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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
Dupilumab for moderate to severe atopic dermatitis (June 2017)
Dupilumab is an interleukin (IL)-4 receptor alpha antagonist approved by the US Food and Drug Administration (FDA) for adults with moderate to severe atopic dermatitis not adequately controlled with topical therapies. In a phase III trial of over 700 patients with moderate to severe atopic dermatitis and inadequate response to topical corticosteroids, one year of treatment with dupilumab improved symptoms relative to placebo . All patients received topical corticosteroids or topical calcineurin inhibitors. These results support the use of dupilumab for the long-term treatment of moderate to severe atopic dermatitis when topical therapies alone are insufficient and other systemic treatments are contraindicated. (See "Treatment of atopic dermatitis (eczema)", section on 'Dupilumab'.)
Dupilumab for moderate to severe atopic dermatitis (April 2017)
Dupilumab is an interleukin-4 receptor alpha antagonist being evaluated in atopic dermatitis. In two 16-week clinical trials (SOLO1 and SOLO2), dupilumab was more effective than placebo in improving the signs and symptoms of atopic dermatitis . Based on these results, the US Food and Drug Administration has approved dupilumab for the treatment of adult patients with moderate to severe atopic dermatitis not adequately controlled with topical prescription therapies . While the role for dupilumab is still evolving, it appears to be a reasonable option for adult patients with severe disease who have failed other systemic therapies. (See "Treatment of atopic dermatitis (eczema)", section on 'Dupilumab'.)
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'.)
AUTOIMMUNE AND SYSTEMIC DISEASES
Rituximab plus prednisone for initial treatment of pemphigus (May 2017)
Although rituximab primarily has been used for the treatment of refractory pemphigus, data from an open-label randomized trial support the efficacy of rituximab, combined with prednisone, as a first-line treatment . The trial compared rituximab plus a reduced-dose, short-term regimen of prednisone versus a higher-dose, long-term regimen of prednisone alone as initial therapy in 90 patients with newly diagnosed pemphigus vulgaris or pemphigus foliaceus. The rituximab group had increased rates of complete remission off therapy after 24 months (89 versus 34 percent) and lower rates of severe adverse effects. This trial supports the use of rituximab plus prednisone as an alternative to prednisone monotherapy for the initial treatment for pemphigus, particularly for patients with moderate to severe disease or who are less favorable candidates for high-dose, long-term prednisone therapy. Further study is necessary to clarify optimal doses and best practices for the use of rituximab in the initial treatment of pemphigus. The high cost of rituximab is a limiting factor for use in some settings. (See "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'Efficacy'.)
Doxycycline versus prednisolone for the initial treatment of bullous pemphigoid (March 2017)
Tetracyclines have a long history of use for the management of bullous pemphigoid; however, high-quality data on the efficacy of tetracyclines are limited. In a multicenter randomized trial including approximately 250 patients receiving initial treatment for bullous pemphigoid, doxycycline was noninferior to oral prednisolone, with fewer associated severe, life-threatening, or fatal events . Although topical and systemic corticosteroids remain our standard first-line treatments for bullous pemphigoid, these results support doxycycline as an alternative treatment. Doxycycline may be particularly useful when topical corticosteroid therapy is impractical and systemic corticosteroid therapy is likely to be poorly tolerated. (See "Management and prognosis of bullous pemphigoid", section on 'Antibiotics and nicotinamide'.)
INFECTIONS AND INFESTATIONS
Treatment of nonpurulent cellulitis (June 2017)
Empiric antibiotic therapy for nonpurulent cellulitis (ie, with no purulent drainage and no associated abscess) should be active against beta-hemolytic streptococci and methicillin-susceptible Staphylococcus aureus (MSSA) but not necessarily methicillin-resistant S. aureus (MRSA). This approach is supported by a randomized trial of nearly 500 patients with nonpurulent cellulitis, in which cephalexin plus placebo (active against beta-hemolytic streptococci and MSSA) and cephalexin plus trimethoprim-sulfamethoxazole (TMP-SMX, which adds activity against MRSA) resulted in statistically similar clinical cure rates (69 versus 76 percent) . Although there was a trend toward higher cure rates with the addition of TMP-SMX, the results were likely skewed by a relatively large number of patients who did not complete the full course of therapy. (See "Cellulitis and skin abscess in adults: Treatment", section on 'Cellulitis'.)
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 [10,11]. 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'.)
Management of a positive sentinel lymph node biopsy in patients with cutaneous melanoma (June 2017)
Historically, completion dissection of all involved nodal basins was considered the standard treatment approach for patients with cutaneous melanoma and a positive sentinel lymph node biopsy (SLNB). In the phase III Multicenter Selective Lymphadenectomy Trial II (MSLT II), patients with a positive SLNB were randomly assigned to either completion lymph node dissection or observation that included ultrasound evaluation of the appropriate lymph node basins at each follow-up visit . Melanoma-specific survival at three years was the same for both groups, although the incidence of recurrence in regional lymph nodes was higher in patients managed with observation and ultrasound surveillance. The incidence of lymphedema was higher in patients who underwent immediate lymph node dissection. For patients with a positive SLNB, we suggest clinical observation coupled with ultrasound surveillance of the positive nodal basin. Completion lymph node dissection is indicated if, in the absence of distant metastases, there is evidence of regional lymph node recurrence. (See "Evaluation and treatment of regional lymph nodes in melanoma", section on 'Multicenter Selective Lymphadenectomy Trial II'.)
URTICARIA AND ANGIOEDEMA
Systemic symptoms in patients with chronic idiopathic urticaria (June 2017)
Patients with chronic idiopathic urticaria (CIU) sometimes report accompanying systemic symptoms, although the prevalence of such symptoms has not been specifically examined. In a study of 155 CIU patients presenting to a referral allergy clinic, 66 percent reported systemic symptoms, including headache, fatigue, joint pain or swelling, wheezing, flushing, gastrointestinal symptoms, and palpitations . Patients with systemic symptoms had a greater disease burden compared with those without symptoms. Although this study population was probably skewed towards more severe disease, it is helpful to recognize that systemic symptoms are not uncommon in CIU. (See "Chronic urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history", section on 'Systemic symptoms'.)
Glucocorticoids not necessary for simple acute urticaria (May 2017)
Although patients with urticaria and symptoms involving other organ systems are treated with epinephrine given the likelihood of anaphylaxis, H1 antihistamines are the initial treatment for those with isolated urticaria. For such patients, the additive benefit of glucocorticoids is not well defined. In a randomized trial of 100 adults presenting to the emergency department with isolated urticaria (without angioedema, anaphylaxis, or fever) of ≤24 hours duration, patients received the H1 antihistamine levocetirizine plus either prednisone or placebo for four days . There was no significant difference in the rate of symptom resolution, and most patients were symptom-free within two days. This study supports our suggestion to reserve glucocorticoids for those patients with new urticaria who have prominent angioedema or whose symptoms persist despite antihistamines. (See "New-onset urticaria", section on 'Glucocorticoids'.)
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'.)
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