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Atopic Disorders in Ankylosing Spondylitis and Rheumatoid Arthritis M Rudwaleit, B Andermann, R Alten, H Sörensen, J Listing, a Zink, J Sieper, J Braun

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Atopic Disorders in Ankylosing Spondylitis and Rheumatoid Arthritis M Rudwaleit, B Andermann, R Alten, H Sörensen, J Listing, a Zink, J Sieper, J Braun 968 Ann Rheum Dis: first published as 10.1136/ard.61.11.968 on 1 November 2002. Downloaded from EXTENDED REPORT Atopic disorders in ankylosing spondylitis and rheumatoid arthritis M Rudwaleit, B Andermann, R Alten, H Sörensen, J Listing, A Zink, J Sieper, J Braun ............................................................................................................................. Ann Rheum Dis 2002;61:968–974 Background: The prevalence of atopic disorders in ankylosing spondylitis (AS) is unknown. AS and rheumatoid arthritis (RA) exhibit divergent T helper (Th) cell cytokine patterns. Objective: To test the hypothesis that Th2 polarised atopic disorders may be decreased in Th1 polar- ised RA but increased in AS, which is characterised by an impaired Th1 cytokine pattern, by assessing the prevalence of atopic disorders in AS and RA. Methods: 2008 subjects (380 patients with AS, 728 patients with RA, 900 controls) from Berlin, Ger- many, were considered in this cross sectional study. A questionnaire incorporating questions from the European Community Respiratory Health Service (ECRHS) and the International Study of Asthma and Allergies in Childhood (ISAAC) protocol was mailed to all subjects. Disease severity was assessed by the modified Health Assessment Questionnaire (mHAQ). Results: 1271 (63.3%) people responded to the questionnaire. The prevalence of any atopic disorder See end of article for was 24.6% (61/248) in patients with AS, 20.7% (111/536) in controls, and 13.1% (64/487) in authors’ affiliations patients with RA (p=0.0009 for AS v RA; p=0.001 for controls v RA). Hay fever was reported by ....................... 40/248 (16.1%) patients with AS, 82/536 (15.3%) controls, and 42/487 (8.6%) patients with RA Correspondence to: (p=0.002 for AS v RA; p=0.001 for controls v RA). Atopic dermatitis was reported by 19/248 (7.7%) Dr M Rudwaleit, patients with AS, 26/536 (4.9%) controls, and 14/487 (2.9%) patients with RA (p=0.003 for AS v Rheumatology, RA), and asthma by 18/248 (7.3%) patients with AS, 35/536 (6.5%) controls, and 21/487 (4.3%) Medizinische Klinik I, patients with RA. The differences were related neither to age nor to drugs. Disease severity was less in Universitätsklinikum atopic patients with RA who had the atopic disorder before the onset of RA (median mHAQ 0.75) than Benjamin Franklin, Hindenburgdamm 30, in patients in whom RA preceded the atopic disorder (median mHAQ 1.75; p=0.027). 12200 Berlin, Germany; Conclusions: Atopic disorders are decreased in RA but only slightly and non-significantly increased in [email protected] AS. This may imply that atopy confers some protection from RA but only little if any susceptibility to AS. Accepted It may further indicate that the cytokine deviation towards an impaired Th1 pattern in AS is less strong 27 February 2002 than the cytokine deviation towards Th1 in RA, a finding which may affect future therapeutic ....................... approaches. http://ard.bmj.com/ nkylosing spondylitis (AS) is a systemic inflammatory described as an impaired Th1 cytokine pattern.12 13 It is there- disease affecting predominantly the axial skeleton but fore similar but not identical to that of atopic disorders and also the peripheral joints, entheses, the eye, and clearly different from that in RA. A 1 occasionally the aortic root. Rheumatoid arthritis (RA) is also The generation of a Th1 immune response is inhibited in the a systemic inflammatory disease but in contrast with AS presence of Th2 cytokines and vice versa.7 Based on the recip- affects primarily the joints of the hand and feet in a rocal inhibition of the development of Th1 and Th2 responses on September 24, 2021 by guest. Protected copyright. symmetrical fashion. The primary site of inflammation in RA it has been suggested that Th1 and Th2 polarised immune is the synovium but in AS appears to be the enthesis and sites responses and also Th1 and Th2 polarised diseases mutually where ligaments insert into bone.2 AS usually begins in the exclude each other.14–17 Because the cytokine patterns in AS second or third decade whereas the onset of RA is rarely before and RA are not restricted to inflamed tissue but to some extent the fourth decade. AS affects more men than women, which is a systemic feature of each disease10 13 we suggested that the in contrast with the female preponderance in RA. Both impaired Th1 cytokine pattern in AS may well be compatible diseases result in substantial and almost equal morbidity.3 with the coexistence of atopic disorders whereas the strong Atopic disorders comprise hay fever, allergic asthma, and Th1 pattern in RA is less compatible with such coexistence. We atopic eczema/neurodermatitis and usually arise in early therefore studied the prevalence of asthma, hay fever, and childhood.45Key pathogenetic features of atopic disorders are atopic eczema in large cohorts of patients with AS, patients raised levels of IgE and a characteristic T helper cell cytokine with RA, and controls in West Berlin. pattern.6 Among T helper cells (Th) two opposite poles of immune responses can be distinguished based on the PATIENTS AND METHODS secretion of cytokines: the Th1 cytokine pattern with Patients and controls predominant secretion of interferon γ (IFNγ) and induction of At the end of 1997, patients with RA and AS were identified 3 a cellular immune response, and the Th2 cytokine pattern from the German Rheumatological Database. Entries to this with predominant secretion of interleukin (IL) 4, IL5, and IL13 and induction of the humoral immune response.7 While ............................................................. atopic disorders are associated with a Th2 cytokine pattern, Abbreviations: RA is considered to be a Th1 polarised disease.6 8–11 The AS, ankylosing spondylitis; ECRHS, European Community Respiratory Health Survey; IFNγ, interferon γ; IL, interleukin; cytokine pattern of AS and other spondyloarthropathies with ISAAC, International Study of Asthma and Allergies in Children; mHAQ, low production of IFNγ and tumour necrosis factor α (TNFα) modified Health Assessment Questionnaire; RA, rheumatoid arthritis; RF, without relevant changes in IL4 production can best be rheumatoid factor; Th, T helper; TNFα, tumour necrosis factor α www.annrheumdis.com Atopic disorders in AS and RA 969 Ann Rheum Dis: first published as 10.1136/ard.61.11.968 on 1 November 2002. Downloaded from Table 1 Demographic data of patients and controls p = 0.001 p = 0.0009 Numbers Age (years) Disease duration (years) (n) (mean (SD)) (mean (SD)) 30 AS 248 47.9 (12.3) 14.1 (10.6) 24.6 RA 487 60.3 (12.5) 12.2 (9.7) Controls 536 49.8 (15.6) – 20.7 20 13.1 database are made voluntarily by rheumatologists at univer- sity hospital outpatient clinics, other rheumatology hospitals, 10 or in private rheumatological practice. Diagnoses were made according to the 1987 American Rheumatism Association cri- Prevalence of atopy (%) teria (RA) and the 1984 modified New York criteria (AS). In order not to include in the RA group patients with 0 spondyloarthropathies incorrectly diagnosed as “rheumatoid Controls (n = 536) AS (n = 248) RA (n = 487) factor (RF) negative RA”, only patients with RA who were positive for RF were selected from the database for this study. Figure 1 Prevalence (%) of any atopic disorder in controls, patients Hospital staff members from the Benjamin Franklin Hospi- with AS, and patients with RA. The differences between AS and RA, and between controls and RA, respectively, were significant as tal (n=750), of whom about half were involved in patient care indicated by the p value. and half in hospital administration, were chosen as controls. Elderly patients without any known inflammatory rheumatic disease who were attending an osteoporosis outpatient clinic actual presence of asthma, hay fever, or atopic eczema in that (n=150) were additionally selected as controls to allow com- person was already highly likely. However, before considering parisons, particularly with the RA group for whom a higher this person as atopic we required in addition a positive answer mean age was expected. to the following question: “Did a doctor or general practitioner All patients and controls selected for this study were ever diagnose you as having asthma, hay fever, or atopic residents of West Berlin because differences in the prevalence eczema?” of atopy between West and East Germany have been Further questions of the questionnaire were about sex, age, reported.18–20 Patients and controls willing to respond to the disease duration, onset of AS or RA, onset of the atopic disor- questionnaire were asked to indicate their name and address der, and other allergies. The modified Health Assessment but could also respond anonymously in order to increase the Questionnaire (mHAQ) was applied to assess disease severity response rate; this approach, however, did not allow a second of AS and RA.25 For each atopic patient with RA we tried to contact to non-responders. identify a non-atopic patient with RA among the responders who was matched for sex, age, and disease duration, and Questionnaire assessed details of the patient’s drugs, including steroid During a three month period, from January to March 1998, a dosage, by a telephone interview. questionnaire was mailed to all patients and controls. The http://ard.bmj.com/ questionnaire comprised standardised questions extracted Sample size and statistics from the European Community Respiratory Health Survey Based on preliminary results, which were fully published later, 26 27 (ECRHS)21 and from the International Study of Asthma and reporting a 50% decrease of hay fever in patients with RA Allergies in Children (ISAAC) protocol.22 23 The ECRHS proto- and a small pilot study of our own conducted in Berlin and col assesses bronchial symptoms related to atopic asthma in Oxford, UK (Bowness P, personal communication), a power adults.
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