Higher levels of physical activity are associated with less evasive coping, better physical function and quality of life in patients with axial spondyloarthritis.

OBJECTIVE: To evaluate daily physical activity (PA) in relation to psychosocial factors, such as anxiety, depression and different types of coping strategies, as well as patient- and disease-related factors in patients with axial spondyloarthritis (axSpA). METHODS: Consecutive outpatients from the Groningen Leeuwarden AxSpA (GLAS) cohort completed the modified Short Questionnaire to assess health-enhancing PA (mSQUASH), Hospital Anxiety and Depression Scale (HADS) and Coping with Rheumatic Stressors (CORS) questionnaires, as well as standardized patient- and disease-related assessments. Univariable and multivariable linear regression analyses and comparison of lowest and highest PA tertiles were performed to explore associations between the HADS, CORS, patient- and disease-related factors and PA. RESULTS: In total, 84 axSpA patients were included; 60% male, mean age 49 (SD ±14) years, median symptom duration 20 (25th-75th percentiles: 12-31) years, mean ASDAS 2.1 (±1.0). Higher PA levels were significantly associated with better scores on patient-reported disease activity (BASDAI), physical function (BASFI) and quality of life (ASQoL). Furthermore, higher levels of PA were associated with less impact of axSpA on wellbeing and lower HADS depression scores. In the multivariable linear regression model, less use of the coping strategy 'decreasing activities' (ß: -376.4; p 0.003) and lower BMI (ß:-235.5; p: 0.030) were independently associated with higher level of PA. Comparison of patients from the lowest and highest PA tertiles showed results similar to those found in the regression analyses. CONCLUSION: In this cohort of axSpA patients, higher levels of daily PA were associated with better patient-reported outcomes and lower depression scores. Additionally, the passive coping strategy "decreasing activities" and lifestyle factor BMI were independently associated with PA. Besides anti-inflammatory treatment, coping strategies and lifestyle should be taken into account in the management of individual axSpA patients. Incorporating these aspects into patient education could increase patient awareness and self-efficacy. In the future, longitudinal studies are needed to better understand the complex relationship between patient-, disease- and psychosocial factors associated with daily PA.

Patients' Perspectives on Axial Pain in Relation to Inflammation and Structural Damage in a Large Cohort of Axial Spondyloarthritis Patients.

OBJECTIVE: The objective of this study was to explore to what extent patients with axial spondyloarthritis (axSpA) link experienced pain in the neck, back, and hips to inflammation and/or structural damage. METHODS: Patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort visiting the outpatient clinic between 2016 and 2019 filled out two additional questions in relation to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) question 2: (1) "To what extent do you think the pain you experience in your neck, back, and hips is related to inflammation caused by axSpA?" and (2) "To what extent do you think the pain you experience in your neck, back, and hips is related to damage of the spine and joints caused by axSpA?" Answers had to be depicted on a numeric rating scale from 0 (none) to 10 (very much); a difference of ≥2 points between the scores of these questions was considered clinically relevant in favor of the highest scoring question. RESULTS: A total of 688 patients with axSpA (24% with nonradiographic axSpA [nr-axSpA]) were included (62% male, mean ± SD age 48 ± 14 years, and mean ± SD Ankylosing Spondylitis Disease Activity Score [ASDAS] 2.3 ± 1.0). Seventy-five percent of patients could not link the origin of their pain, 15% linked axial pain predominantly to inflammation, and 10% linked axial pain predominantly to damage. Patients in the inflammation group were younger, had shorter symptom duration, were more frequently diagnosed with nr-axSpA, had higher ASDASCRP , had more often elevated CRP levels, had fewer comorbidities, had better spinal mobility, and had less spinal radiographic damage. CONCLUSION: In our large observational cohort, the majority of patients with axSpA could not differentiate the origin of experienced axial pain. If patients were able to link axial pain to clinical inflammation or damage, it was in concordance with clinical assessments and radiographic outcome, which may be helpful in establishing the origin of pain and supporting better patient-centered treatment decisions.

The Effect of Two Years of Secukinumab Treatment on Bone Metabolism in Patients with Radiographic Axial Spondyloarthritis: Results from Daily Clinical Practice.

Background: Our objective was to explore bone-related outcome and bone turnover markers (BTM) during 2 years of secukinumab treatment in patients with radiographic axial spondyloarthritis (r-axSpA) in daily clinical practice. Methods: Included were consecutive r-axSpA outpatients from the Groningen Leeuwarden axSpA (GLAS) cohort treated with secukinumab for 2 years. At baseline and 2 years, spinal radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; 0-72), cervical facet joint involvement according the "de Vlam" scoring method (0-15) and radiographic vertebral fractures (VF) using the "Genant" method (grade 0-3). At all visits, BTM reflecting collagen resorption (serum type I collagen C-telopeptide; sCTX), collagen formation (procollagen type 1 N-terminal peptide; PINP) and bone mineralization (bone-specific alkaline phosphatase; BALP) were measured and expressed in Z-scores to correct for the normal influence of age and gender. Results: 17 r-axSpA patients were included; 53% male, mean age was 47±15 years, mean Ankylosing Spondylitis Disease Activity Score (ASDAS) 3.9±1.2, and 53% was biological naïve. The median 2-year progression rates were 1.1 for mSASSS and 0.5 for facet joints, which was less than the smallest detectable change. One traumatic VF (grade 3) occurred. Serum levels of sCTX and PINP remained stable during secukinumab treatment and BALP decreased significantly after 2 years, with median 0-2 year change in Z-scores of +0.1, -0.4, and -1.2, respectively. Conclusion: This explorative study of r-axSpA patients treated with secukinumab in daily clinical practice showed low radiographic spinal progression during 2 years of follow-up. Collagen resorption and formation markers remained stable, whereas mineralization marker BALP decreased significantly after 2 years. Our results are in line with the results of in vitro studies demonstrating that inhibition of IL17-A resulted in suppression of osteogenic differentiation with significant decrease in mineralization.

Psoriasis seems often underdiagnosed in patient with axial spondyloarthritis.

BACKGROUND: Axial spondyloarthritis (axSpA) is known to be associated with several extra-skeletal manifestations (ESM), including the inflammatory skin disease psoriasis. It is important to recognize and diagnose psoriasis timely in axSpA in order to provide optimal treatment and outcome for both axSpA and psoriasis. METHODS: In this observational study, all patients from the Dutch Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort included before June 2016 were sent a questionnaire with self-screening psoriasis questions including prototypical color pictures. RESULTS: Of the 592 questionnaires sent, 448 (75.7%) were eligible for analysis. Of these 448 respondents, 58 (13%) had a positive self-screening for psoriasis symptoms, currently or in the past. In 28 (48%) of 58 patients, psoriasis diagnosis could be verified by medical records, resulting in a psoriasis prevalence rate of 6.3%. In comparison with patients with a confirmed psoriasis diagnosis, patients reporting psoriasis symptoms without a verified diagnosis mentioned more mild than moderate-severe psoriasis symptoms (25% vs. 3%, p = 0.02), and their psoriasis lesions were less often located on the torso area (3% vs. 18%, p = 0.04), the intergluteal cleft (0% vs. 25%, p = 0.02), and legs (7% vs. 43%, p < 0.01). Of the 31 axSpA patients who reported currently active psoriasis, 74% had only mild psoriasis symptoms. CONCLUSIONS: Especially mild psoriasis seems often underdiagnosed in patients with axSpA using a patient questionnaire with prototypical pictures of psoriasis lesions. This questionnaire could be beneficial in tracing patients with undiagnosed psoriasis in daily clinical practice. As a next step, further validation of this questionnaire is needed.

Patients' Needs Concerning Patient Education in Axial Spondyloarthritis: A Qualitative Study.

INTRODUCTION: Within the EULAR recommendations, patient education (PE) is stated as the basis of the management of axial spondyloarthritis (axSpA). However, educational needs are scarcely qualitatively studied in axSpA. Therefore, we aimed to explore experiences and needs of PE in patients with axSpA. METHODS: A phenomenological approach was used, with semi-structured in-depth interviews with patients with axSpA including broad variation in characteristics. Thematic analysis was applied. To enhance credibility, data saturation, research triangulation, peer debriefing, member checking, theoretical notes, and bracketing were performed. RESULTS: Three interrelated themes regarding PE were identified from 20 interviews: illness perception, content, and 'availability'. Illness perception affects how patients experience and process PE, which consequently influences coping strategies. Prognosis, treatment, and coaching to self-management were identified as the most important content of PE. Regarding 'availability', face-to-face PE is preferred for exploring needs, supplemented by self-education, which can be freely applied. Additionally, sufficient time and a comprehensible amount of information were important and participants emphasized the need for axSpA-tailored information for relatives and friends. Participants reported a trusting patient-healthcare provider (HCP) relationship, and multidisciplinary and interdisciplinary attunement between HCPs as prerequisites for effective PE. CONCLUSIONS: This first qualitative study exploring patients' experiences and needs of PE in axSpA revealed that prognosis, treatment, and coaching to self-management are important regarding content, and the combination of face-to-face contact and self-education the preferred modalities. It seems essential that patients' illness perceptions are taken into account for effective PE. These results add relevant insights for future PE guidelines in axSpA.

[Whipple's disease, a non-rheumatoid cause of seronegative arthritis]. / De ziekte van Whipple, een niet-reumatische oorzaak van seronegatieve artritis.

BACKGROUND: In 15-25% of patients with rheumatoid arthritis, the presence of pathognomonic autoantibodies (anti-citrullinated protein (aCCP) or rheumafactor (RF) is lacking. In these cases of seronegative rheumatoid arthritis, diagnosis is based on clinical presentation. However, some of the patients with seronegative rheumatoid arthritis are misdiagnosed. CASE DESCRIPTION: Here we discuss a case of a 64 year old female, with a diagnoses of seronegative rheumatoid arthritis for 18 years. Although extensively treated with immunosuppressive medication, she did not reach remission. After second opinion in our hospital we diagnosed Whipple's disease. CONCLUSION: This case report illustrates the importance of a broad differential diagnosis of seronegative arthritis as well as the importance of re-assessment of patients diagnosed with seronegative rheumatoid arthritis, who do not reach remission upon immunosuppressive treatment.

[Whipple's disease, a non-rheumatoid cause of seronegative arthritis]. / De ziekte van Whipple, een niet-reumatische oorzaak van seronegatieve artritis.

BACKGROUND: In 15-25% of patients with rheumatoid arthritis, the presence of pathognomonic autoantibodies (anti-citrullinated protein (aCCP) or rheumafactor (RF) is lacking. In these cases of seronegative rheumatoid arthritis, diagnosis is based on clinical presentation. However, some of the patients with seronegative rheumatoid arthritis are misdiagnosed. CASE DESCRIPTION: Here we discuss a case of a 64 year old female, with a diagnoses of seronegative rheumatoid arthritis for 18 years. Although extensively treated with immunosuppressive medication, she did not reach remission. After second opinion in our hospital we diagnosed Whipple's disease. CONCLUSION: This case report illustrates the importance of a broad differential diagnosis of seronegative arthritis as well as the importance of re-assessment of patients diagnosed with seronegative rheumatoid arthritis, who do not reach remission upon immunosuppressive treatment.

[An atypical presentation of tuberculosis]. / Een atypische presentatie van tuberculose.

BACKGROUND: In 2020 there were 623 known TB infections in the Netherlands according to the Dutch ministry of health (RIVM). About 4% were located in bones and joints. The incidence of Multi Drug Resistant (MDR) TB in The Netherlands is about 1%. CASE: We describe the case of a 46-year-old female with a painful and swelling of the mid phalangeal bone of the fourth left digit. Quantiferon was positive and PCR of the biopsy for Mycobacterium tuberculosis complex (MTC) in Ziehl-Neelsen staining confirmed tuberculous osteomyelitis. The strain was resistant for rifampicin, isoniazid, ethambutol and pyrazinamid classifying it as MDR. Treatment in a specialized center with second line drugs was indicated due to rare resistance. CONCLUSION: Tuberculosis may manifest anywhere throughout the body, also as an (atypical) swelling of the hand. The golden diagnostic standard for bone and joint TB is biopsy with Ziehl-Neelsen staining.

Baseline serum biomarkers of inflammation, bone turnover and adipokines predict spinal radiographic progression in ankylosing spondylitis patients on TNF inhibitor therapy.

OBJECTIVE: To analyze whether biomarker levels at baseline or their change after 3 months or 2 years predict radiographic spinal progression in ankylosing spondylitis (AS) patients treated with TNF-α inhibitors (TNFi). METHODS: 137 AS patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included before starting TNFi. Serum biomarkers were measured at baseline, 3 months and 2 years: Markers of inflammation (calprotectin, matrix metalloproteinase-3, vascular endothelial growth factor), bone turnover markers (bone-specific alkaline phosphatase, serum C-terminal telopeptide fragments of type I collagen (sCTX), osteocalcin, osteoprotegerin, procollagen type I and II N-terminal propeptide, sclerostin) and adipokines (high-molecular-weight adiponectin, leptin, visfatin). Spinal radiographs were scored at baseline, 2 and 4 years. Logistic regression was performed to examine the association between biomarker values and radiographic spinal progression, adjusting for known risk factors for radiographic progression. RESULTS: Baseline calprotectin and visfatin levels were associated with mSASSS progression ≥2 points (OR 1.195 [95%CI 1.055-1.355] and 1.465 [1.137-1.889], respectively), while calprotectin was also associated with new syndesmophyte formation after 2 years (OR 1.107 [1.001-1.225]). Baseline leptin level was associated with mSASSS progression ≥4 points after 4 years (OR 0.614 [0.453-0.832]), and baseline sCTX level with syndesmophyte formation after 4 years (OR 1.004 [1.001-1.008]). Furthermore, change of visfatin and leptin levels over the first 2 years showed significant association with radiographic progression after 4 years. CONCLUSION: Independent of known risk factors, serum levels of biomarkers at baseline are able to predict radiographic spinal progression over 2 and 4 years in AS patients on TNFi therapy.

Central sensitization has major impact on quality of life in patients with axial spondyloarthritis.

INTRODUCTION: Persistent pain has large potential impact on quality of life (QoL). During the course of the disease, many patients with axial spondyloarthritis (axSpA) report persistent pain. Central sensitization (CS) may explain part of this chronic pain. However, the role of CS in relation to QoL has been sparsely studied in axSpA. Therefore, our aim was to explore the relationship between CS and QoL in patients with axSpA. METHODS: Consecutive outpatients from the Groningen Leeuwarden axSpA (GLAS) cohort completed the Central Sensitization Inventory (CSI; range 0-100) and the AS Quality of Life (ASQoL; range 0-18). Multivariable linear regression analysis was used to explore the relationship between CSI and ASQoL scores correcting for potential confounders. RESULTS: Of the 178 included axSpA patients, mean CSI score was 38.0 ± 14.1 and 45% scored ≥40, which indicates a high probability of CS. Mean ASQoL score was 6.0 ± 5.3 and mean ASDASCRP 2.1 ± 1.0. A CSI score ≥40 was significantly associated with higher ASQoL score (mean 9.7 vs. 3.3), higher ASDASCRP (mean 2.6 vs. 1.7), female gender (60% vs. 29%) and more often entheseal involvement (61% vs. 26%). In univariable analysis, CSI score explained a large proportion of the variation in ASQoL (B = 0.06, 95%CI: 0.05-0.07; R2=0.46). This association remained significant after correction for ASDASCRP, gender, entheseal involvement, comorbidities, symptom duration, smoking status, BMI class and educational level (B = 0.04, 95%CI: 0.03-0.05). CONCLUSION: CS is strongly related to patient-reported QoL in patients with axSpA independently from other patient- and disease-related aspects.

Optical imaging compared to clinical examination in 484 rheumatoid arthritis patients: the Leeuwarden Handscan Registry.

The Handscan is a novel objective optical imaging device for disease follow-up and management in rheumatoid arthritis patients. We aim to examine the association between the baseline outcomes of the Handscan, disease activity levels and joint swelling. The Handscan measures differences in laser light absorption between joints of fingers and wrists and adjacent reference tissue, indicating the presence or absence of inflammation. The device gives an optical spectral transmission (OST) index per joint. The average of these indices is represented in the total optical score (TOS). Associations between TOS and DAS28 at subject level and OST and swelling at joint level were examined. 484 RA patients were included. Compared to patients with high disease activity (defined by DAS28), TOS was significantly lower in patients with moderate (estimated coefficient B: - 7.09, P < 0.001), low disease activity (B: - 6.99, P < 0.001) and patients in remission (B: - 7.72, P < 0.001) but could not distinguish between the latter three disease states. TOS was significantly lower in females (B: - 3.2, P < 0.001). OST was significantly higher in swollen than non-swollen joints (B: 0.28, P < 0.001). TOS was significantly higher in patients with high disease activity than in those in remission or with low and moderate disease activity. The difference in TOS between males and females should be accounted for in the interpretation of this outcome. The OST at joint level discriminates swollen from non-swollen joints and could be a more promising tool than the overall optical activity reflected in TOS.

Extraskeletal Manifestations in Axial Spondyloarthritis Are Associated With Worse Clinical Outcomes Despite the Use of Tumor Necrosis Factor Inhibitor Therapy.

OBJECTIVE: To investigate the prevalence and 4-year incidence of acute anterior uveitis (AAU), inflammatory bowel disease (IBD) and psoriasis (PsO), and to explore associations of newly developed extraskeletal manifestations (ESMs) with clinical disease outcome in a large cohort of patients with axial spondyloarthritis (axSpA). METHODS: All consecutive patients included in the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort between 2004 and 2011 were analyzed. History of ESMs at baseline and newly developed ESMs during 4-year follow-up were only recorded when diagnosis by an ophthalmologist, gastroenterologist, or dermatologist was present. RESULTS: Of the 414 included patients with axSpA, 31.4% had a positive history of ≥ 1 ESMs: 24.9% AAU, 9.4% IBD, and 4.3% PsO. History of PsO was significantly associated with more radiographic damage, especially of the cervical spine. Of the 362 patients with 4-year follow-up data, 15.7% patients developed an ESM: 13.3% patients had AAU (of which 3.6% had a first episode and 9.7% had recurrent AAU), 1.9% developed IBD, and 0.8% developed PsO. Patients with newly developed ESMs (without history of ESMs) had worse Ankylosing Spondylitis Quality of Life scores (mean 10.0 vs. 5.8, P = 0.001), larger occiput-wall distance (median 6.3 vs. 2.0, P = 0.02) and more limited modified Schober test (mean 12.6 vs. 13.6, P = 0.01) after 4 years of follow-up. The majority of patients developing an ESM used anti-tumor necrosis factor therapy. CONCLUSION: History of ESMs was present at baseline in one-third of patients with axSpA. The 4-year incidence of ESMs was relatively low, but patients who developed a new ESM reported worse quality of life.

Change in disease activity is associated with TNF-α inhibitor serum levels in patients with axial spondyloarthritis in daily clinical practice.

OBJECTIVES: To investigate, in daily clinical practice, TNF-α inhibitor serum trough levels in patients experiencing an increase in axial spondyloarthritis (ax-SpA) related symptoms. Secondly, to explore if these serum trough levels are associated with disease activity (DA) and/or change in DA. METHODS: Patients from the GLAS cohort treated with TNF-α inhibitors who had a serum trough level measurement during follow-up because of an increase in ax-SpA related symptoms between June 2015 and June 2018 were included. Serum trough levels were stratified in a therapeutic and below therapeutic range, based on published reference values of Sanquin in 2019. DA was assessed by ASDAS and BASDAI and change in DA (i.e. ΔASDAS or BASDAI compared to the visit before increasing symptoms). RESULTS: 31 patients had a serum trough level measurement because of increasing symptoms. These patients had a median treatment duration of 4.8 years (IQR 0.9-8.6). 22 (71%) had active disease according to ASDAS (score ≥2.1) and 15 (47%) had therapeutic drug levels. The increase in DA was significantly larger in patients with below therapeutic drug levels compared to patients with therapeutic levels (ΔASDAS: 0.94±0.81 vs. -0.07±1.26, p<0.05; ΔBASDAI: 1.72±1.73 vs. -0.53±1.8, p<0.005). No significant differences were found in absolute DA scores between patients with or without therapeutic drug levels. CONCLUSIONS: In this observational study in daily clinical practice, approximately half of ax-SpA patients who experienced an increase in symptoms had below therapeutic TNF-α inhibitor serum trough levels. Change in DA and not absolute DA scores was significantly associated with drug levels.

The mSQUASH; a valid, reliable and responsive questionnaire for daily physical activity in patients with axial spondyloarthritis.

AIM: Adaptation of the Short QUestionnaire to Assess Health-enhancing physical activity (SQUASH) in order to improve measurement properties in axSpA patients. METHODS: The original SQUASH was adapted using a qualitative stepwise approach with in-depth interviews including healthcare professionals and patients. Content validity was explored by comparing modified-SQUASH (mSQUASH) and original SQUASH. Next, mSQUASH was validated according to the OMERACT filter. International Physical Activity Questionnaire (IPAQ) was used as comparator and tri-axial accelerometer as gold standard for criterion validity and classification accuracy of intensity. Construct validity was assessed using Spearman correlations with clinical outcome assessments. For test-retest reliability, intra-class correlation coefficients (ICCs) were calculated. Responsiveness was assessed using standardized response mean (SRM), stratified by Anchor method. RESULTS: The mSQUASH measured a systematically higher activity count and had less missing values (8% vs. 16%) then SQUASH. mSQUASH correlated better with accelerometer compared to IPAQ (ρ = 0.60 vs. ρ = 0.34). Accelerometer measured most activity in light intensity, whereas mSQUASH and IPAQ predominately measured moderate intensity. Correlations with ASDAS, BASDAI, BASFI and ASQoL were better for mSQUASH then IPAQ. Test-retest reliability was good in both questionnaires. In contrast to IPAQ, responsiveness was in correspondence with self-reported changes in physical activity for mSQUASH (SRM -0.84 for improvement and 0.88 for decrease). The average completion time of the mSQUASH was 7 minutes. CONCLUSIONS: The development of the mSQUASH resulted in an easy applicable, valid, reliable and responsive questionnaire for the assessment of daily physical activity in axSpA patients, which can be used in research and daily clinical practice.

Central sensitization, illness perception and obesity should be considered when interpreting disease activity in axial spondyloarthritis.

OBJECTIVES: Many patients with axial spondyloarthritis (axSpA) report persistent pain even when treated with anti-inflammatory agents. Our aim was to explore the presence of central sensitization (CS) and different types of illness perceptions in patients with axSpA, and to assess their associations with disease activity assessments. METHODS: Consecutive outpatients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort were included. Besides standardized assessments, patients filled out the Central Sensitization Inventory (CSI), Illness Perception Questionnaire (IPQ-R) and Pain Catastrophizing Scale (PCS). Univariable and multivariable linear regression analyses were used to investigate the association between questionnaire scores, patient characteristics and disease activity assessments ASDASCRP, BASDAI and CRP. RESULTS: We included 182 patients with a mean symptom duration of 21.6 years. Mean ASDASCRP was 2.1, mean BASDAI 3.9, and median CRP 2.9. Mean CSI score was 37.8 (scale 0-100) and 45% of patients scored ≥40, indicating a high probability of CS. CSI score, IPQ-R domain identity (number of symptoms the patient attributes to their illness), and IPQ-R domain treatment control (perceived treatment efficacy), and obesity were significantly and independently associated with both ASDASCRP and BASDAI, explaining a substantial proportion of variation in these disease activity scores (R2=0.35 and R2=0.47, respectively). Only obesity was also independently associated with CRP. CONCLUSION: CS may be common in patients with long-term axSpA. CS, as well as specific illness perceptions and obesity were all independently associated with the widely used (partially) patient-reported disease activity assessments ASDASCRP and BASDAI. Treating physicians should take this into account in the follow-up and treatment of their patients.

Bone mineral density improves during 2 years of treatment with bisphosphonates in patients with ankylosing spondylitis.

AIMS: To evaluate whether 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements has an effect on lumbar spine and hip bone mineral density (BMD) in ankylosing spondylitis (AS) patients starting tumour necrosis factor-α inhibitors or receiving conventional treatment. Secondly, to explore the development of radiographic vertebral fractures. METHODS: Patients from the Groningen Leeuwarden AS cohort receiving bisphosphonates based on clinical indication and available 2-year follow-up BMD measurements were included. BMD of lumbar spine (L1-L4) and hip (total proximal femur) were measured using dual-energy X-ray absorptiometry. Spinal radiographs (Th4-L4) were scored for vertebral fractures according to the Genant method. RESULTS: In the 20 included patients (median 52 years, 14 males), lumbar spine and hip BMD Z-scores increased significantly; median from -1.5 (interquartile range [IQR] -2.2 to 0.4) to 0.1 (IQR -1.5 to 1.0); P < .001 and median from -1.0 (IQR -1.6 to -0.7) to -0.8 (IQR -1.2 to 0.0); P = .006 over 2 years, respectively. In patients also treated with tumour necrosis factor-α inhibitors (n = 11), lumbar spine and hip BMD increased significantly (median 2-year change +8.6% [IQR 2.4 to 19.6; P = .009] and +3.6% [IQR 0.7-9.0; P = .007]). In patients on conventional treatment (n = 9), lumbar spine BMD increased significantly (median 2-year change +3.6%; IQR 0.7 to 9.0; P = .011) and no improvement was seen in hip BMD (median -0.6%; IQR -3.1 to 5.1; P = .61). Overall, younger AS males with limited spinal radiographic damage showed most improvement in lumbar spine BMD. Four mild radiographic vertebral fractures developed in 3 patients and 1 fracture increased from mild to moderate over 2 years in postmenopausal women and middle-aged men. CONCLUSION: This explorative observational cohort study in AS showed that 2 years of treatment with bisphosphonates in combination with calcium/vitamin D supplements significantly improves lumbar spine BMD. Mild radiographic vertebral fractures still occurred.

High prevalence of hip involvement and decrease in inflammatory ultrasound lesions during tumour necrosis factor-α blocking therapy in ankylosing spondylitis.

OBJECTIVES: To assess the prevalence of clinical, US and radiographic hip involvement in AS patients with active disease and to explore the associations between these assessments. Furthermore, to evaluate the effect of 6 months of TNF-α blocking therapy on tender and inflammatory power Doppler US lesions of hip joints. METHODS: Consecutive AS patients starting TNF-α blocking therapy were evaluated for hip joint involvement. At baseline, patient-reported history of hip involvement was assessed and radiographic evaluation (BASRI-hip) was performed. Clinical examination (tender hip joints) and US examination took place before and after 6 months of treatment. RESULTS: Of the 111 included patients, 20% reported a history of hip involvement. At baseline, tender hip joints were present in 23% of patients. US examination showed inflammatory lesions in 17% of patients, of which 74% had positive power Doppler. Structural lesions were present in 20% of patients, of which 55% had osteophytes. Structural radiographic damage was seen in 10% of patients. Highest concordance was found between history of hip involvement and radiographic hip involvement (phi coefficient 0.333). After 6 months of TNF-α blocking therapy, significant decrease was found in tender hip joints (from 29 to 11), total number of inflammatory US lesions (from 29 to 9) and positive power Doppler (from 22 to 6). CONCLUSION: The prevalence rate of hip involvement in AS patients varies from 10 to 23%, depending on the type of hip assessment. TNF-α blocking therapy significantly improved tender hip joints, and inflammatory US lesions including positive power Doppler.

High prevalence of hidradenitis suppurativa symptoms in axial spondyloarthritis patients: A possible new extra-articular manifestation.

BACKGROUND: Spondyloarthritis (SpA), a chronic inflammatory, rheumatic disease, and hidradenitis suppurativa (HS), a chronic, debilitating, inflammatory skin disease, share several clinical and pathophysiological features, such as the association with inflammatory bowel disease and elevated cytokine levels IL-17 and TNF-α. Recently, SpA was reported to be more prevalent (2.3-28.2%) in patients with HS than in the general population. Conversely, the prevalence of HS in SpA is not exactly known. OBJECTIVE: To determine the prevalence of HS in patients with axial SpA, a subtype of SpA primarily of the axial skeleton. Secondly, to identify patient characteristics associated with the presence of HS in axial SpA. METHODS: In this cross-sectional study, a self-screening questionnaire based on validated diagnostic HS questions was sent to all participating axial SpA patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort fulfilling the ASAS axial SpA criteria. Self-reported HS symptoms were confirmed by previous medical diagnosis or verification by phone using highly specific validated questions. RESULTS: In total, 75.6% (449/592) questionnaires were eligible for analyses. Included patients had a mean age of 50 ± 13 years, 64% was male, mean symptom duration was 23 ± 13 years, and 79% was HLA-B27 positive. HS diagnosis could be confirmed in 41 patients, resulting in an estimated prevalence of 9.1%. In comparison to patients without a positive history of HS, these patients were more often female (54% vs. 35%, P = 0.02), showed higher axial SpA disease activity (mean BASDAI 4.5 vs. 3.6, p = 0.01 and ASDASCRP 2.6 vs. 2.2, P = 0.003) and worse quality of life (QoL) (median ASQoL 9.0 vs. 4.0, P < 0.001). Also, a history of heel enthesitis and dactylitis was more prevalent (34% vs. 19%, P = 0.03 and 15% vs. 6%, P = 0.05, respectively). Multivariable analysis showed that a higher score on ASDAS was independently associated with HS (OR: 1.639, 95% CI: 1.176-2.284). CONCLUSION: In our cohort of axial SpA patients, HS is more prevalent than in the general population (9.1% versus 0.053-4.1%). HS is associated with female gender, lower QoL, and especially higher axial SpA disease activity.

Although female patients with ankylosing spondylitis score worse on disease activity than male patients and improvement in disease activity is comparable, male patients show more radiographic progression during treatment with TNF-α inhibitors.

BACKGROUND: The clinical presentation of ankylosing spondylitis (AS) differs between genders. Our aim was to investigate differences in disease activity, disease outcome and treatment response between male and female AS patients before and after starting tumor necrosis factor (TNF)-α inhibitors in daily clinical practice. METHODS: Patients from the Groningen Leeuwarden AS (GLAS) cohort who started TNF-α inhibitors and who had visits at baseline and after 3 months and/or 2years of follow-up were included. RESULTS: Of 254 included AS patients, 69% were male. At baseline, female patients scored significantly higher on BASDAI, ASDAS, and tender entheses than male patients. In contrast, CRP, swollen joints, and history of extra-articular manifestations were comparable between genders. Women experienced significantly worse physical function and QoL, whereas men showed significantly more kyphosis and spinal radiographic damage. After 3 months and 2years of follow-up, all clinical assessments improved significantly, with comparable mean change scores for female and male patients; mean 2-year change in BASDAI -2.7 vs. -2.7, ASDAS -1.50 vs. -1.68, tender entheses -2.4 vs. -1.4, CRP -8 vs. -8, BASFI -2.2 vs. -2.1 and ASQoL -5 vs. -4, respectively. Radiographic progression was significantly higher in male patients. Female patients switched more frequently to another TNF-α inhibitor during 2years of follow-up (32% vs. 14%). CONCLUSION: Although female patients experienced higher disease activity, worse physical function and quality of life, and switched TNF-α inhibitors more often, clinical improvement during treatment with TNF-α inhibitors was comparable between genders. However, male patients showed more radiographic spinal damage after 2years.