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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
Expert panel recommendations for the management of acne fulminans (July 2017)
There is a paucity of high-quality data on the management of acne fulminans, a rare, severe form of acne vulgaris. New recommendations from clinicians with expertise in severe acne vulgaris support prompt initiation of an oral glucocorticoid followed by the delayed addition of oral isotretinoin as the preferred first-line therapy . We agree with the recommendations, which also discuss a new classification system for acne fulminans, prevention, and an algorithmic approach to treatment. (See "Treatment of acne vulgaris".)
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'.)
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'.)
Systemic therapy for melanoma brain metastases (June 2017)
Patients with central nervous system involvement from melanoma historically have had a very poor prognosis. Preliminary reports from two phase II studies suggest that the combination of nivolumab plus ipilimumab has important clinical activity against intracranial metastases [12,13]. Antitumor activity has also been observed with targeted therapy for patients whose melanoma has a BRAF V600 mutation. A multidisciplinary approach that considers all available treatment modalities is essential for the proper treatment of the patient with melanoma brain metastases. (See "Management of brain metastases in melanoma", section on 'Nivolumab plus ipilimumab'.)
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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- Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet 2017; 389:2287.
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- Ruzicka T, Hanifin JM, Furue M, et al. Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis. N Engl J Med 2017; 376:826.
- Joly P, Maho-Vaillant M, Prost-Squarcioni C, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet 2017; 389:2031.
- Williams HC, Wojnarowska F, Kirtschig G, et al. Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial. Lancet 2017; 389:1630.
- Moran GJ, Krishnadasan A, Mower WR, et al. Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole vs Cephalexin Alone on Clinical Cure of Uncomplicated Cellulitis: A Randomized Clinical Trial. JAMA 2017; 317:2088.
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- Lebwohl M, Strober B, Menter A, et al. Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. N Engl J Med 2015; 373:1318.
- Papp KA, Reich K, Paul C, et al. A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol 2016; 175:273.
- Long GV, Atkinson V, Menzies AM, et al. A randomized phase II study of nivolumab or nivolumab combined with ipilimumab in patients with melanoma brain metastases: the Anti-PD1 Collaboration (ABC) (abstract 9508). 2017 American Society of Clinical Oncology annual meeting.
- Tawbi HA, Forsyth PA, Algazi AP, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with melanoma metastatic to the brain: results of the phase II study Checkmate 204 (abstract 9507). 2017 American Society of Clinical Oncology annual meeting.
- Faries MB, Thompson JF, Cochran AJ, et al. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med 2017; 376:2211.
- Doong JC, Chichester K, Oliver ET, et al. Chronic Idiopathic Urticaria: Systemic Complaints and Their Relationship with Disease and Immune Measures. J Allergy Clin Immunol Pract 2017.
- Barniol C, Dehours E, Mallet J, et al. Levocetirizine and Prednisone Are Not Superior to Levocetirizine Alone for the Treatment of Acute Urticaria: A Randomized Double-Blind Clinical Trial. Ann Emerg Med 2017.
- Bae JM, Choi KH, Jung HM, et al. Subsequent vitiligo after hematopoietic stem cell transplantation: A nationwide population-based cohort study from Korea. J Am Acad Dermatol 2017; 76:459.