Highlights from the European Congress of Internal Medicine

FLORENCE, ITALY—Early treatment can help patients with systemic sclerosis (SSc) take advantage of a growing number of medication options, said Luc Mouthon, MD, PhD, head of the Internal Medicine department and Reference Center for Rare Systemic Autoimmune and Autoinflammatory Diseases of Ile de France, East and West, Cochin Hospital and Université Paris Cité.

Dr. Mouthon was one of several speakers who addressed topics related to rheumatology at the European Congress of Internal Medicine (ECIM) in Florence, Italy, in March.

Systemic Sclerosis

Dr. Mouthon

Diagnosing diffuse vs. limited SSc and determining organ involvement can have an impact on treatment selection, according to Dr. Mouthon.

Although many SSc-related deaths are associated with pulmonary arterial hypertension and interstitial lung disease (ILD), cardiac, gastrointestinal, renal or skin involvement often contributes to mortality, Dr. Mouthon explained. The failure to treat concurrent organ involvement or ILD has a negative impact on a patient’s survival.

“Unfortunately, the prognosis is the worst if we consider all the connective tissue diseases. … To treat early and efficiently, we have to get a better understanding of the pathophysiology, and identify biomarkers,” said Dr. Mouthon.

Treatment

Dr. Mouthon gave an overview of the available and upcoming treatments for SSc. For example, early diffuse SSc can be treated with low-dose glucocorticoids; immunosuppressants, including methotrexate, mycophenolate mofetil and cyclophosphamide; classical support; and early rehabilitation.

Autologous stem cell transplantation—a treatment being investigated for SSc—may be indicated for more severe cases, such as for patients with early diffuse disease, those with a severe increase on the modified Rodnan skin score or those with additional organ involvement, said Dr. Mouthon. However, it should be avoided in patients who have had SSc for more than five years or who have severe organ involvement, such as respiratory insufficiency, severe renal insufficiency or cardiac insufficiency. Patients with an inflammatory or fibrotic profile based on transcriptomics in peripheral blood mononuclear cells may respond to stem cell transplantation better than those with a sub-normal transcriptomic profile.

Abatacept is being investigated as a treatment for diffuse cutaneous SSc. Although a 2020 phase 2 trial with 88 participants found that abatacept did not lead to a significant change in the modified Rodnan skin score, the drug was well-tolerated, Dr. Mouthon said.¹

Nintedanib, an anti-fibrotic agent that targets fibroblasts and is authorized in primary pulmonary fibrosis, is a U.S. Food & Drug Administration-designated breakthrough treatment for ILD.

In a 2019 randomized trial of 576 patients with ILD associated with SSc, nintedanib slowed lung function decline more over a year than placebo.²

Nintedanib is associated with side effects, including diarrhea, which can be more common in patients with SSc than patients with other diseases.

Proton pump inhibitors are often added to the treatment of patients with SSc-associated ILD because gastroesophageal reflux may worsen ILD, Dr. Mouthon said.

A double-blind, investigator-initiated, randomized, placebo-controlled trial called DESIRES demonstrated the safety and efficacy of rituximab in SSc. Patients receiving rituximab showed improvement in modified Rodnan skin scores and limited the decline of forced vital capacity.³

Chimeric antigen receptor (CAR) T cell therapy, targeting CD19, which involves the use of activated T cells in vitro that are re-injected into the patient, is already used to treat hematological malignancy and is becoming a more common treatment for systemic lupus erythematosus (SLE) and SSc, Dr. Mouthon said. There are ongoing randomized clinical trials in Europe investigating these applications.

Other studies are evaluating newer treatments, such as targeting the interferon alpha pathway with anifrolumab or treating pulmonary arterial hypertension with sotatercept, for SSc.

Dr. Mouthon cited a recent review article in Nature Reviews Rheumatology, which he co-authored, as a useful overview on the future of SSc research.⁴

PMR Management

Although polymyalgia rheumatica (PMR) is commonly seen by internal medicine specialists, patients with suspected PMR should be referred to a rheumatologist if they have atypical features, are young, have prominent peripheral arthritis or have an inadequate response to or difficulty with glucocorticoid tapering, according to Enrica Cipriano, MD, rheumatology researcher at Sapienza University of Rome.

Up to 30% of patients with PMR can develop giant cell arteritis (GCA), said Dr. Cipriano. GCA can precede, accompany or follow a PMR diagnosis.

“When we screen a patient for PMR, we always have to search for warning symptoms of [GCA],” said Dr. Cipriano. These may include vision loss, a severe headache or tongue pain among other symptoms.

Additionally, “High fever, weight loss and adenopathy could [indicate] giant cell arteritis or malignancies,” she said.

Some patients with PMR who also have GCA can manifest swelling of the hands.

Imaging techniques are not always needed to diagnose PMR but can help with an unusual presentation. “Ultrasonography has a central role in the diagnosis and screening of patients because it allows us to see joints and peri-articular tissue and to study the artery wall,” Dr. Cipriano said.

A CT exam is also useful if there’s strong suspicion of GCA, she added. She cited the 2021 EULAR/ACR classification criteria for PMR, which include being 50 years or older with bilateral shoulder pain not explained by other pathology, morning stiffness lasting more than 45 minutes, an elevated C-reactive protein or erythrocyte sedimentation rate, and new hip pain.⁵

Late-onset rheumatoid arthritis (RA) can mimic PMR, particularly because RA can present with symptoms of PMR, said Dr. Cipriano. Because of this, all patients with PMR should be screened for RA antibodies.

PMR can also be an immune-related adverse event in about 5% of patients using immune checkpoint inhibitors, she said. The majority of these patients respond well to treatment with glucocorticoids. EULAR’s 2021 statement regarding the diagnosis and management of people who develop rheumatic adverse events from cancer immunotherapy with checkpoint inhibitors is instructive, she added.⁶

Dr. Cipriano also addressed the link between PMR and malignancies. Although not every patient with PMR needs to be screened for malignancies, she said that patients who do not respond to therapy should be checked.

Most PMR patients respond well to glucocorticoids—typically a slowly tapered, 12 mg to 25 mg dose of prednisone or equivalent. It’s important to be aware of comorbidities or risk factors that can lead to adverse events.

“If disease flare-up occurs, we can increase the pre-relapse dose and slow the tapering. If we have patients who are contraindicated for long-term therapy with steroids or who can develop adverse events related to therapies, the indication is to start immunosuppressive drugs early,” Dr. Cipriano said. Most commonly, this will be methotrexate.

Autoimmune Testing

In her presentation, Pitfalls of Autoimmune Serological Markers, Chiara Bellocchi, MD, PhD, shared indications that a patient requires serological testing and questions to help determine if a patient has rheumatic disease.

Dr. Bellocchi

Dr. Bellocchi is a researcher in the Department of Clinical and Community Sciences, University of Milan, and clinical immunologist, Department of Internal Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan. Here are a few pearls she shared:

• About 10–20% of the population will test positive for anti-nuclear antibodies. Their presence could be normal but could also indicate future autoimmune disease. It’s often a useful first test for suspected connective tissue disease or idiopathic inflammatory myopathies;
• Anti-dsDNA is highly specific to SLE and presents in fewer than 2% of other autoimmune diseases. However, patients with drug-induced lupus will test negative for anti-dsDNA;
• Low levels of C3 or C4 may indicate an immune-complex disease, such as SLE or vasculitis;

Questions to help diagnose connective tissue disease:

• Do you have a family history of systemic autoimmune disease?
• Have you ever had a low-grade fever for a few weeks for no specific reason?
• Do you have dry eyes or dry mouth?
• Do your fingers turn white, blue or red when exposed to temperature changes?
• Have you ever had pericarditis?

Questions to help diagnose arthritis:

• Do you have a family history of systemic autoimmune disease?
• Do you have joint pain or swelling?
• Do you have psoriasis?
• Have you had recent infections?
• Do you have a history of inflammatory bowel disease?

Be prepared to ask about family history twice. It may take patients a few minutes to reflect on their family’s health background and see how that may connect to autoimmune disease.

Rheumatology Poster Highlights

In the ECIM’s poster sessions, researchers led by Javier Martinez de Victoria- Carazo, MD, San Cecilio Clinical University Hospital, Granada, Spain, reported on a 29-year-old woman who had been diagnosed with SLE in 2006 and was on regular treatment to achieve remission. Her treatments included aspirin, hydroxychloroquine and deflazacort.

In 2020, the patient presented with lower limb weakness and ascending sensory loss at T6. She previously had a febrile episode with acute urinary retention. A neurological examination confirmed motor deficit and sensory loss below T6. An analysis led to the diagnosis of transverse myelitis as a rare lupus manifestation and was thought to be triggered by a herpes virus reactivation.

Immunocompromised patients with neurological symptoms need a swift differential diagnosis to pinpoint the cause of neurological issues, the researchers concluded.

Researchers from the rheumatology department at PAGNI General Hospital, Herakilon, Greece, led by Konstantinos Giakoumakis, shared the case of a 46-year-old patient who presented with a fever for 20 days, despite treatment for a suspected respiratory infection. Other symptoms included dyspnea, peripheral edema and splenomegaly. He also had a chronic perineal furuncle that was drained weekly.

Lab testing confirmed cytomegalovirus (CMV) and positive serology for anti-nuclear antibodies (ANA 1:640), anti-cardiolipin antibodies and elevated immunoglobulin levels. “This case illustrates the diagnostic complexity of SLE, especially when coexisting with infections such as CMV,” the authors concluded.

Vanessa Caceres is a writer in Bradenton, Fla.

References

1. Khanna D, Spino C, Johnson S, et al. Abatacept in early diffuse cutaneous systemic sclerosis: Results of a phase II investigator-initiated, multicenter, double-blind, randomized, placebo-controlled trial. Arthritis Rheumatol. 2020 Jan;72(1):125–136.
2. Distler O, Highland KB, Gahlemann M, et al. Nintedanib for systemic sclerosis-associated interstitial lung disease. N Engl J Med. 2019 Jun 27;380(26):2518–2528.
3. Ebata S, Yoshizaki A, Oba K, et al. Safety and efficacy of rituximab in systemic sclerosis (DESIRES): Open-label extension of a doubleblind, investigators-initiated, randomised, placebo-controlled trial. Lancet Rheumatol. 2022 Aug;4(8):e546–e555.
4. Abraham D, Black CM, Denton CP, et al. An international perspective on the future of systemic sclerosis research. Nat Rev Rheumatol. 2025 Mar;21(3):174–187.
5. Dasgupta B, Cimmino MA, Maradit-Kremers H, et al. 2012 provisional classification criteria for polymyalgia rheumatica: A European League Against Rheumatism/American College of Rheumatology collaborative initiative. Ann Rheum Dis. 2012 Apr;71(4):484–492.
6. Kostine M, Finckh A, Bingham CO, et al. EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors. Ann Rheum Dis. 2021 Jan;80(1):36–48.