Annals ofthe Rheumatic Diseases 1992; 51: 655-657 655

Chronic : a new extra-articular Ann Rheum Dis: first published as 10.1136/ard.51.5.655 on 1 May 1992. Downloaded from manifestation in ankylosing spondylitis?

A E Camilleri, I R C Swan, E Murphy, R D Sturrock

Abstract steroidal anti-inflammatory drugs (NSAIDs), Foliowing a study reporting a fourfold increase second line drug treatment, age of onset of in the occurrence of chronic otitis media in ankylosing spondylitis, duration of ankylosing patients with ankylosing spondylitis, this spondylitis, HLA-B27 status, peripheral joint prospective study examines this association disease, erythrocyte sedimentation rate, wall to with respect to severity, duration of disease, tragus distance, spondylometry, presence of and acute phase in ankylosing spondylitis. extra-articular manifestations (uveitis and aortic Forty two consecutive patients with classical incompetence), duration of early morning stiff- ankylosing spondylitis seen at the rheumato- ness, presence of rheumatoid factor, and serum logy clinic of a teaching hospital where the levels of C reactive protein, IgA, IgG, and IgM. features of ankylosing spondylitis were re- All serum levels and measurements were current corded had an otological examination by an or within the previous three months. Clinical otolaryngologist. The occurrence of chronic otological examination was carried out after otitis media (all categories) was 12/42 (29%). cleaning the external auditory canals where The acute phase serum markers (C reactive necessary to allow inspection of the whole protein and IgG) were increased in patients tympanic membrane. with active or inactive chronic otitis media. Chronic otitis media was categorised as active, Extra-articular manifestations were signifi- inactive, or healed.4 Active chronic otitis media candy more common in the chronic otitis was defined as a chronic perforation of the media group than in those with no history of tympanic membrane with signs ofinflammation, chronic otitis media. The results of this study such as mucopus or oedema, present in the suggest that chronic otitis media may be middle . Inactive chronic otitis media was another extra-articular manifestation of an- defined as a chronic perforation of the tympanic kylosing spondylitis. Alternative explana- membrane with no signs of in the

tions, however, include similar aetiological . Healed chronic otitis media was http://ard.bmj.com/ factors for the two conditions or a previously defined as an intact tympanic membrane with unrecognised increased occurrence of HLA- evidence of previous perforation or marked B27 in patients with chronic otitis media. . Statistical analysis was performed by examin- ing the variation in features of ankylosing We have previously reported a fourfold increase spondylitis between patients with and without in the occurrence of chronic otitis media in a

chronic otitis media (all categories). As our pre- on September 26, 2021 by guest. Protected copyright. group of patients with ankylosing spondylitis' vious study had only shown a significant compared with the general population. The increase in the occurrence of active or inactive occurrence of active or inactive chronic otitis chronic otitis media in patients with ankylosing media in the study group was 19% (8/42) spondylitis, a second analysis examined the compared with 5% in the control population same features in patients with active or inactive (p<0-01).2 There was no difference in the chronic otitis media compared with the normal number of patients with healed chronic otitis group, i.e. excluding the healed group from the media in the two groups. The explanation for analysis. A third analysis examined the same of these two conditions was not Department of the relationship features in patients with active or inactive Otolaryngology, immediately apparent and it was suggested that chronic otitis media compared with the healed Royal Infirmary, chronic otitis media may have a previously Glasgow, unrecognised association with the HLA-B27 or normal group. United Kingdom The discrete variables (social class, sex, history A E Camilleri histocompatibility antigen. of use of NSAID second line drug treatment, I R C Swan In this study, we have attempted to clarify HLA-B27 status, presence of peripheral joint Department of further the nature of this relation by examining disease, extra-articular manifestations and Rheumatology, which, if any, of a variety of clinical and Royal Infwrmary, of rheumatoid factor) were cross tabulated using Glasgow, laboratory features ankylosing spondylitis the x2 test with and without Yates's correction. United Kingdom were associated with the occurrence of chronic Conover argues that Yates's correction reduces E Murphy otitis media. R D Sturrock the power of the analysis and thus hides Correspondence to: biologically significant associations.5 Mantel Dr. A E Camilleri, Patients and methods and Greenhouse consider it prudent to use Department of Otolaryngology, Forty two consecutive patients with classical Yates's correction in all 2 x 2 contingency tables.6 Royal Infirmary, ankylosing spondylitis3 were seen at the rheu- In view of the controversy over the use of Glasgow G4 OSF, United Kingdom matology clinic where the following information Yates's correction for 2x2 tables, both values Accepted for publication was recorded from the patient's history and are quoted in the analysis of extra-articular 19 September 1991 medical notes: social class, age, sex, use of non- manifestations. 656 Camilleri, Swan, Murphy, Sturrock

Table I Categories of patients with chronic otitis media any increase in the acute phase serum markers Status oftympanic membrane* No of patients (%) in patients with ankylosing spondylitis may be due to factors other than rheumatological Ann Rheum Dis: first published as 10.1136/ard.51.5.655 on 1 May 1992. Downloaded from Normal 30 (71) Healed COM 4 (10) disease and full examination should be carried Inactive COM 7 (17) out before specific management is planned. Active COM 1 (2) Total 42 (100) The more interesting finding is the association between chronic otitis media and the subset of *COM=chronic otitis media. patients with extra-articular manifestations. Our original study' showed an increase in the Table 2 Association between extra-articular manifestations occurrence of active or inactive but not healed (EAM) and chronic otitis media (COM) chronic otitis media in patients with ankylosing Status of EAM EAM X2 test with x2 test without spondylitis. The current analysis seems to middle ear present absent Yates's correction Yates's correction indicate that the extra-articular manifestations COM of ankylosing spondylitis are more associated Active with all categories of chronic otitis media than Inactive 7 3 Healed just the active or inactive group. This apparent p=0 048 p=0-017 anomaly may be due to the small sample size Normal 8 21 used in the original study. Active Ankylosing spondylitis is known to be strongly Inactive 5 2 p=0084 p=0030 associated with the presence of HLA-B27. It is Normal 8 21 not known if the incidence of HLA-B27 in Active chronic otitis media is different from the general Inactive 5 2 population and we are currently undertaking a p=O 121 p=0048 Normal further study to assess the occurrence of HLA- Healed 10 22 B27 in an unselected group of patients with chronic otitis media. If there is an association between chronic otitis media and HLA-B27, this could explain both the increased incidence of chronic otitis media in ankylosing spondylitis The Mann-Whitney U test was used for the and the particular association with extra-articular non-parametric continuous variables (age of manifestations as uveitis, the most common onset of ankylosing spondylitis, C reactive extra-articular manifestation seen in our group protein, erythrocyte sedimentation rate, wall to of patients, is known to be more common in tragus distance, spondylometry, IgG, duration HLA-B27 positive subjects without ankylosing of early morning stiffness, and duration of spondylitis. Brewerton found that 58% of 100 ankylosing spondylitis) and the two sample t patients presenting to an eye department with

test was used for continuous variables (age, IgA, acute anterior uveitis were positive for HLA- http://ard.bmj.com/ IgM) with a normal distribution. B27 compared with 7% (22/300) ofasymptomatic control subjects.7 A further explanation for these findings may Results be that chronic otitis media is, in fact, a The occurrence of chronic otitis media (all previously unrecognised extra-articular mani- categories) was 12/42 (29%). Table 1 shows the festation of ankylosing spondylitis. It may be

number of patients in the various categories. relevant in this regard that a combination of on September 26, 2021 by guest. Protected copyright. There was a significant increase in IgG levels topical steroid and antibiotic drugs has been (p=0035) and there was a trend towards an shown to be more effective than antibiotics increase in C reactive protein (p=0078) in the alone in treating patients with active chronic patients with active or inactive chronic otitis otitis media.8 media compared with normal subjects (which An alternative explanation for the apparent included the patients with healed chronic otitis association between ankylosing spondylitis and media). chronic otitis media would be if the two condi- Extra-articular manifestations were signifi- tions shared aetiological factors. Gram negative cantly more common in the chronic otitis media bacteria, particularly Klebsiellapneumoniae, have group in all three analyses. Table 2 shows the been suggested as possible bacterial triggers in 2x2 contingency tables for the three analyses, ankylosing spondylitis. Further evidence to including the p values for each with and without support this has come from the finding that Yates's correction. there is some cross reactivity between an epitope None of the other features were significantly of HLA-B27 and Klebsiella pneumoniae.9 The related to either the chronic otitis media or bowel has previously been thought to be the normal groups. Missing data accounted for portal of entry for any bacterial trigger but it is 1-8% of the total data required when analysing interesting that coliform bacteria are the most the features ofankylosing spondylitis. common organisms to be cultured from the of patients with chronic otitis media.'0 It could therefore be suggested that chronic middle ear Discussion acts as a trigger for ankylosing spon- The presence of an association between active or dylitis in susceptible subjects. Ebringer et al inactive chronic otitis media and increased found that episodes of acute anterior uveitis levels of C reactive protein and IgG is not were associated with faecal carriage ofklebsiella. surprising as this probably reflects the acute Our study may be detecting a similar pheno- phase response to such an episode. It shows that menon with middle ear infection rather than Chronic otitis media in ankylosing spondylitis 657

gastrointestinal colonisation as a 3 Moll J M. Diagnosis and diagnostic criteria. In: Ankylosing acting trigger Spondylitis. London: Churchill Livingstone, 1980: 138-9.

for episodes of uveitis. 4 Browning G G. Pathology of inflammatory conditions in the Ann Rheum Dis: first published as 10.1136/ard.51.5.655 on 1 May 1992. Downloaded from In summary, we present a new association external and middle ear. In: Kerr A G, ed. Scott-Brown's otolaryngology. Vol 3. London: Butterworths, 1987: 67-8. between chronic otitis media and ankylosing 5 Conover W J. Some reasons for not using Yates continuity spondylitis, particularly those patients with correction on 2 x 2 contingency tables. Journal of the American StatisticalAssociation 1974; 69: 374-82. ankylosing spondylitis who have extra-articular 6 Mantel N, Greenhouse S W. What is the continuity correc- manifestations. tion? American Statistics 1%8; 22: 27-30. 7 Brewerton D A. HL-A 27 and acute anterior uveitis. Ann Rheum Dis 1975; 34 (suppl): 33. The authors thank Dr S Gatehouse, MRC Institute of Hearing 8 Browning G, Gatehouse S, Calder I. Medical management of Research (Scottish Section) for advice on statistical analysis and active chronic otitis media: a controlled study. Laryngol the staff of the rheumatology department for their assistance Otol 1988; 102: 491-5. during the course ofthis study. 9 Husby G, Tsuchiya N, Schwimmbeck P, et al. Cross-reactive epitope with Klebsiella pneumoniae nitrogenase in articular tissue of HLA B27 positive patients with ankylosing I Camilieri A E, Swan I R C, Sturrock R D. Chronic otitis spondylitis. Arthritis Rheum 1989; 32: 437-45. media and ankylosing spondylitis: an HLA association? 10 Sweeney G, Picozzi G, Browning G. A quantitative study of Clin Otolaryngol. 1991; 16: 364-6. aerobic and anaerobic bacteria in chronic suppurative otitis 2 Davis A C. The prevalence of hearing impairment and media. J Infect 1982; 5: 47-55. reported hearing disability among adults in Great Britain. 11 Ebringer R, Cawdell D, Ebringer A. Klebsiella pneumoniae IntJ Epidemiol 1989; 18: 911-7. and acute anterior uveitis in ankylosis. BMJ 1979; i: 383. http://ard.bmj.com/ on September 26, 2021 by guest. Protected copyright.