What’s new in dermatology

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2019. | This topic last updated: Mar 27, 2019.
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

Coffee consumption and rosacea (December 2018)

Individuals with rosacea are often counseled that consumption of coffee and other hot beverages may exacerbate their disease. In contrast, an analysis of data from over 80,000 women in the Nurses’ Health Study II found that, compared with women with the lowest consumption of caffeinated coffee, women with the highest consumption were less likely to develop rosacea [1]. In addition, there was an inverse relationship between increased caffeine intake and risk of incident rosacea. There was no association between risk for rosacea and consumption of decaffeinated coffee. These findings suggest that restriction of coffee consumption is not necessary for patients with rosacea. (See “Rosacea: Pathogenesis, clinical features, and diagnosis”, section on ‘Exacerbating factors’.)

ATOPIC DERMATITIS AND OTHER DERMATITIS

Lack of efficacy of second-generation antihistamines for atopic dermatitis (March 2019)

First- and second-generation oral H1 antihistamines are widely used in patients with atopic dermatitis as a therapeutic adjunct to alleviate pruritus. However, a 2019 systematic review of 25 randomized trials, including both adults and children, did not find evidence that second-generation, less sedating antihistamines (eg, cetirizine, loratadine, fexofenadine) are effective in improving the signs and symptoms of atopic dermatitis [2]. In the largest trial, including nearly 800 children aged one to two years, cetirizine for 18 months was no more effective than placebo in reducing the Scoring Atopic Dermatitis (SCORAD) score. Given these data, the use of second-generation antihistamines for atopic dermatitis should be limited to patients with concurrent urticaria or allergic rhinitis. (See “Treatment of atopic dermatitis (eczema)”, section on ‘Controlling pruritus’.)

Allergic contact dermatitis to acrylates in artificial nails (March 2019)

Acrylates are widely used in plastics, adhesives, and paints, as well as for application of artificial nails and nail sculpting. In a European study, nearly two-thirds of cases of acrylate-allergic contact dermatitis were caused by nail acrylates [3]. These occurred in women in the vast majority of cases, and were associated with nonoccupational (recreational) use of cosmetic nail products in approximately one-half of the cases. As nail acrylates can be involuntarily transferred to the face, patch testing for acrylates may be appropriate in patients wearing artificial nails with otherwise unexplained facial or eyelid dermatitis. (See “Common allergens in allergic contact dermatitis”, section on ‘Acrylates’.)

Melatonin for atopic dermatitis (January 2019)

Melatonin is a hormone involved in the regulation of sleep and circadian rhythms. Antioxidant, anti-inflammatory, and immunomodulating properties have also been suggested, though not proven. In a randomized trial, 70 children with atopic dermatitis aged 6 to 12 years were given oral melatonin 6 mg or placebo an hour before bedtime for six weeks, while continuing their usual treatment with topical corticosteroids and emollients [4]. Children in the melatonin group had a greater improvement in the total Scoring Atopic Dermatitis (SCORAD) score from baseline and in the total Children’s Sleep Habits Questionnaire score, but not in the pruritus score. Treatment was well tolerated and no adverse effects were reported. However, as atopic dermatitis is a chronic disease requiring long-term treatment, larger studies with a longer follow-up time are needed to assess the efficacy and safety of melatonin as a complementary treatment for atopic dermatitis. (See “Treatment of atopic dermatitis (eczema)”, section on ‘Melatonin’.)

Depression and suicidal ideation in patients with atopic dermatitis (January 2019)

Atopic dermatitis, especially when severe or poorly controlled, may be associated with psychosocial distress and psychiatric comorbidities, driven by multiple factors including disabling pruritus, loss of sleep, social embarrassment, and possible inflammatory effects on neuromodulators. A 2019 meta-analysis of 37 observational studies found a nearly twofold increased risk of depression and suicidal ideation in children and adults with atopic dermatitis, compared with individuals without the disease [5]. These findings suggest that clinicians treating patients with atopic dermatitis should be vigilant for depressive symptoms and the possible need for psychiatric referral, especially among those with severe disease. (See “Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis”, section on ‘Depression and anxiety disorder’.)

Probiotics not effective for atopic dermatitis (December 2018)

There is some evidence that probiotics given prenatally and/or in early life may reduce the risk of developing atopic dermatitis, but their role in treating established disease is controversial. A meta-analysis of 39 randomized trials including nearly 2600 patients of all ages with mild to severe atopic dermatitis did not find a difference between probiotics (Lactobacillus and Bifidobacteria species) and placebo in improving patient/parent-rated severity of atopic dermatitis, pruritus, sleep loss, or quality of life [6]. A modest reduction of uncertain clinical significance in the Scoring Atopic Dermatitis (SCORAD) score was noted in patients taking probiotics compared with placebo. We do not routinely use probiotics as a complementary treatment for atopic dermatitis, because the clinical benefit is minimal at best. (See “Treatment of atopic dermatitis (eczema)”, section on ‘Probiotics’ and “Prebiotics and probiotics for treatment of allergic disease”, section on ‘Eczema’.)

Montelukast not effective for atopic dermatitis (November 2018)

The efficacy of montelukast, an oral leukotriene receptor antagonist used as a steroid-sparing agent for the treatment of asthma and allergic rhinitis, in the management of atopic dermatitis is uncertain. A systematic review evaluated five randomized trials of montelukast, compared with placebo or usual care, for patients (mostly adults) with moderate-to-severe atopic dermatitis and found the overall quality of the evidence to be low [7]. Montelukast did not decrease disease severity, pruritus, or need for topical corticosteroids, compared with placebo; one trial found improvement in disease severity with montelukast compared with usual care but another trial did not. Because of the limited and low-quality available evidence, the role of leukotriene receptor antagonists in the management of atopic dermatitis remains uncertain. While waiting for larger and well-designed studies, we do not support the use of this class of agents for atopic dermatitis. (See “Treatment of atopic dermatitis (eczema)”, section on ‘Leukotriene receptor antagonists’.)

AUTOIMMUNE AND SYSTEMIC DISEASES

Diagnostic strategy for bullous pemphigoid (February 2019)

Early diagnosis of bullous pemphigoid (BP) is sometimes challenging because of varying clinical presentations. A study of over 1100 patients with suspected bullous pemphigoid supports use of both direct immunofluorescence (DIF) microscopy and indirect immunofluorescence (IIF) on human salt-split (basement membrane zone-split) skin as diagnostic tests, with minimal criteria for diagnosis being at least two of the following: pruritus and/or predominant cutaneous blisters, linear IgG and/or C3c deposits in an n-serrated pattern on DIF, and IIF on human salt-split skin demonstrating epidermal side staining of IgG [8]. Our approach is to perform IIF testing in patients with clinical findings suspicious for BP even when DIF findings are negative or inconclusive (algorithm 1). (See “Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid”, section on ‘Our approach’.)

INFECTIONS AND INFESTATIONS

Bedside ultrasonography to evaluate skin abscesses (December 2018)

The role of bedside ultrasonography for abscess treatment was evaluated in a randomized trial of more than 100 patients older than 14 years of age undergoing drainage in the emergency department [9]. Clinical failure rates 10 days after the procedure were lower in patients evaluated with physical examination and ultrasonography compared with physical examination alone (4 versus 17 percent). All providers performing point-of-care ultrasonography in this study were highly experienced. In patients with an abscess, when device and trained providers are available, we suggest ultrasonography to identify the presence, size, and location of the abscess and to facilitate adequate drainage. (See “Technique of incision and drainage for skin abscess”, section on ‘Evaluation for abscess using bedside ultrasonography’.)

PEDIATRIC DERMATOLOGY

Early intervention for high-risk infantile hemangiomas (January 2019)

Specialist referral and/or treatment is warranted for infantile hemangiomas at high risk of complications (eg, functional impairment, ulceration, permanent disfigurement). However, the best timing for starting intervention is often difficult to determine. According to the American Academy of Pediatrics’ Clinical Practice Guideline for the Management of Infantile Hemangiomas, infants with high-risk hemangiomas should start treatment or be referred to a specialist at an early age, ideally by four weeks of age [10]. We agree with this guideline, the rationale being that the most rapid growth of hemangiomas occurs before eight weeks of age, and treatment before the completion of this proliferative phase may prevent poor outcomes. (See “Infantile hemangiomas: Management”, section on ‘When to start treatment’.)

Vaccines and risk of IgA vasculitis (November 2018)

Case reports have described immunoglobulin A vasculitis (IgAV, formerly called Henoch-Schönlein purpura [HSP]) after vaccination, and a case-control study observed a small increased risk of IgAV (HSP) after measles-mumps-rubella (MMR) vaccination, but not after other vaccines. A new case-crossover study of 167 children reported a similar risk of IgAV in the three months before versus after vaccination (odds ratio 1.6, 95% CI 0.8-3.0) [11]. The study was not adequately powered to assess the effect of individual vaccines. These results suggest that vaccination is not a major etiologic factor in IgAV and therefore should not be avoided. (See “IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis”, section on ‘Pathogenesis’.)

PSORIASIS AND OTHER PAPULOSQUAMOUS DISORDERS

Filgotinib, a selective Janus kinase (JAK)-1 inhibitor, for psoriatic arthritis and ankylosing spondylitis (November 2018)

Filgotinib, an investigational selective Janus kinase 1 (JAK1) inhibitor, appears to have activity in both psoriatic arthritis (PsA) and ankylosing spondylitis (AS). In a multicenter randomized trial involving over 130 patients with active PsA and an inadequate response or intolerance to at least one conventional synthetic disease-modifying antirheumatic drug, the addition of filgotinib (200 mg orally once daily) to existing stable therapy resulted in a greater proportion of patients achieving American College of Rheumatology 20 percent improvement response criteria (ACR20) at week 16 compared with placebo [12]. In a separate trial in patients with AS and an inadequate response or intolerance to nonsteroidal anti-inflammatory drugs, the filgotinib group had a greater reduction in the AS Disease Activity Score (ASDAS) at week 12 and was more likely to achieve a clinically significant improvement in the ASDAS score compared with the placebo group [13]. Adverse effects were similar in the two groups. (See “Treatment of psoriatic arthritis”, section on ‘Other therapies’ and “Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults”, section on ‘Investigational agents not yet available for any conditions’.)

New therapies for plaque psoriasis (October 2018)

Increasing knowledge of the pathogenesis of psoriasis and effective therapeutic targets has led to the development of new antipsoriatic therapies. Two identical phase 3 trials found risankizumab, an investigational selective inhibitor of the p19 subunit of IL-23, superior to both ustekinumab (an inhibitor of the p40 subunit of IL-12 and IL-23) and placebo for moderate to severe plaque psoriasis [14]. These findings, in conjunction with preceding trials of the IL-23p19 inhibitors guselkumab and tildrakizumab, support the efficacy of this class of drugs for patients requiring systemic treatment. In addition, a phase 2 trial found the investigational tyrosine kinase 2 (TYK2) inhibitor BMS-986165 effective for improving moderate to severe plaque psoriasis [15]. Additional study is needed to clarify the long-term efficacy and safety of TYK2 inhibition in patients with psoriasis. (See ‘Treatment of psoriasis in adults’, section on ‘Emerging therapies’.)

Dietary interventions for psoriasis and psoriatic arthritis (October 2018)

The role of dietary interventions in the treatment of psoriatic disease has been uncertain. Based upon the findings of a systematic review, the National Psoriasis Foundation Medical Board issued dietary recommendations for adults with psoriasis or psoriatic arthritis [16]. Key recommendations included the roles of weight reduction with a hypocaloric diet for overweight or obese adults and gluten-free diets for patients with celiac disease or positive serologic markers for gluten sensitivity. The recommendations provide useful guidance for counseling patients with psoriasis or psoriatic arthritis. (See “Treatment of psoriasis in adults”, section on ‘Diet’.)

SKIN CANCER

Prognosis of nodular melanoma (February 2019)

There are four major growth patterns of melanoma: lentigo maligna, nodular, superficial spreading, and acral lentiginous. In an observational study of close to 120,000 patients with melanoma, nodular melanoma was an independent risk factor for death, after controlling for thickness, ulceration, and stage [17]. Nevertheless, the eighth edition of the American Joint Committee on Cancer (AJCC) tumor, node, metastasis (TNM) staging system, which relies upon primary tumor thickness and other features, involvement of regional lymph nodes, and presence or absence of distant metastases (table 1), should be used to stage melanomas of any growth pattern. (See “Tumor, node, metastasis (TNM) staging system and other prognostic factors in cutaneous melanoma”, section on ‘Pathologic factors’.)

Skin cancer risk and chronic low-dose methotrexate (November 2018)

Limited evidence has suggested that chronic low-dose methotrexate (MTX) use in rheumatic disease patients may be associated with an increased risk of multiple myeloma and nonmelanoma skin cancers, but the number of cases in most studies has been small. In a recently reported randomized trial of MTX versus placebo for cardiovascular prevention in almost 5000 adults with elevated cardiovascular risk, the incidence of non-basal-cell skin cancers was approximately threefold higher in the MTX group with a median follow-up of 2.3 years [18]. The primary endpoint of the trial showed no benefit of MTX on cardiovascular outcomes. Although the study did not include patients with rheumatic disease, the finding of an increase in skin cancer risk is important, given the relatively large size and duration of this trial compared with most trials in patients with rheumatic diseases, and further study of this association is warranted in patients treated with chronic low-dose MTX for rheumatic disease. (See “Major side effects of low-dose methotrexate”, section on ‘Others’.)

Observation for moderately dysplastic nevi excised with positive margins (November 2018)

Re-excision of atypical nevi with positive margins on histologic examination is a common practice among dermatologists, although there are no universally accepted guidelines. In a multicenter study of over 400 patients with moderately dysplastic nevi resected with positive histologic margins, none developed a melanoma at the biopsy site over a median follow-up of seven years [19]. However, 23 percent developed a melanoma at a separate site. Although observation rather than re-excision is a reasonable management approach for moderately dysplastic nevi resected with positive margins, we suggest close clinical surveillance with whole body skin examination for these patients, due to their increased risk of melanoma at different body sites. (See “Atypical (dysplastic) nevi”, section on ‘Re-excision’.)

Sunscreen for melanoma prevention (October 2018)

Previous studies suggested that regular use of sunscreen may reduce the risk of melanoma. An Australian case-control study including approximately 600 melanoma cases and 1100 controls aged 18 to 39 years found that high use of sunscreen during childhood was associated with a 40 percent risk reduction for developing melanoma before the age of 40 years, after adjusting for total sun exposure and other known risk factors [20]. A similar risk reduction was noted for high lifetime use of sunscreen. Because intense sun exposure in childhood and early adulthood is a major risk factor for melanoma, we counsel children, young adults, and parents about consistent use of sun protection measures, including application of broad spectrum sunscreen with an SPF of at least 30 before sun exposure. (See “Primary prevention of melanoma”, section on ‘Efficacy’.)

SURGICAL AND COSMETIC DERMATOLOGYM

Rarity of immediate allergy to local anesthetics (November 2018)

Local anesthetics (LAs) are a rare cause of immediate allergy (reactions occurring within an hour of administration). They more commonly cause a range of non-allergic effects that can mimic aspects of anaphylaxis (eg, flushing, tachycardia, paresthesias). In a retrospective series, over 400 patients with anaphylaxis-like reactions to LAs were evaluated with skin testing and readministration of the implicated LA [21]. Just 0.5 percent had true immediate allergy to an LA, and an additional 7 percent were diagnosed with spontaneous urticaria or allergy to other agents, including pain medications, antibiotics, and latex. Most reactions were classified as psychosomatic, vasovagal, or related to the pharmacologic effects of the LA or epinephrine. Patients with suspected allergic reactions to LAs should be referred to an allergist for evaluation, as most do not have true allergy to LAs. (See “Allergic reactions to local anesthetics”, section on ‘Prevalence’.)

URTICARIA AND ANGIOEDEMA

Dapsone for refractory chronic spontaneous urticaria (February 2019)

Recent international guidelines for the management of chronic spontaneous urticaria (CSU) emphasized use of omalizumab in patients whose symptoms could not be controlled with high-dose nonsedating antihistamines, in preference to older immunosuppressant drugs with more significant adverse effects. However, omalizumab is not effective in all patients and may not be affordable in many settings, so efficacy data about older therapies remains valuable. In the largest study to date of dapsone for CSU, a retrospective review was performed of 79 patients with symptoms refractory to high-dose antihistamines, and in some cases other drugs including omalizumab, who were treated with dapsone [22]. Improvement was seen in 62 percent at one month, with 10 experiencing lasting remission for periods up to 16 months, and two patients developing serious adverse effects. Dapsone remains a reasonable option for patients with refractory CSU when omalizumab is not effective or feasible. (See “Chronic spontaneous urticaria: Treatment of refractory symptoms”, section on ‘Dapsone’.)

OTHER DERMATOLOGY

Spironolactone for hidradenitis suppurativa (March 2019)

Androgens may play a role in the pathogenesis of hidradenitis suppurativa (HS), a disabling, inflammatory skin condition that is challenging to treat. Efficacy data for the antiandrogenic therapies utilized for females with HS, such as spironolactone, are limited. A retrospective study of women with HS treated with spironolactone found improvements in pain, inflammatory lesion count, and physician-assessed disease severity [23]. Treatment was well tolerated. This study provides support for spironolactone therapy for HS in female patients. However, additional study is needed to confirm efficacy and the optimal regimen. (See “Hidradenitis suppurativa: Treatment”, section on ‘Hormonal therapy’.)

PADI3 mutations in central centrifugal cicatricial alopecia (February 2019)

Central centrifugal cicatricial alopecia (CCCA), a scarring form of alopecia that most commonly occurs in women of African ancestry, has long been thought to have a genetic component, but the specific genes involved have been unclear. A study investigating the molecular basis of CCCA found an association between CCCA and mutations in PADI3, a gene that encodes an enzyme involved in modification of proteins important for normal hair shaft formation [24]. Although the findings support a role for PADI3 in CCCA, PADI3 mutations were detected in a minority of affected patients, suggesting involvement of additional genetic and environmental factors. (See “Central centrifugal cicatricial alopecia”, section on ‘Genetics’.)

Apremilast for hidradenitis suppurativa (February 2019)

Hidradenitis suppurativa (HS) is a distressing and disabling inflammatory skin disorder that is challenging to treat. In the first randomized trial to evaluate apremilast (an oral phosphodiesterase 4 inhibitor) in 20 patients with moderate severity HS, apremilast was more effective than placebo in improving disease severity [25]. Apremilast was generally well tolerated during the 16-week trial; headache, diarrhea, nausea, and the common cold were the most common adverse events. Major limitations of the trial included its small size and short duration. Apremilast may be a new treatment option in the treatment of HS; however, additional study is necessary to confirm efficacy and safety. (See “Hidradenitis suppurativa: Treatment”, section on ‘Apremilast’.)

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