Juvenile idiopathic arthritis in children and adolescents with atopic dermatitis: A Finnish nationwide registry study

Abstract

To the Editor: Atopic dermatitis (AD), the most common chronic skin disease in children,1Langan S.M. Irvine A.D. Weidinger S. Atopic dermatitis.Lancet. 2020; 396: 345-360Google Scholar has multiple associated comorbidities.2Ivert L.U. Wahlgren C.F. Lindelöf B. Dal H. Bradley M. Johansson E.K. Association between atopic dermatitis and autoimmune diseases: a population-based case–control study.Br J Dermatol. 2021; 185: 335-342Google Scholar, 3Kauppi S. Jokelainen J. Timonen M. Tasanen K. Huilaja L. Atopic dermatitis is associated with dermatitis herpetiformis and celiac disease in children.J Invest Dermatol. 2021; 141: 191-193Google Scholar, 4Huang A.H. Roh Y.S. Sutaria N. et al.Real-world comorbidities of atopic dermatitis in the pediatric ambulatory population in the United States.J Am Acad Dermatol. 2021; 85: 893-900Google Scholar Several studies have shown an association between AD and rheumatoid arthritis in adult patients,2Ivert L.U. Wahlgren C.F. Lindelöf B. Dal H. Bradley M. Johansson E.K. Association between atopic dermatitis and autoimmune diseases: a population-based case–control study.Br J Dermatol. 2021; 185: 335-342Google Scholar but studies on AD as a risk factor for rheumatic diseases in children and adolescents are scarce.2Ivert L.U. Wahlgren C.F. Lindelöf B. Dal H. Bradley M. Johansson E.K. Association between atopic dermatitis and autoimmune diseases: a population-based case–control study.Br J Dermatol. 2021; 185: 335-342Google Scholar,4Huang A.H. Roh Y.S. Sutaria N. et al.Real-world comorbidities of atopic dermatitis in the pediatric ambulatory population in the United States.J Am Acad Dermatol. 2021; 85: 893-900Google Scholar We designed this retrospective, nationwide registry-based study to investigate whether there is an increased risk of juvenile idiopathic arthritis (JIA) in children and adolescents with AD compared with the general population. Data on all individuals diagnosed with AD in Finnish hospitals between 1987 and 2018 were extracted from the Finnish Care Register for Health Care. Only patients who were aged <18 years at the time of first AD diagnosis and had it recorded at least twice in the Finnish Care Register for Health Care were included in the study population. A group of age- and sex-matched control individuals was derived from the Finnish Population Register Center database. The prevalence of the preselected codes for JIA for both cases and controls were analyzed, and the associations were evaluated using logistic regression model adjusted for age and sex (Supplementary Methods, available via Mendeley at https://data.mendeley.com/datasets/2drjzz8vpg/1). The study population consisted of 70,584 patients with AD (Table I). The overall prevalence of JIA was higher in AD patients than controls (0.7% vs 0.4%; P < .001). In an adjusted model, the patients with AD had increased risk for JIA (adjusted odds ratio, 1.58; 95% CI, 1.41-1.77) compared with controls (Table II). No significant differences between sexes were found in different subcategories, except that only women had a heightened risk of developing “undifferentiated JIA” (odds ratio, 5.80; 95% CI, 2.20-16.2) compared with men (odds ratio, 0.87; 95% CI, 0.19-2.74). The age at the onset of JIA was significantly higher in patients with AD compared with patients with JIA without AD (P = .004; Table I).Table ICharacteristics of the study and control populationsAtopic dermatitis†Defined by International Classification of Diseases, Ninth and Tenth Revision codes.ControlsP valueN70,584‡Excluding 499 individuals from the final study population with the diagnosis atopic dermatitis recorded only once in the Finnish Care Register for Health Care.270,783§Excluding 299,217 individuals either with no records or with a recorded diagnosis of AD in the Finnish Care Register for Health care.Female45.3%48.3%Male54.7%51.7%Age∗Data given as years, mean ± standard deviation. at the onset of JIA8.28 ± 5.187.63 ± 5.35.004JIA, Juvenile idiopathic arthritis.∗ Data given as years, mean ± standard deviation.† Defined by International Classification of Diseases, Ninth and Tenth Revision codes.‡ Excluding 499 individuals from the final study population with the diagnosis atopic dermatitis recorded only once in the Finnish Care Register for Health Care.§ Excluding 299,217 individuals either with no records or with a recorded diagnosis of AD in the Finnish Care Register for Health care. Open table in a new tab Table IIOdds ratios for Juvenile arthritis according to the International Classification of Diseases with and without atopic dermatitis by the age of 18 yearsComorbidityGroupN (%)OR (95% CI)aORװAdjusted for birth year and sex. (95% CI)All JIA∗JIA defined by the International Classification of Diseases, Ninth and Tenth Revision codes.ADControls487 (0.07)1022 (0.04)1.83 (1.65-2.04)Ref.1.58 (1.41-1.77)Ref. Seropositive JIAADControls87 (0.12)147 (0.05)2.27 (1.74-2.96)Ref.1.86 (1.41-2.46)Ref. Enthesis-related arthritisADControls26 (0.04)44 (0.02)2.27 (1.40-3.68)Ref.1.83 (1.10-3.03)Ref. Systemic-onset JIAADControls22 (0.03)33 (0.01)2.56 (1.47-4.38)Ref.2.13 (1.21-3.75)Ref. Polyarticular JIA, RFADControls196 (0.28)368 (0.14)2.05 (1.72-2.43)Ref.1.82 (1.52-2.19)Ref. Oligoarticular JIAADControls282 (0.40)619 (0.23)1.75 (1.52-2.01)Ref.1.43 (1.24-1.66)Ref. Undifferentiated JIAADControls13 (0.02)20 (0.01)2.50 (1.21-5.01)Ref.2.07 (0.99-4.30)Ref. Psoriatic JIA†Group of psoriatic JIA includes both M09.0 and L40.5 International Classification of Diseases, Tenth Revision codes and corresponding International Classification of Diseases, Ninth Revision codes. None of the patients had a concomitant diagnosis of psoriasis in Finnish Care Register for Health Care by the age of 18 years.ADControls33 (0.05)32 (0.01)3.96 (2.42-6.47)Ref.2.75 (1.64-4.60)Ref.AD‡Including those with AD diagnosis registered by dermatologist at least twice.Controls22 (0.03)32 (0.01)2.64 (1.51-4.54)Ref2.55 (1.48-4.40)RefAD§Including those with AD diagnosis registered either by dermatologist or pediatric allergologist at least twice.Controls24 (0.03)32 (0.01)2.88 (1.68-4.89)Ref2.78 (1.64-4.73)RefAD, Atopic dermatitis; aOR, adjusted odds ratio; JIA, juvenile idiopathic arthritis; OR, odds ratio; Ref, reference; RF, rheumatic factor.∗ JIA defined by the International Classification of Diseases, Ninth and Tenth Revision codes.† Group of psoriatic JIA includes both M09.0 and L40.5 International Classification of Diseases, Tenth Revision codes and corresponding International Classification of Diseases, Ninth Revision codes. None of the patients had a concomitant diagnosis of psoriasis in Finnish Care Register for Health Care by the age of 18 years.‡ Including those with AD diagnosis registered by dermatologist at least twice.§ Including those with AD diagnosis registered either by dermatologist or pediatric allergologist at least twice.װ Adjusted for birth year and sex. Open table in a new tab JIA, Juvenile idiopathic arthritis. AD, Atopic dermatitis; aOR, adjusted odds ratio; JIA, juvenile idiopathic arthritis; OR, odds ratio; Ref, reference; RF, rheumatic factor. In this large population-based register study, we found a positive association between AD and JIA. Interestingly, we found the most marked association with AD and Juvenile psoriatic arthritis (adjusted odds ratio, 3.96; 95% CI, 2.42-6.47). This finding was confirmed using subanalysis among those with AD diagnosed by a dermatologist (Table II). A recent study from the United States demonstrated an association between AD and several autoimmune diseases, but no association was found between AD and juvenile arthritis.4Huang A.H. Roh Y.S. Sutaria N. et al.Real-world comorbidities of atopic dermatitis in the pediatric ambulatory population in the United States.J Am Acad Dermatol. 2021; 85: 893-900Google Scholar The major strength of our study is its comprehensive nationwide study population. We admit that since this is a registry-based study, the accuracy of diagnoses and diagnostic codes cannot be verified. However, it is notable that none of the AD cases with psoriatic JIA had a diagnosis of psoriasis, and a recent study demonstrated the high accuracy of rheumatologic diagnoses in Finnish registries.5Paltta J. Heikkilä H.K. Pirilä L. et al.The validity of rheumatoid arthritis diagnoses in Finnish biobanks.Scand J Rheumatol. 2023; 52: 1-9Google Scholar To ensure higher accuracy of the diagnosis, we required the diagnoses of both AD and arthritis to be recorded at least twice in the Finnish Care Register for Health Care. Here, we demonstrate the association between AD and JIA regardless of sex. The diagnosis of JIA appears to be later in patients with AD. Therefore, it is important to inquire actively about symptoms not directly linked to the patients’ skin disease. Dr Huilaja has received educational grants from Takeda, Janssen-Cilag, Novartis, AbbVie, and LEO Pharma; honoraria from Sanofi Genzyme, Novartis, AbbVie, LeoPharma, and OrionPharma for consulting and/or speaking; and is an investigator for AbbVie and Amgen. Dr Sinikumpu has received honoraria from LEOPharma and Sanofi Genzyme for speaking and is an investigator for AbbVie. Prof Tasanen has received educational grants from Novartis and Pfizer and honoraria from Novartis, AbbVie, Janssen-Cilag, Sanofi Genzyme, and Lilly for consulting and/or speaking. Dr Keskitalo and Mr Jokelainen have no conflicts of interest to declare.