Lymphoma among patients with atopic dermatitis and/or treated with topical immunosuppressants in the United Kingdom

Arellano, Félix; Arana, Alejandro; Wentworth, Charles; Fernández-Vidaurre, Carlos; Schlienger, Raymond G.; Conde, Eulogio

doi:10.1016/j.jaci.2009.02.028

Cited by 80 publications

(81 citation statements)

References 24 publications

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“…In the meta-analysis of the case-control studies the increased risk for lymphomas was insignificant (OR 1.18, 95% CI 0.94 -1.47) (43). Three of the studies involved in this meta-analysis indicated a significant association between severity of atopic dermatitis and lymphoma (21,22,45). In the cohort study by Margolis et al the RR of lymphoma in patients with severe AD was 1.95 (95% CI, 1.15 -3.12) (45) while in the two case control studies the adjusted OR varied from 2.4 (95% CI, 1.5 -3.8) to 3.72 (95% CI, 1.40 -9.87) (21,22).…”

Section: Atopic Dermatitis Per Se and Increased Risk For Lymphomamentioning

confidence: 84%

“…A cohort study by Schneeweiss et al reported no significant association between lymphoma and both TCIs (tacrolimus; RR 1.36, 95% CI, 0.47 -3.98, pimecrolimus: RR 1.63, 95% CI, 0.75 -3.54) (24). In case control studies, the risk for developing lymphoma was even more insignificant (21,22). The low level exposure to TCIs before appearance of lymphoma in the study by Hui et al and in the study by Schneeweiss et al amounting to only 2 to 3 tubes does not support a causal association between TCIs and lymphoma preventing us from drawing a definitive conclusion of potential malignancy risk (43).…”

Section: Resultsmentioning

confidence: 99%

“…Three of the studies involved in this meta-analysis indicated a significant association between severity of atopic dermatitis and lymphoma (21,22,45). In the cohort study by Margolis et al the RR of lymphoma in patients with severe AD was 1.95 (95% CI, 1.15 -3.12) (45) while in the two case control studies the adjusted OR varied from 2.4 (95% CI, 1.5 -3.8) to 3.72 (95% CI, 1.40 -9.87) (21,22). However, considering the potential misclassification bias and possibility of independent association between atopic dermatitis and risk of developing lymphoma, this result should be interpreted with caution (47).…”

Section: Atopic Dermatitis Per Se and Increased Risk For Lymphomamentioning

confidence: 97%

“…Such misdiagnosis probably occurred in the study reported by Hui et al with an overrepresentation of CTLC among tacrolimus users (23). In the meta-analysis by Legendre et al which included two case control studies by Arellano et al (21,22), statistically significant association between highly potent topical corticosteroids and increased risk of lymphoma with an overall OR for lymphoma of 1.73 (95% CI, 1.52 -1.97) might have also been confounded by severity of AD due to low exposure to TCSs before lymphoma occurrence (< 6 months to 12 months). According to the fact that in one case control study by Legendre et al the increased risk disappeared after adjusting for AD severity, this makes the potential link even more questionable (43).…”

Section: Atopic Dermatitis Per Se and Increased Risk For Lymphomamentioning

confidence: 99%

“…Many opinion leaders and medical associations, including the American academy of allergy, asthma and immunology (AAAAI), American college of allergy, asthma and immunology (ACAAI), American academy of dermatology, canadian dermatology association (CDA), and Canadian society of allergy and clinical immunology (CSACI) released position statements, expressing disagreement about box warning, promoting the safety of the TCIs and demanding reconsideration of the alert (15)(16)(17)(18). In September 2010, the FDA released a comprehensive review of TCI safety summarizing data from six studies including more than 6 million patients (19)(20)(21)(22)(23)(24)(25)(26). Later on, in May, 2011 according to a total of 72 cases of malignancy that had been reported in children treated with TCI, the FDA issued an addendum (27,28).…”

Section: The Us Fda "Black Box" Warning For Tcis and Fda Comprehensivmentioning

confidence: 99%

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Topical Calcineurin Inhibitors and Malignancy Risk

et al. 2017

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Context: The approval of topical calcineurin inhibitors (TCIs) has been a significant breakthrough for the treatment of atopic dermatitis due to much lower systemic absorption and not causing skin atrophy even after long-term use that have made them become popular replacements for topical corticosteroids being almost equally effective. In January 2006, the US food and drug administration (FDA), followed later also by the European medicine agency (EMEA), issued the "black box" warning causing controversy regarding a potential increased risk of lymphoma in patients with atopic dermatitis and treated with TCIs. Evidence Acquisition: PubMed and MEDLINE ® databases were systematically searched utilizing a variety of terms relating to the subject matter. Articles written only in English over the past 15 years were analyzed and selected for review. Results: So far, no scientific evidence of the association has been found between use of TCIs, and increased incidence of skin cancers and lymphomas in patients with AD. The systematic review and meta-analysis by Legendre et al. found the role of TCIs unlikely to be a significant risk factor of lymphoma in those patients. Conclusions:Despite an extensive body of evidence regarding the TCIs safety, the box warning still remains leaving the physicians and patients unduly uncertain and confused about the safety of TCI use.

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Section: Atopic Dermatitis Per Se and Increased Risk For Lymphomamentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Section: Atopic Dermatitis Per Se and Increased Risk For Lymphomamentioning

confidence: 97%

Section: Atopic Dermatitis Per Se and Increased Risk For Lymphomamentioning

confidence: 99%

Section: The Us Fda "Black Box" Warning For Tcis and Fda Comprehensivmentioning

confidence: 99%

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Topical Calcineurin Inhibitors and Malignancy Risk

et al. 2017

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Association Between Atopic Eczema and Cancer in England and Denmark

et al. 2020

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IMPORTANCE Associations between atopic eczema and cancer are unclear, with competing theories that increased immune surveillance decreases cancer risk and that immune stimulation increases cancer risk. Establishing baseline cancer risk in people with atopic eczema is important before exploring the association between new biologic drugs for atopic eczema and cancer risk.OBJECTIVE To investigate whether atopic eczema is associated with cancer.

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Association Between Topical Calcineurin Inhibitor Use and Risk of Cancer, Including Lymphoma, Keratinocyte Carcinoma, and Melanoma

et al. 2021

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IMPORTANCE Topical calcineurin inhibitors (TCIs) are commonly used as second-line treatment for atopic dermatitis. In 2006, the US Food and Drug Administration issued a black box warning against TCI use, citing data from case reports and animal studies indicating a potential risk of cancer.OBJECTIVE To evaluate the association between TCI use and risk of malignant neoplasms compared with nonactive and active comparator groups.DATA SOURCES Electronic searches were conducted in MEDLINE via Ovid, Embase via Ovid, and Web of Science from database inception to August 21, 2020.STUDY SELECTION Observational studies investigating the association between treatment with TCIs (ie, tacrolimus and pimecrolimus) and the development of cancer with nonactive or active comparators were included. The population of interest was not limited to any specific disease state, age, or sex. All articles were assessed independently and in duplicate by 2 reviewers. Risk of bias was assessed using the Newcastle-Ottawa scale. Of 2464 nonduplicate records retrieved from the search, 11 studies met the inclusion criteria.DATA EXTRACTION AND SYNTHESIS Data extraction was conducted independently by 2 reviewers according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Random-effects meta-analyses were used to derive pooled relative risk (RR) estimates. Data were analyzed from July 25 to October 25, 2020. MAIN OUTCOMES AND MEASURESRisk of cancer overall and risk of specific cancer types (lymphoma, melanoma, and keratinocyte carcinoma). RESULTSEight unique cohort studies (408 366 treated participants [55.1% female], 1 764 313 nonactive comparator controls, and 1 067 280 controls using topical corticosteroids) and 3 unique case-control studies (3898 cases [55.0% male] and 14 026 cancer-free controls [52.4% male]) were included. There was no association between TCI use and cancer overall compared with nonactive comparators (RR, 1.03; 95% CI, 0.92-1.16). Lymphoma risk was elevated with TCI use with both nonactive (RR, 1.86; 95% CI, 1.39-2.49) and topical corticosteroid comparators (RR, 1.35; 95% CI,. No significant association was found between TCI use and increased skin cancer (melanoma and keratinocyte carcinoma). CONCLUSIONS AND RELEVANCEThe findings of this systematic review and meta-analysis suggest an association between TCI use and risk of lymphoma but not other cancers. Combined with the low absolute risk of lymphoma, the potential increased risk attributable to TCI use for any individual patient is likely very small.

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Lymphoma among patients with atopic dermatitis and/or treated with topical immunosuppressants in the United Kingdom

Cited by 80 publications

References 24 publications

Topical Calcineurin Inhibitors and Malignancy Risk

Topical Calcineurin Inhibitors and Malignancy Risk

Association Between Atopic Eczema and Cancer in England and Denmark

Association Between Topical Calcineurin Inhibitor Use and Risk of Cancer, Including Lymphoma, Keratinocyte Carcinoma, and Melanoma

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