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Axial Pain and Arthritis in Diagnosed Inflammatory Bowel Disease: US National Health and Nutrition Examination Survey Data

Open AccessPublished:September 15, 2022DOI:https://doi.org/10.1016/j.mayocpiqo.2022.04.007

      Abstract

      Objective

      To estimate the nationally representative prevalence of chronic axial pain, inflammatory back pain (IBP), axial spondyloarthritis (axSpA), and peripheral arthritis in persons diagnosed with inflammatory bowel disease (IBD).

      Patients and Methods

      US National Health and Nutrition Examination Survey (NHANES) data from the 1976-1980 and 2009-2010 survey cycles.

      Results

      In NHANES 1976-1980, the chronic axial pain prevalence in participants with diagnosed ulcerative colitis (UC) was 19.5% vs 7.2% in the general population (P<.01). Neck or upper back, lower back, and Amor criteria-based axial pain were also significantly increased (11.2%, 14.5%, and 13.0%, respectively, vs 3%-5% in the general population (P<.01). In those with diagnosed UC, 40% had axial pain onset at an age older than 45 years; 30.2% reported peripheral arthralgias, and 12.2% reported peripheral arthritis. Arthritis findings on examination were uncommon. In NHANES 2009-2010, axial pain in those diagnosed with IBD had similar patterns.

      Conclusion

      Despite high rates of chronic axial pain in those with IBD, few cases met the IBP and axSpA classification criteria. This apparent discrepancy is unexplained. However, in IBD, axial pain onset at an age older than 45 years is common; and these may not meet IBP and axSpA age criteria. Also, neck pain was increased in those with IBD but is not included in most IBP and axSpA criteria. Peripheral arthralgias and chronic arthritis symptoms were common, but examination findings were not, suggesting that tenosynovitis or enthesitis is more likely than frank arthritis to occur in patients with UC.

      Abbreviations and Acronyms:

      AS (ankylosing spondylitis), axSpA (axial spondyloarthritis), ESSG (European Spondyloarthropathy Study Group), IBD (inflammatory bowel disease), IBP (inflammatory back pain), NHANES (US National Health and Nutrition Examination Survey), UC (ulcerative colitis)
      Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease, has high morbidity, burdening patients, families, and the health care system. The global IBD prevalence rates vary widely.
      • Alatab S.
      • Sepanlou S.G.
      • Ikuta K.
      • et al.
      The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.
      The 1999 and 2015 US National Health Interview Surveys estimated the prevalence of medically diagnosed IBD to be 0.9% and 1.3%, respectively, or 1.8 and 3.1 million persons, respectively.
      • Nguyen G.C.
      • Chong C.A.
      • Chong R.Y.
      National estimates of the burden of inflammatory bowel disease among racial and ethnic groups in the United States.
      ,
      • Dahlhamer J.M.
      • Zammitti E.P.
      • Ward B.W.
      • Wheaton A.G.
      • Croft J.B.
      Prevalence of inflammatory bowel disease among adults aged ≥18 years—United States, 2015.
      Extraintestinal, musculoskeletal complications add significantly to IBD morbidity. The chief complication among these is spondyloarthritis, inflammation of appendicular, entheseal, and axial or spinal structures. The classical phenotype of ankylosing spondylitis (AS) develops in some patients; however, the preferred term is axial spondyloarthritis (axSpA). Alternately, patients may have only peripheral joint involvement, termed as peripheral spondyloarthritis (pSpA). Patients may have both axSpa and pSpA. Currently, there is uncertainty about the prevalence of IBD-related axSpA and pSpA. The published rates vary widely: 3%-46% for pSpA and 1%-10% for AS.
      • Arvikar S.L.
      • Fisher M.C.
      Inflammatory bowel disease associated arthropathy.
      ,
      • Garber A.
      • Regueiro M.
      Extraintestinal manifestations of inflammatory bowel disease: epidemiology, etiopathogenesis, and management.
      Reviews have noted that the spectrum of IBD-related spondyloarthritis phenotypes remains incompletely characterized. There is high patient-to-patient variability and significant heterogeneity in the methodologies used to define its features.
      • Schwartzman M.
      • Ermann J.
      • Kuhn K.A.
      • et al.
      Musculoskeletal manifestations in inflammatory bowel disease cohorts: systematic literature review and critical appraisal of study designs.
      ,
      • Karreman M.C.
      • Luime J.J.
      • Hazes J.M.
      • Weel A.E.
      The prevalence and incidence of axial and peripheral spondyloarthritis in inflammatory bowel disease: a systematic review and meta-analysis.
      Currently, there are no US nationally representative estimates for the prevalence of IBD-related axial pain, inflammatory back pain (IBP), axSpA, and pSpA. The US National Health and Nutrition Examination Survey (NHANES) routinely provides US population-based arthritis surveillance data for rheumatoid arthritis, osteoarthritis, and others.
      • Dillon C.F.
      • Weisman M.H.
      US National Health and Nutrition Examination Survey arthritis initiatives, methodologies and data.
      Although not designed as IBD-arthritis studies, 2 NHANES cycles (2009-2010 and 1976-1980) collected nationally representative data on medically diagnosed IBD, axial pain, and peripheral arthritis. The NHANES 2009-2010 cycle was specifically designed to estimate the US prevalence of IBP and axSpA.
      • Weisman M.H.
      • Witter J.P.
      • Reveille J.D.
      The prevalence of inflammatory back pain: population-based estimates from the US National Health and Nutrition Examination Survey, 2009-10.
      ,
      • Reveille J.D.
      • Witter J.P.
      • Weisman M.H.
      Prevalence of axial spondylarthritis in the United States: estimates from a cross-sectional survey.
      The NHANES 1976-1980 cycle collected interview and examination data for UC, axial pain, and peripheral joint arthritis. In both the surveys, the US prevalence of self-reported, physician-diagnosed IBD or UC was consistent with previously reported national survey estimates; furthermore, IBD or UC diagnosis was supported by NHANES clinical data.
      • Nguyen G.C.
      • Chong C.A.
      • Chong R.Y.
      National estimates of the burden of inflammatory bowel disease among racial and ethnic groups in the United States.
      ,
      • Dahlhamer J.M.
      • Zammitti E.P.
      • Ward B.W.
      • Wheaton A.G.
      • Croft J.B.
      Prevalence of inflammatory bowel disease among adults aged ≥18 years—United States, 2015.
      ,
      • Stens O.
      • Kim H.
      • Hou J.K.
      • Miller F.W.
      • Dillon C.F.
      • Weisman M.H.
      Population-based estimates for inflammatory bowel disease prevalence: results from the US National Health and Nutrition Examination Survey.
      This report estimates the US national prevalence of chronic axial pain, IBP, axSpA, and pSpA in patients diagnosed with IBD on the basis of disease classification criteria and NHANES data. These data provide an opportunity to examine how existing IBP and axSpA classification criteria may or may not apply in the IBD setting, potentially bearing on the issues of the underdiagnosis of IBD-related arthritis and the feasibility of fielding future, specifically designed NHANES-based national surveillance studies on IBD arthritis.

      Materials and Methods

      The US National Health and Nutrition Examination Survey is a series of nationally representative, cross-sectional surveys monitoring US population health, including in-person household interviews and health examinations. It uses a complex, demographically based, multistage survey design to ensure nationally representative samples and minimize biases.
      • Curtin L.R.
      • Mohadjer L.K.
      • Dohrmann S.M.
      • et al.
      National Health and Nutrition Examination Survey: sample design, 2007-2010.
      The US National Center for Health Statistics Ethics Review Board approves protocols, operations, and data releases. Written informed consent is obtained from all participants. Publicly available NHANES data were used for analysis.

      NHANES questionnaires, datasets, and related documentation. National Health and Nutrition Examination Survey. Accessed December 1, 2021. https://wwwn.cdc.gov/nchs/nhanes/Default.aspx

      Details about the history of physician-diagnosed UC (both the surveys) and Crohn's disease (NHANES 2009-2010) were obtained via interviews; these self-reports are generally consistent with actual physician-diagnosed IBD. Cases of IBD from NHANES 2009-2010 had high colonoscopy rates at diagnosis, increased rates of characteristic IBD gastrointestinal symptoms, and IBD-related extraintestinal manifestations (uveitis, colon cancer, osteoporosis, and AS). Cases of UC from NHANES 1976-1980 had increased gastrointestinal symptoms, including bleeding, transfusions, anemia, and abdominal operations.
      • Stens O.
      • Kim H.
      • Hou J.K.
      • Miller F.W.
      • Dillon C.F.
      • Weisman M.H.
      Population-based estimates for inflammatory bowel disease prevalence: results from the US National Health and Nutrition Examination Survey.
      Cases of IBD had increased clinical visits and hospitalizations. The sample sizes were as follows: NHANES 2009-2010: 5105 persons, 62 IBD cases; NHANES 1976- 1980: 13,566 persons, 164 UC cases.
      Both the surveys collected axial pain data; peripheral arthritis data were only collected in 1976-1980. Chronic axial pain was defined as pain on most days for 3 or more months. Data on peripheral joint symptoms were obtained for a duration of 6 weeks or more. Oxford criteria were used for analysis.
      • Orchard T.R.
      • Wordsworth B.P.
      • Jewell D.P.
      Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history.
      In NHANES 2009-2010, a cognitively tested questionnaire with pain diagrams was used to estimate the prevalence of axial pain; IBP on the basis of the Calin criteria, European Spondyloarthropathy Study Group (ESSG) criteria, and criteria described by Rudwaleit et al; and axSpA on the basis of the ESSG and Amor criteria.
      • Calin A.
      • Porta J.
      • Fries J.F.
      • Schurman D.J.
      Clinical history as a screening test for ankylosing spondylitis.
      • Rudwaleit M.
      • Metter A.
      • Listing J.
      • Sieper J.
      • Braun J.
      Inflammatory back pain in ankylosing spondylitis: reassessment of the clinical history for application as classification and diagnostic criteria.
      • Dougados M.
      • Linden S.V.
      • Juhlin R.
      • et al.
      The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy.
      • Amor B.
      • Dougados M.
      • Mijiyawa M.
      Criteria of the classification of spondylarthropathies.
      The axial levels were as follows: neck, C1-C7; upper back, T1-T7; mid back, T8-T12; lower back, L1-L5; and buttocks: sacrum and buttocks.
      Amor criteria-based axial pain was characterized by lumbar or dorsal pain (T1-L5) at night or by lumbar or dorsal stiffness in the morning. Assessment of Spondyloarthritis International Society criteria for IBP or axSpA were published after the 2009-2010 survey was fielded and, therefore, were not included.
      • Rudwaleit M.
      • Van der Heijde D.
      • Landewé R.
      • et al.
      The development of Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis (part II): validation and final selection.
      ,
      • Sieper J.
      • van der Heijde D.M.
      • Landewe R.
      • et al.
      New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis International Society (ASAS).
      Furthermore, NHANES 1976-1980 lacked variables needed to estimate IBP and axSpA. Four arthritis variables were reported: interview-based medical diagnosis of arthritis (Table 1); interview-based peripheral joint pain and swelling (Table 2); physical examination-based joint pain and swelling (Table 3); and ESSG or Amor criteria-based axSpA (Table 1).
      Table 1Prevalence of Chronic Axial Pain, Inflammatory Bowel Disease, Axial Spondyloarthritis, and Arthritis Diagnosis in Patients With inflammatory Bowel Disease
      axSpA, axial spondyloarthritis; CI, confidence interval; ESSG, European Spondyloarthropathy Study Group; IBD, inflammatory bowel disease; IBP, inflammatory back pain; NHANES, US National Health and Nutrition Examination Survey; UC, ulcerative colitis.
      ,
      Sample sizes: NHANES 1976-1980: 13,566 (UC cases: 164); NHANES 2009-2010: 5041 (IBD cases: 62).
      NHANES 1976-1980nUC cases, % (95% CI)nNo UC, % (95% CI)P
      Axial pain >3 mo3019.5 (12.9-27.6)8087.2 (6.4-8.1)<.01
      Neck or upper back pain1911.2 (5.8-18.9)3663.2 (2.8-3.7).01
      Mid back pain32.3
      Estimate not statistically reliable, variance estimate not shown.
      1131.0 (0.9-1.2)
      Estimate not statistically reliable, variance estimate not shown.
      Lower back pain1614.5 (8.5-22.6)3815.1 (4.5-5.7)<.01
      Amor axial pain positive1513.0 (7.4-20.5)4474.3 (3.7-4.9)<.01
      Medical diagnosis of arthritis8941.1 (31.3-51.5)375621.1 (19.1-22.3)<.01
      NHANES 2009-2010IBD casesNo IBD
      Axial pain >3 mo2127.7 (11.1-44.3)95919.1 (17.1-21.2).11
      Neck or upper back pain1319.0
      Estimate not statistically reliable, variance estimate not shown.
      4438.5 (7.6-9.4)
      Estimate not statistically reliable, variance estimate not shown.
      Mid back pain31.0
      Estimate not statistically reliable, variance estimate not shown.
      2224.0 (3.3-4.6)
      Estimate not statistically reliable, variance estimate not shown.
      Lower back or buttock pain1620.0
      Estimate not statistically reliable, variance estimate not shown.
      77815.5 (13.8-17.1)
      Estimate not statistically reliable, variance estimate not shown.
      Amor axial pain positive1317.2
      Estimate not statistically reliable, variance estimate not shown.
      63712.4 (11.2-13.7)
      Estimate not statistically reliable, variance estimate not shown.
      Medical diagnosis of arthritis2630.6 (17.8-47.3)104119.1 (17.8-20.3).08
      Calin or ESSG IBP criteria36.1
      Estimate not statistically reliable, variance estimate not shown.
      2715.6 (4.7-6.5)
      Estimate not statistically reliable, variance estimate not shown.
      Rudwaleit IBP criteria positive27.8
      Estimate not statistically reliable, variance estimate not shown.
      ,
      Criteria 7B or 8A positive on the basis of the age group of 20-39 years (subsample size = 3188).
      2354.8 (4.2-5.5)
      Estimate not statistically reliable, variance estimate not shown.
      Any axSpA criteria positive410.0
      Estimate not statistically reliable, variance estimate not shown.
      891.8 (1.2-1.3)
      Estimate not statistically reliable, variance estimate not shown.
      Amor axSpA criteria positive35.8
      Estimate not statistically reliable, variance estimate not shown.
      400.8 (0.5-1.1)
      Estimate not statistically reliable, variance estimate not shown.
      ESSG axSpA criteria positive14.4
      Estimate not statistically reliable, variance estimate not shown.
      691.4 (.09-1.9)
      Estimate not statistically reliable, variance estimate not shown.
      a axSpA, axial spondyloarthritis; CI, confidence interval; ESSG, European Spondyloarthropathy Study Group; IBD, inflammatory bowel disease; IBP, inflammatory back pain; NHANES, US National Health and Nutrition Examination Survey; UC, ulcerative colitis.
      b Sample sizes: NHANES 1976-1980: 13,566 (UC cases: 164); NHANES 2009-2010: 5041 (IBD cases: 62).
      c Estimate not statistically reliable, variance estimate not shown.
      d Criteria 7B or 8A positive on the basis of the age group of 20-39 years (subsample size = 3188).
      Table 2US National Health and Nutrition Examination Survey 1976-1980 Interview-Based Prevalence of Peripheral Arthralgia and Arthritis
      NHANES, US National Health and Nutrition Examination Survey; SE, standard error; UC, ulcerative colitis.
      ,
      Sample sizes: UC = 131cases; no UC = 10,272 persons.
      Joint distributionsPeripheral arthralgiasPeripheral joint arthritis
      Reported peripheral joint arthralgia plus joint swelling and palpable tenderness for 6 weeks or more. Symmetric joint involvement is 1 or more pair of symmetrically involved joints. Pauciarticular and polyarticular definitions are from the study by Orchard et al14 (≤5 joints and >5 joints involved, respectively).
      All UCNo UCPAll UCNo UCP
      n% (SE)n% (SE)N% (SE)n% (SE)
      Any joint involved5530.2 (5.4)216319.0 (0.7).022312.2 (3.4)7716.5 (0.4).01
       Pauciarticular3219.1 (4.4)167816.2 (0.6).12189.9 (2.8)6265.6 (0.4).02
       Polyarticular2214.8 (4.0)4684.3 (0.4).0153.3
      Estimate potentially not reliable, variance estimate not shown.
      1301.0 (0.1)
      Estimate potentially not reliable, variance estimate not shown.
       Symmetric4326.1 (5.4)110410.0 (4.5).01187.6
      Estimate potentially not reliable, variance estimate not shown.
      4053.1 (0.2)
      Estimate potentially not reliable, variance estimate not shown.
       Asymmetric116.3
      Estimate potentially not reliable, variance estimate not shown.
      104210.5 (0.5)
      Estimate potentially not reliable, variance estimate not shown.
      55.1
      Estimate potentially not reliable, variance estimate not shown.
      3515.2 (0.4)
      Estimate potentially not reliable, variance estimate not shown.
      Upper extremities3921.9 (4.6)137113.3 (0.7).03167.8
      Estimate potentially not reliable, variance estimate not shown.
      4524.1 (0.3)
      Estimate potentially not reliable, variance estimate not shown.
       Hand-wrist3216.9 (3.2)8198.3 (0.6).01146.9
      Estimate potentially not reliable, variance estimate not shown.
      3793.4 (0.3)
      Estimate potentially not reliable, variance estimate not shown.
       Elbow1814.2 (4.1)4695.4 (0.4).0363.7
      Estimate potentially not reliable, variance estimate not shown.
      1021.0 (0.1)
      Estimate potentially not reliable, variance estimate not shown.
       Shoulder2316.6 (4.5)7597.6 (0.4).0142.9
      Estimate potentially not reliable, variance estimate not shown.
      1271.1 (0.1)
      Estimate potentially not reliable, variance estimate not shown.
      Lower extremities4428.7 (5.4)146213.1 (0.6).01169.5
      Estimate potentially not reliable, variance estimate not shown.
      4894.4 (0.3)
      Estimate potentially not reliable, variance estimate not shown.
       Hips2419.0 (4.9)5325.1 (0.4).0142.5
      Estimate potentially not reliable, variance estimate not shown.
      740.6 (0.1)
      Estimate potentially not reliable, variance estimate not shown.
       Knee2922.8 (5.3)10579.8 (0.5).02105.5
      Estimate potentially not reliable, variance estimate not shown.
      3232.9 (0.2)
      Estimate potentially not reliable, variance estimate not shown.
       Foot ankle2117.2 (4.8)5865.8 (0.4).0375.5
      Estimate potentially not reliable, variance estimate not shown.
      1671.4 (0.1)
      Estimate potentially not reliable, variance estimate not shown.
      a NHANES, US National Health and Nutrition Examination Survey; SE, standard error; UC, ulcerative colitis.
      b Sample sizes: UC = 131cases; no UC = 10,272 persons.
      c Reported peripheral joint arthralgia plus joint swelling and palpable tenderness for 6 weeks or more. Symmetric joint involvement is 1 or more pair of symmetrically involved joints. Pauciarticular and polyarticular definitions are from the study by Orchard et al
      • Orchard T.R.
      • Wordsworth B.P.
      • Jewell D.P.
      Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history.
      (≤5 joints and >5 joints involved, respectively).
      d Estimate potentially not reliable, variance estimate not shown.
      Table 3US National Health and Nutrition Examination Survey 1976-1980 Peripheral Joint Symptoms and Examination Findings
      CI, confidence interval; DIP, distal interphalangeal; NHANES, US National Health and Nutrition Examination Survey; SR, self-reported; UC, ulcerative colitis.
      nAll UCnNo UCP
      % (95% CI)% (95% CI)
      Reference interview data
       Current SR arthralgias
      Self-reported arthralgia and arthritis. Overall NHANES examined sample sizes: UC = 131 cases; no UC = 10,273.
      4426.9 (16.6-39.4)131812.0 (10.9-13.2).01
       Current SR arthritis
      Self-reported arthralgia and arthritis. Overall NHANES examined sample sizes: UC = 131 cases; no UC = 10,273.
      197.4
      Estimate potentially not reliable, variance estimate not shown.
      6884.1 (3.5-4.7)
      Estimate potentially not reliable, variance estimate not shown.
      Physical examination data
       Any positive exam finding3111.7 (6.4-19.2)10968.2 (5.7-11.3).02
       Upper extremity joints175.0
      Estimate potentially not reliable, variance estimate not shown.
      5635.1 (3.2-7.0)
      Estimate potentially not reliable, variance estimate not shown.
       Lower extremity joints218.6
      Estimate potentially not reliable, variance estimate not shown.
      7535.4 (3.6-7.6)
      Estimate potentially not reliable, variance estimate not shown.
       Palpable joint tenderness199.7
      Estimate potentially not reliable, variance estimate not shown.
      6415.5 (2.7-8.3)
      Estimate potentially not reliable, variance estimate not shown.
       Joint pain, passive motion259.2 (4.9-15.6)8686.5 (4.3-9.5).02
       Palpable joint swelling93.9
      Estimate potentially not reliable, variance estimate not shown.
      3913.4 (2.3-4.4)
      Estimate potentially not reliable, variance estimate not shown.
       Exam pain and swelling73.3
      Estimate potentially not reliable, variance estimate not shown.
      2892.4 (1.4-3.4)
      Estimate potentially not reliable, variance estimate not shown.
      Heberden's nodes—DIP joints3512.4 (6.5-20.9)138610.2 (6.9-14.4).07
      Symptomatic Heberden nodes20.7
      Estimate potentially not reliable, variance estimate not shown.
      540.5
      Estimate potentially not reliable, variance estimate not shown.
      Estimate potentially not reliable, variance estimate not shown.
      a CI, confidence interval; DIP, distal interphalangeal; NHANES, US National Health and Nutrition Examination Survey; SR, self-reported; UC, ulcerative colitis.
      b Self-reported arthralgia and arthritis. Overall NHANES examined sample sizes: UC = 131 cases; no UC = 10,273.
      c Estimate potentially not reliable, variance estimate not shown.
      Survey design variables and sample weights were used to account for differential participant selection probabilities in the complex NHANES sample design for nationally representative estimates. The sample weights accounted for unequal subgroup selection probabilities and adjusted for nonresponse and noncoverage. The US prevalence was calculated using direct standardization. Statistical analysis was performed using SAS and SUDAAN. The IBD data age range was 20-69 years in NHANES 2009-2010 and 25-74 years in NHANES 1976-1980; standard error estimation was performed using Taylor series linearization. Prevalence differences were tested using the t statistic at an α value of 0.05. Minimum acceptable sample size assessment employed survey design effects, degrees of freedom, and specified proportions. Absolute and relative confidence intervals were used to assess statistical estimate reliability.
      • Parker J.D.
      • Talih M.
      • Malec D.J.
      • et al.
      National Center for Health Statistics data presentation standards for proportions.

      Results

      In the 4-year NHANES 1976-1980 dataset, the rates of a history of axial pain lasting 3 or more months were significantly higher in patients with UC than in the general population (19.5% vs 7.2%, respectively; P<.01). Chronic, site-specific pain was significantly increased in the neck or upper back (11.2% vs 3.2%, P=.01) and lower back (14.5% vs 5.1%, P<.01) but not in the mid back. Notably, 53% of neck pain cases had isolated chronic neck pain, without other axial pain. Low rates precluded the analysis of prior history of neck or axial spine injury. On physical examination, the UC cases had significantly higher rates of pain with spinal motion (14.4% vs 7.4%, P=.05) and had limited spinal motion (19.3% vs 9.7%, P=.02). These cases also had significantly increased rates of arthritis diagnosis (41.1% vs 21.1%, P<.01) and Amor criteria-based axial pain (13.0% vs 4.3%, P<.01; Table 1).
      In the smaller, 2-year NHANES 2009-2010 sample, the chronic axial pain rates were also elevated for patients with IBD (27.7% vs 19.1%), a 45% increase over the rates in the general population but nonsignificant, given the study sample sizes. The sample sizes precluded the statistical analysis of site-specific axial pain prevalence; however, similar to NHANES 1976-1980, the crude site-specific rates were increased in the neck or upper back and lower back (Table 1). Most of those with axial pain for 3 or more months had pain onset at an age younger than 45 years. However, those with IBD were more likely to report axial pain onset at an age of 45 years or older (40% vs 26%), more likely to have rest or sleep pain (43% vs 27%), and more likely to report pain awakening from sleep (91% vs 58%) than those without IBD. In NHANES 2009-2010, 28% of IBD cases had a prior arthritis diagnosis vs 19% in the general population (P=.11). Four IBD cases reported an AS diagnosis. The crude prevalence rates of IBP, Amor criteria-based pain, and axSpA in patients with IBD were low, and the sample sizes precluded the statistical analysis.
      The UC cases from NHANES 1976-1980 had increased prevalence of peripheral arthralgias and arthritis symptoms compared with the US population (30.2% vs 19.0%, respectively, P=.02 for arthralgia; 12.2% vs 6.5%, respectively, P=.01 for arthritis; Table 2). The arthralgia rates were significantly increased at the hand wrists, elbows, hips, knees, and feet-ankle areas, most often in polyarticular and symmetric patterns, with all being statistically significant (P<.05). The sample size for self-reported peripheral arthritis (any joint pain and swelling ≥6 weeks) precluded site-specific analysis. The UC cases had increased rates of a positive physician joint examination finding (11.7% vs 8.2%, P=.02), driven by lower extremity findings (10.4% vs 6.2%, P=.08; Table 3). Pain on passive joint motion was significantly increased (9.2% vs 6.5%, P=.02), but palpable joint swelling rates were not. Heberden's node prevalence was similar in patients with IBD and the general population (12.4% vs 10.2%); few were symptomatic.

      Discussion

      We found that the overall rates of axial pain, peripheral arthritis, and arthritis diagnosis were all significantly increased in patients with UC compared with those in the US general population. In the larger NHANES 1976-1980 sample, the chronic axial pain prevalence in patients with UC was 19.5%, whereas in the general population, it was 7.2% (P<.01); the Amor criteria-based axial pain prevalence in patients with UC was 13.0% vs 4.3% in the general population (P<.01). The rates of the medical diagnosis of arthritis were high in the UC cases, with the rates almost double than those seen in the general population.
      In NHANES 2009-2010, participants with IBD had high rates of chronic axial pain; yet, few cases met the IBP or axSpA criteria. If confirmed subsequently in larger population-based studies, these findings could potentially signal that the current IBD classification criteria may not fully capture all IBP or axSpA cases. For example, the expectation that IBP and axSpa principally affect younger adults could possibly function to reduce axSpa screening rates in patients with IBD. The Assessment of Spondyloarthritis International Society criteria for axSpa specify the age of the onset of axial pain to be 45 years or younger, whereas the IBP criteria specify the age of onset to be ranging from 45 years or younger to 29 years or younger.
      • Weisman M.H.
      • Witter J.P.
      • Reveille J.D.
      The prevalence of inflammatory back pain: population-based estimates from the US National Health and Nutrition Examination Survey, 2009-10.
      ,
      • Rudwaleit M.
      • Van der Heijde D.
      • Landewé R.
      • et al.
      The development of Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis (part II): validation and final selection.
      ,
      • Sieper J.
      • van der Heijde D.M.
      • Landewe R.
      • et al.
      New criteria for inflammatory back pain in patients with chronic back pain: a real patient exercise by experts from the Assessment of SpondyloArthritis International Society (ASAS).
      We found that IBD cases were more likely to have chronic axial pain onset at the age of 45 years or older. It is unknown whether this is simply because patients with IBD on average are older, because IBD onset is highest in middle-aged adults,
      • Nguyen G.C.
      • Chong C.A.
      • Chong R.Y.
      National estimates of the burden of inflammatory bowel disease among racial and ethnic groups in the United States.
      ,
      • Dahlhamer J.M.
      • Zammitti E.P.
      • Ward B.W.
      • Wheaton A.G.
      • Croft J.B.
      Prevalence of inflammatory bowel disease among adults aged ≥18 years—United States, 2015.
      or possibly due to biological differences between IBD-related and idiopathic axSpa. It is already known that IBD-related AS is less strongly correlated with human leukocyte antigen B27 than idiopathic AS, suggesting different biological mechanisms.
      • Rudwaleit M.
      • Baeten D.
      Ankylosing spondylitis and bowel disease.
      This raises a concern that many older patients with IBD-related axSpA may be underdiagnosed and better served by developing diagnostic criteria without an age cutoff.
      The distribution of site-specific IBD axial pain observed here differs from that of idiopathic IBP or axSpA because neck or upper back pain was significantly elevated in patients with UC. This finding was not seen in a previous NHANES 2009-2010 study of IBP and axSpA in persons with diagnosed psoriasis.
      • Thom N.
      • Ritchlin C.T.
      • Zhang X.
      • Reveille J.
      • Weisman M.H.
      Prevalence of chronic axial pain, inflammatory back pain, and spondyloarthritis in diagnosed psoriasis.
      Currently, the ESSG IBP or axSpA criteria include neck pain, but the Amor pain criteria and other IBP or axSpA criteria exclude it. Additionally, half of those with IBD who had chronic neck pain had no other axial pain, potentially further reducing axSpA screening rates.
      Moreover, the UC cases had significantly increased rates of pain with the passive motion of peripheral joints but lesser rates of objective joint swelling on examination. This suggests that tenosynovitis or enthesitis play larger roles than synovitis in IBD-related peripheral joint pathology. The NHANES findings are consistent with the observation that peripheral musculoskeletal manifestations in patients with IBD are subtle and may often escape detection in the usual clinical office visit setting.
      Our study has important limitations, especially including the lack of imaging data for the assessment of sacroiliac or spinal disease. However, this is not a limitation for interpreting peripheral arthritis findings, which are typically nonerosive and nondeforming in patients with IBD.
      • Garber A.
      • Regueiro M.
      Extraintestinal manifestations of inflammatory bowel disease: epidemiology, etiopathogenesis, and management.
      Our finding that peripheral joint arthralgias was common in patients with UC but that frank arthritis was not common on examination is consistent with this. Imaging would be important for excluding age-related degenerative spinal disc disease and lumbar spondylosis as study confounders—an issue that could not be addressed, given the data. However, if the lumbar spondylosis and disc disease rates in patients with IBD are the same as those in the general population, then the excess rates of axial pain and arthritis diagnosis over prevalence seen in the general population would yield the proportion directly attributable to IBD. It is relevant here that Heberden’s nodes prevalence was similar in patients with IBD and the general population, and symptomatic nodes were rare. Additionally, the neck and spinal injury rates in those with UC were low and not materially different from the rates in the US population. Furthermore, NHANES has never collected data on fibromyalgia; so, any associations there could not be directly assessed. However, for perspective, the prevalence of chronic widespread pain in the US adult population was 3.6% in NHANES 1999-2004.
      • Hardt J.
      • Jacobsen C.
      • Goldberg J.
      • Nickel R.
      • Buchwald D.
      Prevalence of chronic pain in a representative sample in the United States.
      A chief limitation is that the data analyzed here were not from a specifically designed IBD-arthritis study. Nevertheless, the NHANES survey data are important because they are national in scope and can identify IBD and IBD-arthritis cases not always represented in clinical studies. Inflammatory bowel disease may have a remitting-relapsing course, a percentage of IBD cases remain localized, and many cases are undiagnosed or not well connected to clinical care. Moreover, IBD-arthritis manifestations may occur independently of IBD clinical activity. These groups of cases are fully represented in the NHANES sampling frame. The current study limitations can be addressed in the future because NHANES has the capability for fielding comprehensive arthritis surveys, including examinations, imaging, and laboratory studies.
      • Dillon C.F.
      • Weisman M.H.
      US National Health and Nutrition Examination Survey arthritis initiatives, methodologies and data.
      The results of this study suggest that it is feasible to field such a future study to confirm our observations and assess the US burden of IBD arthritis.

      Potential Competing Interests

      Dr Weisman has received honoraria for consultations from Novartis, Astra Zeneca, and Pfizer; and has received payment for expert witness testimony for Levine vs. State Farm. Dr Stens has received support from NIH Intramural Research Grant. Dr Hou has received grants from PCORI, VA HSR&D, American Regent, NIDDK, Celgene, Abbvie, AHRQ, Crohn’s and Colitis Foundation, and Pfizer. Dr Miller is a government employee of NIEHS and NIH. Dr Dillon has received support from NIH and NIEHS.

      Acknowledgments

      The authors thank Wayne Pereanu and Paul Cacioppo for assistance with editing and graphics and Drs John Davis and Jonathan Kay for their useful comments on the manuscript.

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