Is the impact of biologic agents in enteropathic spondylitis different from other spondylitis? Real life data from the HUR-BIO Registry.

OBJECTIVES: To compare enteropathic spondylitis (ES) with psoriatic spondylitis (PS) and ankylosing spondylitis (AS), in patients on biological disease-modifying anti-rheumatic drug (bDMARD) treatment. METHODS: Patients who were enrolled in the HUR-BIO registry were included. ES patients were considered as the main study group; AS and PS patients were included as the control groups. ES was defined as patients with inflammatory bowel disease (IBD) having inflammatory back pain/spine symptoms plus radiological sacroiliitis. RESULTS: Sixty-four ES patients (46.9% female), 128 AS patients (39.1% female), and 92 PS patients (62% female) were analysed. Baseline erythrocyte sedimentation rate (ESR) was significantly higher in the ES group than in the AS group. Both the baseline ESR and C-reactive protein were also higher in the ES group compared with the PS group. Among the first bDMARD use, infliximab use was higher in the ES group than the other groups. There was a marginal significant difference between the SpA subgroups in the retention rates of the first bDMARDs (log-rank, p=0.059). Ulcerative colitis was a significant predictor for switching of bDMARDs in comparison to Crohn's disease. Regarding the treatment responses, no significant differences were relevant for the three groups in terms of 50% improvement of the initial Bath Ankylosing Spondylitis Disease Activity Index score, the Assessment of Spondyloarthritis International Society partial remission score, and 20% improvement of ASAS score. CONCLUSIONS: A large majority of enteropathic spondyloarthritis patients on bDMARD treatment had radiographic sacroiliitis. ES patients had distinctive features that distinguish them from AS and PS patients.

Pulmonary manifestations of antiphospholipid syndrome: a retrospective analysis of 67 patients.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and/ or venous thrombosis accompanied by persistently elevated levels of antiphospholipid antibodies (aPLs). The aim of this study is to evaluate the pulmonary manifestations of APS and compare the levels of aPLs in patients with and without pulmonary involvement. We retrospectively reviewed the files of patients with the diagnosis of APS between October 2010 and May 2017. Demographic data, clinical, radiological and laboratory findings were recorded. The study included 67 patients (56 female/11 male) with a mean age of 39 ± 13 years. Pulmonary manifestations such as parenchymal and/or vascular involvement were seen in 12 (17.9%) patients. The patients with and without pulmonary manifestations were not significantly different in terms of age (p = 0.46), comorbidities (p = 0.48) and APS duration (p = 0.66). Acute pulmonary thromboembolism (PE) was determined in 11 (16.4%), alveolar hemorrhage in 2 (3%) patients. Four patients with acute PE (36%) developed chronic thromboembolic pulmonary hypertension (CTEPH). One patient developed both CTEPH and diffuse alveolar hemorrhage after acute PE during follow up. Antiphosholipid antibody IgM was highly positive in patients with PE compared to patients without PE (p = 0.005). Other antibodies and lupus anticoagulant were not significantly different in patients with and without PE. None of the patients were deceased due to pulmonary manifestations of APS. PE was the most common pulmonary manifestation of APS. The development of CTEPH was high among APS patients. Patients with APS should be closely followed for the onset of PE and CTEPH.

Rituximab Experience in Patients With Long-standing Systemic Sclerosis-Associated Interstitial Lung Disease: A Series of 14 Patients.

OBJECTIVES: The objective of this study was to report the experience with rituximab treatment in a case series of patients with long-standing systemic sclerosis-associated interstitial lung disease (SSc-ILD). METHODS: We reviewed the charts of 197 SSc patients. Fourteen patients who received rituximab for SSc-ILD participated in this analysis. Pulmonary function tests, high-resolution thorax computed tomography and modified Rodnan skin scores were evaluated at baseline and end of the follow-up. RESULTS: Median age was 53.2 years (interquartile range, 46.8-55.5 years), and median disease duration was 9.1 years (interquartile range, 5.1-13.6 years). At the end of median follow-up (15 months), although the median forced vital capacity value increased compared with baseline, the change was not statistically significant (52.5 vs. 58.0, P = 0.065). Forced vital capacity was improved in 4 patients and stabilized in 10 patients. High-resolution computed tomography was stable in 7 patients and worsened in 3 patients. Modified Rodnan skin scores remained stable at the end of follow-up (8.0 vs. 6.0, P = 0.6). CONCLUSIONS: The improvement or stabilization of pulmonary disease was observed in most SSc patients with longer disease duration and worse pulmonary function. Rituximab might be useful in this patient group who is resistant to conventional immunosuppressive treatments.

How did the updated hemodynamic definitions affect the frequency of pulmonary hypertension in patients with systemic sclerosis?

OBJECTIVE: Pulmonary hypertension (PH) is a one of the major causes of death in patients with systemic sclerosis (SSc). In this study, we investigated the impact of updated hemodynamic definition proposed by the 6th PH World Symposium (6th WSPH) on the frequency of PH and its subtypes in patients with SSc. METHODS: Patients with SSc admitted between 2015 and 2019 and who underwent right heart catheterization (RHC) were included. The frequency of PH and its subgroups based on the hemodynamic definitions of both 2015 European Society of Cardiology/European respiratory Society (ESC/ERS) PH guidelines and 6th WSPH was compared. RESULTS: Of the 65 patients with SSc, 23 (35.4%) had normal mean pulmonary arterial pressure (mPAP), 20 (30.8%) had mildly elevated mPAP (21-24 mm Hg), and 22 (33.8%) had PH [pulmonary arterial hypertension (PAH) (n=16, 24.6%), group 2 PH (n=5, 7.7%), group 3 PH (n=1, 1.5%)] according to the 2015 ESC/ERS PH definition. Based on the updated criteria, 7 (10.8% of total cohort) additional patients were reclassified as having PH [PAH (n=3), group 2 PH (n=3), group 3 PH (n=1)]. CONCLUSION: The impact of the updated definition on the frequency of PH and PAH in our cohort was greater than previously reported, which may be caused by the difference in screening strategies for PAH.

Development of interferon induced sarcoidosis in a patient with familial mediterranean fever.

A 42-year-old male patient, who had been on colchicine therapy for familial mediterranean fever admitted with dyspnea on exertion. He had a history of interferon-alpha (IFN-alpha) administration. The chest X-ray showed diffuse distribution of reticulonodular opacities in both lungs. A computerized tomography scan of the lungs revealed mediastinal and bilateral hilar lymphadenopathies, translucent densities, consolidations, reticular opacities and subpleural milimetric cystic spaces. Pulmonary-function studies demonstrated defects in diffusing and vital capacity. Histopathological evaluation was compatible with granulomatous lymphadenitis. The patient was diagnosed as having pulmonary sarcoidosis. He reflects the characteristics of IFN-induced sarcoidosis, but the duration between the cessation of IFN therapy and the development of symptoms is 42 months, which is longer than usually expected. In this case, history of IFN-alpha administration led us to suspect sarcoidosis because of a possible association between IFN therapy and the development of sarcoidosis.

Rituximab Therapy in Renal Amyloidosis Secondary to Rheumatoid Arthritis.

Secondary amyloid A (AA) amyloidosis is a late and serious complication of poorly controlled, chronic inflammatory diseases. Rheumatoid arthritis (RA) patients with poorly controlled, longstanding disease and those with extra-articular manifestations are under risk for the development of AA amyloidosis. Although new drugs have proven to be significantly effective in the treatment of secondary AA amyloidosis, no treatment modality has proven to be ideal. To date, only in small case series preliminary clinical improvement have been shown with rituximab therapy for AA amyloidosis secondary to RA that is refractory to TNF-α inhibitors (TNF-i) therapy. In these case series, we assessed the efficacy and safety of rituximab therapy for patients with RA and secondary amyloidosis. Hacettepe University Biologic Registry was developed at 2005. The data of the RA patients who were prescribed a biological drug were recorded regularly. Patients with biopsy proven AA amyloidosis patients were screened. Of 1022 RA patients under biologic therapy, 0.7% patients had clinically apparent histologically confirmed amyloidosis. Four of seven patients who were prescribed rituximab at least one infusion enrolled to those case series. Two of four patients showed significant clinical improvement and one of them also had decrease in proteinuria and the other one had stable renal function and proteinuria. The main goal for the treatment of AA amyloidosis is to control the activity of the underlying disorder. In this study, we showed that rituximab may be an effective treatment in RA patients with amyloidosis who were unresponsive to conventional disease modifying anti-rheumatic drugs (DMARDs) and/or TNFi.

Assessment of subclinical atherosclerosis in psoriatic arthritis patients without clinically overt cardiovascular disease or traditional atherosclerosis risk factors.

OBJECTIVE: Cardiovascular disease (CVD) is more prevalent in almost all patients with chronic inflammatory musculoskeletal diseases than in their healthy counterparts. The aim of this study was to assess the presence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) in comparison with patients with rheumatoid arthritis (RA) and healthy controls. METHODS: A total of 30 patients with PsA, 30 patients with RA, and 30 healthy controls were enrolled in this parallel group study. Demographic, clinical, and laboratory data of the groups were recorded. The Disease Activity Score-28 tool was used for joint assessment. The erythrocyte sedimentation rate and C-reactive protein level were measured as acute phase reactants. Flow-mediated dilatation (FMD) and carotid intima media thickness (CIMT) were also measured in all participants. RESULTS: The median duration of disease in patients with PsA was 60 months (range: 8-216 months). A total of 22 of 30 (73.3%) PsA patients had a diagnosis of psoriasis and 13 (48.1%) had active disease. The study groups were similar with regard to age, gender, and body mass index data. In all, 23 (76.7%) of the PsA patients and 5 (16.7%) of the RA patients were using an anti-tumor necrosis factor alpha therapy (p<0.001). The FMD percentage was significantly smaller in both the PsA and the RA patients than in the healthy controls (p<0.001). The median CIMT was greater in the RA patients compared with the PsA patients and the healthy controls (p=0.008). There was no significant difference in FMD or CIMT between patients with and without an active joint lesion. CONCLUSION: Endothelial functions were impaired in PsA, as in RA, in the absence of conventional risk factors or overt CVD. This finding may show a potential association between PsA, atherosclerosis, and CVD.

Increased psoriasis frequency in patients with familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is a periodic fever syndrome caused by MEFV mutations. FMF may be associated with psoriasis in some cases. The prevalence of psoriasis in the normal Turkish population is 0.42%. We aimed to investigate the prevalence of psoriasis among FMF patients and their relatives. METHODS: FMF patients followed at Hacettepe University Adult and Pediatric Rheumatology Departments between January and August 2016 were included. FMF patients/their relatives were accepted to have psoriasis if the diagnosis was made by a dermatologist. RESULTS: A total of 351 FMF patients (177 adults; 174 children) were included. The median (min-max) age of adult and pediatric patients was 35 (19-63) and 10 (2-18) years, respectively. Thirteen (3.7%) FMF patients (11 adults, 2 children) had psoriasis. Psoriasis was more common in adult than pediatric patients (p = 0.02). Psoriasis was present in 22 (12.4%) of adult and 9 (5.2%) of pediatric patients' relatives (p = 0.023). The frequency of psoriasis in ≥1 relatives of FMF patients was found to be 8.8%. Abdominal pain and fever were significantly higher, and arthralgia, arthritis, pleural chest pain, and pericarditis were significantly less frequent in the pediatric group than in adults (p < 0.05). CONCLUSION: Psoriasis was more common in FMF patients than in the normal population. Thus, FMF patients should be questioned and carefully examined for psoriasis lesions and psoriasis family history. Prospective multicenter studies may be important to find the incidence of psoriasis in FMF.

HIBISCUS: Hydroxychloroquine for the secondary prevention of thrombotic and obstetrical events in primary antiphospholipid syndrome.

The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%-21% at 5 years in thrombotic APS and 20-28% in obstetrical APS [2, 3]. Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4-16]. Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency. Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial. This trial consists in two parts: a retrospective and a prospective study. The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.