Patients With AD May Have Greater Risk of Certain Malignancies

Higher incidence rates for cancer were seen among female patients and male patients living with atopic dermatitis (AD), according to an analysis of data from Kaiser Permanente Northern California health plan members published in BMJ Open.

“A growing body of evidence suggests an increased risk of malignancies with chronic inflammatory conditions, including AD,” the study authors wrote. “To better inform clinical and health system decision-making for patients with AD, there is a need for robust epidemiological data that substantiate potential associations between disease severity and malignancy risk.”

Among the patients with moderate (n = 6092) to severe (n = 958) AD in this analysis, the mean (SD) age was 43.5 (16.1). A majority (64.4%) were female patients, Asian (35.9%) or White (35.4%), non-Hispanic ethnicity (46.6%), and never-smokers (58.2%). All cases of AD were diagnosed between January 1, 2007, and December 31, 2018.

The highest overall rates, per 1000 person-years, were seen for nonmelanoma skin cancer (NMSC) and breast cancer, with the latter only being evaluated among the female patients:

• NMSC: 4.8 (95% CI, 4.1-5.6)
• Breast cancer: 2.1 (95% CI, 1.5-2.8)

When breaking these results down by patient cohort—moderate AD or severe AD—the finds were similar, with the incidence rates for NMSC being 4.6 (95% CI, 3.9-5.5) and 5.9 (95% CI, 3.8-9.2), respectively, and the rates for breast cancer being 2.2 (95% CI, 1.6-3.0) and 0.5 (95% CI, 1.6-3.0). In contrast, the lowest incidence rates in moderate AD and severe AS were seen for lymphoma, at 0.3 (95% CI, 0.2-0.6) and 0.6 (95% CI, 0.1-2.3), respectively, and lymphoproliferative disorders, at 0.1 (95% CI, 0.0-0.3) and 0.3 (95% CI, 0.0-2.1).

In between, the investigators saw incidence rates of 0.4 (95% CI, 0.2-0.7) and 0.6 (95% CI, 0.1-2.3) for melanoma among the patients with moderate or severe AD, respectively.

Lung cancer rates, meanwhile, varied significantly, with all incidences of this cancer (n = 13 cases) seen among the patients with moderate AD vs severe AD: 0.5 (95% CI, 0.3-0.8) vs 0.0. When doing a subanalysis comparing incidence rates between men and women, however, the rate was only slightly higher among the men: 0.7 (95% CI, 0.3-1.5) vs 0.4 (95% CI, 0.2-0.8).

There were, however, statistically significantly elevated rates seen overall among the men compared with the women in 2 of the cancers evaluated:

• NMSC: 7.7 (95% CI, 6.1-9.5) vs 3.3 (95% CI, 2.5-4.2)
• Basal cell carcinoma: 5.6 (95% CI, 4.3-7.2) vs 1.7 (95% CI, 1.2-2.4)

An additional subanalysis compared outcomes between former smokers and never-smokers, respectively, with the following results seen:

• Patients with moderate to severe AD:
  • NMSC: 7.3 (95% CI, 5.1-10.5) vs 3.7 (95% CI, 2.8-4.7)
  • Squamous cell carcinoma (SCC): 4.2 (95% CI, 2.6-6.8) vs 1.4 (95% CI, 0.9-2.1)
• Patients with moderate AD:
  • NMSC: 7.8 (95% CI, 5.4-11.4) vs 3.5 (95% CI, 2.6-4.6)
  • SCC: 4.3 (95% CI, 2.6-7.1) vs 1.1 (95% CI, 0.7-1.8)
• Patients with moderate AD:
  • Lymphoproliferative disorders: 2.0 (95% CI, 0.3-14.0) vs 0
  • Melanoma: 2.0 (95% CI, 0.3-14.0) vs 0

The study investigators noted several reasons for the potential association between AD and subsequent malignancies. Patients with AD have a heightened immune response, there is upregulation of inflammatory mediators and recruitment of immune cells that may promote tumor growth, and epidermal barrier defects.

“Chronic inflammation, such as that underlying AD pathogenesis, is associated with higher risk of cancer and promotes all stages of tumourigenesis,” they added. “The standard of care for AD includes the potential need for long-term treatment with immunosuppressive topical and systemic therapies, which may enhance malignancy risk by inhibiting innate antitumour immune responses.”

Moving forward, they investigators recommend that studies investigating the incidence of malignancies among patients who have AD include a cohort of health patients for comparison.

Reference

Hedderson MM, Asgari MM, Xu F, et al. Rates of malignancies among patients with moderate to severe atopic dermatitis: a retrospective cohort study. BMJ Open. Published online March 10, 2023. doi:10.1136/bmjopen-2022-071172