Lessons of the month 3: Haemophagocytic lymphohistiocytosis following COVID-19 vaccination (ChAdOx1 nCoV-19).

A 36-year-old woman presented to hospital 9 days after receiving her first dose of the ChAdOx1 nCoV-19 vaccine with fever, myalgia and a sore throat. She was previously fit and well with no prior vaccine reactions.There was no clinical response to initial treatment with intravenous (IV) antibiotics. Microbiology tests including for COVID-19 were negative. At day 5, she developed pleuritic pain and a pericardial rub. Echocardiography and subsequent cardiac magnetic resonance imaging showed evidence of constrictive pericarditis. Computed tomography revealed gross hepatomegaly and moderate splenomegaly. Blood tests showed raised inflammatory markers, deranged clotting, low platelets and a marked hyperferritinaemia.A presumptive diagnosis of a multi-system inflammatory disorder secondary to recent COVID-19 vaccination was made and high-dose IV methylprednisolone initiated. Following a high 'H score' of 70%-80% a diagnosis of secondary haemophagocytic lymphohistiocytosis (HLH) was made. She was treated with IV immunoglobulin with subsequent clinical response.HLH is a rare syndrome of acute and rapidly progressive systemic inflammation characterised by cytopenias, excessive cytokine production and hyperferritinaemia. The adult form has multiple triggers, including recent vaccination. This case prompts awareness among clinicians of HLH as a rare complication of COVID-19 vaccination but should not discourage individuals from vaccination.

Constitutional morphological features and risk of hip osteoarthritis: a case-control study using standard radiographs.

OBJECTIVES: To evaluate the risk of association with hip osteoarthritis (OA) of 14 morphological features measured on standard antero-posterior pelvis radiographs. METHODS: A case-control study of 566 symptomatic unilateral hip OA cases and 1108 controls without hip OA, using the Genetics of OA and Lifestyle database. Unaffected hips of cases were assumed to reflect pre-OA morphology of the contralateral affected hip. ORs with 95% CI adjusted for confounding factors were calculated using logistic regression. Hierarchical clustering on principal component method was used to identify clusters of morphological features. Proportional risk contribution (PRC) of these morphological features in the context of other risk factors of hip OA was estimated using receiver operating characteristic analysis. RESULTS: All morphological features showed right-left symmetry in controls. Each feature was associated with hip OA after adjusting for age, gender and body mass index. Increased sourcil angle had the strongest association (OR: 6.93, 95% CI 5.16 to 9.32). Three clusters were identified. The PRC varied between individual features, as well as between clusters. It was 35% (95% CI 31% to 40%) for all 14 morphological features, compared to 21% (95% CI 19% to 24%) for all other well-established risk factors. CONCLUSIONS: Constitutional morphological variation strongly associates with hip OA development and may explain much of its heritability. Relevant morphological measures can be assessed readily on standard radiographs to help predict risk of hip OA. Prospective studies are required to provide further support for causality.

An evaluation of tofacitinib for the treatment of psoriatic arthritis.

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory condition that is associated with progressive joint destruction and reduced quality of life. Despite the common use of disease-modifying anti-rheumatic drugs (DMARDs) in PsA, their influence has been investigated in a number of studies with conflicting results. There is also concern about their safety and tolerability. Tofacitinib is an orally administered Janus kinase (JAK) inhibitor that has recently been approved for the treatment of PsA by various international regulatory authorities, including the FDA, EMA, and NICE. Areas covered: In this review, the mechanism of action and the pharmacokinetic properties of tofacitinib are discussed. The data from two large phase III clinical studies evaluating the use of tofacitinib in PsA is also discussed in addition to the findings from other relevant studies. Expert opinion: The clinical data demonstrate significant improvement in disease activity in PsA patients using tofacitinib. There is also an acceptable clinical safety profile for the drug. Tofacitinib has various advantages over several existing drug treatments for PsA including an oral route of administration, a short half-life and a fast onset of action. Consequently, we anticipate that tofacitinib will become an increasingly used targeted synthetic DMARD (tsDMARD) for active PsA over the coming years.

Apremilast: a PDE4 inhibitor for the treatment of psoriatic arthritis.

INTRODUCTION: The evidence base for disease-modifying anti-rheumatic drugs used in psoriatic arthritis (PsA) is surprisingly weak, with most having little robust evidence to support their clinical use. Furthermore, there remain safety and tolerability concerns with both these and more recently available biological therapies. Apremilast , a novel, small molecule, represents the first oral therapy specifically developed for PsA. AREAS COVERED: This review describes the pharmacokinetic properties of apremilast and available data demonstrating significant benefits to both clinical and histological features of inflammatory arthritis. The key findings from a large Phase III clinical program will also be discussed, including short- and long-term efficacy outcomes and, importantly, the safety profile. Indications other than PsA will also be briefly reviewed. Given the recent nature of much of the data, published literature as well as information available only in the abstract format are included in this review. EXPERT OPINION: Studies show that treatment with apremilast results in significant improvement in both skin psoriasis and PsA symptoms. Apremilast has been approved by both the United States FDA and European Medicines Agency for treatment of PsA. Use of this medication is recommended in active PsA patients, according to local licensing.