mortality.

Patient characteristics associated with nocturnal emergency department visits for asthma.

STUDY OBJECTIVES: To identify patient characteristics associated with nocturnal emergency department (ED) visits for asthma. METHODS: Asthmatic patients 18 to 55 years of age who visited Ontario EDs between April 1, 2003 and March 31, 2004, were identified through an administrative clinical database. Patients' time of ED presentation was analyzed for circadian pattern using histogram and polynomial regression. Risk of nocturnal visit (presentation at the ED between midnight and 8 AM) was modeled through generalized estimating equations with patient age, gender, and asthma severity level as covariates. The effect of nocturnal visit on return rate to the ED within 14 days after the initial visit was determined through Cox regression. RESULTS: During study period there were 31,490 ED visits for asthma made by 23,253 patients. Their time of ED visits displayed a distinct circadian pattern with peak between 7 and 8 PM, and trough at 5 AM. Approximately 22% of visits (6,868) occurred at night. Men had higher odds of presenting at night than women (OR 1.61; 1.49-1.73). Patients with mild asthma were significantly less likely to visit the ED at night than patients with moderate or severe asthma. Nocturnal presentation was not associated with higher odds of subsequent returns to the ED (HR 1.00; 0.89-1.14). CONCLUSION: Higher odds of nocturnal visits in men suggest the existence of gender-differences in health-seeking behavior in asthmatics. Although nocturnal visits are associated with more severe asthma, they do not lead to higher return rates.

Is fetal gender associated with emergency department visits for asthma during pregnancy?

BACKGROUND: To investigate if fetal gender (1) affects the risk of having an emergency department (ED) visit for asthma; and (2) is associated with adverse pregnancy outcomes among women who had at least one visit to the ED for asthma during pregnancy. METHODS: We linked two provincial administrative databases containing records on in-patient deliveries and ED visits. The study sample included women who delivered a live singleton baby between April 2003 and March 2004. Pregnant women who made at least one ED visit for asthma were counted as cases and the rest of the women as control subjects. We performed a multivariable analysis using logistic regression to model the risk of having an ED visit for asthma, with fetal gender being one of the predictors. In addition, a series of multivariable logistic regressions were also constructed separately for cases and controls for the following adverse delivery outcomes: low birth weight baby, preterm delivery, and delivery via Caesarian section. RESULTS: Among 109,173 live singleton deliveries, 530 women had visited ED due to asthma during pregnancy. While having an ED visit for asthma was positively associated with teenage pregnancy, low income, and presence of pregnancy-induced hypertension, it was not associated with fetal gender (OR 1.01, 95% CI 0.85-1.19). Fetal gender was not a significant predictor of adverse pregnancy outcomes among women who had an asthma ED visit during pregnancy. CONCLUSION: Fetal gender does not affect the risk of having an ED visit for asthma during pregnancy, and it is not associated with adverse pregnancy outcomes among women who had an asthma-related ED during pregnancy.

Does a birthday predispose to vascular events?

OBJECTIVE: To examine the influence of birthdays on the onset and course of vascular events such as stroke, TIA, and acute myocardial infarction (AMI). METHODS: This population-based study included all emergency department (ED) admissions due to ischemic stroke, TIA, or AMI from April 2002 to March 2004 in Ontario, Canada. All cases were identified through the National Ambulatory Care Reporting System. Calculations of daily and weekly numbers of events were centered on the patient's birthday and the week of the birthday. Statistical analyses include binomial tests and logistic regression. RESULTS: During the study period, there were 24,315 ED admissions with acute stroke, 16,088 with TIAs, and 29,090 with AMI. The observed number of vascular events during the birthday was higher than the expected daily number of visits for stroke (87 vs 67; p = 0.009), TIA (58 vs 44; p = 0.02), and AMI (97 vs 80; p = 0.027) but not for selected control conditions (asthma, appendicitis, head trauma). Vascular events were more likely to occur on birthday (242 vs 191; odds ratio [OR] = 1.27). No significant differences were observed during the birthday week for any of the conditions. Multivariate logistic regression showed that birthday vascular events were more likely to occur in patients with a history of hypertension (OR = 1.88; 95% CI 1.09 to 3.24). Sensitivity analyses with alternative definitions of birthday week did not alter the results. CONCLUSIONS: Stress associated with birthdays may trigger vascular events in patients with predisposing conditions.

Sex differences in hospital admissions from emergency departments in asthmatic adults: a population-based study.

BACKGROUND: Women represent the majority of adult patients hospitalized for asthma. Analyzing the course of emergency department (ED) visits before hospital admission can help understanding of the mechanisms behind the excess of hospitalizations in women. OBJECTIVE: To investigate sex differences in hospital admission rates in adult patients with asthma visiting EDs in Ontario. METHODS: Asthmatic patients 18 to 55 years old who visited Ontario EDs between April 1, 2003, and March 31, 2004, were identified using the Canadian Institute for Health Information's National Ambulatory Care Reporting System. The generalized estimating equations for binary outcome were used to model rates of hospital admission with sex, age, and triage (severity) score as covariates. Analysis was further stratified by the ED volume. RESULTS: Women represented 62.2% of all ED visits. They were on average older than men, but both groups had similar distributions of triage scores. Female patients accounted for more hospital admissions than male patients (7.4% vs 4.5%). After adjusting for age and triage score, women were more likely to be admitted than men (odds ratio, 1.64; 95% confidence interval, 1.41-1.90). The interaction found between sex and triage level indicates that hospitalized women may have less severe asthma than hospitalized men. Analysis by ED volume did not significantly alter the results. CONCLUSION: The higher admission rates in women may be related to sex differences in the subjective perception of dyspnea, management of asthma by ED physician, or inadequate ambulatory care strategies in women and thus merit further investigation.