Rheumatologists should play ‘active role’ in sarcoidosis management

SAN DIEGO — Rheumatologists may be the best clinicians to manage the challenges presented by sarcoidosis, which include a complex disease course and few treatment options, said a presenter at the 2024 Congress of Clinical Rheumatology West.

“Rheumatologists should be playing an active role in managing sarcoidosis,” Matthew C. Baker, MD, MS, clinical chief in the division of immunology and rheumatology at Stanford University, and the co-director of the Stanford multidisciplinary sarcoidosis program, told attendees.

In his talk, Baker aimed to “dispel the myth” that sarcoidosis is only a pulmonary disease.

“I would make the case that many sarcoidosis patients do not have meaningful pulmonary involvement,” he said.

According to Baker, sarcoidosis is often a multisystemic disease that can involve the central nervous system or the skin with a lupus pernio rash. Patients may additionally experience cardiac involvement, incidental granulomatous inflammation in the spleen or nodules in a perilymphatic distribution, among other complications.

“Many patients have other manifestations that are overlooked or not being treated,” Baker said. “There is a need for multidisciplinary care. A rheumatologist can serve as the point person to coordinate care for all these specialties.”

Moreover, sarcoidosis can mimic IgG4 or Sjögren’s disease.

“Unlike in those diseases, where we are managing the entire picture, with sarcoidosis, we are only called in if the patient develops chronic arthritis,” Baker said.

Although investigators have yet to paint a full picture of the etiology of the disease, he suggested that there is likely a background of genetic risk that is triggered by an infectious agent or autoantigen. The T cells Th1 or Th17.1 are activated and secrete cytokines like TNF, interferon-gamma and GMCSF, according to Baker.

“B cells are quite under studied in this disease,” he added. “What we do not understand is that some patients have a resolution of this disease but others develop a chronic condition.”

Importantly, not all patients with sarcoidosis require treatment, at least in part because of the subgroup of patients who experience spontaneous resolution, Baker said. However, those with uveitis, serious cutaneous involvement, cardiac, splenic or neurological complications require management.

“These more serious manifestations need treatment,” Baker said.

Meanwhile, approximately one-third of patients will resolve and another one-third will have a “relapsing, remitting” course of disease, he added.

“Then others have chronic fibrotic disease no matter what treatments we give them,” Baker said.

All of this information informs research in the pipeline.

For example, researchers have studied infliximab (Remicade, Janssen) and reported some efficacy in extra-thoracic disease for patients with heart and skin involvement, according to Baker.

Janus kinase (JAK) inhibitors, particularly those in the JAK1 and TYK2 classes, are also under investigation, as is the anti-GMCSF inhibitor namilumab (Micromet), the MTOR inhibitor sirolimus (Rapamune, Pfizer) and the neuropilin-2 modulator efzofitimod (aTyr Pharma).

“We are entering a new era of treatment that is really exciting,” Baker said.

However, most of these agents are still not widely used in the clinic. Until FDA approvals are in place, sarcoidosis is primarily managed using prednisone in the first line, followed by methotrexate and then infliximab.

“Then consider something like rituximab (Rituxan, Genentech) or a JAK inhibitor,” Baker said.

Guidelines are available, but may not be as helpful as similar documents for other diseases. “The only strong recommendation is for glucocorticoids,” Baker said. “Everything else is conditional because of low or very low quality of evidence.”

With a complicated patient population, scant treatments and few studies, Baker returned to his initial point.

“It is key that rheumatology gets involved in managing sarcoidosis,” he said.