Comorbidities in Atopic Dermatitis

Atopic dermatitis (AD) is the most common inflammatory skin disease, affecting up to 20% of children and 10% of adults.¹^,² Loss-of-function mutations in the filaggrin gene, which contribute to skin barrier dysfunction, are frequently observed in patients with AD. This impaired barrier function, along with a T cell–mediated immune response to environmental allergens, plays a central role in disease pathogenesis. Beyond its clinical manifestations, AD imposes a substantial burden on patients, families, and healthcare systems, and is often accompanied by a wide range of comorbidities. These can be categorized as atopic (including asthma, allergic rhinitis, and food allergy) and nonatopic, such as mental health disorders, infections, and cardiovascular disease. In this article, as part of a series on comorbidities associated with immune-mediated skin diseases, we explore the spectrum of comorbidities linked to AD.

Pathophysiology 

AD presents with a heterogeneous spectrum of clinical phenotypes, likely reflecting the diverse endotypes and immunologic pathways underlying its pathogenesis. These immunologic signatures not only shape disease expression but also contribute to the development of AD-associated comorbidities. While a Th2-skewed immune response remains the dominant pathway in AD, additional T-cell subsets and their cytokine products play important roles as well—for example, IL-25.³

Classification of Comorbidities

A wide spectrum of comorbidities has been described in association with AD. These can be divided into atopic and nonatopic categories, with the presence of atopic comorbidities often supporting the diagnosis of AD.⁴ Other special situations and their associated comorbidities are listed in the Table. To aid in clinical recognition, Silverberg et al proposed the mnemonic VINDICATE-P, which encompasses vascular/cardiovascular, infectious, neoplastic and neurologic, degenerative, iatrogenic, congenital, atopic and autoimmune, traumatic, endocrine/metabolic, and psychiatric comorbidities.⁵ Awareness of these associations is essential for guiding treatment decisions and ensuring optimal long-term management of patients with AD.

Cardiovascular and Metabolic Disease

The relationship between AD and cardiovascular disease (CVD) is increasingly recognized, though the association appears weaker than that observed in psoriasis. Systemic inflammation is a known contributor to atherosclerosis and vascular dysfunction, and patients with AD are not exempt from this risk. However, the evidence linking AD to specific cardiovascular outcomes remains mixed. For example, AD does not appear to be significantly associated with hypertension, and the correlations with congestive heart failure, myocardial infarction, stroke, and cardiovascular mortality are uncertain, particularly in cases of mild AD.⁴ Similarly, findings regarding the prevalence of metabolic syndrome, hyperlipidemia, and obesity among patients with AD have been inconsistent across populations.⁴ Interestingly, some studies have suggested a potentially decreased incidence of type 2 diabetes in individuals with AD.⁴ At present, there are no formal recommendations for enhanced cardiovascular surveillance in patients with AD.

Infections

AD is associated with an increased susceptibility to both viral and bacterial skin infections. Colonization with Staphylococcus aureus occurs at rates up to 20 times higher in patients with AD compared with the general population, and this colonization strongly correlates with disease severity.² In addition, patients with AD are at increased risk of cutaneous viral infections, including varicella, molluscum contagiosum, verruca, and herpes simplex virus.

Neuropsychiatric and Sleep Disorders

Chronic pruritus in AD often leads to sleep disturbances, which can contribute to mental health issues, including anxiety and depression. In addition, disrupted sleep, combined with the low vitamin D levels frequently observed in patients with AD and the resulting impairment in bone metabolism, has been associated with an increased risk of traumatic fractures.⁴ Impaired sleep has also been linked to a higher likelihood of attention disorders.⁶

Immune-Mediated and Autoimmune Conditions

Patients with AD are at an increased risk of developing other immune-mediated conditions compared with the general population. Population-based studies have demonstrated particularly strong associations between AD and both alopecia areata (AA) and chronic spontaneous urticaria.⁴ Notably, individuals with AD have an approximately 10-fold higher risk of developing AA.²

Atopic and Allergic Conditions

The association between AD and other atopic or allergic conditions is well established. Asthma is approximately 3 times more prevalent in individuals with AD, as are food allergies and the acute urticaria that often accompanies them. The likelihood of developing asthma and food allergies increases with the severity of AD. Pediatric patients with both AD and asthma are also more likely to experience persistent AD into adulthood. While the impact of coexisting food allergies on AD management remains unclear and warrants further study,⁴ allergic rhinitis is consistently associated with AD. The evidence linking AD to allergic conjunctivitis, however, is less robust than that for asthma and allergic rhinitis in adults.⁴ Individuals with AD are 4 times more likely to develop hand eczema over their lifetime.²

Malignancy Risk

The risk of cancer in patients with AD has been investigated in multiple studies. Systematic reviews, however, have not demonstrated an increased risk for keratinocyte, central nervous system, or pancreatic cancers. Observational studies have suggested a modestly increased risk of lymphoma in individuals with AD, although this finding has not been consistently confirmed in case-control studies. Potential contributors to cancer risk in AD include chronic systemic inflammation and the use of certain immunomodulatory treatments.²

Atopic Eruption of Pregnancy

Atopic eruption of pregnancy (AEP) is the most common dermatosis observed during pregnancy and encompasses the spectrum of AD manifestations in this setting. AEP can arise from exacerbations of preexisting AD (approximately 20% of cases) or from new-onset AD (the remaining 80%). Pregnancy-related immunologic adaptations that prevent fetal rejection involve upregulation of the Th2 immune response and suppression of Th1/Th17 pathways; these same mechanisms are thought to contribute to the development of AEP.⁷ While approximately 20% of women may experience some improvement in preexisting AD during pregnancy, most patients either experience worsening symptoms or no significant change.

With the rapid expansion of novel therapies for AD, understanding the spectrum of associated comorbidities is essential. Such insights not only deepen our knowledge of the heterogeneous mechanisms underlying AD but also help guide therapeutic decision-making to optimize patient management. 

The authors report no relevant financial disclosures.

References

1. Broderick C, et al. Biomarkers associated with the development of comorbidities in patients with atopic dermatitis: a systematic review. Allergy. 2023;78(1):84-120.

2. Thyssen JP, et al. Comorbidities of atopic dermatitis—what does the evidence say? J Allergy Clin Immunol. 2023;151(5):1155-1162.

3. Schuler CFT, et al. Novel insights into atopic dermatitis. J Allergy Clin Immunol. 2023;151(5):1145-1154.

4. Davis DMR, et al. American Academy of Dermatology Guidelines: awareness of comorbidities associated with atopic dermatitis in adults. J Am Acad Dermatol. 2022;86(6):1335-1336.e18.

5. Silverberg NB, Lee-Wong MF, Silverberg JI. VINDICATE-P: a mnemonic for the many comorbidities of atopic dermatitis. Dermatol Clin. 2024;42(4):559-567.

6. Gonzalez-Uribe V, et al. Comorbidities & burden of disease in atopic dermatitis. Asian Pac J Allergy Immunol. 2023;41(2):97-105.

7. Munera-Campos M, Carrascosa JM. Atopic dermatitis: fertility, pregnancy, and treatment perspectives. Am J Clin Dermatol. 2024;25(1):55-66.