Real-World Data Reveal Increased NMSC Risk in Atopic Dermatitis

Nonmelanoma skin cancer (NMSC), comprising basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is one of the most common malignancies worldwide, accounting for nearly one-third of all cancers diagnosed annually.¹ Ultraviolet (UV) radiation exposure remains the principal risk factor, but immune dysfunction and chronic inflammation also play key roles in its pathogenesis.²

Patients with immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) are known to carry an elevated risk of NMSC, attributed to disease-related immune dysregulation and, in some cases, immunomodulatory therapy. Atopic dermatitis (AD) shares immunologic and inflammatory characteristics with other immune-mediated conditions.³ While some studies have suggested a possible association between AD and skin cancer, prior evidence has been inconsistent.

To clarify this relationship, a recent large-scale retrospective cohort study utilized US administrative claims data to evaluate the incidence and relative risk of NMSC among patients with AD compared with matched controls without AD and with patients with RA.⁴

Study Design and Methods

This observational study analyzed data from the Optum Clinformatics Data Mart (CDM), a database containing verified and de-identified administrative health claims from commercial and Medicare Advantage plans across all 50 US states.

Cohort Selection

• AD and RA cohorts: Adults aged ≥18 years with at least 1 qualifying diagnosis for AD or RA between March 2017 and December 2019 (extended to 2023 for moderate to severe disease) and at least 1 year of continuous plan enrollment.
• Controls: Individuals without AD, matched 1:1 to AD patients by age, sex, and cohort entry date (CED).
• Moderate to severe disease: Defined by treatment with dupilumab for AD or biologic/JAK inhibitor exposure for RA.
• Exclusions: History of NMSC within 180 days before cohort entry.

The primary endpoint was incident NMSC, identified by at least 2 diagnostic codes for NMSC ≥30 days apart. Crude incidence rates (per 100 person-years [PY]) were calculated, and adjusted hazard ratios (HRs) were estimated using multivariable Cox models.

Results

Cohort Characteristics

Data included 391,753 patients with AD (7,136 with moderate to severe AD) and 97,445 with RA (35,846 moderate to severe). The mean age was approximately 58 years for AD and 67 years for RA. Over half of participants were women, and most were White. Median follow-up ranged from 2.8 to 3.3 years.

Incidence of NMSC

• Overall AD vs controls: NMSC incidence was 2.12 per 100 PY in AD versus 1.74 per 100 PY in matched non-AD controls.
• Moderate to severe AD vs controls: 2.11 vs 1.28 per 100 PY, respectively.
• Subtype incidence: Both BCC and SCC occurred more frequently in AD cohorts than in controls.

Patients with RA demonstrated slightly higher rates of both BCC and SCC compared with AD overall, but the difference was modest.

Relative Risk

After adjustment, the risk of NMSC was 32% higher in patients with AD compared with matched controls (adjusted HR 1.32; P < 0.001). In moderate to severe AD, risk was 36% higher than in non-AD controls (adjusted HR 1.36; P < 0.01).

No significant difference in NMSC risk was observed between AD and RA cohorts. Among patients with AD, risk was especially high in those with:

• A history of NMSC (HR 6.45)
• Other malignancies (HR 1.35)
• Organ transplantation (HR 1.49)

Women and individuals identifying as Asian, Black, or Hispanic had lower relative risks compared with White men.

Discussion

This large real-world study demonstrates a statistically significant increase in NMSC risk among patients with AD compared with matched controls, regardless of disease severity. Risk levels were similar to those observed in RA, an immune-mediated disease already recognized for elevated NMSC susceptibility.

Researchers suggested the mechanisms underlying this association are likely multifactorial. Potential contributors include compromised epidermal barrier function (e.g., filaggrin deficiency) that allows greater UV or carcinogen penetration, chronic inflammation driving local immune activation, and baseline immune dysregulation that may impair tumor surveillance. Prior phototherapy exposure may also play a secondary role.

Importantly, researchers noted these results help contextualize safety findings from clinical trials of advanced AD therapies. In those trials, NMSC incidence rates were generally lower (0.2–0.4 per 100 PY for agents like dupilumab, upadacitinib, and lebrikizumab) than the real-world rates observed here—suggesting that part of the background NMSC signal arises from disease-related risk rather than treatment effect alone.

Study investigator Christopher Bunick, MD, PhD, Dermatology Times editor-in-chief and associate professor of dermatology at Yale School of Medicine, highlighted the clinical relevance of these findings:

“This study reminds us that patients with atopic dermatitis already have a higher background risk of nonmelanoma skin cancer, roughly similar to rheumatoid arthritis. Safety events reported in studies should be read against that higher baseline, while we keep sun protection and routine full-skin exams part of long-term care.”

Clinical Implications

For clinicians, these findings emphasize the importance of:

• Regular skin cancer screening for patients with AD, particularly those with prior malignancy or immunologic comorbidities.
• Ongoing sun protection counseling, including use of broad-spectrum sunscreen and protective clothing.
• Contextual interpretation of NMSC safety events in long-term AD therapy trials.

Though causation cannot be inferred, the study’s national scale, large cohort size, and consistent methodology provide strong evidence that AD itself confers a measurable elevation in NMSC risk—informing both patient management and safety monitoring.

References

1. Ciążyńska M, Kamińska-Winciorek G, Lange D, et al. The incidence and clinical analysis of non-melanoma skin cancer. Sci Rep. 2021;11(1):4337. Published 2021 Feb 22. doi:10.1038/s41598-021-83502-8
2. Slavinsky V, Helmy J, Vroman J, Valdebran M. Solar ultraviolet radiation exposure in workers with outdoor occupations: a systematic review and call to action. Int J Dermatol. 2024;63(3):288-297. doi:10.1111/ijd.16877
3. He MM, Lo CH, Wang K, et al. Immune-mediated diseases associated with cancer risks. JAMA Oncol. 2022;8(2):209-219. doi:10.1001/jamaoncol.2021.5680
4. Lebwohl M, Yue E, Krueger WS, et al. Risk of nonmelanoma skin cancer in patients with moderate-to-severe atopic dermatitis: A United States population-based study. Dermatol Ther (Heidelb). Published online October 13, 2025. doi:10.1007/s13555-025-01559-z