‘Treatment is not one size fits all’: Sarcoidosis management must be individualized
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DESTIN, Fla. — Complicated disease pathogenesis and a lack of FDA-approved therapies makes sarcoidosis a significant clinical challenge, according to a presenter at the 2023 Congress of Clinical Rheumatology-East.
“Sarcoidosis is a chronic disease of unknown etiology,” Nadera Sweiss, MD, a professor of medicine at the University of Illinois, told attendees. “The hallmark of the disease is the presence of noncaseating granulomas.”
The aim of her presentation was to discuss the challenges in diagnosing and treating this disease, which occurs more frequently in African American individuals compared with white individuals. The disease is also more severe in the African American population.
“This is a disease of middle-aged and young people,” Sweiss added, noting that it occurs most commonly in individuals in their 40s and 50s, with women being more impacted than men.
Difficult Diagnosis Amid ‘Cascade of Events’
It is believed that an environmental insult or trigger in a predisposed host will activate both the innate and adaptive immune systems, leading to a “cascade of events.”
The toll-like receptors may be triggered, as may chemokines, cytokines and macrophages.
In as many as 50% of patients, the disease will resolve on its own with no intervention, according to Sweiss. “But in a small percentage, the granulomas persist,” she said.
It is also unknown why the granulomas persist in some patients, or why some patients develop fibrosis.
Despite these unknowns, there are some reliable clinical factors rheumatologists should consider. “Löfgren’s syndrome is the most perfect clinical syndrome of sarcoidosis,” Sweiss said. “That’s all you need.”
However, not all patients demonstrate this syndrome. Mutation in HLA-DRB1*0301/DQB1 may also be present. This variation is associated with 100% recovery after 2 years, according to Sweiss.
Heerfordt’s syndrome, which is marked by fever, parotid enlargement, facial palsy and anterior uveitis, may also be present, along with systemic symptoms and organ-specific symptoms. “It may resemble many other diseases,” Sweiss said.
Patients with manifestations in the brain or heart may be particularly difficult to diagnose, according to Sweiss. “Close follow-up is very important,” she said.
Lung complications are most common. “Lung involvement is the most important cause of morbidity and mortality in patients with sarcoidosis,” Sweiss said.
For patients with suspected sarcoidosis but with no clear indication, a host of tests may prove useful, ranging from complete blood count, renal function and liver function tests to serum calcium, tuberculosis screen or total immunoglobulins.
Chest CT scan may be used, along with eye exam, bone density scan or FDG-PET scan. “It is not one test that will help you diagnose this disease,” Sweiss said.
Step Carefully in Treatment
Regarding treatment, Sweiss recommended a “stepwise approach.” However, she warned that there are significant complications at each step.
The first line is corticosteroids. “However, the dose and duration of corticosteroids are not well defined based on organ involvement,” Sweiss said. “In general, corticosteroids are overutilized in treatment of sarcoidosis.”
Methotrexate, azathioprine, leflunomide or mycophenolate may be considered for the second step. “The best experience is with methotrexate,” she said.
However, liver enzymes may be elevated with methotrexate. Leflunomide has been associated with neuropathy, while azathioprine may increase infection risk.
The third step includes tumor necrosis factor (TNF) inhibition using either infliximab or adalimumab.
While TNF inhibitors have shown some success, not all patients will respond. “We have seen no response or partial response to anti-TNF therapy,” she said.
The next step includes biologic therapies. However, there are several factors mitigating their use, ranging from suboptimal response, toxicities, cost and increase rate of infections.
Recent data have shown that inhibition of the janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway can improve sarcoidosis symptoms. However, further investigation is necessary.
Regarding step four, B-cell depleting therapies like rituximab have been used, as have interleukin-1 and IL-6 targeting therapies.
“Third-line and fourth-line therapies are used off-label in patients with sarcoidosis with variable success,” Sweiss said.
But Sweiss stressed that some patients require these interventions. “More aggressive treatment is necessary for clinical features that pose immediate threat to life or to the function of critical organs,” she said.
Her other overarching point was that every patient is different, and that interventions must be individualized. “Treatment is not one size fits all,” she said.
Patience is also essential when managing sarcoidosis. “It is not a one-day or even one-month thing,” she said, noting that 1, 2 or even 5 years may be required for patients to resolve all manifestations.
Looking to the future, Sweiss called on researchers to investigate IL-18, efzofitimod (Atyr Pharma), abatacept, namilumab (Amgen/Izana Bioscience/Takeda) and other medications in the JAK/STAT class.
“If we know the target, it is easy to gather our equipment and nail the target,” Sweiss said. “But targets are not well-established, outcomes are suboptimal and there are no FDA-approved therapies.”
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Sweiss N. Update on sarcoidosis. Presented at: Congress of Clinical Rheumatology-East annual symposium; May 4-7, 2023.
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