Key points are not available for this paper at this time.
Dear Editor, In patients with psoriasis, the risk of lymphoma has been a subject of controversy, and data from larger studies are limited.1,2,3,4 We therefore investigated the 5‐year risk of new‐onset Hodgkin lymphoma (HL), non‐Hodgkin lymphoma (NHL) excluding cutaneous T‐cell lymphoma (CTCL) and CTCL, respectively, in patients with psoriasis. We performed a cohort study of the Danish population (≥ 18 years old) between 1 January 2008 and 31 December 2012. Information on vital statistics, morbidity, pharmacotherapy and income was gathered from administrative registries that can be cross‐linked at the individual level.5 Patients with psoriasis were identified by diagnostic code or receipt of at least two prescriptions of topical vitamin D derivates (standard first‐line therapy in Denmark and not used for the treatment of other diseases). The psoriasis cohort was stratified based on receipt of systemic therapy for psoriasis (methotrexate, psoralen–ultraviolet A, retinoids, ciclosporin, adalimumab, efalizumab, etanercept, infliximab or ustekinumab) consistent with severe disease.5,6 The study end points, decided a priori, were first‐time HL (ICD‐10 C81), NHL excluding CTCL (ICD‐10 DC82‐C85, excluding DC84, DC84·0, DC84·0A, DC84·0B, DC84·0C, DC84·1, DC84·5B, DC84·5C) and CTCL (ICD‐10 L41·2, DC84, DC84·0, DC84·0A, DC84·0B, DC84·0C, DC84·1, DC84·5B, DC84·5C). Lymphoma incidence rates (IRs) per 10 000 person‐years were calculated. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were estimated using Cox regression analysis and adjusted for age, sex, socioeconomic status and systemic treatment. The study was approved by the Danish Data Protection Agency (ref. 2007‐58‐0015/int. ref. GEH‐2014‐018/I‐Suite 02736). We identified 58 138 patients with psoriasis (51·2% women, mean age ± SD 54·8 ± 16·1 years) and 4 303 731 general population controls (50·8% women, mean age 48·6 ± 18·0 years). There was an overrepresentation of smoking (16·1% vs. 9·8%) and alcohol misuse (2·0% vs. 1·4%) among patients with psoriasis compared with the general population. Socioeconomic status was evenly distributed among control participants, whereas there were fewer patients with psoriasis in the lowest income group (lowest 12·4%, below average 23·5%, average 21·6%, above average 20·2% and highest 22·4%). Among the psoriasis group, 24·5% had received systemic treatment, of which methotrexate was most frequently used (13·4%). Retinoids were used in 5·1%, psoralens in 2·9%, ciclosporin in 1·8% and biologics in 1·3% of patients. The baseline prevalence of lymphoma was 0·5% and 0·3%, among participants with psoriasis and controls, respectively, and these participants were censored for further analyses. Higher IRs were observed for patients with psoriasis compared with the general population for most outcomes (Table 1). In adjusted models, psoriasis was associated with an increased risk of HL (HR 1·50, 95% CI 1·01–2·23), albeit the results were nonsignificant in stratified analyses of severe psoriasis. We only found increased risk of NHL in patients with psoriasis with severe disease (HR 1·64, 95% CI 1·12–2·40). The most marked association was found for CTCL in patients with psoriasis receiving systemic treatment (HR 13·63, 95% CI 6·72–27·64) (Table 1). In a subanalysis, where systemic treatments were regarded as time‐dependent variables the association between psoriasis and lymphomas did not achieve statistical significance; HRs 1·40 (95% CI 0·92–2·12, P = 0·119) for HL, 0·92 (95% CI 0·75–1·13, P = 0·434) for NHL and 0·61 (95% CI 0·26–1·43, P = 0·258) for CTCL. Summary of number of patients analysed, follow‐up time, number of events, incidence rates per 10 000 person‐years and hazard ratios IR, incidence rate; PY, person‐years; HR, hazard ratio; CI, confidence interval. aExcluding cutaneous T‐cell lymphoma; badjusted estimates: age, sex, socioeconomic status and systemic treatment; cadjusted estimates: age, sex, socioeconomic status. Summary of number of patients analysed, follow‐up time, number of events, incidence rates per 10 000 person‐years and hazard ratios IR, incidence rate; PY, person‐years; HR, hazard ratio; CI, confidence interval. aExcluding cutaneous T‐cell lymphoma; badjusted estimates: age, sex, socioeconomic status and systemic treatment; cadjusted estimates: age, sex, socioeconomic status. Explanations for an association between chronic inflammatory diseases and lymphoma include persistent immune activation that may lead to the appearance of a dominant clone, and the impact of immunosuppressive treatments.1,7 CTCL may also be misdiagnosed as psoriasis at initial presentation as seen for atopic dermatitis.8 However, the lack of association between mild psoriasis and CTCL does not favour this theory. In conclusion, patients with severe psoriasis had a higher co‐occurrence of NHL, especially CTCL. Patients with mild psoriasis had a slightly increased risk of HL. The relative contribution of initial incorrect diagnosis, possible overlap in disease pathogenesis and effects of systemic medication needs further investigation. Funding sources: J.P.T. is supported by an unrestricted grant from the Lundbeck Foundation, unrelated to the submitted work. Conflicts of interest: L.S. has received consultancy and/or speaker honoraria from AbbVie, Pfizer, Janssen‐Cilag, Merck Sharp & Dohme and LEO Pharma and is a member of the advisory boards of AbbVie, Janssen‐Cilag, Eli Lilly, Sanofi, Almirall, LEO Pharma, Celgene and Novartis. C.Z. has served as a scientific consultant for AbbVie, Pfizer, Janssen‐Cilag, Merck & Co., Inc., Eli Lilly, Takeda, Almirall and Novartis and a clinical study investigator for AbbVie, Amgen, Eli Lilly, Merck & Co., Inc., Takeda, LEO Pharma, Boehringer‐Ingelheim and Novartis. J.P.T. is supported by an unrestricted grant from the Lundbeck Foundation. A.E. has received research funding from Pfizer and Eli Lilly, and honoraria as consultant and/or speaker from Pfizer, Eli Lilly, Novartis, Galderma and Janssen Pharmaceuticals.
Kamstrup et al. (Sat,) studied this question.