What's new in rheumatology

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

CRYSTAL DISEASE

Colchicine versus prednisone for acute calcium pyrophosphate deposition disease (August 2023)

Calcium pyrophosphate deposition disease (CPPD) is a common cause of acute inflammatory arthritis in patients aged 65 years or older, but data to support various therapeutic approaches are limited. In an open-label, multicenter trial in over 100 hospitalized patients aged 65 years and older with an acute flare of CPPD arthritis within 36 hours of symptom onset, patients randomly assigned to colchicine or prednisone for two days had similar improvements in self-reported pain at 24 hours [1]. Adverse effect profiles differed among the treatment groups, with more patients on colchicine reporting diarrhea and more patients on prednisone experiencing hypertension and hyperglycemia. For patients with acute CPPD who receive systemic anti-inflammatory therapy, choice of therapy should be based on the patient's history of treatment response in prior flares and an evaluation of the risks of therapy. (See "Treatment of calcium pyrophosphate crystal deposition (CPPD) disease".)

ORTHOPEDICS, SPINE, AND SOFT TISSUE RHEUMATIC DISORDERS

Barbotage procedure for calcific tendinopathy of shoulder (January 2024)

To date, few high-quality studies have assessed the effectiveness of barbotage, an ultrasound-guided procedure to remove deposits in patients with calcific tendinopathy of the shoulder. In a recent, multicenter trial, 220 adults with calcific tendinopathy of at least three months duration were randomly assigned to one of three treatment arms: barbotage plus injection with glucocorticoid and analgesic; sham barbotage plus injection with glucocorticoid and analgesic; or, sham barbotage plus injection of analgesic alone [2]. At four months, patients in all three groups experienced moderate improvement in shoulder symptoms and function, but no significant differences were noted among treatment groups. At 24 months, neither barbotage with glucocorticoid injection nor glucocorticoid injection alone was superior to sham treatment (ie, analgesic injection alone). While barbotage is likely less effective than previously thought, we believe it remains a useful therapy for some patients. (See "Calcific tendinopathy of the shoulder", section on 'Barbotage'.)

PEDIATRIC RHEUMATOLOGY

Baricitinib for refractory juvenile idiopathic arthritis (November 2023)

Janus kinase (JAK) inhibitors are one of several options for children with polyarticular juvenile idiopathic arthritis (pJIA) that is refractory to conventional therapy (eg, methotrexate with or without a biologic tumor necrosis factor inhibitor). In a phase 3, randomized trial of 220 children aged 2 to 17 years with JIA (66 percent with pJIA) who had inadequate response or intolerance to standard therapy, patients assigned to the investigational JAK inhibitor baricitinib had a longer time to disease flare compared with placebo [3]. During the study period, fewer patients receiving baricitinib had a flare compared with placebo (17 versus 51 percent, respectively), but more infections occurred in the baricitinib group than the placebo group. However, rates of serious adverse events were similar in both groups. Baricitinib compares favorably with tofacitinib, another JAK inhibitor used in refractory pJIA, but is not yet approved for this indication. (See "Polyarticular juvenile idiopathic arthritis: Treatment", section on 'Baricitinib'.)

RHEUMATOID ARTHRITIS

Triglycerides and cardiovascular risk in rheumatoid arthritis (January 2024)

Triglycerides may be particularly important to the pathogenesis of cardiovascular disease among patients with rheumatoid arthritis (RA). In a nationwide, population-based cohort study of >15,000 statin-naïve patients with RA in Korea, the risk of major adverse cardiovascular events was higher among patients with the highest baseline triglyceride levels (≥149 mg/dL) compared with those with the lowest triglyceride levels (≤72 mg/dL; adjusted hazard ratio 1.7) [4]. The same relationship was not seen with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or total cholesterol. This study implies that careful management of triglycerides may be particularly important to prevent cardiac events among patients with RA. (See "Coronary artery disease in rheumatoid arthritis: Pathogenesis, risk factors, clinical manifestations, and diagnostic implications", section on 'Risk factors specific to rheumatoid arthritis'.)

SCLERODERMA AND OTHER SYSTEMIC RHEUMATIC DISEASES

Phosphodiesterase type 5 inhibition for Raynaud phenomenon (January 2024)

Phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil and tadalafil are widely used to treat digital ischemia from Raynaud phenomenon. In an updated meta-analysis of nine randomized trials comprising 411 patients with Raynaud phenomenon (most of whom had scleroderma), treatment with PDE5 inhibition resulted in three fewer attacks weekly and a reduction in the average duration of the attacks by five minutes [5]. However, PDE5 inhibition led to minimal to no reduction in the pain associated with Raynaud phenomenon. This study implies that while PDE5 inhibition has a modest impact on the duration and frequency of Raynaud attacks, it might not be adequate to address all symptoms experienced by patients with severe disease. (See "Treatment of Raynaud phenomenon: Initial management", section on 'Phosphodiesterase type 5 inhibitor'.)

Genes associated with an increased risk for Raynaud phenomenon (October 2023)

A genetic basis for Raynaud phenomenon (RP) is supported by family and twin studies, but robust evidence for specific causal genes has been lacking. A genome-wide association study has identified two candidate genes associated with an increased risk for RP: ADRA2A and IRX1 [6]. The potential role of these genes in the pathogenesis of RP requires further study. (See "Pathogenesis and pathophysiology of Raynaud phenomenon", section on 'Genetic factors'.)

Revised criteria for pregnancy morbidity in antiphospholipid antibody syndrome (September 2023)

Obstetric antiphospholipid syndrome (APS) is sometimes used to describe patients with pregnancy morbidity, a positive test for antiphospholipid antibodies within three years of the pregnancy morbidity, and findings not attributable to another APS domain. The American College of Rheumatology and European Alliance of Associations for Rheumatology have recently updated the classification criteria for pregnancy morbidity in APS [7]. Changes included more explicit criteria for gestational age and placental insufficiency (table 1). (See "Antiphospholipid syndrome: Obstetric implications and management in pregnancy", section on 'Adverse pregnancy outcomes defining APS'.)

SYSTEMIC LUPUS ERYTHEMATOSUS AND SJOGREN'S SYNDROME

Daratumumab for lupus nephritis resistant to standard therapy (August 2023)

Lupus nephritis (LN) that is resistant to standard therapies is associated with high morbidity and mortality, and treatment options are limited. The efficacy of daratumumab, an anti-CD38 monoclonal antibody, was evaluated in a case series of six patients who received this agent over 12 months; all patients had LN resistant to mycophenolate- and/or cyclophosphamide-based regimens, as well as other therapies such as rituximab and belimumab [8]. At 12 months, five patients had an improvement in mean proteinuria, mean serum creatinine, and a systemic lupus erythematosus disease activity index; one patient had no response after six months and discontinued therapy. While these results are promising, further studies are needed to evaluate the potential role for daratumumab in treatment of LN resistant to standard therapy. (See "Overview of the management and prognosis of systemic lupus erythematosus in adults", section on 'Agents under investigation'.)

VASCULITIS

Tocilizumab and short prednisone tapers for giant cell arteritis (January 2024)

Tocilizumab may allow patients with giant cell arteritis to tolerate very short prednisone tapers. In a recent study, 30 patients with newly diagnosed or relapsing giant cell arteritis were treated with 52 weeks of subcutaneous tocilizumab (162 mg weekly) and an eight-week prednisone taper (starting with 60 mg daily) [9]. All patients entered remission after four weeks of therapy; 77 percent remained in a glucocorticoid-free remission by one year. Among patients who relapsed, the mean time to relapse was 16 weeks. Although select patients receiving tocilizumab for giant cell arteritis may be appropriate for a very short prednisone taper, larger studies are needed before broad implementation. (See "Treatment of giant cell arteritis", section on 'Unproven or ineffective agents'.)

OTHER RHEUMATOLOGY

Revised classification criteria for antiphospholipid antibody syndrome (November 2023)

Antiphospholipid antibody syndrome (APS) presents with a wide array of clinical manifestations that can cause significant morbidity, making it both an important area for research and also challenging to define in studies. The American College of Rheumatology and the European Alliance of Associations for Rheumatology have recently updated the classification criteria for APS to allow more rigorous classification in research; these criteria should not substitute for clinical judgment when diagnosing APS [7]. The new criteria include a broader range of clinical manifestations (eg, microvascular complications, cardiac valve disease, thrombocytopenia, changes to pregnancy morbidity), risk stratification of macrovascular events, and a more nuanced weighting system for antiphospholipid antibodies (eg, considering immunoglobulin G versus immunoglobulin M isotypes). (See "Diagnosis of antiphospholipid syndrome", section on 'Classification criteria'.)

Eplontersen for polyneuropathy related to hereditary transthyretin amyloidosis (November 2023)

Hereditary transthyretin amyloidosis (ATTR) is a rare but serious form of amyloidosis that can cause a rapidly progressive, sensory-motor and autonomic polyneuropathy. The efficacy of eplontersen, an antisense oligonucleotide that inhibits hepatic production of transthyretin (TTR), was evaluated in an open-label trial in nearly 170 patients with ATTR amyloidosis and polyneuropathy who received this agent for up to 66 weeks [10]. Patients treated with eplontersen had greater reductions in serum TTR concentrations, less neuropathy-related impairment, and better quality of life compared with historical controls receiving placebo. This trial contributed to US Food and Drug Administration approval of eplontersen in December 2023 for treatment of polyneuropathy of ATTR in adults [11]. (See "Overview of amyloidosis", section on 'Therapies for individual amyloid types'.)

Bleeding in Ehlers-Danlos syndromes (September 2023)

Ehlers-Danlos syndromes (EDS) are a group of rare genetic disorders of connective tissue that may cause skin hyperextensibility, joint hypermobility, tissue fragility, and vascular abnormalities. Bruising or bleeding can also occur, but EDS may not be considered due to its rarity and uncertainty about the magnitude of the bleeding phenotype. In a new study that evaluated bleeding scores in 52 individuals with several EDS subtypes, 62 percent had an abnormal score; the mean score was 9.1, well over the threshold for diagnosing a bleeding disorder [12]. Common sites of bleeding included oral, nasal, muscular, and heavy menstrual bleeding; 14 percent of females had life-threatening bleeds. This study highlights the value of considering EDS in individuals with unexplained bleeding. (See "Approach to the adult with a suspected bleeding disorder", section on 'Vascular and connective tissue disorders' and "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes", section on 'Overview'.)