Atopic disorders in ankylosing spondylitis and rheumatoid arthritis. (Extended Report).

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 polarised 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, Germany, 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 was 24.6% (61/248) in patients with AS, 20.7% (111/536) in controls, and 13.1% (64/487) in 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 (p = 0.002 for AS v RA; p = 0.001 for controls v RA). Atopic dermatitis was reported by 19/248 (7.7%) patients with AS, 26/536 (4.9%) controls, and 14/487 (2.9%) patients with RA (p = 0.003 for AS v RA), and asthma by 18/248 (7.3%) patients with AS, 35/536 (6.5%) controls, and 21/487 (4.3%) patients with RA. The differences were related neither to age nor to drugs. Disease severity was less in atopic patients with RA who had the atopic disorder before the onset of RA (median mHAQ 0.75) than in patients in whom RA preceded the atopic disorder (median mHAQ 1.75, p = 0.027).

Conclusions: Atopic disorders are decreased in RA but only slightly and non-significantly increased in AS. This may imply that atopy confers some protection from RA but only little if any susceptibility to AS. It may further indicate that the cytokine deviation towards an impaired Th1 pattern in AS is less strong than the cytokine deviation towards Th1 in RA, a finding which may affect future therapeutic approaches.

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Ankylosing spondylitis (AS) is a systemic inflammatory disease affecting predominantly the axial skeleton but also the peripheral joints, entheses, the eye, and occasionally the aortic root. (1) Rheumatoid arthritis (RA) is also a systemic inflammatory disease but in contrast with AS affects primarily the joints of the hand and feet in a symmetrical fashion. The primary site of inflammation in RA is the synovium but in AS appears to be the enthesis and sites where ligaments insert into bone. (2) AS usually begins in the second or third decade whereas the onset of RA is rarely before the fourth decade. AS affects more men than women, which is in contrast with the female preponderance in RA. Both diseases result in substantial and almost equal morbidity. (3)

Atopic disorders comprise hay fever, allergic asthma, and atopic eczema/neurodermatitis and usually arise in early childhood. (4 5) Key pathogenetic features of atopic disorders are raised levels of IgE and a characteristic T helper cell cytokine pattern. (6) Among T helper cells (Th) two opposite poles of immune responses can be distinguished based on the secretion of cytokines: the Th1 cytokine pattern with predominant secretion of interferon [gamma] (IFN[gamma]) and induction of a cellular immune response, and the Th2 cytokine pattern 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, RA is considered to be a Th1 polarised disease. (6 8-11) The cytokine pattern of AS and other spondyloarthropathies with low production of IFN[gamma] and tumour necrosis factor [alpha] (TNF[alpha]) without relevant changes in IL4 production can best be described as an impaired Th1 cytokine pattern. (12 13) It is therefore similar but not identical to that of atopic disorders and clearly different from that in RA.

The generation of a Th1 immune response is inhibited in the presence of Th2 cytokines and vice versa. (7) Based on the reciprocal inhibition of the development of Th1 and Th2 responses it has been suggested that Th1 and Th2 polarised immune responses and also Th1 and Th2 polarised diseases mutually exclude each other. (14-17) Because the cytokine patterns in AS and RA are not restricted to inflamed tissue but to some extent a systemic feature of each disease (10 13) we suggested that the impaired Th1 cytokine pattern in AS may well be compatible with the coexistence of atopic disorders whereas the strong Th1 pattern in RA is less compatible with such coexistence. We therefore studied the prevalence of asthma, hay fever, and atopic eczema in large cohorts of patients with AS, patients with RA, and controls in West Berlin.

PATIENTS AND METHODS

Patients and controls

At the end of 1997, patients with RA and AS were identified from the German Rheumatological Database. (3) Entries to this database are made voluntarily by rheumatologists at university hospital outpatient clinics, other rheumatology hospitals, or in private rheumatological practice. …