Indian Journal of Rheumatology 2010 MarchConsensus Statement

Volume 5, Number 1; pp. 16–34

Indian Rheumatology Association consensus statement on thediagnosis and treatment of axial spondyloarthropathies

AN Malaviya1, S Shankar2, V Arya3, V Dhir4, V Agarwal5, S Pandya6, K Shanmuganandan2, VP Chaturvedi7, CJ Das8

1A&R Clinic and ISIC Superspeciality Hospital, New Delhi, 2Department of Internal Medicine, Armed Forces Medical College, Pune,3Department of Medicine, PGIMER and Dr RML Hospital, New Delhi, 4Department of Medicine, All India Institute of Medical Sciences, NewDelhi, 5Department of Clinical Immunology, SGPGIMS, Lucknow, 6Vedant, Nr Samved Hospital Ahmedabad, Gujarat, 7Department of Medicine,Army Base Hospital, Basistha, Guwahati, 8Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi.Correspondence: Dr AN Malaviya, email: anand_malaviya@yahoo.com

EPIDEMIOLOGY OF

SPONDYLOARTHROPATHY

Prevalence of spondyloarthropathy in India

Indian data on the epidemiology of spondyloarthropathy(SpA) are scarce. Prevalence data from the first IndianCommunity Oriented Program from Control of RheumaticDiseases (COPCORD) survey showed the rural prevalenceof back pain to be 17.3%. This included both inflammatoryand mechanical back aches.1 Of all the people with lowbackache, about 1–2% are likely to have SpA. From thisrural cohort, the SpA prevalence can be estimated at about0.17–0.34%.

Data from a large clinic in North India (with over 800patients of rheumatic diseases on follow-up) suggests thatthe ratio of rheumatoid arthritis (RA) to ankylosing spondyli-tis (AS) is about 3.2:1 (unpublished data). Since the preva-lence of RA in India is about 0.7%, that of AS is likely to beabout 0.2%. The prevalence of AS in a population is directlyrelated to the frequency of HLA-B27 antigen. The frequencyof HLA-B27 in the North Indian population is 6%, similarto that in Caucasians.2,3 The prevalence of AS in Caucasiansis 0–1%.4

Hence, the prevalence in India is likely to be similar.Thus, by three ways of reasoning, we can estimate the preva-lence of SpA in India to be between 0.1 and 0.2%.

Gender distribution

Males outnumber females by a ratio of 5:1 to 18.7:1.5–8

This most probably reflects: (1) Increasing awareness aboutAS-SpA manifestations among rheumatologists, especiallythat it is not uncommon among females; (2) Females may

have an atypical presentation with more extra-articular man-ifestations and root joint involvement. (3) Societal character-istics where males are able to seek medical help more easilyand effectively than females. It has been suggested thatperipheral arthritis is more frequently seen in females.7

In another small study that looked at 10 female and 72 male patients suffering from AS, low lumbar backacheand inactivity stiffness were common presenting complaintsin females with later age of onset. Females were also foundto be symptomatically milder, with a more benign course ofthe disease.9 A recent study on 70 patients with AS showedthat females had more root joint involvement and extra-articular manifestations.5

CLINICAL FEATURES AND DIAGNOSIS

1. The most important and essential clinical feature ofAS-SpA is inflammatory back pain (IBP). The diagnosisof IBP is suggested by the following features:a. Duration > 3 monthsb. Age: In more than 95% of AS-SpA patients, the dis-

ease starts before the age of 45 years.5,10,11 Onsetbefore 18 years occurs in 20–30%.8,11,12

These are entry criteria without which a diagnosis of IBPis not considered, however, they are non-specific. Themore specific features are:c. Onset: Insidious onset (the patient cannot remember

the exact date or time or the activity he was doingwhen the pain started).

d. Stiffness: The presence of stiffness in the morningon waking up (lasting at least 30 minutes), or onassuming a constant sitting posture (like workingover a computer) or a disturbed night sleep. This

Diagnosis and treatment of axial spondyloarthropathies Consensus Statement 17

stiffness should improve on movement (or stretchingor exercise) and worsen with rest.

e. Pain: In the low back and especially in the buttocks.It will often accompany stiffness in the morning andon assuming a constant posture and in the night.This should improve on movement or stretching orexercise but worsen with rest.

f. Response to treatment: The presence of a dramaticresponse to non-glucocorticoidal anti-inflammatorydrugs (NSAIDs) lasting 1–2 days may suggest IBP.

The expert group did not include male gender as apointer to SpA as it was felt that this might lead to underdiagnosis among females.

A combination of these features is required to make adiagnosis of IBP. A comparison of different criteria proposedfor the diagnosis of IBP is shown in Table 1 (See Appendix 1).The expert group recommends that the presence and durationof morning stiffness must be noted although it is not a partof the ASAS criteria set. Importantly, a diagnosis of IBP doesnot equal a diagnosis of AS-SpA. It increases the likelihoodof making a correct diagnosis of AS-SpA by a factor of2.5–4 (Appendix 1, Table 1). Thus, many patients of mechan-ical low back ache may also fulfill these criteria! In youngpatients with low back pain and stiffness (typically not im-proving with movement) and a duration of less than 6 months,it is important to rule out infection, especially tuberculosis.13

2. The other clinical features (in addition to the presenceof IBP) which serve to further establish a diagnosis ofAS are:a. Strong pointers:

i. Arthritis or history of arthritis in a lower limbperipheral joint like knee or ankle—Mono oroligoarthritis (Present in up to 1/3 to 2/3 ofIndian AS patients)5,11,12

ii. First or second degree relative with features sug-gesting AS (stoop, question mark posture,decreased neck movement) OR diagnosed asspondyloarthritis (present in 15–30% of IndianAS patients).12

iii. Tenderness of the SI joints (by tests which stressthis joint)—present in one study in up to 65%patients.14

b. Moderately strong pointers:i. Associated history of uveitis: Anterior uveitis is

associated with AS in 11–25% of patients.5,8,11

In a large case series from North India, AS wasthe commonest cause of anterior uveitis (13.2%of all cases and 1/3 of all cases for which an eti-ology could be established)15

c. Pointers which are uncommon but may be of use:i. Dactylitis

ii. Psoriasisiii. Inflammatory bowel disease.

Thus, the presence of IBP along with oligoarthritis ofthe large joints of lower limbs will lead to a likelihood ratio(LR) of 3.0 × 3.7 = 11.1 for a diagnosis of AS-SpA. Add tothis, definite tenderness of SI joints, a LR of 42.2 (11.8 ×3.2) which would be almost diagnostic. However, a radio-graph of the pelvis is recommended in every case of suspectedAS-SpA irrespective of the clinical features.

The likelihood ratios of various clinical features (includ-ing components of IBP) are given in Table 2 in Appendix 1.3. Investigations are valuable after a proper history and

examination. The mandatory investigations in everycase of AS-SpA are a radiograph of the pelvis andacute phase reactants. Tests like MRI and HLA-B27,although have high LR, are expensive and are requiredonly in a minority of cases to make a confident diagno-sis of AS-SpA. Among Indians, the prevalence of HLA-B27 is around 4–6%.11,16,17 The expert group felt thatits usefulness for diagnosis of SpA in our country is ex-pected to be higher than that found in Western litera-ture. The features on investigation which suggest adiagnosis of AS–Axial SpA are:a. Strong pointers:

i. X-ray evidence of clear cut sacroiliitisii. MRI evidence of clear cut sacroiliac joint

inflammationiii. HLA-B27 +

b. Moderately strong pointersi. ESR or CRP elevated in the absence of other

causes like antecedent infection, fever etc.The likelihood ratios of various investigations in making

a diagnosis of AS-SpA is given in Table 3 (see Appendix 1).4. Various criteria have been proposed for the diagnosis

of axial SpA-AS. All of these criteria include separatedefinitions of inflammatory low back ache (which is amandatory criterion in most cases). The expert grouprecommends the ASAS criteria for te diagnosis of SpAbecause of its comprehensiveness and high LR. Theseare given in Table 4 (see Appendix 1).

5. The expert group suggests an algorithmic approach tothe step-wise diagnosis of axial SpA as depicted in theflow diagram in Appendix 1.

ASSESSMENT IN ANKYLOSING SPONDYLITIS

The principles of patient assessment in AS are to• quantify the disease activity• follow disease progression and damage

18 Indian Journal of Rheumatology 2010 March; Vol. 5, No. 1 Malaviya et al.

• measure its effect on the patient’s quality of life• measure the effect of any intervention on these

parameters.The ASAS group has recently defined a core set of do-

mains and instruments that covers the most important aspectsof disease assessment in AS. These should be measured indifferent situations, including the ASAS core set for clinicalrecord keeping recommended for use in clinical practice18

(see Table 1 in Appendix 2).The core set has been updated regularly and has led

to the development of response criteria for clinical trials(ASAS20, ASAS40, ASAS 5/6 and ASAS partial remission),the validation of measurement instruments for radiographicdamage and progression and for magnetic resonance imag-ing, and recently the development of a new index for mea-suring disease activity, the AS Disease Activity Score(ASDAS)19 (see Table 2 in Appendix 2). The indices pro-posed by ASAS group are all expert opinion-based and thedomains have been selected following a Delphi exercise.

Symptoms and disease activity

Acute symptoms include pain, morning stiffness, extra-axialsymptoms and patient-based general health.

PainNocturnal spinal pain and general spinal pain are the twouseful measures for monitoring pain in AS. Pain can bemeasured by visual analogue scales (VAS) or numerical rating scales (NRS). A change of 15% in pain scores re-presents the minimum clinically important difference(MCID), and a change of 33% can be interpreted as muchimproved.20

Recommendation: Use VAS 10 cm or NRS for meas-urement of pain in AS.

FatigueFatigue is an important cause of morbidity in AS 21, 22 andnegatively impacts the quality of life. Since fatigue is animportant component of the Bath Ankylosing SpondylitisDisease Activity Index (BASDAI)23, the ASAS group hasrecommended the BASDAI question on fatigue as the pre-ferred instrument to assess fatigue in AS.

Recommendation: Use BASDAI question no 1.

StiffnessIt can be quantitated either as duration or severity of morningstiffness or a combination of the two. Both severity and dura-tion of morning stiffness can be measured by 10-cm VAS.

Recommendation: Use VAS 10 cm

Spinal mobilityThe ASAS core sets initially recommended the use of threemeasures: the occiput-to-wall distance (OWD) to reflect cer-vical and thoracic mobility,24 chest expansion24 and the mod-ified Schober index24 to measure lumbar mobility. Anothermeasure that can be used is Bath Ankylosing SpondylitisMetrology Index (BASMI)25 (see Table 3 in Appendix 2).The OWD has been reported to have test–retest intraclasscorrelations (ICC) between 0.94 and 0.96, indicating thatthe measure is sufficiently reliable for individual patientevaluation (ICC > 0.90).26

Reliability of chest expansion has been reported to bepoor,27 but it is the only method to assess thoracic cage move-ment. The modified Schober index has an ICC between0.90 and 0.94, and correlates well with other measures ofspinal mobility and patient-assessed health measures such asthe BASDAI and quality-of-life measures.28 Cross-sectionalstudies have shown good correlations between spinal mobil-ity measures and radiological changes in the sacroiliac jointsand the lumbar spine.29 The BASMI is a validated compos-ite index of spinal and hip mobility.

Recommendation: Use OWD, chest expansion, modifiedSchober index and lateral lumbar flexion or BASMI.

Peripheral joints and enthesesApproximately, 25% of patients with AS have active periph-eral joint involvement. A 44-joint count (as used in originalDAS scoring system),30 covering the joints commonly in-volved in AS, has been proposed to measure the peripheraljoint involvement (see Figure 1 in Appendix 2). The numberof tender and swollen joints is recorded.

There are currently three validated instruments used formeasuring enthesitis. The Mander Enthesis Index (MEI) wasthe first standardized instrument.31 It includes 66 enthesealsites, each one assessed for tenderness on a scale of 0 (notenderness) to 3 (patient winces or withdraws). The MEI haspoor interobserver reliability (discrimination), is time con-suming and can be unacceptable to a patient with multipletender sites (feasibility). More recently, two other indiceshave been described and validated; the Maastricht Anky-losing Spondylitis Enthesitis Scale (MASES)32 (see Figure 3in Appendix 2) and the Berlin Enthesitis Index (BEI).33 TheMASES was developed from the MEI, includes 13 sites andscores each site as 0 (‘no pain’) or 1 (‘painful’), giving a totalpossible score of 0–13. The BEI consists of 12 lower limbentheseal sites, scored similarly to the MASES giving a pos-sible score of 0–12. Both of these are much easier to admin-ister than the MEI and correlate with the disease activityand with patient-reported entheseal pain measured by VAS;however, neither correlate with acute-phase reactants. TheBEI has not been validated in clinical trials.

Diagnosis and treatment of axial spondyloarthropathies Consensus Statement 19

Recommendation: Use 44 joint counts for peripheralarthritis and Maastricht Ankylosing Spondylitis EnthesitisScale for enthesitis.

Patient-assessed general healthThe patient global assessment (PGA) measures the overallimpact of AS on the patient. The ASAS group recommendsusing a 10 cm VAS to measure global well-being due to AS ‘on an average over the last week’. The PGA is regardedas the best single AS measure for use in clinical practice,being quick and easy to perform and responsive to changesin individual patients. The MCID has been demonstrated to be 1.5 cm, reflecting the smallest difference in the scorethat patients perceive as beneficial (a good deal better ormore).34

Recommendation: Use VAS 10 cm

Disease activityDisease activity in AS is generally assessed as a combinationof pain, fatigue, stiffness and discomfort, and the standardinstrument used in both daily practice and clinical trials isthe BASDAI. It is a self-administered composite index ofsix 10-cm VAS scales which has good clinimetric proper-ties and has been extensively validated in AS patients.35,36

(see Figure 4 in Appendix 2). The MCID is relatively smallat 1.0 cm,34 and the best cut-off indicating patient-perceivedsymptom relief lies at 3.9 cm.37

Recently, ASAS has developed a disease activity scorefor use in AS, the ASDAS.19 The development processresulted in four candidate ASDAS scores (see Table 2 inAppendix 2). The four ASDAS are highly discriminatory indifferentiating patients with different levels of disease activ-ity and patients with different levels of change. There wereno major differences between the four ASDAS scores. Basedon feasibility, the ASAS membership has selected the ASDASincluding back pain, duration of morning stiffness, patientglobal, peripheral joints complaints and CRP as the preferredASDAS. Very recently, ASDAS-CRP has been validatedagainst BASDAI.38

Recommendation: Use ASDAS with ESR or BASDAI

Structural damageThe term structural damage represents the irreversiblechanges that accompany AS; spinal syndesmophytosis and ankylosis, destruction and ankylosis of sacroiliac andhip joints. Plain radiographs should include at least lateralviews of the lumbar spine, lateral views of the cervicalspine and a pelvic X-ray that includes sacroiliac joints and both hips. The most commonly used radiographic scor-ing methods are the modified-Stoke Ankylosing Spon-dylitis Spinal Score (mSASSS)39 and the Bath Ankylosing

Spondylitis Radiographic Index (BASRI). Both measureshave been assessed for validity using the OMERACT filter40,with the mSASSS performing better than the BASRI or theearlier SASSS with regard to reproducibility, interobserverreliability and sensitivity to change over 2 years. Plain radi-ography of the spine is included in the ASAS core set foruse in clinical trials of disease-controlling anti-rheumatictherapy, and the mSASSS has recently been added as therecommended scoring system.41

The emerging imaging technique for the assessment ofAS is magnetic resonance imaging (MRI). Details of itsapplication in the imaging of spondyloarthritis are reviewedin a subsequent section of this document.

Recommendation: Use mSASSS for radiologic scoringand ASspiMRI for MRI scoring.

Physical functionBath Ankylosing Spondylitis Functional Index (BASFI)42

(see Figure 5 in Appendix 2) and the Dougados FunctionalIndex (DFI)43 are the two validated indices that are recom-mended for measuring the physical function in AS. HealthAssessment Questionnaire modified for spondyloarthritides(HAQ-S)44 revealed a considerably different pattern, withmany more health concepts, including many activities andparticipations involving upper arm and hand use. TheHAQ-S was derived by adding five extra items to the origi-nal HAQ45 developed for RA. Both the BASFI and the DFIhave been shown to perform well with regard to validity,reliability and responsiveness across a range of settings,36,46

although the DFI may not be as responsive to small changesas the BASFI.

Recommendation: Use BASFI

Health-related quality of lifeThe ASAS core sets for measuring AS does not include the domain health-related quality of life (HRQoL). TheAnkylosing Spondylitis Quality of Life (ASQoL) question-naire47 is the best studied disease-specific measure avail-able to assess HRQoL in AS patients, is easy to administerand correlates well with the generic medical outcomes sur-vey SF-36.48

Recommendation: Use ASQoL

Response to treatmentThe ASAS international working group has developed specific criteria to measure treatment response in AS trials(see Figure 2 in Appendix 2). The initial improvement crite-ria identified four relevant and responsive domains: physi-cal function, spinal pain, patient global assessment andinflammation. These improvement criteria were based onfive short-term NSAIDs trials. Short-term improvement

20 Indian Journal of Rheumatology 2010 March; Vol. 5, No. 1 Malaviya et al.

was defined as an improvement of at least 20% and 10 units(scales of 0–100 on VAS) in each of the three domains with-out deterioration of a similar magnitude in the fourth do-main. The short-term improvement criteria have since becomeknown as the ASAS 20% response criteria (ASAS20).49

They have been validated against expert opinion and in sub-sequent clinical trials of anti-TNF therapy.50 For assessingthe efficacy of the anti-TNF agents, ASAS40 response cri-teria have been recommended. The ASAS 5/6 which re-quires a 20% or 10-unit improvement in five of six domainswere found to be more appropriate.49 The latter responsecriteria include the four domains of the ASAS20 and theadditional domains spinal mobility and CRP. Partial remis-sion criteria were defined as a VAS score < 20 (on a scale of0–100) in each of the four domains at the end of the thera-peutic trial.

The ASAS response criteria as described above weredeveloped for use in clinical trials and have not been vali-dated for use in clinical practice. A simpler definition oftreatment response which is applicable to daily patient careis the BASDAI 50% response, requiring an improvementfrom baseline of 50% or an improvement of two units on a 10-unit scale. This definition has been recommended asthe best indicator of the efficacy of anti-TNF therapy in clin-ical practice; if a BASDAI 50% response is not achievedafter 6–12 weeks of therapy, discontinuation should be considered.51,52

Recommendation: Use ASAS 20/40/70 for clinical trials

IMAGING IN SACROILIITIS

Plain radiographs

Sacroiliitis is a defining feature of AS. Although the Fergusonview shows the SI joints more clearly, it is the AP view whichhas been recommended by most guidelines.

The sacroiliitis grading system associated with themodified NY criteria is as follows53

• Grade 0: normal findings• Grade 1: suspicious changes• Grade 2: minimum abnormality, defined as small lo-

calized areas with erosion or sclerosis without alter-ation in the joint width

• Grade 3: unequivocal abnormality• Grade 4: total ankylosisGrades 0 or 1 are not sufficient for the diagnosis of def-

inite AS. The radiographic changes start as a loss of or blur-ring of the subchondral cortex followed by the developmentof small erosions (rat bite erosions) along the iliac side, as

well as subjacent mild sclerosis. As the disease progresses,the erosions become larger and involves the sacral side. Thejoint space widens, and the sclerosis around the joint be-comes more prominent. If the disease continues to progress,ankylosis of the joint occurs, with resolution of the sclero-sis. The classic sacroiliac joint involvement is symmetricand bilateral.54 In approximately 10% of cases, the initialradiographic evidence of sacroiliitis is unilateral with even-tual bilateral involvement.55

CT scanning

Studies indicate that CT is more sensitive than radiographsin identifying sacroiliitis, leading to an earlier diagnosis of sacroiliitis and AS.56,57 With the introduction of multidetector CT (MDCT), the findings of sacroiliitis and os-teoarthritis can be delineated in greater detail. Althoughsacroiliitis in AS has frequently been graded radiograph-ically using the NY criteria, this grading is not ideal for use with CT scans.58 Only erosions seem to be a valid sol-itary diagnostic sign. Inflammatory sclerosis may be dis-tinguished from degenerative sclerosis, and can sometimessupport early diagnosis. Joint space width, joint shape,bone mineral content, or enthesopathy have no place in sa-croiliitis diagnosis on CT.58 CT scan is best used in patientswith clinically suspected AS who have equivocal plain radiographs of the sacroiliac joints, especially with a con-traindication for MRI.

MRI

Early inflammatory changes can be picked up on an MRI scanbefore they become evident on conventional radiographs orCT scans.59 Dynamic contrast-enhanced MRI seems to bemore sensitive than CT and radiography in detecting sacroili-itis in patients with documented AS or an undifferentiatedspondyloarthropathy, based on the European Spondylo-arthropathy Study Group criteria.60 The main use for MRI(usually 1.5 or 3 T system) in the management of AS is inestablishing early diagnosis and in distinguishing active in-flammatory axial disease from non-inflammatory causes.59

The inflammation in SpA is usually limited to the bone/SIjoint and does not cross anatomical borders, unlike inflamma-tion due to infection (septic sacroiliitis) which often crossesanatomical borders and spreads to adjacent soft tissues.61

Inflammatory changes reflecting active sacroiliitisinclude62

• Bone marrow oedema (BMO/osteitis)• Synovitis

Diagnosis and treatment of axial spondyloarthropathies Consensus Statement 21

• Enthesitis and• CapsulitisBMO is depicted as a hyperintense signal, typically

located periarticularly (subchondral bone marrow) on STIR images (TR/TE/TI: 4000/60/150 ms, slice thickness3–4 mm) and hypointense signal on T1 images (TR/TE:500/10 ms). The signal intensity corresponds to the grade ofinflammation. A hyperintense signal on contrast-enhanced,fat-saturated T1-weighted images (TR/TE: 660/16) suggestosteitis. A strong hyperintense signal is similar to that ofblood vessels. The sacral interforaminal bone marrow signalforms the reference for normal signal in the bone.63 BMO/osteitis is, however, non-specific. Published studies showedthat contrast-enhanced T1-weighted images were more sen-sitive for detecting the presence and extent of acute inflam-matory changes than STIR and fat-saturated T2-weightedimages.64–66 However, STIR sequence is particularly helpfulin detecting active inflammation which precludes the use ofgadolinium-based MRI contrast.67

Synovitis is best detected as a hyperintense signal oncontrast-enhanced, T1-weighted, fat-saturated images in thesynovial part of the SI joints. Synovitis on MRI alone doesnot suffice for making a diagnosis of sacroiliitis.

Enthesitis is depicted as a hyperintense signal on STIRimages and/or on contrast-enhanced, T1-weighted, fat-saturated images at sites where ligaments and tendonsattach to bone. The signal may extend to bone marrow andsoft tissue.68

Capsulitis has similar signal characteristics to those ofsynovitis and may extend medially and laterally into theperiosteum.

Structural changes representing sequelae of previousinflammation or a burnt out inflammatory process mayappear as

• Subchondral sclerosis• Erosions• Fatty marrow replacement and• Bony ankylosis.Sclerotic areas are depicted as low-intensity signal by all

sequences extending at least 5 mm from the SI joint spaceand do not show enhancement after contrast administration.

Erosions are bony defects at the joint margin. Erosionsinitially appear as single lesions and later confluence of ero-sions may give rise to pseudo-widening of the SI joints. Ero-sions are of low signal intensity on T1-weighted images andhigh signal intensity on STIR images, if active. T1-weightedsequences with fat saturation or T2-weighted gradient echosequences (TR/TE 180/7.15 ms) may better visualize theerosions.

Periarticular fat deposition displays increased signal onT1-weighted images.

Bony ankylosis of the SI joint appears as a low intensitysignal on all pulse sequences, sometimes surrounded by highintensity signal on T1 due to fat deposition.

Diffusion weighted imaging (DWI) can quantify the dif-fusion coefficients of lesions, which can discriminate betweennormal and involved subchondral bone.69,70

INHERITANCE, PROGNOSIS AND OUTCOME

IN ANKYLOSING SPONDYLITIS

Inheritance

A positive family history of AS can be found in 15–20% ofcases. Monozygotic twins have a concordance for the dis-ease of 63–75% compared with 12.5% in dizygotic twins.71

This suggests a major genetic component in the patho-genesis of the disease.

From twin recurrence risk studies, the heritability ofsusceptibility to AS has been estimated at 97% (95% confi-dence interval, 92–99%).

Susceptibility genes in the HLA region include B27, B60and DRB1. Data from Indian patients showed that HLAB*2704 is the predominant subtype in the AS group (70.8%)compared to its frequency of 47% in healthy controls(RR = 2.73).72

However, MHC genes account for less than 50% of thegenetic risk for AS with only 20–50% of total risk con-tributed by HLA-B27. Disease concordance is no more than24% in HLA-B27-positive dizygotic twin pairs, comparedwith 60–70% in HLA-B27-positive monozygotic twins,clearly supporting a role for additional genetic loci.73

Data from linkage and genome-wide association stud-ies have lead to the identification of several non-MHCgenes involved in the genetic susceptibility to AS. The IL-1(Interleukin-1) gene complex on chromosome 2 and the IL-23 receptor gene on chromosome 1 are two such loci.74,75

Studies have also explored the role of the gender of theaffected parent in the inheritance of AS. The chances of off-spring developing AS are higher if the mother has AS thanif the father has the disease.76

Prognosis

The following features are associated with a poorer prognosisin AS77,78

• Older age at onset (level of evidence IIIB)• Male sex (level of evidence IIIB)• Smoking (level of evidence IIIB)

22 Indian Journal of Rheumatology 2010 March; Vol. 5, No. 1 Malaviya et al.

• Longer disease duration and greater severity• Hip involvement• Extra-axial involvement (number of peripheral joints

affected, extent of enthesitis)• Eye involvement• Raised acute phase reactants (erythrocyte sedimenta-

tion rate, C-reactive protein), haemoglobin levels• Poor response to NSAIDs• Presence of radiological changes at baseline• Presence of HLA-B*4100, DRB1*0804, DQA1*0401,

DQB1*0603, DRB1*0801 and DPB1*0202 alleles(level of evidence IIIB)

In women, AS is generally milder, begins later and ismore often associated with extra-spinal involvement, espe-cially peripheral arthritis and uveitis.79,80

Impact on functioning at work

The rate of withdrawal from work in patients with AS exceeds20% in most series as against 10% in the general population.81

The attributable fraction of risk due to the disease in prematurewithdrawal from work is variable, ranging from 15% to 35%.82

Mortality

The survival rate in AS at 5 years is 92%, at 10 years 84%,at 15 years 76% and at 25 years 62%.83 Standardized mor-tality ratio (SMR) for patients with AS varies from 1.32 to1.5 in different populations, implying a one-third to half ofexcess mortality compared to a normal population.84 Thefactors found to correlate with mortality are age, ESR andthe number of inflamed joints at study entry. Circulatorydeath, including ischaemic heart disease, other cardiovascu-lar disease and cerebrovascular disease, is the leading causeof death in all published studies.85 Coupled with recentstudies that show increased atherosclerosis and an excess ofcardiovascular morbidity and mortality in AS86 these dataemphasize the importance of preventing and managing car-diovascular disease in these patients.

TREATMENT OF ANKYLOSING

SPONDYLITIS—I. PHYSIOTHERAPY AND

EXERCISE

There is ample evidence that physiotherapy in the form ofexercises is effective (level A evidence) in the managementof AS-SpA. However, scientific evidence of long-term

effectiveness is not yet available.87 In a randomized controlledtrial, a program of supervised physiotherapy in groups wasfound to be superior to individualized programs in improvingthoracolumbar mobility and fitness.88 The clinical benefitsof such treatments can be achieved at acceptable costs.89

Level A evidence from a recent Cochrane review on theefficacy of physiotherapeutic interventions, including exer-cises have revealed the following90

• Home exercise programs are better than no interven-tion and

• Supervised group physiotherapy is better than homeexercise

Recommendations for Exercise91,92

1. Lying prone for 15–30 minutes once or several times aday reverses the tendency toward kyphosis, and flexioncontractures of hip joints.

2. Patients should sleep fully supine on a firm mattresswith only a small neck support pillow.

3. Formal instruction in proper posture and exercises, em-phasizing spinal mobility and strengthening of spinalextensors should be provided to every patient initiallyand reemphasized periodically.

4. Range-of-motion exercises for the neck, shoulders andhips, as well as deep-breathing exercises to maintainchest expansion, should also be emphasized.

5. Swimming is an excellent modality for achieving allthese goals. Canes or walkers may be necessary forpatients with severe spinal kyphosis, or lower extremityarthritis. Soft cervical collars should be used by patientswith neck fusion or subluxation in situations in whichthey are exposed to possible injury.

TREATMENT OF ANKYLOSING

SPONDYLITIS—II. USE OF

NON-BIOLOGICAL AGENTS

Goals of treatment

• To provide maximum relief or completely eliminatesymptoms such as pain and stiffness.

• To restore function/functional capacity as best as possible.• To prevent progressive bony erosions, ankylosis of the

spine or development of spinal deformities; to preserveand maintain spinal mobility and function.

• To prevent complications of spinal disease—e.g. spinal frac-tures, flexion contractures, especially of the cervical spine.

Diagnosis and treatment of axial spondyloarthropathies Consensus Statement 23

• To minimize extra-spinal and extra-articular manifesta-tions—(e.g. uveitis, aortic valve insufficiency, others).

General comments

In the treatment of AS, the following facets need to be takeninto account in order to tailor it to the individual patient:1. Factors pertaining to the specific patient and his/her

close relatives, friends, especially those who would payfor the treatment:• Age and gender of the patient• Disease duration and disease severity• Comorbidities and the drugs being taken by them• Personal history including level of education, smok-

ing, alcohol consumption, substance abuse, level ofphysical activity, eating habits.

• Mental and emotional attitude of the patient and his/her close relatives, friends, towards the disease in-cluding the degree of understanding of the disease,disease process, the current knowledge about its cau-sation, and short- and long-term outcome.

• Attitude of the patient and his/her close relatives,friends, towards modern scientific treatment vs. othersystems of treatment.

• Wishes and expectations of the patient his/her closerelatives, friends, especially those who would pay forthe treatment.

• Level of family support that would be available dur-ing the chronic course of the disease.

Note: Lack of health insurance often puts the burden ofpayment on patients themselves. This influences the choiceof treatment irrespective of any specific characteristics ofthe disease or disease status.2. Factors pertaining to the disease:

Treatment of AS addresses four distinct components.• Axial disease• Peripheral disease• Enthesitis• Extra-articular manifestationsAdditional clinical features occasionally seen in patients

with long-standing AS include:• Osteoporosis• Premature cardiovascular disease• AA-amyloidosis• Increased incidence of malignancyHowever, the group felt that these aspects were outside

the purview of this working-group, therefore, no recommen-dations were made for these complications of AS.

In this section, only the pharmacological treatment ofaxial disease will be addressed.

Non-biological drug treatment of AS (axial SpA)

As no head-to-head studies are available for comparingpharmacological and non-pharmacological treatments, theconsensus of this working group is that both are of value inthe initial and long-term treatment of AS.

NSAIDs are recommended as the first-line drug treat-ment for patients with AS, with pain and stiffness. In thosewith increased gastrointestinal (GI) risk, non-selectiveNSAIDs plus a gastroprotective agent, or a selective COX-2inhibitor could be used.

There is convincing evidence (level Ib) that conventionalNSAIDs as well as coxibs improve spinal pain, and functionover a short- as well as long-term period (6 weeks; 52 weeks)in ∼50% of patients.93–95 In 2005, a randomized controlledtrial (RCT) reported on comparative efficacy of continuouscelecoxib treatment for AS with intermittent on demanduse. The results showed that continuous treatment retardedradiographic disease progression in 2 years96 (evidencelevel IIa). This is the first study to show a possible diseasemodifying effect of continuous treatment although the dif-ferences between treatment and placebo group were small.Coxibs are equally effective, showing large improvementsin spinal pain and function in patients with AS. Comparativestudies of different NSAIDs have not shown one preparationto be clearly better than the others.

However, there is evidence (level IIa) that etoricoxibmay be superior to naproxen in treating AS for up to 52 weeks.97 Based on the available evidence, the workinggroup recommends the use of conventional NSAIDs or cox-ibs as the first-line drug in patients with AS. As there are nohead-to-head trials comparing the various NSAIDs andcoxibs (except the one that compared naproxen and etori-coxib), the working group recommends the practical andtime-honoured menu approach for choosing NSAID/coxibfor a particular patient (i.e. let the patient decide which ofthe available NSAIDs/coxibs has been most effective forsymptomatic control of AS symptoms). However, the treat-ing physician must ensure that full dose has been given foradequate period of time before labelling that drug to beineffective and switching over to the next one. The groupalso emphasized that two conventional NSAIDs/coxibsshould never be combined and should never be prescribedtogether.

The working group recommends careful risk stratifica-tion while prescribing these drugs as they are not free oftoxicities. Age, concomitant comorbidities (hypertension,renal disease) and other drugs (e.g. glucocorticoids) mustbe taken into account if NSAIDs are being prescribed. Inthose predisposed to GI toxicity, gastroprotective agents mustbe prescribed concomitantly. There is good evidence (IIa)

24 Indian Journal of Rheumatology 2010 March; Vol. 5, No. 1 Malaviya et al.

that coxibs have a lower risk of serious GI events thanNSAIDs98 and may be preferred in patients at higher risk ofGI toxicity.

The evidence for cardiovascular toxicity related to anti-inflammatory drugs is rapidly evolving.95

The working group recommends careful risk stratifica-tion from the cardiovascular disease stand point (age, obesity,hypertension, diabetes, smoking, hypothyroidism, dyslipi-demia, previous history and family history of CVD) beforedeciding on coxib treatment. The available evidence (levelIIIb) suggests that non-coxib NSAIDs may possibly sharesome of this effect (evidence level IIIc).99 In general, thechoice of NSAID or coxib should be based on the GI andCVD risk profile of the patient.

The evidence for any direct correlation between diseaseduration and response to drug treatment is either not avail-able or available only for anti-TNF therapy. However, acommon sense of approach to treatment is recommended;namely diagnose early, treat effectively and ensure goodcompliance.

1. Analgesics (e.g. paracetamol and opioids) mightbe considered for pain control in patients in whomNSAIDs/coxibs are insufficient, contraindicatedand/or poorly tolerated.

In the absence of prospective studies on the use of thesedrugs in AS, they can not be recommended.

2. Corticoglucocorticoid injections directed to thelocal site of musculoskeletal inflammation may beconsidered.

Small RCTs have shown effective control of inflamma-tory sacroiliitis with intra-articular or periarticular depot-glucocorticoid injections.100,101 There are no good clinicalstudies on the efficacy of local depot-glucocorticoid injec-tions at sites of enthesitis. However, these agents may behelpful in selected cases. Potential toxicity including tendonrupture must be considered before undertaking these proce-dures. Also these procedures must be carried out by well-trained rheumatologists.

The use of systemic glucocorticoids for axial

disease—is there any evidence?

According to the ASAS/EULAR statement, the use of sys-temic glucocorticoids is not supported by evidence.95 How-ever, an old open trial of pulsed methylprednisolone in severeAS showed temporary improvement in symptoms (level ofevidence IVc).102

There is one small RCT comparing high dose (1000 mg)vs. moderate dose (375mg) methylprednisolone intravenouslygiven over three consecutive days (evidence level IVc).103

In the absence of a placebo group, the authors concludedthat both regiments were effective for pain relief and im-provement in spinal mobility. However, a small RCT didnot find any benefit from this form of treatment (evidencelevel IIa).104

The working group expressed concern over reportedcardiac arrhythmia with this treatment. However, anotherstudy failed to find such an adverse effect.105 Other well-known adverse effects of high-dose IV glucocorticoid ad-ministration namely—diabetes, hypertension and glaucomamust be kept in mind. Considering all these reports, thefinal recommendation of the working group was that sys-temic glucocorticoids therapy is not recommended in ASfor routine use.

There is no evidence for the efficacy of disease modify-ing anti-rheumatic drugs (DMARDs), including sulpha-salazine (SSZ) and methotrexate (MTX), for the treatmentof axial disease. SSZ may be considered in patients withearly axial AS with severe disease. SSZ may also be effec-tive in recurrent uveitis.

A Cochrane Review on SSZ in AS showed level Ia evi-dence that SSZ improves morning stiffness and the ery-throcyte sedimentation rate (ESR) in AS.106 It is not clearwhether it improves pain, function (physical ability), move-ment of the spine and overall well-being.

Long-term trials of SSZ in spondyloarthritis, in gen-eral, support an effect on peripheral joints but not spinalinflammation—especially not in patients with longer dis-ease duration. In an extended trial, patients treated with SSZover three years had significantly fewer episodes of periph-eral joint symptoms than the placebo group.107 One obser-vational study failed to show any effect of SSZ on peripheralenthesitis (level IV evidence).108

It is recommended that patients with early AS, with ac-tive disease may be treated with SSZ as they may improvewith it. However, SSZ is more effective for peripheral jointsymptoms than for axial disease. One RCT showed thatSSZ decreases the occurrence of recurrent acute uveitis inpatients with AS (level Ib evidence).109

Therefore SSZ could be given in AS with recurrentuveitis. Toxicity with SSZ is common but usually mild: GIsymptoms, mucocutaneous manifestations, hepatic enzymeabnormalities and haematological abnormalities have beendescribed.95

In the absence of any meta-analysis of MTX for AS, theworking group relied only on the systematic review that wasunable to combine results. Therefore, based on some RCTs(level Ib evidence), MTX did not show significant effect ofMTX on spinal pain or function.110–112 The most commonlyreported side effects occurring with MTX treatment includenausea and hepatic abnormalities.95

Diagnosis and treatment of axial spondyloarthropathies Consensus Statement 25

Other non-biological drugs for axial AS

Intravenous pamidronate has been reported (level III evi-dence) to have a beneficial effect on both axial pain andfunction.113 However, a report from India (level IIIc evidence)did not find any beneficial effect.114 There is level IV evi-dence from India that a combination of intravenous pulsedmethylprednisolone synchronized with pamidronate on thebackground of NSAIDs + SSZ + MTX is effective in axialdisease.115 Pamidronate should not be avoided in patients withelevated serum creatinine. Adverse effects include transientpost-infusional arthralgias and myalgias and an acute phaseresponse with lymphopaenia and raised CRP.113,116

Results from open trials suggest a beneficial effect ofthalidomide on spinal disease (level IIIc evidence).117 How-ever, the reported toxicity was substantial, including poten-tially irreversible peripheral neuropathies. The associationof thalidomide with severe birth defects is well recognized.

The working group surmised that the use of pamidronateand thalidomide for axial AS cannot be recommended.However, there are AS patients not responding to standardNSAIDs/coxibs who are unable to afford biologicals.Pamidronate or thalidomide may be tried in such patientswith the full understanding of limited proof of their efficacyand significant toxicity.

TREATMENT OF ANKYLOSING

SPONDYLITIS—III. USE OF BIOLOGICAL

AGENTS

The following criteria should be fulfilled before initiatingbiological agents

• A definitive diagnosis of AS• The presence of active disease for at least 4 weeks, as

defined by both a sustained BASDAI of at least 4 (on ascale of 0–10) and an expert opinion based on clinicalfeatures, acute phase reactants and imaging modalities.

• The presence of refractory disease defined by failureof at least two NSAIDS during a 3-month period, fail-ure of intra-articular glucocorticoids if indicated andfailure of SSZ in patients with peripheral arthritis.

Before starting biological agents, a relevant history, exami-nation and laboratory investigations should be carried out.These include a history of any chronic disease and themeasurement of disease activity using BASDAI.

The following are contraindications to the use of bio-logical agents

• Active tuberculosis• Pregnancy

• Breast feeding• Active infection• Septic arthritis of a native joint within the last 12 months• Sepsis of a prosthetic joint within the last 12 months

or indefinitely if the joint remains in situ.• New York Heart Association (NYHA) grade 3 or 4

congestive cardiac failure with an ejection fraction< 45% (for infliximab)

• Clear history of demyelinating disease• Patients with immune compromise• Recent malignancyThe following laboratory investigations should be per-

formed before initiating biological agents• Complete haemogram• Acute phase reactants—ESR, CRP• Radiographs of the dorsolumbar spine and pelvis• Radiograph of the chest• CT scan of chest—in case of doubtful opacity in

chest X-ray• Mantoux test• Hepatitis B surface antigen• Any other appropriate laboratory/radiological test in

a specific clinical setting

Choice of biological agent

Although there are various anti-TNF-α blocking agents beingused , the working group recommends the use of infliximaband etanercept, as these two biological agents have beenused and studied extensively .

InfliximabThe working group recommends injection infliximab, slow ivinfusion over 2 hours @ 5 mg/kg at weeks 0, 2, 6 and there-after every 6–8 weeks.

The short-term efficacy of infliximab has been provedin several trials118–120

There is evidence to suggest that infliximab can be givenas long-term administration till 3 years with very high effi-cacy, as shown by the German RCT, where 69 patients werecontinuously treated with infliximab for 3 years, with thesame dose given every 6 weeks.121 Interestingly, as seen inthis trial, when infliximab was stopped after 3 years of ther-apy, patients relapsed between week 7 and 45, and by week52 all except one patient out of 41 (97.6%) had active dis-ease. However, when treatment with infliximab was com-menced again, all except one patient responded similarly asin the first instance and the drug was well tolerated.

Based on this evidence, the working group strongly rec-ommends administration of infliximab for a long duration.

26 Indian Journal of Rheumatology 2010 March; Vol. 5, No. 1 Malaviya et al.

However, in a resource constrained setting like ours, onehas to exercise careful judgement in this regard.

There is concern over some of the frequent side effectswith infliximab such as serious bacterial infections—mainly,upper respiratory infections, reactivation of chronic infec-tions like tuberculosis and opportunistic infections alongwith other side effects like nausea, headache, sinusitis, rashand cough.

Note: In view of the high incidence of tuberculosis inour country, it is common practice to omit the loading doseof infliximab. Doing so, decreases the risk of tuberculosiswhile leaving the efficacy of the drug unaffected.

EtanerceptIt is usually administered in a dose of 25 mg subcutaneously,twice weekly or 50 mg subcutaneously once per week.

There is strong evidence of short-term efficacy of etaner-cept, as shown by several double-blind placebo-controlledtrials122–124

Long-term follow-up data for 2 years from an open ex-tension phase of the original RCT125 showed that when treat-ment with etanercept was stopped after 3 months, a diseaserelapse occurred at a mean of 6.2 weeks and at 35 weeks all30 patients had a relapse. But when treatment was startedagain, the response rate was similar to that at first treatment.

The working group also expressed concern over someof the frequent local side effects with etanercept like ery-thema, pain, swelling, itching at the site of injection, as it isgiven as a subcutaneous injection.

The ASAS group has published comprehensive, evi-dence-based consensus statements for the initiation of anti-TNF treatment in AS to identify appropriate therapeuticcandidates.126,127

Prevention of tuberculosis infection (TBI) flare amongAS-SpA patients is to be initiated on anti-tumour necrosisfactor (TNF)-α biological.

Background

The use of TNF-α agents in patients with AS-SpA has been shown to be associated with increased risk of TBI(level IIIc evidence).128 Tuberculosis occurring among AS-SpA patients being treated with iTNF-α biologicals in Indiahas been reviewed by Kumar.129 Based on level IIIc evi-dence, the review summarized the results as follows: Re-activation tuberculosis developed in 10.6% of the SpAgroup treated with iTNF-α using the standard 5 mg/kg bodyweight dose and loading dose regimen. Patients treatedwith lower doses of infliximab without loading dose did notdevelop tuberculosis.

There are certain important features of TBI seen amongpatients receiving iTNF-α treatment.

1. In the majority of these patients, it is extrapulmonaryTB occurring in ∼ 60% of the cases.130

2. The median time to onset of TBI is relatively short(within the first 12–21 weeks from first infusiondose of infliximab), consistent with reactivation ofLTBI.130,131

3. In contrast, studies of TB occurring in patients re-ceiving a soluble TNF-α receptor, etanercept, re-ported a median time to onset that was 3–5 timeslonger consistent with re-infection.130,131

This means that if appropriate screening procedures fordetecting LTBI are followed, the problem of TBI flare amongthese patients could be eliminated. Therefore, screening forLTBI is a standard prerequisite for iTNF-α treatment.95

Recommendations for the screening of LTBI

This subject has been extensively reviewed in recentyears.130–132 These reviews bring out the fact that there is nogold standard for the screening of LTBI.

There are four methods available for LTBI screening1. Detailed clinical history focusing on past contact

with patients with TBI, past history of TBI, and itstreatment, family history of TBI, characteristics ofenvironment where the person lives and other stan-dard issues related to TB-tracing, thorough physi-cal examination keeping in mind the possibility ofextra-pulmonary TB

2. Standard chest radiograph3. Tuberculosis skin test (TST )4. Newly introduced interferon-gamma release assays

(IGRA)Each method has its own sensitivity, specificity, positive

and negative predictive value. It is now universally recom-mended that, if available, the national guidelines should befollowed. Based on this recommendation and taking intoaccount the fact that TB prophylaxis guidelines of the IndianRheumatology Association (IRA) are already available,133

the working group felt that these could be followed as suchfor patients being initiated on iTNF-α treatment. LikeBritish guidelines,134 these guidelines neither recommendTST nor IGRA-based tests for the screening of LTBI.

The recommendations of these guidelines were as follows:• TB risk stratification through thorough history and

physical examination combined with• Standard chest radiograph for detecting TBI/LTBI;

followed by three monthly repeat chest radiographsfor the duration of treatment.

Diagnosis and treatment of axial spondyloarthropathies Consensus Statement 27

These recommendations were made prior to the avail-ability of any IGRA-based LTBI screening studies in India.The guidelines also raised concerns related to widespreadBCG vaccination as well as environmental non-tuberculousmycobacteria that could affect the interpretation of TST.133

Since then, a study that has extensively evaluated TSTas well as one of the IGRA tests among Indian patients with inflammatory rheumatic diseases (IRDs) has been pub-lished.135 This report also discusses the issues related to theeffect of past BCG vaccination and environmental mycobac-teria on standard TST results. LTBI screening was carriedout in this study with standard risk stratification question-naire related to clinical history followed by physical exami-nation for TBI, not giving loading dose of infliximab, usingmodified-TST protocol along with QuantiFERON-TB GoldIn-tube (QFT-IT; Cellestis, Carnegie, Australia), standardchest radiograph and contrast-enhanced computerised tomog-raphy (CECT) of chest. Using this strategy, the authors re-ported a significant reduction in TBI flare among patientsbeing initiated on iTNF-α. In a follow-up of the same studyit was demonstrated that CECT chest at the baseline may notbe necessary for every patient and may only be reserved forthose having positive clinical risk factors, TST, suspiciouschest radiograph or QFT-IT in any combination.136 Usingthis strategy, no new cases of TBI were detected among 33patients followed for more than 2 years.135

Recommendations on the treatment of LTBI

As per the Indian guidelines• Prophylaxis is not required in patients with a past his-

tory of TB that has been adequately treated.• Patients with a history of inadequate anti-tuberculous

treatment (ATT) or radiographic scarring without pre-vious history of ATT should be offered TB prophylaxis.

• TST using 10 TU-RT23 PPD Mantoux test to be per-formed. If the induration of 10mm or more is observedbetween 48 and72 hours, it should be considered tobe positive indicating LTBI or TBI. If the chest X-rayis negative or it shows only old scarring, it is consid-ered confirmatory of LTBI. If the lesions are suspi-cious, a CECT chest should be done to see if active TBIis present. Depending on whether the imaging con-firms LTBI or TBI, further treatment for prophylaxisor active TB is carried out as described below.

• If TST is negative and there is no financial con-straints, QuantiFERON-TB Gold In-tube (QFT-IT;Cellestis, Carnegie, Australia) test can be done. Ifnegative, the patient can be given anti-TNF-α treat-ment without any further tests. If the test is positive,

then based on the chest imaging findings (whetherLTBI or TBI), further treatment for prophylaxis oractive TB is done as described below.

• Patients with negative clinical history, no previoushistory of TB, no family history, no known TB con-tact, normal chest radiographs and negative TST andnegative QuantiFERON-TB Gold In-tube (QFT-IT;Cellestis, Carnegie, Australia) (among those withoutfinancial constraints), may be started on anti-TNFagents without any further testing or treatment forTB. Those detected to have LTBI or TBI according tocriteria stated above, should be offered TB prophylaxis.The Indian guideline recommends 6–9 months ofisoniazid (INH) for latent TB as recommended by theavailable British and American guidelines and foundto be based on high level of scientific evidence.137

Alternately, it recommends twice weekly directly ob-served therapy (DOTS) that could be substituted for dailytherapy. It recommends rifampicin for 4 months for thoseintolerant to INH and for those with exposure to INH-resistantstrains. TNF blockers should be started after completingthis treatment. However, if the clinical situation so warrants,anti TNF-α therapy can be initiated 1 or 2 months after thestart of INH prophylaxis.

This is in accordance with the internationally prevail-ing recommendations.138

The treatment of TBI must be exactly according to the rec-ommendations of the World Health Organization (WHO) withany local modifications as suggested by the national agency.

TREATMENT OF ANKYLOSING

SPONDYLITIS—IV. EXTRA-ARTICULAR

MANIFESTATIONS

General considerations

Extra-articular manifestations of SpA are protean and rare.The exception is acute anterior uveitis which is seen in upto 25% of patients.139,140 Aortic regurgitation and variabledegrees of atrioventricular or bundle-branch block occur inapproximately 5% of patients with AS. Osteoporosis is awell-recognized feature that occurs even in the early, mildform of AS and leads to an increased rate of fractures.141

Treatment recommendations for uveitis

Evidence from rigorous trials is not available and recom-mendations are based on clinical experience.

28 Indian Journal of Rheumatology 2010 March; Vol. 5, No. 1 Malaviya et al.

Initial treatment of uveitisTopical glucocorticoids and a cycloplegic-like cyclopento-late (1%).

Posterior uveitis is generally not responsive to topicalmedication. Treatment with periocular and intraocular glu-cocorticoid injections, sustained release glucocorticoid im-plants, or oral glucocorticoids is advocated at a dose of40–60 mg of prednisone per day for 1–2 weeks.

Role of DMARDs in uveitisEvidence regarding the use of DMARDs is based largely oncase series and non-randomized trials. Indications include:

• bilateral disease• active inflammation• failure to respond adequately to glucocorticoid therapy• severe disease which interferes with activities of

daily living

Individual DMARDs

SSZ—Some studies have found that SSZ can help preventattacks of HLA-B27-associated iritis.109,142

Other immunomodulators like azathioprine, mycophe-nolate mofetil, MTX, cyclosporine and tacrolimus havebeen advocated in recalcitrant cases.143

Anti-tumour necrosis factor-alpha agents

Etanercept has shown encouraging responses in patientswith iritis and juvenile RA, but controlled trials using etan-ercept for uveitis have been less positive.144,145

Management of enthesitis

Rest, orthotics with soft heel supports and local non-steroidalanti-inflammatory drugs (NSAIDs) and glucocorticoid in-jections have formed the mainstays of therapy.146

Radiotherapy and fasciotomy have been reserved forpatients who have isolated resistant enthesitis, although theprocedures are not employed commonly.

NSAIDs have been the mainstay of therapy for enthesitisfor many decades.

Glucocorticoid therapy for enthesitisGlucocorticoids have long been used in the therapy of enthe-sitis with local injections, often providing good sympto-matic relief. Concerns about osteoporosis, which is alreadya problem in patients who have spinal enthesitis, has limited

the use of these agents in patients who have AS. However,with serial MRI to track spinal enthesitis and use of bispho-sphonates to prevent glucocorticoid-induced osteoporosis,local intralesional glucocorticoids are not precluded.147

DMARDs for enthesitisThough the efficacy of disease-modifying drugs with res-pect to inflammatory polyenthesopathies has not been dem-onstrated convincingly,148 a few small studies suggest theefficacy of MTX in entheseal-based disease.149

Bisphosphonates in enthesitisPamidronate has been shown to be efficacious in treatingAS.113

However, the inflammatory indices remained high fol-lowing therapy, suggesting the need for longitudinal MRIstudies following the spinal changes.

Biological blockade with anti-tumour necrosis factorThe TNF blockers, infliximab and etanercept, have shownstriking resolution of spinal enthesitis and osteitis in patientswho have AS and SpA.150

TREATMENT OF ANKYLOSING

SPONDYLITIS—V. SURGICAL TREATMENT

Hip surgery

Total hip replacement is indicated in AS whenever there issevere, persistent pain or severe limitation in mobility due tohip involvement. With technical advancement and refinementin surgical skills, excellent short- and long-term results arefound in patients with AS.

The proportion of prosthetic hips that did not requirerevision at 10, 15 and 20 years following surgery was 90, 78and 64%, respectively.

Heterotopic ossification following joint replacement is now an unusual and rare complication. Prophylactic ther-apy with a non-selective NSAID beginning on the day ofsurgery and perioperative radiation therapy mitigates thiscomplication.95,151–153

Spinal surgery—Atlanto axial dislocation

Cervical fusion is indicated for patients who develop at-lantoaxial subluxation with impairment in neurologic func-tion. This problem is managed in a fashion similar to that in RA. It is presently unclear whether patients without signs

Diagnosis and treatment of axial spondyloarthropathies Consensus Statement 29

of compression, but with severe subluxation (> 8 mm) orprogressive symptoms, also require surgical intervention.Patients with severe subluxation but without signs of cordcompression are at risk for severe injury and perhaps deathdue to a variety of insults. These include small falls, whiplashinjuries and intubation.

Although the subject of some controversy, stiff cervicalcollars should be prescribed for stability. Collars that arenot rigid (and therefore, more comfortable for the patient)give reassurance to both physician and patient, but providelittle structural support. Spinal manipulation is contraindi-cated. Patients with pain due to irritation of C2 nerve root,but who do not have evidence of cord compression, may ben-efit from agents used for chronic neuropathic pain. Wedgeosteotomy is indicated in those patients who develop flex-ion deformities severe enough to impair the ability to lookin a forward direction.154,155

Vertebral fractures

Patients with AS have osteopenic or osteoporotic spineseven in the early stages of disease. This makes them 3.5 timesmore likely to sustain a fracture of spine. Traumatic atlanto-axial dislocation, odontoid fractures and occipitocervicaldissociation are often seen in these patients. Traumatic spinalfractures in patients with AS are typically the result ofhyperextension injuries.

Note: The appendicies and tables are accesible in theweb version of this document at www.indianjrheumatol.com

Expert Committee: A Aggarwal (Lucknow), SN Amin(Mumbai), DS Bhakuni (New Delhi), A Chopra (Pune), BG Dharmanand (Bengaluru), A Ghosh (Kolkata), RajivaGupta (New Delhi), SJ Gupta (New Delhi), R Handa (NewDelhi), VR Joshi (Mumbai), V Krishnamurthy, A Kumar(New Delhi), U Kumar (New Delhi), KM Mahendranath(Bengaluru), RN Misra (Lucknow), K Narayanan (NewDelhi), G Narsimulu (Hyderabad), URK Rao (Hyderabad)

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