Lupus, antiphospholipid syndrome, and stroke: An attempt to crossmatch.

Cerebrovascular accidents (CVAs) or strokes are part of the common thrombotic manifestations of Systemic Lupus Erythematosus (SLEs) and Antiphospholipid syndrome (APS). Such neurological thrombotic events tend to occur in patients with SLE at a higher frequency when Antiphospholipid antibodies (aPLs) are present, and tend to involve the large cerebral vessels. The mechanism of stroke in SLE can be driven by complement deposition and neuroinflammation involving the blood-brain barrier although the traditional cardiovascular risk factors remain major contributing factors. Primary prevention with antiplatelet therapy and disease activity controlling agent is the basis of the management. Anticoagulation via warfarin had been a tool for secondary prevention, especially in stroke recurrence, although the debate continues regarding the target international normalized ratio (INR). The presence of either of the three criteria antiphospholipid antibodies (aPLs) and certain non-criteria aPL can be an independent risk factor for stroke. The exact mechanism for the involvement of the large cerebral arteries, especially in lupus anticoagulant (LAC) positive cases, is still to be deciphered. The data on the role of non-criteria aPL remain very limited and heterogenous, but IgA antibodies against ß2GPI and the D4/5 subunit as well as aPS/PT IgG might have a contribution. Anticoagulation with warfarin has been recommended although the optimal dosing or the utility of combination with antiplatelet agents is still unknown. Minimal data is available for direct oral anticoagulants (DOACs).

Role of pro-inflammatory interleukins in osteoarthritis: a narrative review.

PURPOSE: This manuscript will summarize the role of pro-inflammatory cytokines and tackle newly discussed ones within the scope of OA pathogenesis as mentioned in the recent literature. This will allow for a better understanding of the mechanisms behind such a complicated disease. MATERIAL AND METHODS: Relevant articles were obtained by searching key terms including "pro-inflammatory cytokines," "inflammation," "pathophysiology," "cartilage damage," and "OA" in PubMed and Google Scholar databases. The year ranges set for the selection of the articles was between 2015 -2021. Inclusion criteria was based on the relevance and contribution to the field of the study. RESULTS: Osteoarthritis (OA) has a complex multifactorial pathophysiology which is attributed to molecular and biomechanical changes that disrupt the normal balance of synthesis and degradation of articular cartilage and subchondral bone. Pro-inflammatory cytokines, with their wide range of action and intricate signaling pathways, are the constant subject of new discoveries revolving around this inflammatory disease. The available literature indicates that some of these cytokines such as IL-33, IL-17, IL-6, and IL-22 have a direct relation to cartilage degradation, while others like IL-15, IL-1, IL-7, and IL-34 have an indirect one. CONCLUSIONS: Inflammation has an essential role in the manifestation of osteoarthritis clinical events. Specifically, certain cytokines exhibit pro-inflammatory properties that are markedly activated during the course of the disease and notably alter the homeostasis of the joint environment. However, clinical trials and observational studies remain insufficient to navigate the varying nature of this disease in humans.

Antiphospholipid antibodies and cerebrovascular thrombosis in the pediatric population: Few answers to many questions.

Most of the knowledge in pediatric antiphospholipid syndrome (APS) is derived from studies performed on the adult population. As in adults, antiphospholipid antibodies (aPL) can contribute to thrombosis, especially cerebrovascular thrombosis, in neonates and children. Since aPL have the potential to cross the placental barrier, and since the pediatric population is prone to infections, re-testing for their positivity is essential to specify their role in cerebrovascular thrombosis.In this review, we aimed at assessing the prevalence of aPL, criteria or non-criteria, in neonatal and childhood ischemic stroke and sinovenous thrombosis trying to find an association between aPL and cerebrovascular thrombosis in the neonatal and pediatric population. Also, we looked into the effect of aPL and anticoagulants/antiplatelets on the long term neurological outcomes of affected neonates or children. The questions regarding the prevalence of aPL among pediatric patients with cerebrovascular thrombosis, the relationship between the titers of aPL and incidence and recurrence of cerebrovascular events, the predictability of the long term neurological outcomes, and the most optimal anticoagulation plan are still to be answered. However, it is crucial for clinicians to screen neonates and children with cerebrovascular thrombosis for aPL and confirm their presence if positive.

COVID-19 and antiphospholipid antibodies: A position statement and management guidance from AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION).

Coronavirus disease 2019 (COVID-19) is associated with a high rate of thrombosis. Prolonged activated partial thromboplastin times (aPTT) and antiphospholipid antibodies (aPL) are reported in COVID-19 patients. The majority of publications have not reported whether patients develop clinically relevant persistent aPL, and the clinical significance of new aPL-positivity in COVID-19 is currently unknown. However, the reports of aPL-positivity in COVID-19 raised the question whether common mechanisms exist in the pathogenesis of COVID-19 and antiphospholipid syndrome (APS). In both conditions, thrombotic microangiopathy resulting in microvascular injury and thrombosis is hypothesized to occur through multiple pathways, including endothelial damage, complement activation, and release of neutrophil extracellular traps (NETosis). APS-ACTION, an international APS research network, created a COVID-19 working group that reviewed common mechanisms, positive aPL tests in COVID-19 patients, and implications of COVID-19 infection for patients with known aPL positivity or APS, with the goals of proposing guidance for clinical management and monitoring of aPL-positive COVID-19 patients. This guidance also serves as a call and focus for clinical and basic scientific research.

Nurse-led care for the management of rheumatoid arthritis: a review of the global literature and proposed strategies for implementation in Africa and the Middle East.

Globally, increasing demand for rheumatology services has led to a greater reliance on non-physician healthcare professionals (HCPs), such as rheumatology nurse specialists, to deliver care as part of a multidisciplinary team. Across Africa and the Middle East (AfME), there remains a shortage of rheumatology HCPs, including rheumatology nurses, which presents a major challenge to the delivery of rheumatology services, and subsequently the treatment and management of conditions such as rheumatoid arthritis (RA). To further explore the importance of nurse-led care (NLC) for patients with RA and create a set of proposed strategies for the implementation of NLC in the AfME region, we used a modified Delphi technique. A review of the global literature was conducted using the PubMed search engine, with the most relevant publications selected. The findings were summarized and presented to the author group, which was composed of representatives from different countries and HCP disciplines. The authors also drew on their knowledge of the wider literature to provide context. Overall, results suggest that NLC is associated with improved patient perceptions of RA care, and equivalent or superior clinical and cost outcomes versus physician-led care in RA disease management. Expert commentary provided by the authors gives insights into the challenges of implementing nurse-led RA care. We further report practical proposed strategies for the development and implementation of NLC for patients with RA, specifically in the AfME region. These proposed strategies aim to act as a foundation for the introduction and development of NLC programs across the AfME region.

Henoch-Schönlein purpura: Another COVID-19 complication.

Whether affecting children or adults, SARS-CoV-2 infection (COVID-19) can have multi-organ involvement mediated by an inflammatory cascade. Immunoglobulin A (IgA) is one of the key components of the inflammatory cascade that can lead to endothelial injury and inflammation. IgA vasculitis or Henoch-Schönlein purpura (HSP) has been rarely reported in the context of COVID-19. In this report, we highlight a case of HSP occurring 2 days after diagnosis of COVID-19 in a 16-year-old boy, who presented with palpable purpura of the lower extremities and buttocks, diffuse abdominal pain, hemoptysis, and hematochezia. He was treated with oral prednisolone with rapid clinical improvement.

A glimpse into the history of description of the antiphospholipid syndrome.

Prior to 1983, several landmark reports prepared the stage for a detailed description of the Antiphospholipid (Hughes) syndrome (APS). Formerly depicted as lupus-like, APS exhibits a wide spectrum of symptoms that overlap with Sjogren's, Hashimoto, and other autoimmune diseases. In this review, we take a glimpse into the history of description of APS, discussing the events that led to its recognition as one of the most common autoimmune diseases and the enormous impact of that recognition in the rheumatology field.

The Fibromyalgia Bladder Index in 100 consecutive women with fibromyalgia.

INTRODUCTION AND HYPOTHESIS: The Fibromyalgia Bladder Index (FBI) is a validated instrument to quantify bothersome bladder symptoms specifically in women with fibromyalgia syndrome (FMS). The FBI includes two sub-scales: one addressing urinary urgency and bladder pain (UP), the other addressing urinary frequency and nocturia (FN). The objectives of this study are to evaluate the FBI in a cohort of patients with FMS, to correlate it with certain characteristics in this cohort, and to compare it with controls. METHODS: We performed a case-control study of 100 women with FMS and 155 controls. Demographic data, comorbidities, and other characteristics were registered. Comparison between FBI scores of participants with and without FMS, as well as correlation of FBI scores with the characteristics of FMS patients, were undertaken using independent two-sample t test for continuous outcomes and Pearson's Chi-squared test for categorical outcomes. RESULTS: The mean UP subscale score of the FBI was significantly higher in the FMS group (10.29 ± 5.61) compared with the controls (1.65 ± 2.65; (p = 0.001). The mean FN subscale score was significantly higher in the FMS group (9.93 ± 5.37) compared with the controls (2.95 ± 3.27; p = 0.001). FMS patients diagnosed >3 years ago had a higher UP subscale score and a higher FN subscale score compared with FMS patients diagnosed <3 years ago (p = 0.020 and p = 0.024 respectively). Menopause and parity significantly increased the FBI scores. Smoking and a history of depression did not significantly affect any of the FBI subscale scores in the FMS group. CONCLUSION: Women with FMS suffer from bothersome bladder symptoms that can be readily identified and quantified.

Management of antiphospholipid syndrome.

Antiphospholipid syndrome, also known as 'Hughes Syndrome', is an autoimmune disease characterised by a set of clinical manifestations, almost all of which are direct or indirect sequelae of a hypercoagulable state involving the venous, and to a lesser extent the arterial vasculature. The incidence and prevalence of antiphospholipid syndrome are estimated at approximately 5 de novo cases per 100 000 per year and 40-50 cases per 100 000 individuals, respectively. The clinical spectrum of antiphospholipid syndrome involves haematological (thrombocytopaenia, venous thrombosis), obstetrical (recurrent pregnancy loss), neurological (stroke, transient ischaemic attack, migraine, seizures, cognitive dysfunction, chorea, transverse myelitis, multiple sclerosis), cardiovascular (cardiac valve disease), dermatological (livedo reticularis and racemosa, skin ulceration and necrosis), renal (glomerulonephritis, renal thrombotic microangiopathy) and orthopaedic (avascular necrosis of bones, non-traumatic fractures) manifestations, among others. In addition to the classical antiphospholipid antibodies, namely anticardiolipin antibodies and lupus anticoagulant, new autoantibodies and antibody complexes of different immunoglobulin subtypes (IgA, IgG, IgM) are now recognised as significant contributors to the pathogenesis of antiphospholipid syndrome. Anticoagulation remains the cornerstone in the management of antiphospholipid syndrome; nevertheless, new drugs and therapeutic strategies are being tested, and some have been found effective for the primary and secondary thromboprophylaxis in antiphospholipid syndrome.

Disease burden and treatment challenges of psoriatic arthritis in Africa and the Middle East.

Psoriatic arthritis (PsA) is a chronic, inflammatory arthropathy occurring in up to 30% of patients with psoriasis, and is characterized by multiple manifestations including peripheral arthritis, enthesitis, dactylitis, spondylitis, and psoriatic skin and nail disease. This complex and heterogeneous disease is poorly understood and its diagnosis and treatment are suboptimal, particularly in Africa and the Middle East, where very few studies into the impact of PsA have been carried out. This article aims to highlight the disease burden of PsA in the region as well as to identify unmet clinical needs. A non-systematic review was carried out in the PubMed database and the most relevant publications were selected. Expert rheumatologists practicing in Africa and the Middle East provide an insight into the challenges of treating PsA in daily practice, along with recommendations for improvements.

A review of current management of vasculo-Behcet's.

PURPOSE OF REVIEW: To give an overview of recently published articles about the management of vasculo-Behcet's with particular emphasis on anticoagulation. RECENT FINDINGS: Biologic agents are emerging as a potential therapeutic option in refractory vasculo-Behcet with a good safety profile. Evidence further shows that following nonpulmonary aneurysm repair, there is a reduced risk of recurrent aneurysmal formation at the operative site in patients treated with immunosuppressants in addition to their surgery, than those undergoing surgical intervention alone. SUMMARY: Behcet disease patients are at risk of developing multiple vascular complications including thrombosis and aneurysms. Treatment should focus on reducing inflammation; and the role of anticoagulation is still debatable.

Rheumatological complications of beta-thalassaemia: an overview.

Beta-thalassaemia, an autosomal recessive haemoglobinopathy, ranks among the most frequent monogenetic diseases globally. The severe form of the disease, beta-thalassaemia major, is accompanied by progressive involvement of multiple organ systems as a result of the disease pathophysiology as well as iron overload from blood transfusions on a regular basis. Some of the manifestations might also be caused by medications used to manage iron overload. The purpose of this review is to highlight the rheumatological complications of beta-thalassaemia, which include musculoskeletal manifestations, such as arthritis and arthropathies, joint effusions, osteoporosis, bone fractures and myalgias, in addition to CTDs, such as pseudoxanthoma elasticum. Rheumatologists are strongly encouraged to take part in a multidisciplinary approach to the management of this debilitating disease.

SuPAR, an emerging biomarker in kidney and inflammatory diseases.

Soluble urokinase plasminogen activator receptor (suPAR) is a circulating form of a physiological and pathophysiological important cell surface receptor, implicated in inflammation. Recent studies showed that suPAR is a promising biomarker, useful for diagnosis, assessment and prognosis of several diseases. This review summarises the majority of preliminary studies and analyses the significance and the clinical application of suPAR in various clinical conditions. SuPAR seems to have a significant value in the diagnosis as well as prognosis of many diseases; nonetheless, it merits large-scale studies to set cut-off values that help physicians in following up their patients and accordingly tailor their treatment plans.

Risk factors for incident shoulder soft tissue rheumatic disorders: a population-based case-control study in Lebanon.

BACKGROUND: Soft tissue rheumatic disorders (STRDs) are very common and impact enormously general population, working groups and physiotherapist practices. However, they do not have neither a clear case definition nor objective tests to be accurately diagnosed rendering them neglected with poorly-estimated burden. Shoulder is one of the most frequent sites for STRDs. AIM: The aim of this study was to identify risk factors for shoulder STRDs among Lebanese adults aged ≥ 15 years. METHODS: A case-control study was designed based on data from the Community Oriented Program for Control of Rheumatic Diseases (COPCORD) study conducted in Lebanon in 2009. Cases were defined as those who recently suffered from shoulder pain, tenderness or stiffness with duration not exceeding 12 months (52 cases). These were frequency-matched by age and gender with 208 controls who never experienced any musculoskeletal pain. RESULTS: Area of residence, physical activity, family history and stress-induced sleep difficulty were significantly associated with shoulder STRDs after adjusting for cigarette smoking, job nature and family monthly income. CONCLUSION: Factors associated with shoulder STRD among the Lebanese population include geographical location, psychosocial factors, physical activity and familial predisposition. Further longitudinal studies are needed to establish a temporal sequence and explore other potential determinants, especially among the working population.

Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment.

BACKGROUND: It has been hypothesized that adaptation of health practice guidelines to the local setting is expected to improve their uptake and implementation while cutting on required resources. We recently adapted the published American College of Rheumatology (ACR) Rheumatoid Arthritis (RA) treatment guideline to the Eastern Mediterranean Region (EMR). The objective of this paper is to describe the process used for the adaptation of the 2015 ACR guideline on the treatment of RA for the EMR. METHODS: We used the GRADE-Adolopment methodology for the guideline adaptation process. We describe in detail how adolopment enhanced the efficiency of the following steps of the guideline adaptation process: (1) groups and roles, (2) selecting guideline topics, (3) identifying and training guideline panelists, (4) prioritizing questions and outcomes, (5) identifying, updating or conducting systematic reviews, (6) preparing GRADE evidence tables and EtD frameworks, (7) formulating and grading strength of recommendations, (8) using the GRADEpro-GDT software. RESULTS: The adolopment process took 6 months from January to June 2016 with a project coordinator dedicating 40% of her time, and the two co-chairs dedicating 5% and 10% of their times respectively. In addition, a research assistant worked 60% of her time over the last 3 months of the project. We held our face-to-face panel meeting in Qatar. Our literature update included five newly published trials. The certainty of the evidence of three of the eight recommendations changed: one from moderate to very low and two from low to very low. The factors that justified a very low certainty of the evidence in the three recommendations were: serious risk of bias and very serious imprecision. The strength of five of the recommendations changed from strong to conditional. The factors that justified the conditional strength of these 5 recommendations were: cost (n = 5 [100%]), impact on health equities (n = 4 [80%]), the balance of benefits and harms (n = 1 [20%]) and acceptability (n = 1 [20%]). CONCLUSION: This project confirmed the feasibility of GRADE-Adolopment. It also highlighted the value of collaboration with the organization that had originally developed the treatment guideline. We discuss the implications for both guideline adaptation and future research to advance the field.

Mania induced by adalimumab in a patient with ankylosing spondylitis.

Objectives Monoclonal antibodies such as antagonists of tumor necrosis factor-alpha have been shown to have beneficial effects on the well-being of patients with inflammatory illnesses. However, mood episodes triggered by such agents have been reported. We herein report the case of mania induced by adalimumab treatment in an adult with ankylosing spondylitis, which later resolved once adalimumab was discontinued and mood stabilizers were initiated. Methods A 25-year-old man, with prior history of dysthymia, was diagnosed with ankylosing spondylitis and started on adalimumab. He gradually developed manic symptoms over seven to eight months, while maintained on adalimumab. As his condition did not improve with outpatient management, the patient was admitted to the Psychiatry inpatient unit. Results Valproate and aripiprazole were initiated, and adalimumab was substituted with non-steroidal anti-inflammatory agents. Mood symptoms resolved within days, and the patient was discharged. Upon follow-up, the patient was euthymic and compliant to his psychotropic medications. He was started on certolizumab, a different immunomodulatory, for his ankylosing spondylitis. Conclusions Immunological modulation might be a key factor in triggering, maintaining, or treating mood symptoms. Further research in this field is warranted to better understand the pathophysiology of mania. To our knowledge, manic symptoms induced by adalimumab have not been previously reported in the literature, which is why our case report can have an impact in recognizing this important clinical adverse effect.

Antiphospholipid syndrome: an update.

BACKGROUND: Antiphospholipid syndrome (APS) or 'Hughes syndrome' is a prothrombotic disease characterized by thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). More than three decades have passed, and experts are still uncovering new pieces of this disease complex pathogenesis and management. MATERIALS AND METHODS: We searched in literature using MEDLINE and PubMed databases focusing on the latest development on disease pathogenesis, risk assessment of thrombosis and treatment of APS. RESULTS: The phosphatidylinositol 3-kinase (PI3K)-AKT-mTORC pathway was most recently identified to have a crucial role in activating inflammation among endothelial vessel wall causing vascular lesions in APS. Additionally, new variables are being implemented to assess the risk of thrombosis in patients with APS. Global APS Score (GAPSS) utilizes cardiovascular risk factors and new autoimmune antibodies as part of the score assessment and is the most valid so far. It can be a promising tool in the future for prediction of thrombosis. Anticoagulation remains the cornerstone in APS; however, many new potential therapeutic agents are developing and are currently under investigation. CONCLUSIONS: The most recent advances in pathogenesis, risk stratification and treatment provide a platform for high yield studies with the ultimate goal of providing the optimal management to patients with APS.

An update on the endocrine manifestations of antiphospholipid syndrome.

Antiphospholipid Syndrome (APS), characterized by hypercoagulability and pregnancy morbidity, poses a significant clinical challenge when involving organ systems, such as the endocrine system. APS can directly and indirectly influence the anterior and posterior lobes of the pituitary gland. The thyroid gland exhibits involvement, especially in patients with positive anticardiolipin antibodies, yet the clinical significance of the relationship with APS remains elusive. The pancreas, often overlooked, manifests in diverse ways, from pancreatitis to implications in diabetes. Adrenal insufficiency emerges as a common endocrine manifestation of APS, with adrenal hemorrhage or infarction being a presenting manifestation. Adrenal gland involvement has also been reported in the context of catastrophic APS. Pregnancy complications and infertility might be effects of APS on the female ovaries, while testicular torsion and decreased sperm concentration and total sperm count have been reported as rare effects of APS on male testes.