Abstract
Ankylosing spondylitis (AS) is strongly associated with the major histocompatibility complex (MHC) class I antigen HLA-B27. This may have influence on the physiologic immune response. Whether it leads to an increased prevalence of infections and/or allergy in AS patients is unclear. This study aims to determine the prevalence of infections and allergic symptoms in patients with AS and to detect a possible association with clinical symptoms. Data on 1,080 AS patients and on 102 disc prolapse patients were collected by questionnaire. The proportion of patients with a symptomatic infection in the last year was 65.5% in AS patients in comparison with 25.5% in disc prolapse patients (p=0.0001). AS patients reported more gastrointestinal (GI) [odds ratio (OR) 5.07, 95% confidence interval (CI) 2.20–11.71], urinary tract (OR 2.81, 95%CI 1.41–5.72), and respiratory (OR 5.83, 95%CI 3.38–10.08) infections than did disc prolapse patients. Multiple infections were more common in AS patients across all infection types. Allergic symptoms were reported by AS patients more frequently than by disc prolapse patients (OR 5.13, 95%CI 3.49–8.80). Patients reporting concurrent inflammatory bowel disease were more likely to report GI (OR 3.0, 95%CI 1.9–4.8) and urinary tract (OR 1.7, 95%CI 1–2.8) infection than primary AS patients. In AS patients, infection was independently associated with female gender (OR 1.96, 95%CI 1.47–2.56), a history of significant peripheral joint inflammation (OR 1.55, 95%CI 1.18–2.05), and increasing pain duration (p=0.05). A high prevalence of common infections and allergic symptoms is seen in patients with AS, most of which are HLA-B27-positive. This may have implications both for underlying mechanisms of disease and for therapeutic options.
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Appendix
Appendix
Translated wording of questions in our questionnaire (from German):
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1.
Which diagnosis was given for your disease?
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Ankylosing spondylitis
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Reiter's disease or reactive arthritis
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Alternative question given to control group:
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1.
Which diagnosis was given for your disease?
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Disc prolapse
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Degenerative back pain
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2.
Was the diagnosis given or confirmed by a physician?
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Yes
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No
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I don't know
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3.
Was the diagnosis checked by radiography, computed tomography, or magnetic resonance imaging?
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Yes
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No
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I don't know
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4.
In which area did your symptoms first start? (multiple answers possible)
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cervical spine
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hip joints
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buttocks/thighs
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knee joints
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lumbar spine
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ankle joints
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Achilles tendons
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in none of these
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I don’t remember
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5.
How old were you when the first complaints occurred which you attribute to the disease?
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(… years)
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6.
How old were you when the diagnosis marked in item 1 was given for the first time?
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(… years)
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7.
What is your present age?
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(… years)
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8.
What is your sex?
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Male
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Female
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9.
Are you HLA-B27 positive?
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Yes
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No, HLA-B27 negative
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I don't know
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10.
Which of the following diseases has been diagnosed in addition? (Multiple answers possible)
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Psoriasis
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Crohn's disease or ulcerative colitis (inflammatory bowel diseases)
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Reactive arthritis or Reiter's disease in addition to ankylosing spondylitis
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None of these
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11.
Have you had a bowel infection (diarrhoea) in the past 4 weeks?
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Yes
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Once
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2 times
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3 times
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4 times
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More frequently
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No
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12.
Have you had a urinary infection (urinary burning or discharge) in the past 12 months?
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Yes
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Once
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2 times
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3 times
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4 times
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More frequently
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No
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13.
Have you had a respiratory infection (nose, windpipe, lungs) in the past 12 months?
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Yes
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Once
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2 times
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3 times
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4 times
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More frequently
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No
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14.
Have you had allergic symptoms in the past 12 months? (Multiple answers possible)
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Yes, with difficulties
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In the nasal passages (hay fever)
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On the skin
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In the lungs (asthma)
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No, I had no allergies in these places
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15.
Have you had repeated episodes or at least one month of one of the following joint inflammations? (more than one answer possible)
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Inflammation of one or both hips
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Inflammation of one or both knees
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Inflammation of one or more other joints, excluding the spine?
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None of these joint inflammations
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16.
Have you had at least one episode of eye inflammation (iritis)?
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Yes, and since the beginning of my disease I have had iritis:
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Once
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2–3 times
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4–7 times
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8–15 times
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16–30 times
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More than 30 times
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And in the last 12 months I have had iritis:
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I have not had iritis in the last 12 months
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1–2 times
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3–4 times
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More often
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No, I have never had iritis
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17.
How often in the past 4 weeks have you had back or joint pain?
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Continuously
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Generally, more than 12 hours per day
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Generally, more than 2 hours per week
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Less often or not at all
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18.
On how many days in the last 12 months have you had back or joint pain?
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Not at all, or less than 30 days
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Between 30 and 90 days
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Between 90 and 270 days
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More than 270 days
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19.
How many days in the last 12 months were you unable to go to work due to your spine and joint disease?
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_____days
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I am/was not employed in the last 12 months/was off work for other reasons for more than 3 months
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20.
Were you admitted to hospital due to your spine and joint disease in the last 12 months?
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Yes, _____ days in an acute hospital (not rehabilitation)
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Yes, _____ days in a rehabilitation facility
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No
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21.
Have you needed to take non-steroidal anti-inflammatory drugs in the last 12 months? (Multiple answers possible)
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Yes, and (on average) daily: (Respondents were given dosage options for various NSAIDs, including:
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Celecoxib (Celebrex) — up to 200 mg, 400 mg, 600 mg, more than 600 mg
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Diclofenac (Voltaren) — up to 50 mg, 100 mg, 150 mg, more than 150 mg
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Ibuprofen (Brufen, Imbun) — up to 600 mg, 1200 mg, 1800 mg, more than 1800 mg
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Indomethacin (Amuno) — up to 50 mg, 100 mg, 150 mg, more than 150 mg
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Meloxicam (Mobec) — up to 7.5 mg, 15 mg, 22.5 mg, more than 22.5 mg
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Naproxen (Proxen, Naprosyn) — up to 500 mg, 1000 mg, 1500 mg, more than 1500 mg
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Piroxicam (Felden) — up to 10 mg, 20 mg, more than 20 mg
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Rofecoxib (Vioxx) — up to 12.5 mg, 25 mg, 50 mg, more than 50 mg
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Another non-steroidal anti-inflammatory drug
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No, no non-steroidal anti-inflammatory drug necessary
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22.
If you have marked more than one medication, go ahead to Question 24. If you only marked one medication: How well does the medication work for you?
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I have no more pain
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Pain reduced to 1/4
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Pain reduced to 1/2
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Pain reduced to 3/4
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The medication has no effect
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23.
Have you had any serious side-effects from these medications? (Multiple answers possible)
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Yes, and they were
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Nausea
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Abdominal pain
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Stomach ulcer
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Headache, dizziness
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Colon problems
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Bleeding in the GI tract
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Black-coloured faeces
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Other serious side-effects
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No, I have not had any serious side-effects
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24.
How long have you been taking one of the non-steroidal anti-inflammatory drugs?
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For less than a year
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For 1–2 years
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For 2–4 years
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For more than 4 years
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25.
Have you changed your medication during this time?
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No (move on to Question 28)
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I don't know (move on to Question 28)
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Yes
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26.
Why did you change medications? (Multiple answers possible)
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Because of serious side-effects, which were:
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Nausea
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Abdominal pain
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Stomach ulcer
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Headache, dizziness
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Colon problems
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Bleeding in the GI tract
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Black-coloured faeces
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Other serious side-effects
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Because the drug(s) did not work well
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For other reasons
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27.
The medication that was stopped was:
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Celecoxib (Celebrex)
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Diclofenac (Voltaren)
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Ibuprofen (Brufen, Imbrun)
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Indometacin (Amuno)
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Meloxicam (Mobec)
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Naproxen (Proxen, Naprosyn)
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Piroxicam (Felden)
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Rofecoxib (Vioxx)
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A different non-steroidal anti-inflammatory drug
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28.
Have you ever had a vertebral fracture?
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Yes, when I was ____ years old
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As the result of an accident/trauma
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It was not the result of an accident/trauma
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No, I have not had a vertebral fracture
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29.
Did any of the following significant events happen in the 2 years before your disease began? (Multiple answers possible) How long before your first symptoms did they occur? (Choice between ‘less than 3 months’, ‘3–6 months’, ‘6–9 months’, ‘9–12 months’, ’12–18 months’ or ’18–24 months before my first symptoms’ for each event option).
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Severe accident with bone fracture
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Severe accident with joint injury
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Other severe accident
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Non-accident related orthopaedic surgery
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Other serious surgery
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Bowel infection (diarrhoea)
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Urine infection (burning or discharge)
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Respiratory infection (bronchitis, pneumonia)
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Allergic symptoms
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In the nasal passage (hay fever)
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In the lungs (asthma)
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On the skin
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Pregnancy
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Heavy physical activity
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Work-related
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Competitive sport
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Intensive recreational sport
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Death of a closely related person
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Severe family-related problems
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Severe work-related problems
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No such event occurred in the 2 years leading up to the onset of the disease
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30.
How exactly do you remember when the event occurred?
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To the day
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To the week
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To the month
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Not exactly to the month
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Zochling, J., Bohl-Bühler, M.H., Baraliakos, X. et al. The high prevalence of infections and allergic symptoms in patients with ankylosing spondylitis is associated with clinical symptoms. Clin Rheumatol 25, 648–658 (2006). https://doi.org/10.1007/s10067-005-0130-0
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DOI: https://doi.org/10.1007/s10067-005-0130-0