New AAD Guideline Seeks to Improve Awareness of Comorbidities Associated With Atopic Dermatitis

In a new guideline publication, the American Academy of Dermatology (ADD) reviewed and appraised evidence on comorbidities associated with atopic dermatitis (AD), ranging from bone health to immune-mediated disorders. The guidelines, which were published online in the Journal of the American Academy of Dermatology, do not provide recommendations on the management of AD-associated comorbidities but instead aims to raise awareness of these comorbid disorders among dermatologists and other clinicians involved in the care of patients with AD.

The guidelines were developed by a multidisciplinary work group which performed a systematic review and meta-analysis of the evidence on select comorbidities associated with AD. After grading the evidence, the AAD work group developed statements on these associations as well as with the strength and overall evidence quality of the estimated association between selected comorbidities and AD. Provided below is a summary of these statements made by the AAD guideline panel.

Allergies

In a meta-analysis of the reviewed literature, the AAD work group found that the pooled prevalence of asthma in adults with AD is 24.8% (95% CI, 22.2%-27.5%) but noted substantial heterogeneity across the analyzed studies. The panel found that compared with the general population without AD, adults with AD are 3 times as likely to have asthma.

Based on the evidence, the panel also estimated prevalence of food allergies in adults with asthma is 11% (95% CI, 6%-16%), but this estimate was reportedly limited by study heterogeneity. The group also noted that allergic rhinitis is also recognized as a common AD-related comorbidity, although few studies have reported conclusive evidence linking AD with allergic conjunctivitis and eosinophilic esophagitis (EoE).

Corresponding statements made by the AAD include:

• AD is associated with asthma (moderate-quality evidence)
• Greater AD severity is associated with increasing asthma prevalence (moderate-quality evidence)
• AD in adults is associated with food allergies (high-quality evidence)
• Greater AD severity is associated with increasing food allergy prevalence (moderate-quality evidence)
• AD in adults is associated with allergic rhinitis (moderate-quality evidence)
• The association between AD in adults and allergic conjunctivitis is uncertain (low-quality evidence)
• AD in adults may be associated with EoE (low-quality evidence)

Bone Health

The guideline panel summarized previous study data showing associations between AD and an increased risk for osteoporosis and fractures. According to the AAD work group, more research is needed to identify the mechanism underlying these associations.

Corresponding statements made by the AAD include:

• AD in adults is associated with osteoporosis (high-quality evidence)
• AD in adults is associated with bone fractures (moderate-quality evidence)

Cardiovascular (CV) Disease (CVD)

Given the role of systemic inflammation in CVD, the AAD panel wrote that inflammatory skin diseases like AD may be a potentially modifiable risk factor for CVD. The researchers noted the mounting epidemiologic evidence for small associations between AD and hypertension, congestive heart failure (CHF), peripheral and coronary artery disease (CAD), as well as myocardial infarction (MI) and CV death. Severity of AD may dictate the risk of certain CV-related events, the work group suggests.

Corresponding statements made by the AAD include:

• AD in adults is probably associated with hypertension (moderate-quality evidence)
• AD in adults is probably associated with CAD (moderate-quality evidence)
• AD in adults is probably associated with peripheral artery disease (moderate quality evidence)
• The association between AD in adults and MI is uncertain (low-quality evidence)
• Severe AD in adults may be associated with MI (low-quality evidence)
• The association between AD in adults and stroke is uncertain (very-low-quality evidence)
• AD in adults is probably associated with CHF (moderate-quality evidence)
• AD in adults is probably associated with thromboembolic diseases (moderate-quality evidence)
• AD in adults may be associated with CV death (low-quality evidence)

Immune-Mediated Conditions

The guideline panel cited epidemiologic studies which have previously identified an association between alopecia areata (AA) and AD. In addition, the panel noted that research data point to a strong association between AD and chronic urticaria.

Corresponding statements made by the AAD include:

• AD in adults is associated with AA (moderate-quality evidence)
• AD in adults is associated with urticaria (moderate-quality evidence)

Mental Health and Substance Use

Based on the available evidence, the AAD work group indicates AD is associated with symptoms of anxiety and depression. The group’s analysis of 4 studies comprising 11,244 adults with AD and 149,713 control participants found that AD was associated with double the odds of patient-reported or clinician-diagnosed depression (95% CI, 1.53-2.59). Also, the pooled odds ratio of anxiety in 157,222 adults with AD vs 300,719,113 control participants was 1.40 (95% CI, 1.12-1.75).

The guideline committee also found some evidence to support a possible association between AD and substance use, but this evidence was reportedly limited. The panel noted that many studies discussing the association between AD and substance use are cross-sectional, thereby limiting the ability to determine causality.

Corresponding statements made by the AAD include:

• AD in adults is associated with clinician-diagnosed depression (moderate quality evidence)
• AD in adults is associated with clinician-diagnosed anxiety (moderate quality evidence)
• AD in adults may be associated with suicide (low quality evidence)
• AD in adults may be associated with alcohol abuse disorders (low quality evidence)
• AD in adults may be associated with cigarette smoking (low quality evidence)

Metabolic Disorders

The AAD work group summarized current evidence which shows a small association between AD and dyslipidemia and obesity in adult patients. For instance, the work group cited pooled data from 8 cross-sectional studies which showed AD was associated with 36% increased odds of obesity (95% CI, 1.01-1.83) and 13% increased odds of hypercholesterolemia (95% CI, 1.09-1.18) when compared with the non-AD population. In addition, the guideline panel stated that there may be an inverse association between AD and diabetes.

Corresponding statements made by the AAD include:

• AD in adults is probably associated with obesity (moderate-quality evidence)
• AD in adults is probably associated with dyslipidemia (moderate-quality evidence)
• AD in adults may not be associated with diabetes (low-quality evidence)
• The association between AD in adults and metabolic syndrome is uncertain (very-low-quality evidence)

Skin Infections

The guideline panel provided evidence to highlight the well-known association between AD and staphylococcal skin infection. In their summary, the AAD work group discussed evidence linking AD with serious cutaneous infections as well as herpes superinfection.

The corresponding statement made by the AAD included:

• AD in adults is associated with skin infection (moderate-quality evidence)

Patient Education

The AAD guideline panel emphasized the importance of patient education to improve awareness of AD-associated comorbidities and to support individualized treatment of and shared decision-making for AD. “Discussing the relationship of various comorbidities with AD can empower patients to better understand their skin condition and overall health and enable them to make treatment decisions that are best for them,” the guideline authors wrote.

Additionally, although dermatologists play a central role in managing AD and improving health-related quality of life associated with the disease, the guideline authors stated that patients should also be encouraged to visit with a primary care physician to manage comorbidities that are “beyond the scope of dermatologic practice.”

Disclosure: Multiple guideline authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.

Reference

Davis DMR, Drucker AM, Alikhan A, et al.  AAD Guidelines: awareness of comorbidities associated with atopic dermatitis in adults. J Am Acad Dermatol. Published online January 24, 2022. doi:10.1016/j.jaad.2022.01.009