Ultrasound Assessment of Psoriatic Arthritis Patients With Clinically Normal Nails and Evaluation of its Correlation With the Disease Activity: A Case-Control Study.

OBJECTIVES: Nail unit is one of the targets of ultrasound (US) assessment. We aimed to compare ultrasound parameters of clinically normal nail unit in psoriatic arthritis (PsA) patients with healthy controls (HC) and evaluate their correlations with disease activity. METHODS: This was a cross-sectional study including patients with PsA and matched HC. Tender (TJC) and swollen joint count (SJC), Psoriasis Area and Severity Index (PASI), and Disease Activity in Psoriatic Arthritis (DAPSA) were collected in PsA patients. Patients underwent US assessment of fingernails with a study of morphological changes and measurement of the thickness of nail bed (NBT), nail plate (NPT), and adjacent skin (ST). Correlation between nail unit parameters and disease activity was studied. RESULTS: We evaluated 22 PsA patients (219 nails) and 21 HC (210 nails). Mean DAPSA was 21.56 ± 14.36 and mean PASI was 2.19 ± 3.8. PsA patients had more US morphological changes than HC (16.89 vs 3.33%, P = .03). NPT comparison between identical fingernails of PsA and HC did not reveal significant difference. However, NBT was significantly higher in HC (1.77 vs 2.07 mm, P = .027) as well as ST (2.26 vs 2.59 mm, P = .003). TJC and ST were positively correlated (r = .46, P = .03). No correlation was noted between disease activity scores and NPT, NBT, or ST in PsA patients. In biologic parameters, ESR was negatively correlated with ST (r = -.41, P = .05). CONCLUSIONS: Nail bed and adjacent skin US morphological changes were contributive to distinguish psoriatic from healthy nails. Adjacent skin thickness measurement was positively correlated with TJC and ESR, suggesting that it could be used as an indicator of disease activity in PsA.

No Correlation between Anti-drug Antibodies and Therapeutic Response in Tunisian Patients with Chronic Inflammatory Diseases Treated by TNF Blockers.

INTRODUCTION: Tumor necrosis factor alpha (TNF alpha) blockers such as infliximab (IFX) and adalimumab (ADA) had significantly changed the course of inflammatory diseases such as rheumatoid arthritis (RA), spondyloarthritis (SpA) and Crohn's disease (CD). However, about 30% of patients do not respond to these treatments. This lack of response may be due to the formation of antibodies against these drugs (anti-drug antibodies: ADAbs). The aim of this study was to determine the prevalence of ADAbs against IFX and ADA, and the trough serum concentration of IFX and ADA in RA, SpA or CD patients and to assess their impact on the therapeutic response. METHODS: A cross sectional, multi-centric study was conducted, including patients with RA, SpA or CD treated with IFX or ADA as a first biotherapy for at least 6 months. ADAbs and trough levels were measured by an Enzyme Linked Immunosorbent assay (ELISA). RESULTS: 197 patients were included (57 RA, 73 SpA and 67 CD). ADAbs were positive in 40% of cases for IFX and 25% for ADA. They were positive in 40% of SpA, 35% of RA, and 21% of CD. The presence of ADAbs was inversely correlated to the trough levels of IFX and ADA during RA (p = 0.01 and p < 0.0001), SpA (p < 0.01 and p < 0.0001) and CD (p = 0.001 and p = 0.04). For all pathologies, the presence of ADAbs was not correlated with disease activity. Concomitant methotrexate significantly reduced immunogenicity. CONCLUSION: In our study, the presence of ADAb and low trough levels seem to not affect the therapeutic response in patients on TNF alpha antagonists. Other tracks more than immunogenicity should be investigated to explain the loss of response to these biotherapies.

Psoriatic Arthritis Quality of Life questionnaire: Translation, cultural adaptation and validation into Arabic language.

BACKGROUND: Psoriatic arthritis (PsA) is a multifaceted inflammatory disease that has a strong negative impact on the quality of life (QoL) of patients. The Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire was the first disease-specific patient-derived instrument developed to measure the QoL in patients with PsA. Our objective was to translate the PsAQol into Arabic language and evaluate its reliability and validity in patients with PsA. METHODS: This was a cross-sectional study including patients with PsA. A clinical and biological assessment of the patients was performed at inclusion. The translation of the original PsAQoL into Arabic was performed by a professional bilingual and lay panel. Eight patients were interviewed to assess face and content validity. A separate sample of PsA patients (n = 30) were invited to participate in a test-retest postal study in order to investigate reproducibility and construct validity. One week separated the two administrations. The Arabic version of Health Assessment Questionnaire (HAQ) was used as a comparator instrument for convergent validity. RESULTS: Face and content validity were satisfactory. The Arabic version of the PsAQoL was found to be relevant, understandable and easy to complete in only a few minutes. One item was excluded (item 16). It had no correlation with either the other 19 items or the total score of PsAQol. The Arabic PsAQol had excellent internal consistency (Cronbach's a = 0.926), and test-retest reliability (r = 0.982). There was a positive correlation between the total score of the PsAQoL and the Arabic version of HAQ (Spearman's r = 0.838, p < 10-3 ). Exploratory factor analysis had extracted two factors explaining 55% of the total variance. CONCLUSION: Nineteen items were selected to compose the Arabic version of PsAQoL, which was found to be relevant and understandable and has excellent reliability and construct validity. The new measure will be a valuable new tool for use in routine care for patients' assessment.

Impact of FCGR2A R131H, FCGR3A F158V and FCGR3B NA1/NA2 polymorphisms on response to Fc-containing TNF inhibitors in Tunisian rheumatoid arthritis patients.

OBJECTIVES: Single nucleotid polymorphisms (SNPs) of Fc-gamma receptors (FcgRs), by inducing a variation of their affinity to the Fc-region of immunoglobulins, might influence the efficacy of Fc-containing biologics prescribed in rheumatoid arthritis (RA). Our aim was to investigate associations of FCGR2A, FCGR3A and FCGR3B SNPs with TNF-inhibitors (TNFi)' response in Tunisian RA patients. METHODS: A cross-sectional, observational and analytic multicentric cohort study was conducted in a group of 47 Tunisian RA patients treated with (etanercept [ETA], adalimumab [ADL] and infliximab [IFX]). Treatment outcome was evaluated after 6 months. R131H-FCGR2A, F158V-FCGR3A and NA1/NA2-FCGR3B SNPs were genotyped. RESULTS: The analytic study including all types of TNFi showed that FCGR3A-F/F low-affinity receptor was associated with a greater decrease of DAS28, while FCGR3B-NA1/NA1 high-affinity receptor was associated with a lower decrease of DAS28 in ADL group. Furthermore, both of high affinity receptors FCGR3B-NA1/NA1 and FCGR3A-V/V were more prevalent in non-responders to ADL, according to EULAR criteria. CONCLUSIONS: Identifying reliable biomarkers of response to biologics in RA is necessary to improve responsiveness, preserve joints' functions and structure, and reduce treatment's cost. Our study showed that FCGR3A and FCGR3B polymorphisms might have an impact on TNFis' response in RA Tunisian patients since bad response was more frequent in homozygous carriers of high affinity alleles FCGR3A-V and FCGR3B-NA1.

Assessment of the influence of Fc-γ receptor polymorphisms on biologics' pharmacokinetics in Tunisian rheumatoid arthritis patients.

AIMS: This study aims to determine whether a modification in Fc-γ receptors' (FcgRs) affinity to Fc portion, caused by single nucleotide polymorphisms such as rs1801274-R131H FcgRIIa, rs396991-F158V FcgRIIIa and NA1/NA2-FcgRIIIb, might impact clearance of therapeutic monoclonal antibodies and thus serum drug levels and the development of anti-drug antibodies. METHODS: A cross sectional, multicentral and noninterventional study was conducted in Tunisian RA patients treated with rituximab (RTX), etanercept (ETA), infliximab (IFX) and adalimumab (ADL). Serum drug level (SDL) of the different biologics and ADA against them were measured. All patients were genotyped for the 3 FcgR single nucleotide polymorphisms. RESULTS: A total of 81 patients were included: 47 were under tumour necrosis factor inhibitors (18 ETA, 13 ADL and 16 IFX), and 34 were under RTX. Regardless of the type of biotherapy, SDL was in therapeutic range, in 35 patients (43.2%), of whom only 1 was treated with RTX. Fourteen patients (22.2%) developed ADA, but none of the patients treated with ETA had detectable ADA levels. There was no association between SDL positivity and FcgR polymorphisms. However, the high affinity FcgR2A 131 H/H receptor was statistically more prevalent in patients with detectable ADA treated with ADL, IFX and RTX (P = .018). The same result was obtained in the monoclonal antibody tumour necrosis factor inhibitor subgroup (n = 29, P = .022) as well as in patients treated only with IFX (n = 16, P = .029). CONCLUSION: Our work supports the hypothesis of an impact of FcgR single nucleotide polymorphisms on biologics' immunogenicity, particularly FcgR R131H polymorphism, but further studies with larger cohorts need to be undertaken to confirm these results.

Variation of homocysteine levels in rheumatoid arthritis patients: relationship to inflammation, cardiovascular risk factors, and methotrexate.

BACKGROUND: The aim of this study was to evaluate the variation of homocysteine (Hcy) levels in patients with rheumatoid arthritis (RA) and to analyze the relationship to inflammatory parameters, cardiovascular risk, and methotrexate (MTX). METHODS: This cross-sectional study assessed disease activity and treatment in RA patients. The European League Against Rheumatism (EULAR) 2015 HeartSCORE was performed for cardiovascular (CV) risk estimation and levels of plasma Hcy, serum folate concentrations, vitamin B12, and erythrocyte sedimentation rate (ESR) were measured. RESULTS: A total of 103 participants with mean age 53 ± 10 years and mean disease duration 10.55 ± 7.34 years were included. Patients were treated with MTX in 69.9% of cases and corticosteroid in 80.5% of cases. Of all patients, 13% had a cardiovascular inheritance, 25% were hypertensive, and 18% had diabetes. The EULAR 2015 HeartSCORE was high and very high (≥5%) in 35% of cases. Mean Hcy level was 12.54 ± 4.2 µmol/L [6.89-32.92] and hyperhomocysteinemia was noted in 20.4% of patients. Analytic study demonstrated that hyperhomocysteinemia was associated with male gender (p = 0.01), MTX use (p = 0.01), smoking (p = 0.008), renal failure (p = 0.04), and high disease activity (p = 0.05), but there was no association with the HeartSCORE (p = 0.23). Hcy level was negatively correlated with folate (p = 0.009) and vitamin B12 level (p = 0.02) and positively with age (p = 0.01), C­reactive protein (CRP; p = 0.05), and Simplified Disease Activity Index (SDAI; p = 0.03). In multivariate logistic regression analysis, current MTX use, levels of vitamin B12 and creatine, and Clinical Disease Activity Index (CDAI) appeared to be independent factors associated with hyperhomocysteinemia. CONCLUSION: MTX use, CDAI, and the levels of vitamin B12 and creatine are independent factors associated with hyperhomocysteinemia.

Synovial Chondromatosis of the Shoulder in Rheumatoid Arthritis: A Case Report and Brief Review of the Literature.

BACKGROUND: Synovial chondromatosis is an uncommon benign condition characterized by synovial membrane proliferation and metaplasia. Synovial chondromatosis cases in patients with rheumatoid arthritis have been reported. However, involvement of the glenohumeral joint is rare. CASE PRESENTATION: We herein report a case of a rare association of synovial chondromatosis involving the shoulder in a rheumatoid arthritis patient. The symptoms have improved with anti-tumor necrosis factor drugs. Consequently, there was no need for invasive therapy to treat synovial chondromatosis. CONCLUSION: Synovial chondromatosis can be aggressive and destructive. More trials are needed to establish a better clinical diagnostic strategy and pharmacological management.

Fibromyalgia in Spondyloarthritis: Prevalence and Effect on Disease Activity and Treatment.

BACKGROUND: Fibromyalgia may be associated to Spondyloarthritis with which it shares some common symptoms such as sleep disorders, fatigue and diffuse pain, leading to diagnostic and treatment dilemmas. OBJECTIVES: We aimed to determine the prevalence of fibromyalgia in axial spondyloarthritis and to determine how fibromyalgia might influence the assessments of disease activity and how it might impact treatment. METHODS: An observational cross-sectional study was conducted. The study included 100 patients with axial spondyloarthritis according to the Assessment of SpondyloArthritis international Society criteria. Fibromyalgia was diagnosed based on the 2010 American College of Rheumatology criteria. Demographics, disease characteristics, activity parameters and treatment were compared between patients with and without fibromyalgia. Patients were recruited from the hospitalization unit and the outpatient clinic of rheumatology. RESULTS: The mean age of patients was 44.65 ± 13.13 years, with a sex ratio equal to 2. The prevalence of fibromyalgia was 20%. Fibromyalgia associated factors were advanced age and a late age at the onset of axial spondyloarthritis. Disease activity parameters such as global pain VAS, BASDAI, ASDAS-ESR, ASDAS-CRP, BASFI and BAS-G as well as MASES and BASMI were significantly higher in the presence of FM. Doses of paracetamol were significantly higher among FM+ patients. Also, treatment duration of the current anti-TNF alpha agent was significantly shorter among FM+ patients. CONCLUSION: Our study showed that fibromyalgia was associated with axial spondyloarthritis in 20% of patients. Its presence was associated with higher disease activity parameters and negative impact on the treatment.

Tophaceous gout in a young man with Gitelman syndrome: a case report with an overview.

Gitelman syndrome represents the clinical manifestations of inactivation of the Slc12a3 genes encoding the thiazide-sensitive sodium chloride cotransporter and the Trpm6-Mg genes encoding the magnesium transporters in the distal convoluted tubule. In fact, the biochemical findings resemble those with thiazide diuretics such as hypokalemia, hypomagnesaemia, hypocalciuria, metabolic alkalosis, and low normal blood pressure. He is usually associated with calcium pyrophosphate deposition. Serum uricemia level is rarely affected in Gitelman syndrome. We aimed to report a rare association of chronic gout with Gitelman syndrome, hence the interest of our case. We describe a 29-year-old male patient with a history of Gitelman syndrome associated with articular gout including pelvic localization. We provided pictorial evidence of extensive and diffuse monosodium urate deposition in articular and periarticular structures to confirm the gout origin. A literature review illustrates 4 reported cases of Gitelman syndrome associated with gout. The gender distribution was equal with a mean age of 40 years.

Unexpected diagnosis of vertebral osteolysis.

This is the case of a 50-year-old patient suffering from inflammatory low back pain. Radiological exploration showed posterior vertebral damage compatible with discovertebral pseudo-tumor tuberculosis. Pathological examination found no malignant cells, but caseous necrosis was present. The patient was put on antitubercular drugs. The evolution was favorable under treatement.

Lumbar Spinal Involvement in Calcium Pyrophosphate Dihydrate Disease: A Systematic Literature Review.

Background: Calcium-pyrophosphate-dihydrate-disease (CPPD) is a crystal-induced arthropathy. The lumbar-spinal involvement is rare and often under-diagnosed. This study aimed to report the case of a lumbar spine CPPD involvement and to perform a systematic review of clinical, imaging features of lumbar involvement in CPPD patients, and treatments that have been implemented. Methods: This systematic review was conducted in accordance with the Preferred-Reporting-Items-for-Systematic-Reviews and Meta-Analyses (PRISMA) guidelines. Results: One hundred and sixty-seven articles met the search criteria using electronic databases searches. We retained 28 articles (20 case reports, 2 case series, 1 family survey, 4 retrospective studies, and 1 prospective study) involving a total of 62 patients. The age ranged between 39 and 89 years old. Among patients with lumbar spine CPPD, 32 were women. The duration of symptoms varied between one day and 8 years. The affection has been discovered during back pain in most cases. In 5 studies, the diagnosis was made on histological specimens of patients operated on for another pathology. X-ray showed calcifications in 2 cases. CT-scan detected calcium deposit in 7 cases. MRI showed lesions going from the increased signal of the disk, to calcified or not-cystic lesion of the facet joints, an intramedullary mass mimicking a schwannoma. Histological examination established the diagnosis of CPPD in 21 patients in all studies. Medical treatment included NSAIDs, Colchicine, Interleukin-1-receptor-antagonist, and antibiotics. Surgery was performed on 13 patients and allowed to establish the histological diagnosis. Conclusion: In the case of inflammatory back pain in elderly subjects, without an infectious gateway, diagnosis of CPPD should be considered, especially for patients with a history of spinal surgery or degenerative radiography changes. CT scan is more sensitive than conventional radiographs. The discovertebral biopsy is the Gold-Standard and should be performed whenever the diagnosis was uncertain. Treatment includes the medical and surgical components.

Unusual presentation in amyloidosis.

We report a case of osteolytic polyarthritis and atlanto-axial lesion revealing multiple myeloma-associated amyloid arthropathy in a 56-year-old man. Only histological exam of the salivary gland biopsy demonstrating the presence of amyloid deposits stained with congo red could confirm the diagnosis.

Complications of Paget Bone Disease: A Study of 69 Patients.

INTRODUCTION: Paget bone disease (PBD) is characterized by a disorder in the bone remodeling activity at sites of involvement. This can produce dramatic alterations of local bone architecture and causes most of the complications. We aimed to focus on the characteristics of complications of PDB among hospitalized patients. MATERIAL AND METHODS: A retrospective study was conducted, on PBD patients hospitalized in two rheumatology centers from 1994 to 2019. Characteristics of the PBD complications were studied. RESULTS: Sixty-nine patients were collected with a sex ratio of 0.76 and a mean age of 75.4±6.4 years [43-101]. The diagnosis of PBD was established in the average age of 64.2±11.5 years. The primary reason for consultation was pain (78.3%). The PBD was localized in the pelvis (58%), lower limb (42%), spine (36.2%), skull (23.2%) and upper limb (5.8%). It was polyostotic in 44.9% of cases. Dosage of ALP was 324 [68-8390]. The PDB complication rate was 52.2% and it decreased over time. The main complication was osteoarthritis (23.2%), followed by deafness (17.4%), fracture (15.9%), hydrocephalus (7.2%), neurological disease (7.2%) and osteosarcoma (1.4%). The presence of complications was significantly associated with the polyostotic form (p=0.01), the skull localization (p=0.04), an increased ALP (p=0.02). CONCLUSION: According to our study, the incidence rate of PBD among hospitalized cases is higher among elderly women and decreases over time. Complications related to PDB are frequent (52%). It concerns patients with a polyostotic form, skull localization and high ALP.

Diffuse large B cell lymphoma presenting with renal failure and bone lesions in a 46-year-old woman: a case report and review of literature.

Renal involvement in large B-cell lymphoma represents an exceptional manifestation of non-Hodgkin lymphomas. Renal failure and bone metastasis by lymphomatous infiltration is extremely rare. We describe a 46-year-old woman presenting with a renal failure and a 5-month history of intermittent left knee pain that was previously misdiagnosed with osteoarthritis. It was due to a bilateral primary renal lymphoma (PRL) associated with bone metastasis. Knee MRI showed a permeative lesion and an abnormal signal in the metaphysis and diaphysis of the left proximal tibia with periosteal reaction and surrounding soft tissue swelling. The CT body scan showed a bilateral nephromegaly and multiple lytic bone lesion of aggressive appearance at the right iliac wing and right sacral ala evoking lymphomatous involvement. Node biopsy with immunohistochemistry study confirmed a diagnosis of large B-cell lymphoblastic lymphoma. In this article, we focus on clinical, radiological, immunohistochemical presentation, differential diagnosis and review the literature. Ten cases including our case were reported in our literature review of both renal and bone lymphoma. There was a male predominance, with a mean age of 55.1 years old. We noted a high frequency of renal failure in diagnosis. In X-rays, the metaphysis is the most common site of occurrence in long bones and the main sign was osteolytic bone destruction. The subtype of lymphoma was DLBCL stage IV in most cases except in one case where it was a hystiocytic lymphoma. Finally, prognosis was poor, more than half of patients died. PRL with bone metastasis is a rare malignancy that is difficult to diagnose. Clinicians should increase the awareness of the disease and consider a differential diagnosis of bone lesions. Early diagnosis and active treatment can improve patient prognosis.

Immunogenicity of antitumor necrosis factor therapy in patients with spondyloarthritis.

Objectives To evaluate the serum dosage of the biomedicine (DBM) and the incidence of antidrug antibody (ADA) against antitumor necrosis factor (TNF) in spondyloarthritis, and to demonstrate the influence of these parameters on the clinical efficiency. Methods We conducted a cross-sectional multicentric study including patients with spondylarthritis (SpA) under antiTNF (infliximab [INF], etanercept [ETA] and adalimumab [ADL]) for at least 6 months. A dosage of the ADA and DBM were practiced by the immuno-enzymatic essay. Result Seventy one patients were recruited. Disease modifying antirheumatic drugs (DMARDs) were associated with anti-TNF in 30%. ADA was positive in 54% for INF, 33% for ADL and 0% for ETA with a significant difference(p<0.0001). Immunogenicity was correlated to a bad therapeutic response (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]≥4)(p=0.04). The DBM was inversely correlated with the rate of ADA for patients treated with INF(p<0.0001) and ADL(p<0.0001). The DBM was also inversely correlated with BASDAI of INF(p=0.03) and ADL (p=0.01). ADA was significantly associated with an anterior switch of anti TNF(p=0.04), the use of INF(p=0.002), presence of coxitis(p=0.01) and higher body mass index (BMI)(p=0.007). DMARDs associated with anti TNF were not a protective factor for positive ADA. In a multivariate study, only INF and BMI were independent factors of positive ADA. Conclusion The ADA formation lowered the DBM and favored the therapeutic failure.

Paget's Disease of Bone in Tunisia: A Study of 69 Patients.

CONTEXT: Paget's disease of bone is a common bone disease with a striking variation in its incidence and characteristics in different parts of the world. It is uncommonly reported in African patients. AIMS: Given the lack of studies describing the characteristics of patients with Paget's disease of bone in North Africa, we aimed to describe demographic, clinical, biochemical, and imaging characteristics, as well as treatment outcomes of Tunisian patients with Paget's disease of bone. SUBJECTS AND METHODS: This bicentric and retrospective study included patients with Paget's disease of bone. Clinical, laboratory, radiological profile, and response to treatment were analyzed. RESULTS: Sixty-nine patients were identified. The mean age was 64.9 ± 11.6 years and 52.2% were women. One patient reported a positive family history. Seven patients were asymptomatic. Bone pain was the most common presenting symptom. Eight patients had a history of malignancy. In three patients, Paget's disease of bone was diagnosed as part of a metastatic workup. Monostotic disease was found in half of the cases. The most commonly involved sites were pelvis (43.5%), femur (21.7%), and spine (21.7%). The mean serum alkaline phosphatase level at presentation was 591 U/L (68-8380). Two patients received salmon calcitonin (2.8%) and 47 patients (68.1%) received bisphosphonates. After a mean follow-up of 55 months (2-240 months), bone pain improved in 43.1% of patients and the serum alkaline phosphate levels had normalized in 22 of them (43.1%). During follow-up, there was no malignant transformation. CONCLUSIONS: In this series of Tunisian patients, Paget's disease of bone had a female predominance and was usually monostotic. The clinical and radiological presentations were similar to the European series.