Immunosuppressive and immunomodulating therapy for atopic dermatitis in pregnancy: an appraisal of the literature.

Atopic dermatitis (AD) is the most common dermatological diagnosis during pregnancy. Treatment of AD during pregnancy can be challenging, due to the unpredictable course and the fact that the therapy needs to be safe for both the mother and the fetus. Here we present an up-to-date appraisal of the literature on the treatment options available for AD in patients planning pregnancy, during pregnancy, and during breastfeeding. All patients with AD are recommended to supplement any medical treatment with daily applications of emollients. The first step in the medical treatment for AD during pregnancy are topical corticosteroids, and/or topical tacrolimus. If required, UV-light therapy can also be considered. Treatment with systemic therapy during pregnancy should always rely on a careful risk-benefit assessment and be based on shared-decision making between the treating physician and patient. The first-line systemic treatment option is cyclosporine A, whereas azathioprine may be considered in patients already receiving this treatment prior to pregnancy. Systemic glucocorticoids may also be used. Treatment with systemic JAK inhibitors is not recommended, whereas treatment with mycophenolate mofetil and methotrexate is contraindicated. Targeted therapy with dupilumab is not generally recommended, due to lack of experience in human pregnancies, yet some case-reports on their use are emerging. These recommendations are based on the authors appraisal of existing literature and the current recommendation from the European Task Force on Atopic Dermatitis. It is always the responsibility of the treating physician to stay updated on the newest guidelines and literature when treating patients with AD during pregnancy.

Association Between Atopic Dermatitis and Educational Attainment in Denmark.

IMPORTANCE: Atopic dermatitis (AD) may affect academic performance through multiple pathways, including poor concentration associated with itching, sleep deprivation, or adverse effects of medications. Because educational attainment is associated with health and well-being, any association with a prevalent condition such as AD is of major importance. OBJECTIVE: To examine whether a childhood diagnosis of AD is associated with lower educational attainment. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used linked routine health care data from January 1, 1977, to June 30, 2017 (end of registry follow-up), in Denmark. The study population included all children born in Denmark on June 30, 1987, or earlier with an inpatient or outpatient hospital clinic diagnosis of AD recorded before their 13th birthday (baseline) and a comparison cohort of children from the general population matched by birth year and sex. A secondary analysis included exposure-discordant full siblings as a comparison cohort to account for familial factors. Data were analyzed from September 11, 2019, to January 21, 2021. EXPOSURES: Hospital-diagnosed AD. MAIN OUTCOMES AND MEASURES: Estimated probability or risk of not attaining specific educational levels (lower secondary, upper secondary, and higher) by 30 years of age among children with AD compared with children in the matched general population cohort. Corresponding risk ratios (RRs) were computed using Poisson regression that was conditioned on matched sets and adjusted for age. The sibling analysis was conditioned on family and adjusted for sex and age. RESULTS: The study included a total of 61 153 children, 5927 in the AD cohort (3341 male [56.4%]) and 55 226 from the general population (31 182 male [56.5%]). Compared with matched children from the general population, children with AD were at increased risk of not attaining lower secondary education (150 of 5927 [2.5%] vs 924 of 55 226 [1.7%]; adjusted RR, 1.50; 95% CI, 1.26-1.78) and upper secondary education (1141 of 5777 [19.8%] vs 8690 of 52 899 [16.4%]; RR, 1.16; 95% CI, 1.09-1.24), but not higher education (2406 of 4636 [51.9%] vs 18 785 of 35 408 [53.1%]; RR, 0.95; 95% CI, 0.91-1.00). The absolute differences in probability were less than 3.5%. The comparison of 3259 children with AD and 4046 of their full siblings yielded estimates that were less pronounced than those in the main analysis (adjusted RR for lower secondary education, 1.29 [95% CI, 0.92-1.82]; adjusted RR for upper secondary education, 1.05 [95% CI, 0.93-1.18]; adjusted RR for higher education, 0.94 [95% CI, 0.87-1.02]). CONCLUSIONS AND RELEVANCE: This population-based cohort study found that hospital-diagnosed AD was associated with reduced educational attainment, but the clinical importance was uncertain owing to small absolute differences and possible confounding by familial factors in this study. Future studies should examine for replicability in other populations and variation by AD phenotype.

Immunosuppressive and Immunomodulating Therapy for Atopic Dermatitis in Pregnancy: An Appraisal of the Literature.

The aim of this appraisal of the literature is to elucidate the effects of immunosuppressive and immunomodulating agents used to treat atopic dermatitis (AD) on risk factors for fertility, pregnancy, and breastfeeding. Negative side effects of the psychological and physical stresses associated to AD flairs and uncontrolled AD are discussed, in order to evaluate the consequences of abstaining from treatment. Research on pregnancies in Danish women suggests a tendency towards an increased use of topical steroids and ultraviolet light therapy during pregnancy, compared to before conception, confirming the need for these patients to receive treatment, as well as decreased use of systemic treatments, suggesting a tendency towards undertreatment in this patient population. It is important that effective treatment be provided to pregnant women with AD. Here we present an appraisal of current knowledge on treatments for AD and the risks of exposure for the fetus and breastfed infant. Since little is known about the association between AD, pregnancy, and systemic treatment, we generalize conclusions based on studies on treatments of pregnant women who have undergone organ transplantation and who have inflammatory bowel disease, rheumatic disease, and autoimmune disease. The majority of recommendations are therefore based on a low or very low quality of evidence according to the GRADE system. The selected studies reflect the authors' assessment regarding originality and importance in the context of this appraisal. It is always the treating doctor's responsibility to stay updated on current literature when treating patients, especially pregnant patients.

Atopic dermatitis and risk of atrial fibrillation or flutter: A 35-year follow-up study.

BACKGROUND: Atopic dermatitis is characterized by chronic inflammation, which is a risk factor for atrial fibrillation. OBJECTIVE: To examine the association between hospital-diagnosed atopic dermatitis and atrial fibrillation. METHODS: Using linked population-based Danish registries, we identified persons with an inpatient or outpatient hospital diagnosis of atopic dermatitis during 1977-2013 and a comparison cohort individually matched to the atopic dermatitis cohort. We followed cohorts until death, emigration, atrial fibrillation diagnosis, or end of study (January 1, 2013). We compared 35-year risk of atrial fibrillation and estimated hazard ratios with 95% confidence intervals using Cox regression, adjusting for birth year and sex. We validated 100 atopic dermatitis diagnoses from a dermatologic department through medical record review. RESULTS: We included 13,126 persons with atopic dermatitis and 124,211 comparators and followed them for a median of 19.3 years. The 35-year risk of atrial fibrillation was 0.81% and 0.67%, respectively. The positive predictive value of atopic dermatitis diagnoses was 99%. The hazard ratio was 1.2 (95% confidence interval 1.0-1.6) and remained increased after adjusting for various atrial fibrillation risk factors. LIMITATIONS: Analyses were limited to persons with moderate-to-severe atopic dermatitis, and we had no lifestyle data. CONCLUSION: Patients with hospital-diagnosed atopic dermatitis have a 20% increased long-term risk of atrial fibrillation, but the absolute risk remains low.

Hospital-diagnosed atopic dermatitis and long-term risk of myocardial infarction: a population-based follow-up study.

OBJECTIVE: Atopic dermatitis (AD) is an inflammatory skin disorder with a childhood prevalence reaching 20%. An estimated 50% of patients have a life-long chronic course. The purpose of this study was to estimate the risk of first-time myocardial infarction (MI) in patients with AD compared with a general population cohort. DESIGN: Cohort study. SETTING: Denmark. PARTICIPANTS: Using population-based medical registries, we identified individuals born in Denmark from 1947 to 1983 with at least two hospital-diagnoses of AD following inpatient admissions or hospital-based outpatient visits at any age from 1977 to 2013. Individuals with AD were matched with general population controls (10:1) for birth-year and gender. Unique personal identifiers permitted unambiguous data linkage. PRIMARY OUTCOME MEASURES: Follow-up began on the date of AD diagnosis (index date for general population controls) and continued until death, emigration, MI or the year 2013. We computed the 15-year-cumulative incidence of MI following a diagnosis of AD. Comparing patients with AD with the general population cohort, we computed HRs of MI presented with 95% CIs and adjusted for history of diabetes mellitus, hypertension, hyperlipidaemia or stroke, educational level, birth-year and sex. RESULTS: We identified 4814 patients diagnosed with AD. The cumulative incidence of MI was 0.6% for patients with AD and 0.4% for their matched controls. The corresponding adjusted HR was 1.74 (1.21 to 2.49). The HR for patients who were not in need of systemic treatment was 1.58 (1.02 to 2.45) and it was 2.40 (1.27 to 4.45) for those who were treated with azathioprine, methotrexate or cyclosporine. CONCLUSIONS: Hospital-diagnosed AD was associated with increased risk of MI compared with the general population.

Therapy of severe atopic dermatitis in adults.

Severe atopic dermatitis has a profound effect on many aspects of the patient's life, and a combination of topical and systemic treatment is often necessary to control the disease. Systemic corticosteroids are rapidly effective, but should only be used short term for severe exacerbations because of their many long-term side effects. In chronic cases, starting another systemic immunosuppressant therapy while tapering off corticosteroids should be considered. The usefulness of cyclosporin A, azathioprine, and methotrexate has been documented in clinical trials. Cyclosporin A is rapidly effective, but has a narrow therapeutic index and possible renal toxicity. Azathioprine and methotrexate have a slower onset of action and are good treatment options for many patients, but are not always tolerated. Mycophenolate mofetil, mycophenolate sodium and biologicals are other alternatives, but need to be assessed in larger randomized trials. Despite the available therapeutic repertoire, there remain patients with very severe disease in whom we are unable to obtain satisfactory control. The therapy for patients with severe psoriasis has been revolutionized during the last decade, due to the development of targeted biological therapy, and it is indeed the hope that a similar process is about to emerge also for patients suffering from severe atopic dermatitis.

Abatacept is a promising treatment for patients with disseminated morphea profunda: presentation of two cases.

Morphea profunda is a rare disease that mainly affects young women and often has a progressive course with physical and psychological sequelae. The skin becomes sclerotic after an initial inflammatory reaction and joint contractures can develop. The aetiology is unknown. Until now, no successful therapy has been proven for this morphea variant. On the basis of new insights into the key role of effector T cells in scleroderma, in particular Th-17, T-cell directed therapies are expected to have promising effects. We report here the first two cases of morphea profunda treated with abatacept. Abatacept had a clinical effect on the active disease, in addition to softening old sclerotic lesions.