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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.
ATOPIC DERMATITIS AND OTHER DERMATITIS
Nemolizumab for atopic dermatitis (March 2017)
Some patients with atopic dermatitis do not experience disease control with topical treatments. In a phase 2 trial, 264 patients with moderate to severe atopic dermatitis not controlled by topical corticosteroids or topical calcineurin inhibitors were randomly assigned to monthly subcutaneous nemolizumab, an investigational humanized monoclonal antibody against interleukin-31, at three different doses or to placebo . At 12 weeks, pruritus was reduced by 44, 60, and 63 percent, in the low, medium, and high dose groups, respectively, versus 21 percent in the placebo group. However, nemolizumab did not reduce the body surface area affected by atopic dermatitis. Adverse effects occurred in approximately 70 percent of patients in all study groups and were generally mild, with the most frequent being exacerbation of atopic dermatitis and respiratory tract infections. Although nemolizumab appears to be a promising treatment for pruritus associated with atopic dermatitis, larger studies of longer durations are needed to confirm its efficacy and safety. (See "Treatment of atopic dermatitis (eczema)", section on 'Nemolizumab'.)
Topical crisaborole for atopic dermatitis (December 2016)
A topical preparation containing 2% crisaborole, an investigational boron-based, small-molecule, phosphodiesterase-4 inhibitor, was approved by the US Food and Drug Administration in December 2016 for the treatment of mild to moderate atopic dermatitis in patients two years of age and older . In four-week clinical trials, topical crisaborole was more effective than placebo in reducing pruritus, skin inflammation, excoriation, and lichenification. However, trials comparing topical crisaborole with other topical treatments for atopic dermatitis are lacking. (See "Treatment of atopic dermatitis (eczema)", section on 'Crisaborole'.)
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)".)
AUTOIMMUNE AND SYSTEMIC DISEASES
Management of microvascular damage in systemic sclerosis (December 2016)
Vasoactive drugs are used for systemic sclerosis (SSc) patients with severe Raynaud phenomenon (RP) and digital ulcers. For prevention of recurrent digital ulcers, there may be a benefit from combination therapy with intravenous iloprost and bosentan. In a prospective observational study with 30 SSc patients receiving intravenous iloprost for severe secondary RP, half of the patients were also given bosentan following the development of digital ulcers or pulmonary arterial hypertension . After four years of follow-up, the iloprost plus bosentan group showed evidence of a significant improvement in digital microvasculature structure and function, which also corresponded with a significant reduction in the incidence of new digital ulcers. This limited study needs confirmation but suggests that combination therapy may be helpful in complex SSc patients with recurrent digital ulcers. (See "Treatment of the Raynaud phenomenon resistant to initial therapy", section on 'Recurrent digital ulcers in systemic sclerosis'.)
Tofacitinib for alopecia areata (December 2016)
Support is increasing for the use of tofacitinib, a small molecule selective Janus kinase 1/3 inhibitor, for alopecia areata. A retrospective study of long-term treatment with tofacitinib (with or without adjuvant prednisone) in 90 adults with severe alopecia areata (at least 40 percent scalp hair loss, alopecia totalis, or alopecia universalis) found that over one-half of the 65 patients with a duration of the current disease episode of ≤10 years achieved greater than 50 percent improvement in the Severity of Alopecia Tool [SALT] score, without serious adverse effects . Although these findings suggest benefit of tofacitinib for alopecia areata, controlled trials are needed to confirm efficacy and safety. (See "Management of alopecia areata", section on 'Janus kinase inhibitors'.)
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'.)
INFECTIONS AND INFESTATIONS
Guidelines on diagnosis and treatment of leishmaniasis (January 2017)
Guidelines on the management of leishmaniasis in North America were published by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH) in December 2016 . They emphasize use of multiple diagnostic tools to maximize diagnostic likelihood and submission of relevant specimens to a reference laboratory for parasite species identification. For suspected cutaneous leishmaniasis (CL), a full-thickness skin biopsy from a clean, active-appearing ulcer is recommended; for patients with mucocutaneous leishmaniasis (ML), biopsy specimens should be obtained by an otolaryngologist. For suspected visceral leishmaniasis (VL), bone marrow aspirate is the preferred sample; in addition, serum should be tested for antileishmanial antibodies. The treatment approach to CL depends on several factors, including the extent of disease, the infecting parasite species, and the presence of immunocompromising conditions. For VL, liposomal amphotericin B is the preferred treatment; miltefosine, pentavalent antimonials, and other forms of amphotericin are alternatives. (See "Cutaneous leishmaniasis: Clinical manifestations and diagnosis" and "Cutaneous leishmaniasis: Treatment" and "Visceral leishmaniasis: Clinical manifestations and diagnosis" and "Visceral leishmaniasis: Treatment".)
PSORIASIS AND OTHER PAPULOSQUAMOUS DISORDERS
Brodalumab for moderate to severe plaque psoriasis (February 2017)
Brodalumab, an anti-IL-17 receptor A monoclonal antibody, is a new addition to the armamentarium of highly effective biologic therapies for psoriasis. In February 2017, the US Food and Drug Administration approved brodalumab for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies . Approval of brodalumab was based upon data from three randomized trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) that found brodalumab more effective than placebo [12,13]. However, suicidal ideation and behavior occurred in a small number of patients treated with brodalumab. As a result, the drug will only be available in the United States through a Risk Evaluation and Mitigation Strategy program designed to identify patients who develop new or worsening symptoms of depression or suicidality. (See "Treatment of psoriasis", section on 'Brodalumab'.)
Subcutaneous methotrexate for plaque psoriasis (January 2017)
Although methotrexate is a common treatment for psoriasis, data supporting its use are limited. In a randomized trial of 120 patients with moderate to severe plaque psoriasis, those treated with subcutaneous methotrexate for 16 weeks achieved a 75 percent improvement in the Psoriasis Area and Severity Index score more frequently than those receiving placebo (41 versus 10 percent) . Treatment was generally well tolerated. These data support methotrexate as a treatment option for psoriasis. (See "Treatment of psoriasis", section on 'Methotrexate'.)
Haplotype may predict response to tonsillectomy in chronic plaque psoriasis (November 2016)
Tonsillectomy leads to clinical improvement in some patients with chronic plaque psoriasis, although surgery carries risk, and a reliable predictor of which patients are most likely to respond is lacking. A prospective cohort study of 28 patients with moderate to severe chronic plaque psoriasis and a history of psoriasis exacerbations in association with sore throat and/or streptococcal throat infections suggests that HLA-Cw*0602 homozygotes may derive greater benefit from tonsillectomy than HLA-Cw*0602 heterozygotes and HLA-Cw*0602-negative patients . Additional study is necessary to confirm this finding given the small size of the study. (See "Treatment of psoriasis", section on 'Tonsillectomy'.)
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'.)
Association of vitiligo with hematopoietic stem cell transplantation (February 2017)
Previous reports suggested that recipients of hematopoietic stem cell transplantation (HSCT) have an increased risk of developing vitiligo. In a Korean nationwide population study including approximately 2700 HSCT recipients and 8200 controls, HSCT recipients had a threefold increased risk of developing vitiligo . Risk factors included receipt of an allogeneic versus autologous graft and stem cells derived from the bone marrow rather than peripheral blood. Although the pathogenetic mechanisms underlying the development of vitiligo in HSCT recipients are unclear, they may include adoptive transfer of vitiligo from donor, immunosuppression associated with preparative regimens, or chronic graft-versus-host disease. Clinicians should counsel patients undergoing HSCT regarding the risk of vitiligo. (See "Vitiligo: Pathogenesis, clinical features, and diagnosis", section on 'Etiology'.)
Topical therapy for pyoderma gangrenosum (November 2016)
Pyoderma gangrenosum (PG) can be challenging to treat and often exhibits prolonged healing times. Topical therapy is commonly used for the treatment of mild PG; however, efficacy data have been limited. In the largest prospective cohort study to assess topical treatments for PG, 66 patients received either clobetasol propionate, tacrolimus, or other topical therapies . The majority of patients (74 percent) received clobetasol propionate. By six months, 44 percent of patients receiving topical therapy achieved ulcer healing. These results provide support for the use of topical therapies. (See "Pyoderma gangrenosum: Treatment and prognosis", section on 'Local corticosteroids'.)
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