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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
ACNE AND ROSACEA
Relationship between acne and low-fat or skim milk consumption (August 2016)
Several studies have reported associations between dairy consumption and acne. A new case-control study used three 24-hour diet recall phone interviews to evaluate dietary intake, validated software for data collection, and dermatologist assessment of acne severity . An association was found between acne and higher consumption of low-fat or skim milk, comparing 120 teenagers with moderate facial acne and 105 teenagers without acne. There was no association for full fat milk. Although this study supports a relationship between acne and low-fat or skim milk consumption, further study is needed before specific dietary recommendations can be made for patients with acne. (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris", section on 'Diet'.)
ATOPIC DERMATITIS AND OTHER DERMATITIS
Investigational topical tofacitinib for atopic dermatitis (November 2016)
Tofacitinib is a small-molecule JAK kinase inhibitor that is currently available as an oral therapy for rheumatoid arthritis. An investigational topical preparation was compared with placebo in a randomized trial of 69 adult patients with mild to moderate atopic dermatitis, treated for four weeks . Compared with those receiving placebo, subjects receiving tofacitinib showed greater improvements in eczema area and severity scores, were more likely to be assessed by physicians as clear or almost clear, and tolerated the drug well. Larger studies of longer duration are needed to evaluate long-term efficacy and safety. (See "Treatment of atopic dermatitis (eczema)", section on 'Tofacitinib'.)
Persistence of pediatric atopic dermatitis (November 2016)
Atopic dermatitis (AD) is a chronic disease with a highly variable course. Although most children are thought to “outgrow” it before adolescence, little is known about the factors associated with its persistence into adulthood. A meta-analysis including over 110,000 subjects found that 20 percent of children with AD had persistent disease eight years after the diagnosis, and less than 5 percent had persistent disease 20 years later . Children who developed AD before two years of age had a much lower risk of persistent disease than those who developed AD later in childhood or during adolescence. Other predictors of persistent AD were severity and duration of AD and female sex, whereas hypersensitivity to one or more allergens at disease onset did not seem to influence the persistence of disease. (See "Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)", section on 'Clinical course and complications'.)
Dupilumab for moderate to severe atopic dermatitis in adults (October 2016)
Two 16-week phase III trials of identical design, including nearly 1400 adults, evaluated the efficacy of dupilumab, an investigational monoclonal antibody that targets interleukin 4 and 13, for the treatment of atopic dermatitis not controlled by topical therapies . The primary end point was the proportion of patients to achieve a "clear" or "almost clear" rating, which occurred in approximately 40 and 10 percent of patients receiving dupilumab and placebo, respectively. The drug was well tolerated. Dupilumab is not yet available for clinical use. (See "Treatment of atopic dermatitis (eczema)", section on 'Dupilumab'.)
Investigational topical therapy for atopic dermatitis (September 2016)
Crisaborole is a topical boron-based phosphodiesterase-4 inhibitor with limited systemic absorption, which is under investigation as a novel topical therapy for atopic dermatitis. In two identical, multicenter randomized trials, a total of 1522 patients ≥2 years old with mild to moderate atopic dermatitis were treated with crisaborole 2% ointment or vehicle twice daily for 28 days . More patients in the crisaborole groups than in the vehicle groups achieved the primary end point (an investigator’s global assessment score of 0 [clear] or 1 [almost clear] with a two-grade or more improvement from baseline). Improvement was noted in pruritus, skin inflammation, excoriation, and lichenification. Crisaborole-related adverse events occurred in 4.4 percent of patients and were mild and limited to burning or stinging at the site of application. Although crisaborole appears a promising nonsteroidal topical treatment for mild to moderate atopic dermatitis, studies of longer duration than four weeks are needed to evaluate its efficacy and safety. (See "Treatment of atopic dermatitis (eczema)", section on 'Crisaborole'.)
Water hardness and risk of atopic dermatitis (June 2016)
Epidemiologic evidence has linked high levels of calcium carbonate in domestic water (ie, “hard” water) with increased prevalence of atopic dermatitis in children. A population-based cross-sectional study including 1303 three-month-old infants found that high levels of calcium carbonate, but not of chlorine, in household water were associated with a nearly doubled risk of visible atopic dermatitis compared with low calcium carbonate levels, after adjusting for potential confounders (presence of filaggrin mutation, sex, ethnicity, and maternal age) . However, the results of this study should be interpreted with caution, because residual confounding from unmeasured factors, such as changes in skin care practices associated with presence of eczema or dry skin, cannot be excluded. Further studies are needed to evaluate this association. (See "Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)", section on 'Risk factors'.)
AUTOIMMUNE AND SYSTEMIC DISEASES
Guidelines for the treatment of systemic sclerosis (October 2016)
The British Society for Rheumatology (BSR) and the British Health Professionals in Rheumatology (BHSR) have published a comprehensive set of guidelines for the management of systemic sclerosis (SSc) . Some of the key points include the importance of making an early diagnosis and considering treatment with an immunosuppressive agent in patients with diffuse cutaneous SSc of less than three years' duration. They also review the major therapies for treating organ-based disease and emphasize the importance of referring patients to specialty centers with access to multidisciplinary care. (See "Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults", section on 'General principles of management'.)
Screening and prevention of hydroxychloroquine retinopathy (August 2016)
Antimalarial agents hydroxychloroquine (HCQ) and chloroquine are widely used for the treatment of systemic lupus erythematosus, rheumatoid arthritis, and other inflammatory and dermatologic conditions, and are generally thought to be safe. Retinal toxicity is a known risk, however, and measures to minimize this potential toxicity are necessary. Recently, the American Academy of Ophthalmology issued revised recommendations for screening and prevention of retinopathy . Key changes include the following:
●The maximum daily dose of HCQ should not exceed 5 mg/kg (previously 6.5 mg/kg), and the maximum daily dose of chloroquine should not exceed 2.3 mg/kg (previously 3 mg/kg).
●Real body weight should be used to calculate dose limits instead of ideal body weight.
In addition to exceeding the recommended daily dose, major risk factors for retinal toxicity include antimalarial use for greater than five years, renal disease, concomitant tamoxifen use, and the presence of macular disease. All patients should undergo a baseline eye examination before or within a year of beginning treatment with an antimalarial drug and, if normal, at least annually after five years of exposure for patients without major risk factors. For the treatment of rheumatic diseases, we typically use standard daily doses of HCQ (non-weight-based, eg, up to 400 mg) in individuals weighing 80 kg or more. In patients weighing less than 80 kg, we use a lower daily dose of HCQ up to the maximum of 5 mg/kg of real body weight. (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Ocular health'.)
PSORIASIS AND OTHER PAPULOSQUAMOUS DISORDERS
Secukinumab versus ustekinumab for moderate to severe plaque psoriasis (September 2016)
Previous data from the CLEAR trial, a randomized trial that compared secukinumab to ustekinumab for moderate to severe plaque psoriasis, demonstrated superiority of secukinumab over a treatment period of 16 weeks. An analysis of 52-week data from the CLEAR trial shows sustained superiority of secukinumab with continued treatment . At week 52, 76 percent of patients in the secukinumab group achieved at least 90 percent improvement in the Psoriasis Area and Severity Index score compared with 61 percent in the ustekinumab group. In addition, secukinumab was associated with greater improvement in health-related quality of life. Safety was comparable between the two groups. (See "Treatment of psoriasis", section on 'Secukinumab'.)
Ixekizumab for moderate to severe plaque psoriasis (June 2016)
Similar to the previously published UNCOVER-2 and UNCOVER-3 trials, high efficacy of ixekizumab (a humanized monoclonal antibody against IL-17A) for moderate to severe plaque psoriasis was demonstrated in the UNCOVER-1 trial, which compared every-two-week and every-four-week regimens of ixekizumab with placebo . In addition, data from long-term extension periods of the UNCOVER trials supports efficacy of ixekizumab through 60 weeks of treatment. Adverse effects reported during ixekizumab treatment included candidal infections, neutropenia, and inflammatory bowel disease. These data support the inclusion of ixekizumab in the therapeutic armamentarium for psoriasis. (See "Treatment of psoriasis", section on 'Ixekizumab'.)
USPSTF recommendations for skin cancer screening (August 2016)
In July 2016, the United States Preventive Services Task Force (USPSTF) updated its statement on skin cancer screening and concluded that there is insufficient evidence to assess the balance of benefits and harms of screening for skin cancer in asymptomatic adults with a clinical visual skin examination . Although we agree with the USPSTF conclusion, we suggest that persons at higher risk for fatal melanoma (eg, white men 50 years of age and over), individuals with multiple moles or at least a few clinically atypical moles, and individuals with the “red hair phenotype” have a total body skin examination performed by a clinician who has had appropriate training in the identification of melanoma. (See "Screening and early detection of melanoma", section on 'Recommendations of expert groups'.)
Partner involvement in skin self-examination for early melanoma detection (July 2016)
For patients at increased risk of melanoma, having a partner involved in skin self-examination may increase the rates of self-examination and early melanoma detection. The effect of a structured educational intervention on the performance of skin self-examination and early detection of new melanomas was examined in a randomized trial including 494 melanoma patients and their partners . During the two years of follow-up, a total of 66 patients developed a new melanoma. In the group of 395 patient-partner pairs receiving the intervention, 43 melanomas (33 in situ) were identified by patients or their partners and 10 by clinicians; in contrast, all 16 melanomas in the control group were identified by clinicians and none by the patient-partner pairs. (See "Screening and early detection of melanoma", section on 'Self-examination'.)
MC1R gene variants and risk of melanoma (June 2016)
Variants of the melanocortin-1 receptor (MC1R) gene, a key regulator of skin pigmentation, are associated with the sunlight-sensitive red hair/fair skin phenotype, a known risk factor for melanoma. However, some MC1R variants may carry an increased risk of melanoma independent of phenotypic characteristics and sun exposure. In a case-control study including 991 patients with melanoma and 800 controls, carriers of two or more MC1R variants had an approximately twofold increased risk of melanoma, compared with wild type carriers, after adjusting for age, sex, number of sunburns before age 20, and signs of actinic skin damage . Additional studies are needed to determine the precise role of altered MC1R variants in melanoma tumorigenesis. (See "Risk factors for the development of melanoma", section on 'Genetic background'.)
Adalimumab for hidradenitis suppurativa (August 2016)
Hidradenitis suppurativa, also known as acne inversa, is often challenging to treat. Two similar phase III randomized trials (PIONEER I [n = 307] and PIONEER II [n = 326]) support the efficacy of adalimumab for moderate to severe hidradenitis suppurativa . After 12 weeks, more patients assigned to the adalimumab groups achieved a clinical response (≥50 percent reduction in the total abscess and inflammatory nodule count with no increase in the abscess or draining fistula count) compared with the placebo groups (42 versus 26 percent in PIONEER I and 59 versus 28 percent in PIONEER II). Rates of serious adverse events were similar between the adalimumab and placebo groups. These findings support adalimumab as a treatment option for moderate to severe hidradenitis suppurativa. Improvement, however, is generally only partial. (See "Hidradenitis suppurativa (acne inversa): Treatment", section on 'TNF-alpha inhibitors'.)
New guidelines for the management of Stevens-Johnson/toxic epidermal necrolysis syndrome (August 2016)
The British Association of Dermatologists released new guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), a severe and potentially fatal mucocutaneous drug reaction . The guidelines provide evidence-based recommendations for the diagnosis, severity assessment, and management of SJS/TEN. Specific areas covered include initial management, supportive care, and therapies intended to reduce mortality, such as intravenous immune globulins, systemic corticosteroids, and cyclosporine. The treatment of eye involvement, including systemic therapies and amniotic membrane transplantation to prevent permanent ocular sequelae, as well as the management of oral, urogenital, and airway mucosal involvement are also addressed. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae", section on 'General principles'.)
- LaRosa CL, Quach KA, Koons K, et al. Consumption of dairy in teenagers with and without acne. J Am Acad Dermatol 2016; 75:318.
- Bissonnette R, Papp KA, Poulin Y, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol 2016; 175:902.
- Kim JP, Chao LX, Simpson EL, Silverberg JI. Persistence of atopic dermatitis (AD): A systematic review and meta-analysis. J Am Acad Dermatol 2016; 75:681.
- Simpson EL, Bieber T, Guttman-Yassky E, et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 2016.
- Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol 2016; 75:494.
- Perkin MR, Craven J, Logan K, et al. Association between domestic water hardness, chlorine, and atopic dermatitis risk in early life: A population-based cross-sectional study. J Allergy Clin Immunol 2016; 138:509.
- Denton CP, Hughes M, Gak N, et al. BSR and BHPR guideline for the treatment of systemic sclerosis. Rheumatology (Oxford) 2016; 55:1906.
- Marmor MF, Kellner U, Lai TY, et al. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology 2016; 123:1386.
- Blauvelt A, Reich K, Tsai TF, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: Results from the CLEAR study. J Am Acad Dermatol 2016.
- Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med 2016; 375:345.
- US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for Skin Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2016; 316:429.
- Robinson JK, Wayne JD, Martini MC, et al. Early Detection of New Melanomas by Patients With Melanoma and Their Partners Using a Structured Skin Self-examination Skills Training Intervention: A Randomized Clinical Trial. JAMA Dermatol 2016; 152:979.
- Wendt J, Rauscher S, Burgstaller-Muehlbacher S, et al. Human Determinants and the Role of Melanocortin-1 Receptor Variants in Melanoma Risk Independent of UV Radiation Exposure. JAMA Dermatol 2016; 152:776.
- Kimball AB, Okun MM, Williams DA, et al. Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa. N Engl J Med 2016; 375:422.
- Creamer D, Walsh SA, Dziewulski P, et al. U.K. guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016. Br J Dermatol 2016; 174:1194.