Secrets & Pearls of Rheumatology at ACR Convergence 2025

CHICAGO—At ACR Convergence 2025, the Secrets and Pearls of Rheumatology session presented on important clinical pearls for rheumatologists to know.

Connective Tissue Diseases

Dr. Pope

Janet Pope, MD, FRCPC, MPH, professor of medicine in the Division of Rheumatology at the University of Western Ontario Schulich School of Medicine, London, Ontario, spoke first on connective tissue diseases.

Cutaneous Rashes

To kick the talk off, Dr. Pope explained how different rashes confer different risks of the patients having systemic lupus erythematosus (SLE). For example, 5–10% of discoid patients have SLE, 50% of patients with subacute cutaneous lupus have SLE and nearly 100% of those with true malar rash have SLE.¹

The pathology of cutaneous lupus on a skin biopsy may show interface dermatitis, follicular plugging and/or lymphocytic infiltrates, plus lupus band staining with immunoglobulin M (IgM) +/- C3 deposition. To differentiate lupus rash from myositis on the hands, Dr. Pope said to look at the location. “A lupus rash is between knuckles while the dermatomyositis rash is on the knuckles (Gottron papules),” Dr. Pope explained, “but if either rash is severe, they can look similar, throughout the extensor surfaces of the digits.”

Lupus Nephritis

The first episode concerning for renal involvement in a patient with SLE requires obtaining a kidney biopsy. “The biopsy is important to determine activity or damage, the class of nephritis and the prognosis,” Dr. Pope said.

Dr. Pope explained her opinion that the treatment of lupus nephritis could be improved by both sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) therapy. GLP-1 receptor agonist use demonstrated some protection against renal progression, although limited to observational studies where patients have diabetes or obesity.²

Finally, immunosuppression can be tapered after around five years of remission of nephritis, Dr. Pope said. She referenced the WIN-Lupus Trial that tested withdrawal of immunosuppression in lupus nephritis after two years of treatment, which was not successful; the discontinuation of immunosuppressive therapy was associated with a higher risk of severe SLE flare.³

Myositis

Dr. Pope expressed her opinion that cancer screening beyond the usual recommendations in inflammatory myositis is not recommended for all patients. “This might be controversial, but low-risk patients only need routine cancer screening. You can stratify by clinical and antibody risk,” she said.

For example, an elderly patient with significant weight loss and severe dysphagia should have more extensive investigation for cancer, Dr. Pope noted. Additionally, cancer risk is increased in specific myositis antibodies, such as TIF1-gamma and NXP2.⁴

Labs in Connective Tissue Disease

Dr. Pope said it is important not to order an anti-nuclear antibody (ANA) test if there is low index of suspicion because it can generate false positive results. “This may not only generate patient concern, but is a waste of resources. And don’t repeat a positive ANA; that’s a waste of money,” Dr. Pope quipped.

The extractable nuclear antigen (ENA) test can only be positive in a negative ANA patient in positive Ro/SSA patients.⁵ “The other positive ENA tests are irrelevant if there is a negative ANA,” Dr. Pope said. “And don’t order a dsDNA [double-stranded DNA test] if the ANA is negative, as dsDNA can only be in the nucleus.”

Dr. Pope also advised to stop ordering dsDNA and complements in SLE patients if they have negative tests for several visits, unless clinically indicated.⁶ “The chance of converting to positive is very low if previously repeatedly negative,” she noted.

Raynaud’s Phenomenon

Dr. Pope highlighted a phone application called Magnifier that allows you to visualize nailfolds when evaluating patients with Raynaud’s phenomenon. “Abnormal nailfold capillaroscopy increases the chance of developing a future connective tissue disease,” Dr. Pope said.

Scleroderma

Interstitial lung disease in systemic sclerosis can occur at any time, in both the diffuse and limited subsets, though risk is highest in the first few years, Dr. Pope reviewed.

Sjögren’s Disease

“Repeatedly screening all patients with Sjögren’s disease for lymphoma is unnecessary,” Dr. Pope said. “This is a waste of money.” She suggested instead screening higher-risk patients, such as those with B symptoms or weight loss, or features like persistent salivary gland enlargement, low complement and positive cryoglobulins.⁷

Other Rheumatic Diseases

Dr. Chatham

Walter Winn Chatham, MD, professor of internal medicine, clinical immunology and rheumatology at the Kirk Kerkorian School of Medicine, University of Nevada, Las Vegas, spoke next about clinical pearls in other rheumatic diseases.

Crystalline Arthropathy

Calcium pyrophosphate disease (CPPD) was noted to be a mimic of giant cell arteritis or polymyalgia rheumatica. For example, an elderly patient may present with shoulder/hip girdle pain and high inflammatory markers with neck pain and occipital headache, but have the crowned dens sign of CPPD on radiographs.⁸

Additionally, patients with gout or CPPD may present with systemic inflammatory response syndrome (SIRS)–like phenotype and high C-reactive protein levels. “Consider gout and CPPD in the differential for nosocomial fever in elderly patients, especially after infection is ruled out,” Dr. Chatham said. “Crystalline arthritis can be highly inflammatory.”

Seronegative Syndromes

“Consider seronegative spondyloarthritis if a patient has joint tenderness of the great toe IP [interphalangeal] joint,” Dr. Chatham said, noting it is often a signal enthesal focus. He discussed how polyenthesal tenderness points can sometimes be confused with fibromyalgia.

Patients with psoriatic disease commonly have sicca features including ocular sicca and xerostomia, which is often underappreciated, Dr. Chatham said.⁹

Medications

ANA positivity can commonly develop in patients on anti-tumor necrosis factor (TNF) therapy, and, rarely, drug-induced lupus can occur. The incidence of drug-induced lupus in patients on TNF inhibitors is estimated at 0.2–2%.¹⁰

“When using intravenous immunoglobulin [IVIg], passive antibody transfer with IVIg can have significant impacts that are important to recognize,” Dr. Chatham said. “This includes interfering with autoantibody results due to false positives from passive antibody transfer.” He explained how IVIg can also cause an immune complex vasculitis in patients with cryoglobulin syndrome or immune complexes that contain rheumatoid factor.

Other Miscellaneous Problems

Refractory greater trochanteric bursa pain syndromes are often due to unrecognized or undertreated innominate pelvic rotation and sometimes altered mechanics from genu varum/valgus, Dr. Chatham pointed out.

Acalculous cholecystitis is noted as a bellwether for possible underlying autoimmunity.^11,12 “This is not an uncommon complication of patients with SLE, Sjögren’s and systemic sclerosis,” Dr. Chatham added. “And importantly, this can antedate the diagnosis of these disorders and occur in healthy patients and is not only seen in critical illness.”

Malignancy Pearls

In older adult patients, it is important to recognize IgA vasculitis in the absence of an infectious trigger has a high association with malignancy.¹³ Similarly, macrophage activation syndrome or secondary hemophagocytic lymphohistiocytosis (HLH) phenotype in patients older than 60 years is most likely due to malignancy, requiring malignant HLH to be evaluated thoroughly.¹⁴

Mithu Maheswaranathan, MD, is an assis­tant professor of medicine in the Division of Rheumatology at Duke University School of Medicine, Durham, N.C. and can be followed on X/Twitter @MithuRheum.

References

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