Atopic dermatitis and cancer risk

Wang, H.; Diepgen, Thomas L.

doi:10.1111/j.1365-2133.2005.07077.x

Cited by 61 publications

(66 citation statements)

References 29 publications

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“…The adaptive immune response mounted by TSLP against cancer can eliminate cancerous lesions in the skin and prevent new lesions from developing (1). These findings are consistent with epidemiological data suggesting that patients with allergic skin inflammation are protected from skin cancer (5)(6)(7)(8). TSLP expression and its immune effects in the skin can be induced by calcipotriol (calcipotriene), an FDA-approved topical medication for psoriasis (9)(10)(11).…”

Section: Introductionsupporting

confidence: 79%

Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy

Cunningham

Tabacchi

Eliane

et al. 2016

Journal of Clinical Investigation

138

113

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Premalignant lesions of cutaneous squamous cell carcinoma (SCC) are identified clinically as actinic keratoses (12,13). Several field-directed treatments including 5-fluorouracil (5-FU), diclofenac, ingenol, and imiquimod have been approved for the treatment of sun-damaged skin with multiple actinic keratoses (13-15). However, the long treatment duration and the severity BACKGROUND. Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis. METHODS.The mechanism of calcipotriol action against skin carcinogenesis was examined in genetically engineered mouse models. The efficacy and safety of 0.005% calcipotriol ointment combined with 5% 5-FU cream were compared with Vaseline plus 5-FU for the field treatment of actinic keratosis in a randomized, double-blind clinical trial involving 131 participants. The assigned treatment was self-applied to the entirety of the qualified anatomical sites (face, scalp, and upper extremities) twice daily for 4 consecutive days. The percentage of reduction in the number of actinic keratoses (primary outcome), local skin reactions, and immune activation parameters were assessed. RESULTS.Calcipotriol suppressed skin cancer development in mice in a TSLP-dependent manner. Four-day application of calcipotriol plus 5-FU versus Vaseline plus 5-FU led to an 87.8% versus 26.3% mean reduction in the number of actinic keratoses in participants (P < 0.0001). Importantly, calcipotriol plus 5-FU treatment induced TSLP, HLA class II, and natural killer cell group 2D (NKG2D) ligand expression in the lesional keratinocytes associated with a marked CD4 + T cell infiltration, which peaked on days 10-11 after treatment, without pain, crusting, or ulceration.CONCLUSION. Our findings demonstrate the synergistic effects of calcipotriol and 5-FU treatment in optimally activating a CD4 + T cell-mediated immunity against actinic keratoses and, potentially, cancers of the skin and other organs.TRIAL REGISTRATION. ClinicalTrials.gov NCT02019355. FUNDING. Not applicable (investigator-initiated clinical trial).

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Section: Introductionsupporting

confidence: 79%

Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy

Cunningham

Tabacchi

Eliane

et al. 2016

Journal of Clinical Investigation

138

113

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“…Some studies have reported an increased risk of lymphoma in atopic dermatitis (AD), 3 whereas others have shown inconclusive results or even a decrease in risk of lymphoma. 4 A recent observational study in US patients with AD showed that increasing age, use of oral corticosteroids, and severe AD were associated with an increased risk of lymphoma. Use of high-potency topical corticosteroids (TCS) was associated with a slight increase in lymphoma risk.…”

mentioning

confidence: 99%

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

Arellano¹,

Arana²,

Wentworth³

et al. 2009

Journal of Allergy and Clinical Immunology

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“…A number of epidemiological studies suggested a strong relationship between atopic conditions and hematopoietic cancers [18,23,48,49,50,51]. In these studies performed in allergic subjects, the presence of an increased risk of malignant lymphomas [50] or leukemia [52] has been described [51,53].…”

Section: Discussionmentioning

confidence: 99%

“…Several case reports of the onset of CTCL in patients affected by atopic dermatitis (AD) seem to support the possibility of such an association [18,19,20,21,22], but other epidemiological studies have shown negligible evidence of a causal relationship or even a decreased risk [23,24]. Surprisingly, none of the above mentioned studies evaluated the presence and relevance of a specific IgE response in CTCL cases.…”

Section: Introductionmentioning

confidence: 96%

Specific IgE toward Allergenic Molecules Is a New Prognostic Marker in Patients with Sézary Syndrome

Scala¹,

Abeni²,

Palazzo³

et al. 2011

Int Arch Allergy Immunol

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Background: Sézary syndrome (SS) is the aggressive leukemic form of cutaneous T cell lymphoma characterized by erythroderma, the presence of a malignant circulating T memory cells with skin homing potential, and the ability to produce a variety of Th2 soluble factors, such as IL-4 and IL-5. We measured total and specific IgE in SS patients as a further parameter of a Th2-skewed immune system, and studied their clinical impact. Methods: Specific IgE production in a cohort of 55 SS patients was evaluated by the molecule-based ISAC microarray system. We then evaluated survival times and the hazard ratios in this cohort by Kaplan-Meier and Cox methods. Results: Twenty-four (43.6%) SS patients had specific IgE to both environmental and food allergens. For survival analysis, patients found positive to at least one allergen were defined as IgE+. By comparing IgE+ versus IgE– we found a significant difference in the median survival times, 2.9 versus 8.9 years (p < 0.001). Conversely, no survival difference could be observed when total IgE levels were considered. IgE+ patients had higher levels of CD60+CD49–CD4+ T cells, which also represent another worse prognostic index recently identified. Conclusion: SS patients had specific IgE to both environmental and food allergens. IgE+ SS patients had a significant lower survival rate. High levels of CD60–CD49+CD4+ T cells associated with an IgE– phenotype allow the identification of a restricted group of long survivor SS patients. Therefore, specific measurement of IgE seems to be useful in discriminating survival.

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Atopic dermatitis and cancer risk

Cited by 61 publications

References 29 publications

Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy

Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy

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

Specific IgE toward Allergenic Molecules Is a New Prognostic Marker in Patients with Sézary Syndrome

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