Rheumatology Digest

A 19-year-old woman has three weeks of painful neck swelling, then fever, drenching night sweats, joint and tendon tenderness and a low white-cell count, and broad-spectrum antibiotics change nothing. Work through the case one finding at a time, with fourteen multiple-choice checkpoints covering the infectious, malignant and rheumatic differentials, the clues in the blood tests and imaging, what the biopsy has to show, and what the diagnosis means for her future.

AFFINITY was a 91-patient phase 2a trial of dual blockade, subcutaneous guselkumab (anti-IL-23) 100 mg plus golimumab (anti-TNF) 50 mg versus guselkumab alone, every 4 weeks, in psoriatic arthritis that had not responded to one or two TNF inhibitors. It missed its primary endpoint: minimal disease activity at week 24 was 29% with the combination and 22% with guselkumab alone. ACR50 (44% vs 22%) and physical function favoured the combination, and a post hoc split by CRP found the benefit concentrated in patients with CRP of 0.3 mg/dL or more (MDA 32% vs 5%, ACR50 55% vs 14%), with a reversed signal in the low-CRP group. Skin, enthesitis and dactylitis responses were similar, and no new safety signal appeared through week 36.

A Nature Reviews Rheumatology review argues that the liver is an upstream player in autoimmune rheumatic disease and not only a bystander. Hepatocytes make β2-glycoprotein I, paraoxonase-1 (PON1), complement, CRP, hepcidin and most circulating antioxidants, and they process nutrients, drugs, toxins and gut microbial products. In lupus-prone mice, hepatic mitochondrial oxidative stress and mTOR activation come before autoantibodies, and loss of PON1 may let β2GPI become an immunogenic antigen in lupus and antiphospholipid syndrome. The review also covers lupus hepatitis versus autoimmune hepatitis, MASLD in rheumatic disease, how disease-modifying drugs affect the liver, when to biopsy, and liver-directed treatments, most of which are still experimental.

An expert review in Arthritis & Rheumatology on how to define, predict and treat progressive pulmonary fibrosis (PPF) in systemic sclerosis-associated ILD. It compares the competing definitions of progression (and why they give prevalence estimates from about 14% to 49%), summarises prognosis, screening and monitoring advice, risk factors and biomarkers, and walks through treatment: mycophenolate first, then rituximab, tocilizumab, nintedanib and the newly approved nerandomilast, with combination therapy increasingly used on thin comparative evidence. The authors stress that predicting who will progress is still unsolved and that the PPF label works best as a trigger to escalate treatment.

The 2026 update of the EBMT–ISCT–JACIE consensus sets out when CAR T cells can be considered in severe, refractory autoimmune disease, and how to run the treatment. It covers eligibility and exclusions disease by disease (SLE, systemic sclerosis, rheumatoid arthritis, myositis, Sjögren’s disease, neurological and haematological disorders), drug washout before leukapheresis, lymphodepletion, hospital stay, immune monitoring, management of cytokine release, neurotoxicity, local toxicity (LICATS) and cytopenias, infection prophylaxis, vaccination and 15-year follow-up. The recommendations are expert opinion built on uncontrolled case series and are not graded.

DXA bone density misses many people who go on to fracture, and in some fracture liaison services up to 30% report too little DXA access. This Nature Reviews Rheumatology review, written under a WHO Collaborating Centre, surveys the single-component tools that add to it or stand in for it: heel and pulse-echo ultrasound, REMS, trabecular bone score, finite element analysis, 3D shape modelling from DXA, and AI that reads bone density and vertebral fractures from routine X-rays and CT. Trabecular bone score and REMS are the best established. The harder questions now are validation across populations, calibration, equity of access and whether the tools relieve DXA services.

A reference for interpreting complement tests in rheumatology. It starts from the pattern (low C3 and C4, low C4 with normal C3, low C3 with normal C4, absent CH50 or AH50, or raised levels), then sets out what each pattern points to, the next test to send, and the prognostic weight of low complement in SLE, cryoglobulinaemia, Sjögren’s disease, IgG4-related disease, ANCA vasculitis and antiphospholipid syndrome. It also covers inherited deficiency, laboratory pitfalls and the complement inhibitors now in use.

Reported incidence of antiphospholipid syndrome ranges from 0.75 to 6.49 per 100,000 person-years and prevalence from 6 to 50 per 100,000, but this Nature Reviews Rheumatology article shows that much of that spread comes from how a case is defined, which antibodies are measured, whether positivity is confirmed after 12 weeks, and who gets tested. It explains how the 1999, 2006 and 2023 criteria changed who counts as a case, why a single positive test is common and rarely means APS, and where APS is most likely to be found: unprovoked or recurrent venous thromboembolism, stroke in young adults and selected pregnancy complications.

Ten patients with severe, treatment-refractory systemic sclerosis were given teclistamab, a BCMA × CD3 bispecific T cell engager approved for myeloma, off label. B cells and plasma cells almost disappeared from bone marrow and skin, anti-topoisomerase titres fell by a median of 70.6%, and skin, lung and cardiac measures improved within 12 weeks. The price was universal severe hypogammaglobulinaemia, frequent infections and two deaths in patients with advanced heart disease, in a small, retrospective, uncontrolled series.

Patients with autoimmune rheumatic diseases are at higher risk of vaccine-preventable infections, yet coverage for influenza and pneumococcal vaccines is still poor. This Nature Reviews Rheumatology article argues that commonly used vaccines are safe, that flares and new autoimmune disease after vaccination are uncommon, and that real-world data show protection even when antibody responses are blunted. The main problems are timing around methotrexate, rituximab and obinutuzumab, CAR T cells and bispecific T cell engagers, the avoidance of live vaccines, and the hesitancy that keeps uptake low.