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
Oral isotretinoin therapy for acne and risk for inflammatory bowel disease (March 2023)
Data regarding oral isotretinoin and the risk for subsequent development of inflammatory bowel disease (IBD) continue to increase:
●In a retrospective cohort study of electronic health data from over 150,000 patients, patients given oral isotretinoin for acne and patients given oral antibiotics for acne had similar lifetime risks for Crohn disease and ulcerative colitis, with an increase in risk for ulcerative colitis in the isotretinoin group limited to the first six months of therapy .
●In a second retrospective cohort study of electronic health data from over 850,000 patients, risk for incident IBD within one year did not differ between patients with acne treated with oral isotretinoin and patients with acne who did not receive systemic therapy or who received oral antibiotic therapy. However, there was an association between acne itself and risk for incident IBD .
These findings support the concept that oral isotretinoin therapy may not have a clinically meaningful impact on risk for IBD. (See "Oral isotretinoin therapy for acne vulgaris", section on 'Inflammatory bowel disease'.)
Oral isotretinoin for acne and psychiatric outcomes (March 2023)
Patients are counseled about potential psychiatric adverse effects of oral isotretinoin because of uncertainty about the impact of isotretinoin on risk for depression and suicidal behavior. A retrospective cohort study with over 150,000 patients found an increase in suicidal ideation among patients with a history of acne treated with isotretinoin when compared with patients treated with oral antibiotics, but found no increase in risk for suicidal attempts or major depressive disorder . Risk for several other psychiatric conditions was lower in the patients treated with isotretinoin. This study provides additional support for the relative safety of isotretinoin therapy for multiple psychiatric conditions, but also supports continued investigation of the relationship between isotretinoin and psychiatric outcomes, particularly suicidal ideation. (See "Oral isotretinoin therapy for acne vulgaris", section on 'Psychiatric effects'.)
Laboratory monitoring for isotretinoin therapy (September 2022)
Reduced monitoring of liver function and lipid tests in healthy patients receiving isotretinoin has been proposed based upon data that suggest low utility of monthly testing. A Delphi consensus study in which acne experts responded to a series of surveys found at least 70 percent consensus for checking alanine aminotransferase (ALT) and triglyceride levels within one month prior to isotretinoin therapy and after reaching the peak isotretinoin dose . There was also consensus that several other laboratory tests were not necessary, such as complete blood count panels, basal metabolic panels, and select liver function and lipid tests. Although these findings align with the trend towards reduced laboratory monitoring for healthy patients taking isotretinoin, no consensus was achieved for some commonly obtained tests, and additional study is necessary to confirm the best approach to monitoring. Additionally, individual patient characteristics may warrant a different approach to laboratory testing. (See "Oral isotretinoin therapy for acne vulgaris", section on 'Evidence'.)
ATOPIC DERMATITIS AND OTHER DERMATITIS
Trial of lebrikizumab for atopic dermatitis (March 2023)
Lebrikizumab is a monoclonal antibody that selectively binds to soluble IL-13. In a phase 3 randomized trial that included 211 adults and adolescents with moderate to severe atopic dermatitis (AD), more patients receiving subcutaneous lebrikizumab plus topical corticosteroids achieved an IGA score of clear/almost clear at 16 weeks, compared with those receiving placebo plus topical corticosteroids (41 versus 22 percent, respectively) . Lebrikizumab-related adverse events included conjunctivitis and injection site reaction. Larger and longer-term trials are needed to further evaluate the efficacy and safety of lebrikizumab for AD. (See "Treatment of atopic dermatitis (eczema)", section on 'Anti-IL-13 antibodies (lebrikizumab)'.)
Trial of topical brepocitinib for atopic dermatitis (March 2023)
Brepocitinib is an investigative small molecule tyrosine kinase 2/janus kinase 1 (JAK1) inhibitor that blocks the interleukin (IL) 12 and IL-23 pathways. In a six-week randomized trial that included 292 adolescent and adults with mild to moderate atopic dermatitis, topical brepocitinib 1% once or twice daily induced a greater reduction of the Eczema Area and Severity Index score from baseline, compared with vehicle (-70 and -75 percent versus -44 and -47 percent, respectively) . Adverse events, most frequently nasopharyngitis and worsening of atopic dermatitis, occurred in 34 percent of patients. Although topical brepocitinib appears promising for the rapid improvement of mild to moderate atopic dermatitis, more data on long-term efficacy and safety are needed. (See "Treatment of atopic dermatitis (eczema)", section on 'JAK inhibitors'.)
Allergen immunotherapy for atopic dermatitis (October 2022)
Allergen immunotherapy (AIT) is a well-established treatment for allergic rhinoconjunctivitis and asthma, but studies of its utility for atopic dermatitis (AD) are mixed. In a new meta-analysis, the addition of AIT (either subcutaneous or sublingual, mostly using house dust mites as the allergen) or placebo was evaluated in 23 randomized trials that enrolled nearly 2000 children and adults with AD who were not controlled with standard therapy (either topical corticosteroids or calcineurin inhibitors) . Patients receiving add-on AIT more often experienced a clinically important decrease in AD severity and improvement in quality of life. Thus, add-on AIT may be beneficial for patients who have eczema that is not controlled with conventional therapies and proven sensitization to house dust mites. AIT may be especially helpful for patients with concomitant allergic rhinoconjunctivitis or asthma. (See "Treatment of atopic dermatitis (eczema)".)
AUTOIMMUNE AND SYSTEMIC DISEASES
Long-term cardiovascular and metabolic outcomes for rituximab in pemphigus (December 2022)
Combination therapy with systemic glucocorticoids and rituximab has demonstrated greater efficacy for achieving remission in pemphigus vulgaris and pemphigus foliaceus than systemic glucocorticoids given with mycophenolate mofetil. In a population-based, retrospective study of over 1600 patients with pemphigus, risk for myocardial infarction, stroke, peripheral vascular disease, hypertension, hyperlipidemia, type 2 diabetes, obesity, and osteoporosis was lower among the 961 patients treated with rituximab compared with those treated with mycophenolate mofetil or azathioprine . Pending additional study, these findings suggest additional benefits of rituximab over conventional immunosuppressant therapy for the treatment of pemphigus. (See "Initial management of pemphigus vulgaris and pemphigus foliaceus", section on 'Efficacy'.)
Acute cutaneous graft-versus-host disease with Stevens-Johnson syndrome/toxic epidermal necrolysis-like features (November 2022)
For patients with acute cutaneous graft-versus-host disease (GVHD) and Stevens-Johnson syndrome/toxic epidermal necrolysis- (SJS/TEN)-like features, the prognosis is not well described. In a retrospective cohort study of 31 patients with acute cutaneous GVHD, the 16 patients with SJS/TEN-like features were more likely to have systemic complications (eg, hematologic abnormalities, hepatitis, diarrhea, renal dysfunction, and bacteremia), lower survival rates at two months, and higher risk for mortality at five years . Although limitations of this study necessitate validation of the results and preclude conclusions on contributing factors, the findings provide additional insight into extracutaneous adverse events in patients with SJS/TEN-like acute GVHD. (See "Cutaneous manifestations of graft-versus-host disease (GVHD)", section on 'Diagnosis'.)
Apremilast for refractory cutaneous dermatomyositis (October 2022)
Cutaneous dermatomyositis (DM) can be challenging to treat and often requires immunosuppressive therapy. In the first study to assess efficacy of apremilast, a phosphodiesterase-4 inhibitor, for cutaneous DM, the addition of apremilast to other therapies for cutaneous DM was associated with improvement in the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) in seven of eight patients with refractory cutaneous dermatomyositis . The mean reduction in CDASI was 12.9 points at three months. Apremilast was generally well tolerated. Additional study is necessary to confirm efficacy of apremilast for cutaneous DM. (See "Management of refractory cutaneous dermatomyositis in adults", section on 'Apremilast'.)
INFECTIONS AND INFESTATIONS
Updated guidance on head lice from the American Academy of Pediatrics (October 2022)
The American Academy of Pediatrics released updated guidance on the diagnosis and management of head lice (pediculosis capitis) . The guidance provided continued support for topical permethrin and topical pyrethrins as the preferred first-line treatments in most patients. We agree with this approach and other key principles in the guidance report, such as the restriction of pediculicide treatment to patients with confirmed active lice infestation, the selection of a different class of topical pediculicide as the preferred next step after failure of an initial topical pediculicide, and the elimination of policies that exclude children from school because of head lice. (See "Pediculosis capitis", section on 'Locations with low pyrethroid resistance'.)
PSORIASIS AND OTHER PAPULOSQUAMOUS DISORDERS
Secukinumab for pityriasis rubra pilaris (December 2022)
Secukinumab and other biologic IL-17 inhibitors are used in the treatment of pityriasis rubra pilaris (PRP). However, prior data on secukinumab for PRP has been limited to case reports and case series. In an open-label study of 12 adults with PRP treated with secukinumab for 24 weeks, at least 75 percent improvement in the Psoriasis Area and Severity Index occurred in 6 of 11 patients (55 percent) . RNA sequencing analysis also revealed improvement in gene expression patterns in lesional skin after two weeks of treatment. No patients discontinued treatment because of adverse effects. Although limitations of this small study preclude definitive conclusions on the efficacy of secukinumab, the findings suggest benefit for PRP. (See "Pityriasis rubra pilaris: Prognosis and management", section on 'IL-17 inhibitors'.)
Oral deucravacitinib for moderate to severe plaque psoriasis (October 2022)
Tyrosine kinase inhibition represents a novel approach to psoriasis treatment. Two phase 3 trials support efficacy of oral deucravacitinib, a selective tyrosine kinase 2 inhibitor, for moderate to severe plaque psoriasis [13,14]. In the POETYK PSO-1 and POETYK PSO-2 trials, adults with moderate to severe plaque psoriasis were randomly assigned to deucravacitinib, placebo, or apremilast. At week 16, patients treated with deucravacitinib were more likely to achieve at least 75 percent improvement in the Psoriasis Area and Severity Index score than patients in the placebo or apremilast groups (58, 13, and 35 percent in POETYK PSO-1 and 53, 9, and 40 percent in POETYK PSO-2, respectively). Serious adverse effects were infrequent in both trials. These findings support deucravacitinib as an effective oral treatment for psoriasis and contributed to FDA approval of deucravacitinib for moderate to severe psoriasis in adults who are candidates for systemic therapy or phototherapy. Additional study will be useful for determining long-term efficacy and safety. (See "Treatment of psoriasis in adults", section on 'Deucravacitinib'.)
Nicotinamide does not prevent skin cancer in solid organ transplant recipients (March 2023)
Oral nicotinamide has been shown to reduce the incidence of nonmelanoma skin cancers (NMSC) in immunocompetent individuals with a previous history of NMSC. However, data on solid organ transplant recipients, who have a greatly increased risk of NMSC, are limited and inconsistent. In a recent randomized trial that included 158 solid organ transplant recipients receiving nicotinamide 500 mg or placebo twice daily for 12 months, the number of new NMSCs and actinic keratoses developed during the study period were similar in both groups . Patient education on strict sun protection, frequent skin checks, and prompt treatment of precancerous lesions remain the mainstay of NMSC prevention in this population. (See "Prevention and management of skin cancer in solid organ transplant recipients", section on 'Nicotinamide'.)
URTICARIA AND ANGIOEDEMA
New urticaria in the weeks after COVID-19 vaccination (March 2023)
Urticaria with or without angioedema has been reported in association with coronavirus disease 2019 (COVID-19) as well as messenger ribonucleic acid (mRNA) vaccines and boosters, particularly the Moderna mRNA booster. In a study of over 3.5 million adults from two cohorts who received a first booster dose of COVID-19 vaccine, the crude incidence of chronic spontaneous urticaria was approximately 2 cases per 100,000 persons . Of the 800 patients in two cohorts with newly diagnosed urticaria, more than 90 percent of cases were temporally associated with receiving the Moderna vaccine. Urticaria appeared between one and two weeks after vaccination, occurred most days of the week, and, in most patients, resolved in two to six months. This phenomenon is reminiscent of urticaria associated with viral infections, does not constitute an allergy, and is not a reason to avoid future vaccinations or boosters, although affected patients may prefer to choose a different product. (See "New-onset urticaria", section on 'COVID-19 vaccines and boosters'.)
Oral baricitinib for moderate to severe alopecia areata in adolescents (January 2023)
Randomized trials support efficacy of oral baricitinib (a Janus kinase 1 [JAK1] and JAK2 inhibitor) for severe alopecia areata in adults; however, data in the pediatric population are limited. In a retrospective study, 23 of 29 adolescents (79 percent) with moderate to severe alopecia areata treated with a combination of oral baricitinib and low-dose oral minoxidil achieved at least a 60 percent reduction in the Severity of Alopecia Tool (SALT) score . Onset of hair regrowth occurred in an average of three months. Adverse effects were mild. Although these findings suggest a potential role for oral baricitinib for pediatric alopecia areata, additional study is necessary to confirm safety and efficacy in this population. (See "Alopecia areata: Management", section on 'Oral baricitinib'.)
Topical ruxolitinib for limited nonsegmental vitiligo (October 2022)
Vitiligo is a difficult-to-treat autoimmune skin disease characterized by depigmented patches. In two recent identical randomized trials that included 674 patients with nonsegmental vitiligo involving ≤10 percent of total body surface area, more patients assigned to twice daily ruxolitinib 1.5% cream (a topical Janus kinase inhibitor) achieved a 75 percent reduction in the facial Vitiligo Area Scoring Index at 24 weeks, compared with vehicle (30 versus 7 percent [trial 1] and 31 percent versus 11 percent [trial 2]) . Ruxolitinib-related adverse events included acne and pruritus at the site of application and nasopharyngitis. These studies were the basis for the US Food and Drug Administration approval for this indication. However, due to safety concerns related to systemic absorption of ruxolitinib, we continue to suggest topical corticosteroids and topical calcineurin inhibitors as initial treatments for limited vitiligo. (See "Vitiligo: Management and prognosis", section on 'Localized disease'.)
1 : Isotretinoin and the risk of inflammatory bowel disease and irritable bowel syndrome: A large-scale global study.
2 : A propensity score matched cohort study identifying an association of acne, but not oral antibiotic or isotretinoin use, with risk of incident inflammatory bowel disease.
3 : Isotretinoin and the risk of psychiatric disturbances: A global study shedding new light on a debatable story.
5 : Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adolescents and Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial (ADhere).
6 : Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: a phase IIb, randomized, double-blind, vehicle-controlled, dose-ranging and parallel-group study.
7 : Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms.
8 : Association of Rituximab With Risk of Long-term Cardiovascular and Metabolic Outcomes in Patients With Pemphigus.
9 : Acute graft-versus-host disease presenting as Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective cohort study.
12 : Secukinumab for the treatment of adult-onset pityriasis rubra pilaris: a single-arm clinical trial with transcriptomic analysis.
13 : Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, placebo-controlled phase 3 POETYK PSO-1 trial.
14 : Deucravacitinib versus placebo and apremilast in moderate to severe plaque psoriasis: Efficacy and safety results from the 52-week, randomized, double-blinded, phase 3 Program fOr Evaluation of TYK2 inhibitor psoriasis second trial.
16 : Incidence of Chronic Spontaneous Urticaria Following Receipt of the COVID-19 Vaccine Booster in Switzerland.
17 : Treatment of moderate-to-severe alopecia areata in adolescents with baricitinib: A retrospective review of 29 patients.
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