Dose Tapering and Discontinuation of Biologic DMARDs in Axial Spondyloarthritis: A Narrative Review (2023 SPARTAN Annual Meeting Proceedings).

PURPOSE OF REVIEW: Limited data is available for tapering or discontinuation of biologic therapy in patients with axSpA who are in disease remission. The current review concentrates on published studies regarding dose tapering or withdrawal of biologics in axSpA. RECENT FINDINGS: Recent evidence in light of randomized controlled trials suggests that tapering of b-DMARDs is a feasible strategy to maintain remission or low disease activity in axSpA patients. TNF inhibitors were the studied biologics in most of these trials. The disease flare rates were comparable to those maintained on standard dose in most of these studies, although with variable tapering strategies and follow-up. Additionally, the duration of disease in remission prior to tapering, studied primary outcome, and flare definitions were heterogeneous. Female sex, HLA-B*27 negativity, high physician global score, and high CRP were negative predictors of successful tapering, but not consistently reported in all the trials. Although designed to address efficacy, there were no safety concerns with b-DMARD tapering. Withdrawal or complete discontinuation of biologics met with increased risk of flares compared to standard dosing. Tapering of TNF inhibitors may be feasible in certain axSpA patients with an acceptable disease state; however, discontinuation is not currently recommended owing to increased risk of flare. Future studies with axSpA patients with longer remission duration prior to taper and different doses and types of b-DMARDs may provide more guidance.

Clinical profile and treatment utilisation based on HLA-B*27 status in axial spondyloarthritis: results from ASAS-PerSpA study.

OBJECTIVE: We aimed to characterize differences of clinical features, extra-musculoskeletal manifestations and treatment utilizations based on the patients' HLA-B*27 status in a global axSpA cohort and identify predictors of HLA-B*27 negativity in these patients. METHODOLOGY: In post-hoc analysis of the ASAS-PerSpA study, patients fulfilling the 2009 ASAS classification criteria for axSpA and typed for HLA-B*27 were included. The patient characteristics cwere compared between the HLA-B*27(+) and HLA-B*27(-) subgroups. Multivariablete logistic regression was conducted to identify predictors of HLA-B*27 negativity. RESULTS: Of 2910 patients with axSpA from 24 countries, 2269 were tested for HLA-B*27 [1753 HLA-B*27(+) and 516 HLA-B*27(-)]. The proportion of males was higher in the HLA-B*27 (+) compared to the HLA-B*27 (-) subgroup (72.1 vs 54.3%). Patient population with HLA-B*27 (+) more often had positive family history for axSpA (29.8 vs 15.3%), and younger age at diagnosis, 31.6 years (SD 10.9) vs 37.7 years (SD 12.1). HLA-B*27 (-) patients had significantly higher peripheral arthritis (47.5 vs 42.1%, p<0.05), psoriasis (19.4 vs 10.2), enthesitis (56.6 vs 49.8%) and IBD (12.8 vs 3.4) (p<0.001). The exposure to csDMARDS in HLA-B*27 (-) patients was higher (61.2 vs 55.0%, p< 0.05). On multivariable analysis, HLA-B*27 (-) status was positively associated with enthesitis, psoriasis and IBD with an OR 1.27 (1.02-1.57), 1.84 (1.36-2.48) and 4.84 (3.23-7.30) respectively, and inversely associated with uveitis, OR 0.37 (0.27-0.50). CONCLUSION: HLA-B*27 (-) axSpA patients had a longer delay in diagnosis, more frequently had peripheral arthritis, enthesitis, IBD, psoriasis, and were more often treated with csDMARDs compared to HLA-B*27 (+) subgroup.

All-Cause and Cause-Specific Mortality in Psoriatic Arthritis and Ankylosing Spondylitis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are chronic inflammatory diseases associated with a higher risk of cardiometabolic comorbidities compared to the general population. Individual studies examining mortality in these patients have produced conflicting results. The present study was undertaken to perform a systematic review and meta-analysis to analyze the all-cause and cause-specific mortality in PsA and AS from the available literature. METHODS: A comprehensive database search was performed for studies reporting all-cause or cause-specific mortality in patients with PsA and AS compared with the general population. Pooled relative risks (RRs) were calculated using a random-effects model. RESULTS: We included 19 studies (11 of PsA, 7 of AS, 1 of both). In PsA studies, there was no increased mortality compared to the general population (RR 1.12 [95% confidence interval (95% CI) 0.96-1.30]; n = 10 studies). We found a higher all-cause mortality in female (RR 1.19 [95% CI 1.04-1.36]) but not in male (RR 1.02 [95% CI 0.66-1.59]) PsA patients. Cardiovascular-, respiratory-, and infection-specific mortality risks were significantly higher for PsA patients (RR 1.21 [95% CI 1.06-1.38], RR 3.37 [95% CI 1.30-8.72], and RR 2.43 [95% CI 1.01-5.84], respectively), but not cancer-related mortality (RR 1.01 [95% CI 0.91-1.11]). In AS, we found a higher risk of death from all causes (RR 1.64 [95% CI 1.49-1.80]; n = 6 studies) and cardiovascular causes (RR 1.35 [95% CI 1.01-1.81]; n = 3 studies) compared to the general population. All-cause mortality was high in both male (RR 1.56 [95% CI 1.43-1.71]) and female (RR 1.85 [95% CI 1.56-2.18]) AS patients. The included AS studies did not report mortality data for non-cardiovascular causes. CONCLUSION: This systematic review and meta-analysis showed a significantly increased risk of overall mortality in AS but not PsA. Cardiovascular-specific mortality was higher for both PsA and AS, which emphasizes the importance of early screening and management of cardiovascular risk factors.

COVID-19-Associated Thrombotic Thrombocytopenic Purpura: A Case Report and Systematic Review.

INTRODUCTION: The proliferation of literature regarding the COVID-19 pandemic has served to highlight a wide spectrum of disease manifestations and complications, such as thrombotic microangiopathies. Our review with a brief case presentation highlights the increasing recognition of TTP in COVID-19 and describes its salient characteristics. METHODS: We screened the available literature in PubMed, EMBASE, and Cochrane databases from inception until April 2022 of articles mentioning COVID-19-associated TTP in English language. RESULTS: From 404 records, we included 8 articles mentioning data of 11 patients in our review. TTP was predominantly reported in females (72%) with a mean age of 48.2 years (SD 15.1). Dyspnea was the most common symptom in one third of patients (36.6%). Neurological symptoms were reported in 27.3% of cases. The time to diagnosis of TTP was 10 days (SD 5.8) from onset of COVID-19. All 11 cases underwent plasma exchange (PLEX), with a mean of 12 sessions per patient, whereas 6 cases received Rituximab (54.5%), and 3 received Caplacizumab (27.3%). One patient died from the illness. CONCLUSION: This review of available literature highlights the atypical and refractory nature of COVID-19-associated TTP. It required longer sessions of PLEX, with half of the patients receiving at least one immunosuppressant.

Etiology, pathological characteristics, and clinical management of black pleural effusion: A systematic review.

BACKGROUND: Pleural effusion is characterized by excessive fluid collection in the pleural cavity. Black pleural effusion (BPE) is a rare entity with only limited scientific data. We aimed to review the current literature on black pleural effusion to characterize demographics, etiology, clinical presentation, pathological findings, available treatment strategies, and prognosis of this rare condition. METHODS: We performed a systematic review of case reports and series and synthesized data on demographics, manifestations, management, and outcomes of patients with BPE. We searched Cochrane Library, PubMed, SCOPUS, and Google Scholar for any date until January 10, 2021. All studies (n = 31) that reported black pleural effusion in patients were added to the review. Prospective Register of Systematic Reviews registration number: CRD42020213839. Summary and descriptive analysis was performed on Jamovi version 1.2. RESULTS: The mean age of 32 patients with BPE was 53 years, with male predominance (69%). The commonest risk factor was smoking (n = 9) followed by alcohol intake (n = 8). Dyspnea was the commonest symptom (n = 24, 75%). Pleural fluid was mostly exudative (n = 21). The commonest associated diagnosis was malignancy (n = 14), with 50% secondary to metastatic melanoma. The commonest intervention was therapeutic thoracocentesis (n = 25, 78%), and the effusion recurred in half of the cases where recurrence was reported (n = 13). In our review, we found the mortality rate to be at 20.8% (n = 20.8%). 58.3% of the patients were successfully treated and discharged home (n = 14). CONCLUSION: Although rare, BPE appears to be a relevant symptom as it seems to be frequently associated with modifiable risk factors and underlying malignancy. Our systematic review substantiates a vital research gap as observational research is imperative to characterize BPE further and form a basis for designing tailored diagnostic, preventive, and therapeutic strategies for BPE.

Spontaneous pneumomediastinum mimicking acute pericarditis.

ST elevations on electrocardiogram (ECG) have a broad differential diagnosis that can vary from benign to more ominous pathologies. These include early repolarization, coronary vasospasm, acute pericarditis, ST-elevation myocardial infarction, ventricular aneurysms, and dissecting aneurysm of the aorta reaching the pericardium. ST-segment changes may also provide a clue to the presence of spontaneous pneumomediastinum (SPM). These ECG changes are seldom reported in literature. We describe two SPM cases with concomitant pneumopericardium that closely mimicked acute pericarditis with a deceptive clinical spectrum.

Central Venous Sinus Thrombosis with Subarachnoid Hemorrhage Following an mRNA COVID-19 Vaccination: Are These Reports Merely Co-Incidental?

BACKGROUND Multiple vaccines have been developed against COVID-19 as a collaborative worldwide effort. On March 18, 2021 the European Medicines Agency reported a serious and rare adverse effect of thrombosis with thrombocytopenia syndrome (TTS) after receiving the ChAdOx1 nCoV-19 vaccine; most of these cases were associated with cerebral venous sinus thrombosis (CVST). To date, there are no cases of TTS-related CVST reported after receipt of either of the 2 mRNA COVID-19 vaccines authorized for use in the United States. We report a case of CVST with the Moderna mRNA vaccine. CASE REPORT A healthy 45-year-old male patient without any risk factors presented with new-onset seizures 8 days after the receipt of the 2nd dose of Moderna (mRNA-1273), with concomitant SAH as a complication. One day prior to admission, he noted headaches and neck pain unrelieved by over-the-counter analgesics. Computed tomography (CT) scan brain without contrast revealed a left frontal lobe intracerebral hemorrhage (ICH) along with subarachnoid hemorrhage (SAH). A subsequent contrast-enhanced magnetic resonance imaging (MRI) brain confirmed the CT findings as well as anterior superior sagittal sinus thrombosis. He had normal platelet count with a negative thrombophilia work-up and cancer screening. He was successfully anticoagulated with heparin and discharged on warfarin without neurological sequelae or further seizures. The case was reported to the US Vaccine Surveillance System. CONCLUSIONS mRNA vaccine-related CVST is an extremely rare phenomenon. More data are needed to establish causality and understand the role of vaccine-related immune response resulting in thrombotic events with or without TTS.

Avoiding Anchoring Bias in the Times of the Pandemic!

COVID-19 has a broad spectrum of clinical presentations, including central nervous system manifestations that are not uncommon. The high pretest probability of COVID-19 in pandemic can lead to anchoring. We present a patient of COVID-19 pneumonia who presented with dyspnea and acute confusional state. His initial workup was suggestive of tuberculous meningoencephalitis with lymphocytic pleocytosis, high protein in CSF analysis, and suspicious MRI findings, which was later confirmed with a positive CSF culture. To the best of our knowledge, it is the first such case. Anchoring to the diagnosis of COVID-19 may deter clinicians from considering other concurrent diagnoses and a poor outcome consequently.

Cavitary pulmonary tuberculosis with COVID-19 coinfection.

The COVID-19 pandemic has strained the healthcare system worldwide, leading to an approach favoring judicious resource allocation. A focus on resource preservation can result in anchoring bias and missed concurrent diagnosis. Coinfection of Mycobacterium tuberculosis (TB) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has implications beyond morbidity at the individual level and can lead to unintended TB exposure to others. We present six cases of COVID-19 with newly diagnosed cavitating pulmonary tuberculosis to highlight the significance of this phenomenon and favorable outcomes if recognized early.

The Use of Pleural Fluid to Serum Glucose Ratio in Establishing the Diagnosis of a Not So Sweet PD-Related Hydrothorax: Case Report and Literature Review.

Hydrothorax is a well-known but rare complication of peritoneal dialysis (PD), with an average incidence of 2% mainly in cases of continuous ambulatory peritoneal dialysis (CAPD). In more than 80% of these cases, the hydrothorax is attributed to an abnormal pleuroperitoneal communication. It commonly manifests as unilateral effusion, predominantly on the right. A thoracentesis to determine pleural glucose has been a diagnostic aid well relied on, as the dextrose rich dialysate raises the pleural fluid glucose. A pleural fluid glucose to serum glucose gradient greater than 50 mg/dL is suggestive of a leak with a specificity of 100% according to some studies; however, its sensitivity is variable. Our case illustrates a diagnostic dilemma due to a relatively low pleural fluid to serum glucose gradient of 21 mg/dL that caused a delay in diagnosis. A pleural fluid to serum glucose ratio >1.0 was used as a diagnostic marker that pointed toward a peritoneal leak. For confirmation, a peritoneal scintigraphy with nuclear technetium 99 scan was performed that revealed a pleuroperitoneal fistula as the source of the recurring hydrothorax in the setting of automated peritoneal dialysis (APD). The hydrothorax completely resolved with termination of APD on follow-up as the patient was transitioned to intermittent hemodialysis (HD).

Fungal Malignant Otitis Externa Involves a Cascade of Complications Culminating in Pseudoaneurysm of Internal Maxillary Artery: A Case Report.

BACKGROUND Pseudomonal infection is the most common cause of malignant otitis externa (MOE), which typically affects elderly diabetic patients. Fungi are a rare cause of MOE. MOE can be life-threatening if not recognized and treated promptly. It can result in a wide spectrum of complications, including skull-base osteomyelitis, cranial nerve palsy, cerebral venous thrombosis, and brain abscess. Pseudoaneurysm formation of the intracranial vessels is a life-threatening complication of MOE that is seldom reported in the literature. CASE REPORT We report the case of a 66-year-old diabetic man with MOE who was initially treated with antipseudomonal antibiotics after negative initial culture results. His MOE resulted in a cascade of complications, including facial nerve palsy, skull base osteomyelitis, and sigmoid sinus thrombosis, and culminated in left maxillary artery pseudoaneurysm formation resulting in massive epistaxis and hemodynamic instability. Endovascular embolization resulted in a successful obliteration of the pseudoaneurysm. A subsequent functional endoscopic sinus surgical (FESS) tissue biopsy confirmed Candida glabrata as the etiological agent. The patient was successfully treated with antibiotics and antifungal and anticoagulation therapy, and was discharged home in good condition. CONCLUSIONS A high index of suspicion for the diagnosis of fungal MOE, particularly in intractable cases of MOE with negative initial cultures, should be maintained. Pseudoaneurysm formation is a life-threatening complication of MOE that is seldom reported in the literature and should be suspected in any patient with MOE who presents with epistaxis or intracranial bleeding.

Portomesenteric Thrombosis Secondary to Acute Cholecystitis: A Case Report.

Portomesenteric venous thrombosis (PMVT) is an uncommon clinical problem. Common risk factors include intra-abdominal infections, abdominal surgeries, malignancy, cirrhosis, and inherited thrombophilia. Early recognition and treatment of PMVT are important to avoid serious complications like mesenteric ischemia and infarction. Acute cholecystitis is a clinical condition encountered daily but rarely may be complicated by development of portomesenteric venous thrombosis. Only few cases have been reported of superior mesenteric vein thrombosis secondary to cholecystitis. We report a case of a forty-one-year-old male patient who developed partial portal and superior mesenteric vein thrombosis after mild acute cholecystitis for which surgery had been deferred. Patient had no other identifiable risk factors for thrombosis. Patient was successfully treated with 6 months of anticoagulation with warfarin and complete recanalization of portomesenteric veins was achieved at the end of treatment.

Symptom experience in patients with primary brain tumours: a longitudinal exploratory study.

PURPOSE: This study was undertaken to further understand the symptom experience and the impact of symptoms in daily life in people treated for brain tumours. METHODS: A qualitative prospective longitudinal design was used with 9 people who were interviewed over 4 time points (soon after diagnosis, 3 months, 6 months and 12-months post-diagnosis), providing 21 interviews in total. RESULTS: Key issues for these participants were ongoing fatigue, memory loss and inability to drive. Fatalistic views about the outcomes of their disease were the norm. Participants made adjustments to their lives to accommodate their functional limitations. These included making home alterations, introducing regular exercise to their lives and using complementary therapies. Their expectations did not always match with the reality of the situation, which made several participants angry and dissatisfied with health care professionals. CONCLUSIONS: Issues of quality of life are paramount in this group of poor prognosis patients, therefore, health professionals should provide preparatory information to patients on what to expect from the illness and its treatments. Health professionals should also assist patients to manage debilitating symptoms such as fatigue and cognitive impairment.