Acquired disorders with hypopigmentation: A clinical approach to diagnosis and treatment.

Acquired hypopigmented skin changes are commonly encountered by dermatologists. Although hypopigmentation is often asymptomatic and benign, occasional serious and disabling conditions present with cutaneous hypopigmentation. A thorough history and physical examination, centered on disease distribution and morphologic findings, can aid in delineating the causes of acquired hypopigmented disorders. The second article in this 2-part continuing medical education series focuses on conditions with a hypopigmented phenotype. Early diagnosis and appropriate management of these disorders can improve a patient's quality of life, halt disease progression, and prevent irreversible disability.

Acquired disorders with depigmentation: A systematic approach to vitiliginoid conditions.

Acquired disorders with depigmentation are commonly encountered by dermatologists and present with a wide differential diagnosis. Vitiligo, the most common disorder of acquired depigmentation, is characterized by well-defined depigmented macules and patches. Other conditions, such as chemical leukoderma, can present with similar findings, and are often easily mistaken for vitiligo. Key clinical features can help differentiate between acquired disorders of depigmentation. The first article in this continuing medical education series focuses on conditions with a vitiligo-like phenotype. Early recognition and adequate treatment of these conditions is critical in providing appropriate prognostication and treatment.

Minimally invasive interval cytoreductive surgery in ovarian cancer: systematic review and meta-analysis.

The introduction of minimally invasive surgery in other gynecologic cancers has shown benefits with similar oncologic outcomes. However, the biology and complexity of surgery for ovarian cancer may preclude this approach for ovarian cancer patients. Our objective is to assess feasibility to achieve complete cytoreductive surgery after neoadjuvant chemotherapy for stage IIIC-IV ovarian cancer patients via minimally invasive surgery. Our data sources include PubMed, Embase, Scopus, Biosis, Clinicaltrials.gov, and the Cochrane Library. Meta-analysis was performed using the random-effects model with DerSimonian and Laird estimator for the amount of heterogeneity to estimate the pooled outcomes. A funnel plot and Egger's regression test were used to test publication bias. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the studies. There were 6 studies (3 prospective, 3 retrospective) that met the criteria for meta-analysis with a total of 3231 patients, 567 were in the minimally invasive group and 2664 in the laparotomy group. Both groups were similar in stage and serous histology. Complete cytoreductive surgery was achieved in 74.50% (95% CI 40.41-97.65%) and 53.10% (95% CI 4.88-97.75%) of patients in the minimally invasive and laparotomy groups, respectively. There was no statistical significant difference between these 2 pooled proportions (p = 0.52). Three studies compared minimally invasive surgery vs laparotomy. No significant difference was observed between the 2 groups in obtaining complete cytoreductive surgery [OR = 0.90 (95% CI 0.70-1.16; p = 0.43)]. A symmetrical funnel plot indicated no publication bias. The pooled proportion for grade > 2 postoperative complications was not significant among the laparoscopy group [3.11% (95% CI 0.00-10.24%; p = 0.15)]. Complete cytoreductive surgery appears feasible and safe with minimally invasive surgery in selected advanced ovarian cancer patients after neoadjuvant chemotherapy.

Biology of human melanocyte development, Piebaldism, and Waardenburg syndrome.

Melanocyte development is orchestrated by a complex interconnecting regulatory network of genes and synergistic interactions. Piebaldism and Waardenburg syndrome are neurocristopathies that arise from mutations in genes involved in this complex network. Our understanding of melanocyte development, Piebaldism, and Waardenburg syndrome has improved dramatically over the past decade. The diagnosis and classification of Waardenburg syndrome, first proposed in 1992 and based on phenotype, have expanded over the past three decades to include genotype. This review focuses on the current understanding of human melanocyte development and the evaluation and management of Piebaldism and Waardenburg syndrome. Management is often challenging and requires a multidisciplinary approach.

Evaluating and Optimizing the Diagnosis of Erythematotelangiectatic Rosacea.

Erythematotelangiectatic rosacea is the most prevalent rosacea subtype. Multiple dermatologic conditions may mimic erythematotelangiectatic rosacea. The authors review a comprehensive approach to evaluating subjects with a suspected diagnosis of erythematotelangiectatic rosacea and discuss findings that may warrant further investigation. Differential diagnoses can be narrowed based on the presence of characteristics such as transient erythema, nontransient erythema, and telangiectasias. A thorough history and physical examination are critical in ruling out conditions such as dermatomyositis, lupus erythematosus, atopic dermatitis, and seborrheic dermatitis.

Revisiting Rosacea Criteria: Where Have We Been, Where Are We Going, and How Will We Get There?

Rosacea is one of the most common and misunderstood dermatologic conditions. Currently, rosacea criteria are based on expert opinion; the definition of rosacea is primarily a reflection of opinion that is prone to bias. It has been more than a decade since the initial criteria were created by the National Rosacea Society. Revisiting the criteria and incorporating evidence-based techniques used by rheumatology and psychiatry can improve the validity and reliability of rosacea criteria. Literature from other specialties is reviewed and a method proposed for developing valid criteria. Examples are provided to motivate and highlight the importance of implementing such techniques.

Desoximetasone 0.25% spray, adrenal suppression and efficacy in extensive plaque psoriasis.

BACKGROUND: In extensive psoriasis, topical corticosteroids are generally only used to supplement phototherapy and systemic therapy. Spray formulations are easier than other vehicle preparations to apply and may be an option for treating extensive psoriasis. OBJECTIVE: To evaluate the potential for hypothalamic-pituitary-adrenal axis suppression and efficacy of topical desoximetasone 0.25% spray formulation in patients with extensive psoriasis. METHODS: A multicenter, open label, nonrandomized, clinical trial was conducted. Two groups of 12 adults with moderate to severe plaque-type psoriasis were treated with 0.25% desoximetasone spray for 28 days. Physician global assessment (PGA) and body surface area (BSA) were assessed. Cortisol-induced suppression test was performed at baseline, day 14 and day 28 to assess safety. RESULTS: No statistically significant difference was seen in adrenal suppression; odds ratio of 0.779 (p = .85). The mean PGA improvement from baseline was 1.83 and 1.33 for moderate and severe psoriasis, respectively. Mean BSA involvement at baseline for moderate and severe psoriasis was 11% and 23%, respectively, improving to 5% and 19%, respectively. CONCLUSIONS: Considerable improvement can be achieved with short-term potent topical corticosteroid treatment even in patients with severe, extensive psoriasis. For such use, topical desoximetasone has less risk of HPA-suppression than does topical clobetasol.

Topical 0.25% desoximetasone spray efficacy for moderate to severe plaque psoriasis: a randomized clinical trial.

BACKGROUND: Traditionally, ointments were the vehicle of choice for psoriasis. Poor adherence of traditional vehicles limits the use of topical corticosteroids. Alternative formulations have gained popularity due to their ease of application, improved adherence and efficacy. OBJECTIVE: To evaluate the efficacy of topical desoximetasone 0.25% spray formulation in extensive psoriasis. METHODS: This multicenter, double-blinded, randomized trial compared twice daily topical 0.25% desoximetasone spray to placebo in subjects ≥18 with moderate to severe plaque psoriasis. Primary outcome of the study was the proportion of subjects in each group that achieved clinical success (Physician Global Assessment [PGA] of 0 or 1) and/or treatment success at (target lesion score of 0 or 1) day 28. RESULTS: One-hundred-and-twenty subjects were enrolled. At baseline, 75.0% and 73.3% of the treatment and placebo group had at least moderate PGA, respectively. Clinical success in the intended-to treat and placebo group was 30% and 5% (p = .0003), respectively; treatment success was 39% and 7% (p < .0001), respectively. LIMITATIONS: The lack of standardized outcomes for topical psoriasis treatments limits the ability to compare the results to other treatments. CONCLUSIONS: Topical desoximetasone spray provides rapid control of moderate to severe psoriasis lesions and may be considered for patients awaiting approval of biologicals. TRIAL REGISTRATION: Clinical Trial was registered at clinicaltrial.gov: NCT01206387.

A Randomized, Double-Blind, Placebo-Controlled Study of the Vasoconstrictor Potency of Topical 0.25% Desoximetasone Spray: A High to Super High Range of Potency (Class I to Class II) Corticosteroid Formulation.

BACKGROUND: Topical corticosteroids offer great efficacy in controlling a wide variety of dermatoses. Traditional ointment vehicles are messy and difficult to apply, which might limit adherence. Alternative vehicle formulations such as topical sprays might improve adherence due to their ease of application. The potency of desoximetasone spray is not fully characterized. OBJECTIVE: To evaluate the relative vasoconstrictive potency of desoximetasone 0.25% topical spray formulation. METHODS: This is a randomized, blinded, single-center study comparing the vasoconstrictive properties of desoximetasone 0.25% topical spray to placebo and seven other known potency topical corticosteroid formulations. The primary endpoint was the degree of vasoconstriction measured using a colorimeter device. RESULTS: Thirty-two healthy subjects met eligibility criteria. Desoximetasone 0.25% topical spray (REGWQ Grouping = A) showed a trend toward greater vasoconstrictive potency compared to clobetasol propionate 0.05% spray (REGWQ Grouping = A). No adverse or serious events were reported. LIMITATIONS: The trial enrolled 90% females, which may affect the external validity of the study. Different populations may respond differently to desoximetasone spray. CONCLUSIONS: Desoximetasone 0.25% topical spray is a high to super high range of potency (Class I to Class II) steroid formulation. Given the cosmetic acceptability of spray products, we anticipate that this type of product would be highly effective for the treatment of inflammatory diseases in clinical practice.

J Drugs Dermatol. 2017;16(10):972-975.

Topical Desoximetasone 0.25% Spray and Its Vehicle Have Little Potential for Irritation or Sensitization.

BACKGROUND: Topical corticosteroids are the most common dermatologic medications and are available in numerous different vehicles. Adherence is limited by traditional vehicles because they are messy and time consuming to apply. The preferred spray formulations have the advantage of being applied with ease, resulting in improved adherence and subsequently improved psoriasis. One limitation of topical treatments, especially spray vehicles, is the potential for irritation and sensitization.

OBJECTIVE: To evaluate the irritation and sensitization potential of topical desoximetasone spray formulation.

METHODS: A multicenter, double-blinded, randomized, controlled study assessed the irritancy and sensitization of 0.25% and 0.05% topical desoximetasone spray. Controls included vehicle, a positive control (0.1% sodium lauryl sulfate), negative control (0.9% saline), and an active comparator control (clobetasol spray). The primary outcome of the study was to evaluate the difference in mean cumulative irritation and potential sensitization response of desoximetasone 0.25% and 0.05% topical sprays.

RESULTS: Of the 297 enrolled, 269 completed the study per protocol for the irritation phase and 250 completed the protocol for the sensitization phase. At 22 days, desoximetasone 0.25 and 0.5% spray were less irritating than clobetasol 0.05% spray; mean irritation score difference of -0.46 and -0.57, respectively. Median total irritation score over the 22 days was 0 for all products. No subjects demonstrated any sensitization reaction to any of the six products. No serious adverse reactions were reported.

LIMITATIONS: Selection bias, use of a healthy population, limits the external validity. In addition, the duration of the study was short lived, unlike numerous inflammatory skin diseases. CONCLUSIONS: Desoximetasone spray has little potential for irritation or sensitization. The availability of another spray option for patients desiring less messy treatment may facilitate better adherence and treatment outcomes.

J Drugs Dermatol. 2017;16(8):755-758.

Interleukin-31 pathway and its role in atopic dermatitis: a systematic review.

BACKGROUND: Atopic dermatitis, a chronic inflammatory disease, has a lifetime prevalence of 10-20%. Atopic dermatitis reduces quality of life, primarily due to pruritus. Interleukin-31 and its target receptor are newly discovered entities that are involved in pruritus. PURPOSE: To summarize the current understanding of interleukin-31 and its role in atopic dermatitis, potential therapeutic interventions and future prospects. METHODS: A systematic review was designed to identify articles related to interleukin-31 and its role in pruritus. Predefined queries containing interleukin-31 and related key terms were searched with no past date restriction, through 31 August 2016, using MEDLINE, Cochrane Controlled Trials Register, ClinicalTrials.gov and the International Clinical Trials Registry Platform Search Portal database. RESULTS: Of 151 identified articles, 61 met eligibility criteria. Interleukin-31 receptors are expressed constitutively on the surface of keratinocytes, eosinophils and small diameter neurons. Overexpression of interleukin-31, independent of mast cells and lymphocytes, induces clinical and histological features consistent with atopic dermatitis. In addition, overexpression of interleukin-31 causes reversible alopecia. Human monoclonal interleukin-31 antagonist, CIM331, decreased pruritus in phase-I and phase-II clinical trials. CONCLUSIONS: Interleukin-31 plays an important role in atopic dermatitis and alopecia. Inhibiting this pathway may provide an alternative to antihistamines for the pruritus of atopic dermatitis.

Relative versus absolute risk of comorbidities in patients with psoriasis.

BACKGROUND: Psoriasis is associated with numerous comorbidities, often reported in terms of relative risk. Both doctors and the general population tend to overestimate the effects of exposures when presented in relative terms, leading to anxiety and potentially poor treatment decisions. Absolute risks might provide a better basis for risk assessment. OBJECTIVE: To characterize and compare relative and absolute risks of comorbidities in patients with psoriasis. METHODS: A systematic review using Medline identified comorbidities associated with psoriasis, their relative risks, and information for calculating absolute risks. RESULTS: The comorbidities associated with psoriasis with the highest relative risk were nonmelanoma skin cancer, melanoma, and lymphoma, with relative risks of 7.5, 6.12, and 3.61, respectively; the attributable risk for these 3 conditions were 0.64, 0.05, and 0.17 per 1000 person-years, respectively. To attribute 1 event of these conditions to psoriasis would require seeing 1551; 20,135; and 5823 patients, respectively. LIMITATIONS: Database studies might not fully account for confounders, resulting in overestimates of the risk impact of comorbidities. CONCLUSIONS: Presenting attributable risk in the form of the number needed to harm provides a clearer picture of the magnitude of risk and a basis for wiser medical decision making and patient education.