Clinical and genetic associations of radiographic sacroiliitis and its different patterns in psoriatic arthritis M. Haroon1,2, R. Winchester3, J.T. Giles3, E. Heffernan4, O. FitzGerald1 1Department of Rheumatology, St Vincent’s University Hospital, Dublin, Ireland; 2Division of Rheumatology, Department of Medicine, University Hospital Kerry, Ireland; 3Division of Rheumatology, Columbia University, College of Physicians and Surgeons, New York, USA; 4Department of Diagnostic Imaging, St Vincent’s University Hospital, Dublin, Ireland. Abstract Objective We aimed to 1) identify clinical and genetic associations of sacroiliitis (SI) in patients with psoriatic arthritis (PsA), and 2) describe the different radiographic patterns of SI in PsA and their clinical and genetic associations. Methods 283 PsA patients, fulflling CASPAR criteria, underwent detailed skin and rheumatologic assessments. In addition, HLA-B*27 and B*080101 status was recorded, which have been shown as the key genetic markers of radiographic SI in PsA. Grade 2 Unilateral or bilateral radiographic changes of SI were required for inclusion and involvement was further defned as asymmetrical or symmetrical. Results 70 patients (25%) had radiographic SI; all either with a present or past history of backache. Regression analysis demonstrated a signifcant association of SI with peripheral joint erosions (p=0.043), PASI maximum (p=0.041), younger age of PsA onset (p=<0.001), presence of HLA-B*0801 (p=0.002) and only marginal signifcance with HLA-B*2705 (p=0.059). Asymmetrical SI was noted in 51 patients (73%). In striking contrast to those patients with symmetrical SI, patients with asymmetrical SI were more likely to be female (p=0.04), have a trend towards more severe nail disease (p=0.08) and peripheral joint erosions (p=0.08), more osteolysis (p=0.01), more HLA-B*0801 positivity (p=0.001) and much less HLA-B*270502 positivity (p=<0.001). Conclusion PsA developing at a younger age, severe skin disease, peripheral joint erosions, and HLA-B*0801 are signifcantly associated with SI, and there was only a marginal trend towards signifcance for HLA-B*2705. HLA-B*27 positive Axial-PsA patients resemble AS, while HLA-B*0801 positive Axial-PsA patients have asymmetrical and/or unilateral SI, which are typical of PsA. Key words psoriatic arthritis, HLA alleles, susceptibility, phenotype Clinical and Experimental Rheumatology 2017; 35: 270-276. Radiographic sacroiliitis in psoriatic arthritis / M. Haroon et al. Muhammad Haroon, MB, MMedSc, Introduction commonest susceptibility locus for the MRCPI, PhD Psoriatic arthritis (PsA) is a progres- development of SI among patients with Robert Winchester, MD sive, potentially destructive and disa- PsA (14, 20). It has been shown recent- Jon T Giles, MD, MPH bling immune-mediated infammatory ly that certain HLA genes are associat- Eric Heffernan, MBBCh, FFRRCSI joint disease. There are varied reports ed with particular clinical features that Oliver FitzGerald, MD, FRCPI, FRCP (UK) of its prevalence among patients with collectively defne the PsA phenotype Please address correspondence to: psoriasis (PsO), and it is becoming of a given patient, and, importantly, Dr Muhammad Haroon, clear that PsA is much more common that HLA-B*27 and HLA-B*0801 are Division of Rheumatology, than previously thought. We have associated with different radiographic Department of Medicine, University Hospital Kerry, recently shown that 29% of PsO pa- patterns of SI in patients with PsA(21). Tralee, Co. Kerry, Ireland. tients attending dermatology clinics The objectives of our study were: 1) to E-mail: [email protected] had undiagnosed PsA (1). PsA is char- investigate the genetic and clinical as- Received on April 12, 2016; accepted in acterised by involvement of both the sociations of radiographic SI amongst revised form on September 7, 2016. appendicular and axial skeleton. The an ethnically homogenous consecu- © Copyright CLINICAL AND question whether infammatory axial tive cohort of established PsA; and 2) EXPERIMENTAL RHEUMATOLOGY 2017. disease and PsO represent ankylos- to describe the different radiographic ing spondylitis with PsO, or a subset patterns of SI in PsA and their associa- of PsA named axial PsA (AxPsA), re- tions, if any, with clinical and genetic mains a subject of debate. A number of characteristics. studies have suggested that there are clinical, radiologic, and genetic dif- Methods ferences between AxPsA and AS, sug- All patients who were included in both gesting that these are distinct entities discovery and validation cohorts of our (2-4). Similarly, recent studies examin- earlier genetics study were invited for ing typical AS-associated genetic risks prospective evaluation. In that earlier in AxPsA have largely been negative, study, we performed detailed character- further supporting the theory that spi- isation and quantifcation of genotypes nal involvement in PsA is genetically of PsA patients belonging to a genetical- different from that seen in AS (5). ly relatively homogeneous population. It is common that patients with pe- Of 359 patients (discovery cohort=197, ripheral arthritis have concomitant validation cohort=162), we were able infammatory axial disease, but iso- to approach and assess 283 patients; lated infammatory axial disease oc- the rest of patients either had relocated curs in less than 5% of PsA patients with changed personal contact details, (6). The reported prevalence of axial or they died in the intervening years. disease in patients with PsA is quite All these patients (n=283) fulflled the variable (7-9). Bilateral sacroiliitis is internationally agreed CASPAR criteria more common in PsA than unilateral (Criteria of the ClASsifcation of Psori- involvement (10, 11), but sacroiliitis atic ARthritis), and underwent detailed frequently tends to be asymmetrical. prospective evaluation with the asses- Little is known about the clinical and sors blinded to the previously reported genetic potential predictors of sacroilii- HLA typing results and clinical data. tis, especially regarding the underlying Following informed consent, patients patient’s characteristics, and the corre- underwent a detailed skin and rheuma- lation with skin disease (12-15). HLA- tologic assessment including disease B*27 is a known key genetic risk factor activity measures. For skin psoriasis, for idiopathic AS; however, its con- the extent and severity of skin psoria- tribution towards the development of sis was assessed by the Psoriasis Area axial involvement in PsA remains de- and Severity Index (PASI), which is the batable. Some studies have shown that most widely used tool for the measure- Competing interests: M. Haroon received HLA-B*27 is an important susceptibil- ment of severity of psoriasis. Moreo- an unrestricted educational grant from ity locus for AxPsA (12, 16-17), how- ver, we also measured body surface Abbvie; O. FitzGerald has received ever, other studies, interestingly, have area (BSA) to estimate the extent of honoraria and grant support and has been a member of advisory boards for Pfzer, not agreed with these fndings (18, 19). skin disease. For PsA, physical exami- Abbvie, MSD, Roche, UCB, Janssen and We have shown previously that 37% nation included recording the number Cellgene; the other co-authors have of PsA patients have the HLA-B*0801 of tender and swollen joints using the declared no competing interests. allele, which was also noted to be the 68 tender/66 swollen joint counts, the 271 Radiographic sacroiliitis in psoriatic arthritis / M. Haroon et al. presence of dactylitis, the presence of in this cohort (n=283), since patients sion was performed with signifcance enthesitis using Leeds enthesitis Index, were assessed in a dedicated research set at 5%, resulting in a fnal model. as well as the number of permanently clinic where all above mentioned clini- Intraclass correlation (ICC) coeffcient deformed joints. Clinically deformed cal, laboratory and radiographic details was performed to determine inter-rater joints were defned as the presence of were collected. X-rays of SI joints reliability of radiographic scores of SI. fxed deformities, fail joints, fused were obtained prospectively on the day joints, and surgically replaced joints of assessment in research clinic. Results (22). Additionally, prior usage of In daily practice, PsA patients can be A consecutive cohort of 283 PsA pa- DMARDs, psoriatic disease requiring diagnosed as having AxPsA based on tients [mean age 54.6±12 years; 52% TNF-inhibitors (TNFi), the Bath An- the presence of infammatory back female; mean PsA duration of 19±9 kylosing Spondylitis Disease Activity pain, which we believe has borderline years; 44.5% with radiographic periph- Index (BASDAI) and Bath Ankylosing sensitivity and specifcity (23, 24). We eral joint erosions; 8% with arthritis Spondylitis Functional Index (BASFI), therefore used radiographic evidence mutilans; 60% of patients requiring Ankylosing Spondylitis Quality of Life of SI to defne axial disease, since this TNFi for PsA] was studied. Twenty- questionnaire (ASQoL) were used to is less subjective, more reproducible fve percent (70/283) of the cohort had measure disease severity, activity and and has relatively better inter-assessor radiographic SI, and all patients with functional ability. Infammatory mark- agreement. Dedicated radiographic radiographic SI had either present or ers (CRP: C-reactive protein and ESR: sacroiliac joint views were obtained. past history of backache. We could not erythrocyte sedimentation