Pulmonary sarcoidosis: a common yet poorly understood “rare” inflammatory disease
Pulmonary sarcoidosis remains one of the most enigmatic inflammatory lung diseases (ILDs): common enough to affect millions globally, yet still lacks a clear aetiology, predictable disease course, or targeted therapeutic options. Sarcoidosis is a complex, multisystem inflammatory disease characterised by the formation and accumulation of clusters of immune cells, called granulomas, in affected tissues. While virtually any organ can be involved including the skin, eyes, heart, and nervous system, contributing to its reputation as a highly heterogeneous disease, the lungs are the primary site of disease, representing ~90% of cases.
Despite being perceived as a “rare” condition, the global burden of sarcoidosis is substantial… and growing. Over the past three decades, the global number of people living with sarcoidosis has more than doubled, increasing from ~2.1 million to 4.6 million between 1990 – 2023. In parallel, the broader burden of ILDs including pulmonary sarcoidosis, has risen sharply, with global incidence, mortality, and disability-adjusted life years all increasing by over 100% between 1990 – 2019. Unfortunately, this upward trajectory is expected to persist through 2050, largely driven by an aging and expanding population, notably in higher-income regions.
While sarcoidosis has been recognised for over a century, the underlying cause remains (weirdly) unknown, with current hypotheses pointing toward an exaggerated immune response to environmental or infectious triggers in genetically predisposed individuals. This translates directly to variability in disease course, with some patients experiencing spontaneous resolution of symptoms, while others progress to chronic inflammation and irreversible fibrosis. This heterogeneity, together with the absence of definitive diagnostic markers, makes sarcoidosis difficult to pin down clinically, ultimately delaying diagnosis. As a disease of exclusion requiring the ruling out of multiple other conditions, delays in recognition and treatment are common, often leading to irreversible organ damage.
Despite a long-standing clinical recognition, pulmonary sarcoidosis has attracted remarkably little pharmaceutical investment
For over 50 years, the treatment landscape for pulmonary sarcoidosis has remained largely unchanged, with still no approved disease-modifying therapies available to date. Several medications are used in clinical practice, but corticosteroids remain the mainstay of therapy, alongside off-label immunosuppressive agents. Although effective in suppressing inflammation, the heavy and prolonged use of steroids is known to be associated with significant long-term toxicity, creating what is often described as a “devil’s bargain”, where disease control comes at the expense of treatment-associated morbidity. In some cases, clinicians turn to steroid-sparing approaches like conventional immunosuppressants such as methotrexate and azathioprine, or biologics like TNF inhibitors in more refractory disease, but their use remains largely off-label and lacks high-quality evidence.
After a prolonged therapeutic stagnation, the field may finally be approaching a potential inflection point and a period of renewed momentum, following recent positive developments from aTyr Pharma. In September 2025, the company reported results from the first global Phase 3 EFZO-FIT trial of efzofitimod, a first-in-class biologic immunomodulator. Despite missing the trial’s primary endpoint of daily oral corticosteroid change, efzofitimod demonstrated a statistically significant improvement in quality of life across multiple parameters in patients with pulmonary sarcoidosis. aTyr is now engaging with regulators, with an FDA Type C meeting scheduled for mid-April 2026, which may help define a potential path forward. If successful, efzofitimod could emerge as the first targeted biologic therapy for pulmonary sarcoidosis, marking a long-awaited and impactful shift in a treatment landscape that has remained quiet for decades.
Beyond efzofitimod, a few other targeted approaches for pulmonary sarcoidosis are in earlier-stage, notably OncoArendi Therapeutics’s OATD-01, a chitinase inhibitor currently in Phase 2 development, and Xentria’s XTMAB-16, an anti-TNFα monoclonal antibody in Phase 1/2 development. While encouraging, the pipeline remains constrained, reinforcing the nascency of innovation in this space and reflecting first-mover advantage potential.
But the story of pulmonary sarcoidosis is not only one of limited pharmaceutical interest; for the millions of people affected, the impact of the disease is anything but small
For the millions of patients living with pulmonary sarcoidosis, the disease is not only defined by endpoints, but by the daily reality of living with an unpredictable and often invisible illness. Ayesha Ahmed, a 60-year-old woman who has been living with the disease for several years now, describes a journey shaped by uncertainty, confusion, and a rollercoaster of emotions.
It started off with a long and exhausting path to diagnosis. In Ayesha’s case, her disease progressed silently, with little to no noticeable symptoms until it had already reached an advanced stage. Early on, her symptoms were repeatedly attributed to more common conditions, with recurring courses of antibiotics prescribed over months and multiple hospitalisations before sarcoidosis was finally identified. It was only when her condition had progressed to stage 4, almost 5 years ago, that the true severity of her disease became clear. But by that time, the disease had already progressed to fibrosis and like many others, Ayesha was left asking “why did it take so long to understand what was really happening?”. Just recently, new symptoms started emerging, including skin bruising and rashes, reminders that the disease continues to evolve long after its diagnosis.
With multi-organ involvement, Ayesha takes around 12–13 pills each day – each for a different aspect of the disease or its consequences. From the outside, she may appear “normal,” but the reality is far more complex. There are days marked by persistent coughing and moments where even speaking becomes difficult. There are some holidays spent away from family and in hospital beds instead… for weeks.
But the burden of sarcoidosis is not hers alone. It extends to her family: her husband, her three children, and those closest to her, who have also lived the uncertainty of a chronic condition with no clear trajectory. For Ayesha, maintaining a positive outlook becomes part of the daily effort, even when the physical and emotional toll is significant. At times, she reflects on what the future might hold, as the progression of her disease has brought the possibility of lung transplantation into the conversation. If she were ever considered eligible, the decision wouldn’t be straightforward. “Do I want to go through this? Do I want to put my family through this?”, she asks herself. The prospect of major surgery, lifelong immunosuppression, and uncertain outcomes is not just a clinical decision, but a deeply personal one.
In navigating this reality, community has become an important source of strength. Through her involvement with Windsor Pulmonary Fibrosis Support Group, Ayesha has found connection with others facing similar challenges. In sharing experiences, setbacks, and small wins, she describes a sense of validation, of finally being understood in a disease that is so often invisible to others. Her story is not unique. It reflects the lived experience of many patients with pulmonary sarcoidosis trying to manage not only the physical burden of disease, but the emotional, mental, social, and familial impact that comes with it.
Yet, as the number of sarcoidosis patients globally continues to rise, the disconnect between the growing patient burden and limited therapeutic innovation becomes increasingly difficult to ignore. In a field long defined by minimal investment and few treatment advances, the need is no longer simply to better understand the disease, but to meaningfully address it. For patients like Ayesha, progress will ultimately be measured not by incremental clinical gains alone, but by the ability to restore a sense of normalcy, dignity, and control over their lives.
