Association Between Granuloma Annulare and the Risk of Hematologic Malignancies

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• This study involving 48,132 patients with granuloma annulare and 48,132 matched controls found that patients with granuloma annulare had a significantly increased risk of lymphoma, leukemia, and any hematologic malignancy compared with controls. Age-stratified analyses showed comparable findings among patients aged 51 to 70 years and those older than 70 years, and there was no significant increase in the risk for hematologic malignancies in patients younger than 50 years.
• This study suggests that patients diagnosed with granuloma annulare have an increased risk of hematologic malignancies, emphasizing the need for further research and potential screening strategies, particularly in older age groups.

–  Lillian Sun, MD

Written by

 

 

Misha A. Rosenbach MD

Granuloma annulare and its potential association with hematologic malignancies

Granuloma annulare (GA) is an uncommon but not incredibly rare disease that most dermatologists encounter with some frequency. While there are a number of variants, most patients present with localized disease, some pediatric patients may present with harder-to-recognize subcutaneous lesions, and a minority of patients (approximately 20%) present with generalized disease. Recognizing the disease is only the first step — dermatologists should be familiar with both disease associations/comorbidities and emerging literature on potential drug triggers and maintain familiarity with the evolving landscape of treatment options and algorithms.

Our understanding of the epidemiology of GA and potential disease associations has improved significantly over the past 5 years. Two large epidemiological studies suggest that the incidence of GA is approximately 0.04% to 0.1% of the US population, with the highest rates noted in the fifth decade of life and an approximately a 3–4:1 female:male ratio, and occurs more commonly among White individuals.1,2 There appears to be an association of GA with type 2 diabetes and hyperlipidemia and an increased risk of other autoimmune diseases, including thyroid disease.3,4There does not appear to be an association between GA and solid organ malignancy.5 Prior research had suggested a potential increased risk of hematologic malignancies in patients with GA.3

The study by Garate et al (conflict of interest disclosure: I am a co-author of this study) used analysis of ICD-10 codes (which have been previously validated for this work) in the TriNetX research network to explore that link further. The findings suggest an increased risk for lymphoma, leukemia, and any hematologic malignancy in patients with GA compared with matched controls. This lends further evidence to the observation that patients with GA may have an increased risk of hematologic malignancy. There were similar disease associations in patients aged 51 to 70 years and those older than 70 years, and there was no increased risk for younger patients (due to the rarity of hematologic malignancy, the study may lack the power to exclude a small increased risk in that age group). Notably, hematologic malignancies remain rare overall; hence, even with a potential increase in the risk, most patients with GA will not have or develop a hematologic malignancy.

Prior to this work, I would counsel patients who presented with atypical disease (eg, near-erythroderma), recalcitrant disease (eg, failing to respond to initial first- or second-line therapy), or an unusual demographic (eg, age >65 years) about the need to consider the underlying drivers of their GA, including potential hematologic disease. Practically, this would often mean screening with at least a complete blood count, chest x-ray, and evaluation for paraprotein with a serum protein electrophoresis. Based on this new study, I will likely extend that evaluation to patients older than 50 years, and advise them to report concerning symptoms (easy bleeding/bruising, "B symptoms" of fever, chills, weight loss, night sweats, etc), and keep up to date with their primary care doctor and age-appropriate evaluations (as should all patients!). Over time, this disease association may also impact treatment algorithms, as recent publications have proposed the consideration of off-label use of TNF inhibitors as potential second-line agents for recalcitrant generalized GA.6

References

1. Leasure AC, Damsky W, Cohen JM. Prevalence of Granuloma Annulare in the United States: A Cross-Sectional Study in the All of Us Research Program. Int J Dermatol. 2022;61(8):e301–e302. https://onlinelibrary.wiley.com/doi/10.1111/ijd.15832
2. Barbieri JS, Rodriguez O, Rosenbach M, et al. Incidence and Prevalence of Granuloma Annulare in the United States. JAMA Dermatol. 2021;157(7):824–830. https://jamanetwork.com/journals/jamadermatology/fullarticle/2780648
3. Barbieri JS, Rosenbach M, Rodriguez O, et al. Association of Granuloma Annulare With Type 2 Diabetes, Hyperlipidemia, Autoimmune Disease, and Hematologic Malignant Neoplasms. JAMA Dermatol. 2021;157(7):817–823. https://jamanetwork.com/journals/jamadermatology/fullarticle/2780649
4. Leasure AC, Damsky W, Cohen JM. Comorbities Associated With Granuloma Annulare: A Case–Control Study in the All of Us Research Program. J Am Acad Dermatol. 2022;87(1):197–199. https://www.jaad.org/article/S0190-9622(21)02183-6/fulltext
5. Barbieri JS, Rosenbach M, Rodriguez O, et al. Granuloma Annulare Is Not Associated With Solid-Organ Malignancies: A Cohort Study. J Am Acad Dermatol. 2022;86(6):1352–1354. https://www.jaad.org/article/S0190-9622(21)00986-5/fulltext
6. Berk-Krauss J, Weiner D, Rosenbach M. Results of a Treatment Algorithm for Generalized Granuloma Annulare. J Am Acad Dermatol. 2023 Sep 26. doi: 10.1016/j.jaad.2023.09.050. Online ahead of print. https://www.jaad.org/article/S0190-9622(23)02867-0/fulltext

Abstract

Granuloma annulare (GA) is an inflammatory granulomatous skin condition of unknown etiology that can be a localized or generalized eruption of ringed erythematous plaques, papules, or intertriginous patches. Previous investigations have postulated potential associations between GA and hematological malignancies. However, results from epidemiologic evaluations have been conflicting and have been limited by sample size and imprecision.

Journal of the American Academy of Dermatology

Granuloma annulare is associated with an increased risk of hematologic malignancies: A multicenter cohort study using TriNetX

J Am Acad Dermatol 2023 Dec 24;[EPub Ahead of Print], D Garate, CJ Thang, W Damsky, M Rosenbach, G Golovko, MG Wilkerson, JS Barbieri

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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