Stanford Multidisciplinary Sarcoidosis Program is pleased to announce our designation as a Sarcoidosis Center of Excellence. This certification is granted for an initial 2 year period by the World Association for Sarcoidosis and Other Granulomatous Diseases (WASOG) and the Foundation for Sarcoidosis Research (FSR). We will join a select group of sarcoidosis programs worldwide that are recognized for exceptional patient care and research.  We are the only center of excellence on the West Coast of the United States currently. 

According to FSR “WASOG Sarcoidosis Center of Excellence’ refers to a multidisciplinary team of specialized medical and paramedical professionals with a shared specialized facility that has proven sustainability over years, and provides leadership, best practices, research, support and/or training for sarcoidosis patients and professionals. It should contain sarcoidosis experts in at least two different disciplines.” Centers of excellence distinguish themselves by exceptional care and research in the sarcoidosis field. 

Prior to being selected as a Sarcoidosis Center of Excellence, we were a Sarcoidosis Clinic, working towards this prestigious recognition.  At Stanford, we have a longstanding multidisciplinary collaboration including cardiology, pulmonology, rheumatology, endocrinology, hepatology, nephrology and imaging specialists, among others. In addition to patient care, we have ongoing clinical trials at our center. We look forward to continuing to collaborate with FSR and WASOG to acknowledge the great work our clinicians are doing to advance sarcoidosis knowledge and take care of patients. 

Learn more from WASOG and FSR: https://www.stopsarcoidosis.org/sarc-id/sarcoidosis-clinics/

 It has now been several months since the novel coronavirus (COVID-19) pandemic first emerged, and sarcoidosis patients and providers are seeking guidance on how best to manage immunosuppressive treatments. With our knowledge of COVID-19 constantly evolving, this review is up to date as of July 2020, and may need to be updated periodically as our knowledge of COVID-19 unfolds. We will discuss treatment principles to guide rheumatologists and other sarcoidosis providers as we navigate this unprecedented viral epidemic. 

Patients with sarcoidosis are a unique population, and several factors specific to sarcoidosis must be considered in the context of a novel, contagious respiratory virus.  First, 90-95% of people with sarcoidosis have pulmonary involvement, leading to underlying lung disease and damage.  This may put them at a higher risk than the general population, or even other patients with rheumatic diseases being prescribed immunosuppressive medications. Sarcoidosis patients may have baseline decreased lung capacity and fibrosis related to granulomas. Likewise, treatment for sarcoidosis generally involves immunosuppression, which potentially results in increased susceptibility to infectious diseases. Side effects of immunosuppression—in particular glucocorticoids such as prednisone—are linked to diabetes and hypertension. These comorbidities are frequently cited as factors that appear to put patients at an increased risk for complications related to COVID-19.  The mechanism for this association remains unclear.  Given the complex interplay between sarcoidosis/granuloma formation, the immune system, and new antigens like COVID-19, patients and providers need to weigh the evidence for continuing, modifying, or ceasing therapy for sarcoidosis. They need to balance the risk of recurrent sarcoidosis if treatment is tapered with the theoretical risks of COVID-19 infection if therapy remains unchanged. 

A consensus statement from the American College of Chest Physicians recommends that physicians stratify patients based on the risk of organ damage [1].  Patients with active disease, especially those with a risk of organ damage (uveitis, neurosarcoidosis, cardiac sarcoidosis, progressive pulmonary sarcoidosis) should likely continue their treatments without change. They note that patients with life threatening manifestations of sarcoidosis like cardiac and neuro-sarcoidosis should continue therapy regardless of whether they have quiescent disease. These patients are at risk for organ damage and poor outcomes should they stop therapy, even during a viral pandemic. Patients with stable disease, without risk of organ damage, are further stratified by the type of therapy they are on. It is reasonable to consider reducing TNF inhibitors (either the dose or frequency), reducing steroids to the lowest possible dose, and reducing the dose of disease modifying antirheumatic drugs (DMARDs) such as methotrexate if possible.  Patients should be able to readily access their care team should they experience a flare.  It is important for sarcoidosis patients to remain in close communication with their providers while reducing therapy, so that if a flare occurs, therapy can be re-intensified.

In addition to identifying patients who may be eligible for treatment tapering, providers should also stratify by risk of complications related to COVID-19.  Current knowledge in the general population suggests advanced age, comorbid medical conditions (such as diabetes and hypertension) and smoking status influence COVID-19 related outcomes.  In addition, studies that focus on patients with rheumatologic disease probably best reflect the risks for patients with sarcoidosis, as sarcoidosis is treated with many of the same therapies as other rheumatic conditions. A large global registry of patients with rheumatic diseases that have contracted COVID-19 (the COVID-19 Global Rheumatology Alliance) was recently utilized to conduct a case study of 600 patients [2].  This study demonstrated an increased risk of hospitalization for COVID-19 associated with glucocorticoid use (prednisone ³10mg daily).  As in the general population, comorbid medical conditions like diabetes and cardiovascular disease also increased the risk of COVID-19 related hospitalizations.  Notably, non-glucocorticoid therapies including DMARDS (such as methotrexate), antimalarial drugs (such as hydroxychloroquine and chloroquine), and TNF inhibitors (such as adalimumab and etanercept) did not increase the risk of COVID-19 related hospitalizations.

This review highlights the challenges sarcoidosis patients and providers face in navigating this novel, global pandemic in conjunction with a disease that requires long term immunosuppressive treatment.  Patients and providers should consider the risk of disease flares and the specific risks of organ damage in deciding whether to taper or adjust therapy. They should focus on reducing glucocorticoids whenever possible, and continue other therapies as appropriate.  Finally, patients and providers should remain engaged and up to date as new data emerges from COVID-19 studies, and as our guidance continues to change based on new information. 

1.         Sweiss, N.J., et al., When the Game Changes: Guidance to Adjust Sarcoidosis Management During the COVID-19 Pandemic. Chest, 2020.

2.         Gianfrancesco, M., et al., Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Ann Rheum Dis, 2020. 79(7): p. 859-866.

Questions? Comments? Idea for a future blog post? E-mail ebraley@stanfordhealthcare.org

Case Studies

These days, more and more of my google scholar alerts for ‘sarcoidosis’ include a reference to COVID-19, or the novel coronavirus global pandemic. With coronavirus case numbers growing, clinicians are learning more about the interaction between this virus and patients’ underlying, chronic diseases. Today, we will discuss two recently published case studies exploring the relationship between pulmonary sarcoidosis and COVID-19 on imaging studies. 

Utility of PET Scan for COVID-19 Evaluation

As many clinicians working with sarcoidosis patients know, the granulomas of sarcoidosis are often metabolically active, and therefore well characterized on PET scans. This article describes a case report of a man admitted to a hospital who was known to have sarcoidosis. He was admitted in preparation for intensifying immunosuppression for his sarcoidosis. As part of  his evaluation, he underwent a PET scan where he was found to have ‘extensive pulmonary infiltrates.’ He had a CT 9 days earlier which did not show these findings, so it was thought these infiltrates had developed over a very short time period. Shortly after the PET scan, he developed a febrile illness and was diagnosed with COVID-19. The authors note that the PET scan demonstrated extensive infiltrates and lymphadenopathy. They note that PET scans may be helpful to characterize and prognosticate lung involvement for patients with COVID-19, as well as sarcoidosis. 

Takeaway: A PET scan may help determine severity of COVID-19 lung involvement, sarcoidosis and COVID-19 can co-exist, of course. They should both be considered in a patient with significantly worsening lung disease on a PET scan. 

O’Neill, H., Doran, S., Fraioli, F. et al. A twisted tale- radiological imaging features of COVID-19 on 18F-FDG PET/CT. European J Hybrid Imaging 4, 13 (2020). https://doi.org/10.1186/s41824-020-00082-y

“COVID 19” turns out to be sarcoidosis

This article describes a man who is an emergency medical pilot (exposed to COVID-19 patients) who develops a cough, fever and anorexia for 3 days. His physician suspects COVID-19, but his RT-PCR test is negative. A chest X-Ray demonstrated bilateral hilar adenopathy, which is common in sarcoidosis. He also had an elevated ACE level. He underwent a biopsy which demonstrated non caseating granulomas, also classic for sarcoidosis. It was determined that he in fact had pulmonary sarcoidosis and was treated with steroids. 

Takeaway: This article demonstrates that the acute onset of pulmonary sarcoidosis may mimic COVID-19, particularly if the patient has constitutional symptoms. 

Momenzadeh M, Shahali H, Farahani AA. Coronavirus Disease 2019 Suspicion: A Case Report Regarding a Male Emergency Medical Service Pilot With Newly Diagnosed Sarcoidosis. Air Med J. 2020;39(4):296-297. doi:10.1016/j.amj.2020.04.01

Questions? Comments? Idea for a future blog post? E-mail ebraley@stanfordhealthcare.org

Sarcoidosis is nicknamed the ‘snowflake’ disease because it is so unique. Not only is sarcoidosis a rare disease (just about 200,000 Americans have it), but each patient will have unique manifestations that wax and wane throughout their disease course. Sarcoidosis is a moving target for people who live with this diagnosis. Given the disease pattern and how rare it is, some people with sarcoidosis will be the only patient in their doctor’s practice with sarcoidosis. Many doctors do not routinely treat patients with sarcoidosis, and may not have experience with the unique needs of sarcoidosis patients. Moreover, they may not always consider it when patients are having confusing constellations of symptoms. 

To help patients understand where to seek providers and care with sarcoidosis experience, the Foundation for Sarcoidosis Research (FSR) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) have compiled a list of sarcoidosis clinics and providers. Our Stanford providers and clinic are on both of these lists. We frequently see patients with sarcoidosis so we have unique experience to treat patients who have this disorder. These providers are known to have expertise, training and experience in working with patients with sarcoidosis. 

Another gap Stanford is filling is training future physicians to care for sarcoidosis patients. As a teaching hospital, Stanford is helping to train the next generation of sarcoidosis care providers. In addition to our mandate to do cutting edge sarcoidosis research, we are teaching future doctors and care providers about the disease course and treatment plan for patients with sarcoidosis. Dr. Witteles, the cardiologist who works with our program has been featured by the American College of Cardiology as a physician who trains other doctors to care for sarcoidosis patients. This important work ensures doctors trained at Stanford are comfortable with caring for patients with sarcoidosis. 

Living with sarcoidosis has challenges, but finding a care team that is able to effectively manage this disease makes this chronic disease journey better.

Questions? Comments? Idea for a future blog post? E-mail ebraley@stanfordhealthcare.org

Stanford sarcoidosis program has just released a paper outlining our experience treating patients with cardiac sarcoidosis. Like other manifestations of sarcoidosis, cardiac sarcoidosis is treated with immune modifying drugs. For this reason, many patients with cardiac sarcoidosis are treated by both a cardiologist and a rheumatologist. Our rheumatologist works closely with our cardiologist to develop a treatment plan that manages sarcoidosis disease burden and doesn’t worsen heart failure or arrhythmias due to cardiac effects of sarcoidosis. This paper, just released this month, highlights our collaborative, team-based approach, and our success treating patients with cardiac sarcoidosis using TNF alpha inhibitors.

TNF alpha inhibitors are medications that inhibit Tumor Necrosis Factor (TNF), an inflammatory cytokine (special type of protein) that is increased in people with sarcoidosis. High levels of TNF in the people with sarcoidosis lead to inflammation and granuloma formation. TNF alpha inhibitors block this protein; this reduces inflammation and granuloma formation. TNF inhibitors are already widely used for other rheumatologic conditions like rheumatoid arthritis and psoriasis. Since cardiac sarcoidosis is relatively rare, there hadn’t been significant research on using TNF inhibitors to treat this type of sarcoidosis. Our research shows that TNF inhibitors are both safe and highly effective to treat cardiac sarcoidosis.

This paper describes our cohort of patients who have cardiac sarcoidosis. Many of the patients had tried prednisone and other treatments (like methotrexate and Imuran) but still had ongoing or worsening disease on PET scans. Other patients had worsening heart function or arrhythmias, and needed further management of their sarcoidosis to prevent worsening cardiac symptoms. Using TNF inhibitors, ALL of the patients (100%) had resolution of their disease activity on PET scan within 12 months. Other benefits included being able to reduce patients’ steroid dose and improved heart function. Moreover, none of the patients had worsening heart function or other significant adverse events. This paper emphasizes the safety and efficacy of TNF inhibitors for patients with cardiac sarcoidosis.

We are excited to be able to offer this treatment at Stanford to patients who need it. We are also proud to share this data with other sarcoidosis doctors and patients.

Want to read more- Seminars in Arthritis and rheumatism November issue will have the article. A tweetable link is coming!

Questions? Comments? Ideas for a future blog post? E-mail ebraley@stanfordhealthcare.org. 

A common question in the sarcoidosis community is “What causes sarcoidosis?” While no single cause has been implicated, many genetic and environmental risk factors have been identified in population based studies. Our current understanding is that sarcoidosis is likely the result of a complex interplay between a person’s genetic risks and their environmental exposures. One environmental exposure that may be associated with sarcoidosis is mold exposure.

Patients with sarcoidosis are curious about this exposure since mold is common in so many environments. This blog post will help unpack what we know about mold and sarcoidosis, and what we still need to learn to understand the relationship between the two. 

Mold As a Risk Factor

Several studies suggest that people who have exposure to mold seem to have a higher than expected risk of developing sarcoidosis. 

One study from Sao Paolo, Brazil looked at all the patients treated in their center with sarcoidosis. They found that 30% of their 80 patient sample had mold exposure prior to developing sarcoidosis. A limitation of this study is that the authors didn’t note what percentage of the general population in this area would have mold exposure, so it is difficult to conclude if this is a true risk factor for this sample. Simply viewing the data, one can conclude that about a third of their patients had mold exposure prior to disease onset. 

A case control study done in Ottawa, Canada confirmed that mold exposure is a likely risk factor for the development of cardiac sarcoidosis. Researchers looked at patients who had cardiac sarcoidosis, and patients who were demographically similar and did not have cardiac sarcoidosis. They found that people who developed cardiac sarcoidosis were three times as likely to have been exposed to mold as those who did not develop cardiac sarcoidosis. While the exact mechanism is unclear from this study, they did find a clear increased risk for developing cardiac sarcoidosis after mold exposure. 

Similarly, a matched case control study of 706 patients in the United States found that occupational exposure to mold and mildew increase a person’s risk of developing sarcoidosis in any organ. Agricultural employment and humid environments were also linked to a higher risk for sarcoidosis. The authors suggest that these environmental and occupational risk factors may be mold related. 

Mold Mechanism

Mold is among many risk factors for the development of sarcoidosis- so how does environmental mold exposure lead to sarcoidosis? The mechanism is not entirely clear, but many researchers think a substance in the cell wall of fungus cells may contribute. Fungal cell walls emit a substance called beta glucan. Beta glucan is naturally part of fungus cell walls, but it also seems to influence the production of inflammatory substances in the human immune system. In some susceptible people who are exposed to beta glucan, their immune system may produce more inflammatory substances. These inflammatory substances can form the granulomas that cause sarcoidosis. 

Researchers have tested this hypothesis in a case control study of the homes of 55 people with and without sarcoidosis. Fungal mass in a home was measured using a specialized filter to look at fungal emissions in a home. People with sarcoidosis had significantly higher fungal mass in their homes than people without sarcoidosis. While this is a small study, it does suggest that fungal exposure may be linked to sarcoidosis. Interestingly, higher levels of airborne fungus were associated with more active or recurrent disease. 

What does this mean for me?

Given the small, limited studies evaluating the link between sarcoidosis and mold/fungus it is still too early for researchers to recommend people take specific action against environmental mold to prevent sarcoidosis. Larger studies and randomized controlled  trials are needed to more clearly establish the absolute risk of sarcoidosis from mold. There are many known risk factors for sarcoidosis, and mold exposure is likely one of them. We have a lot more to learn about sarcoidosis. One way you can help is to join a sarcoidosis  registry. This registry helps researchers learn about the characteristics of people with sarcoidosis. Consider joining this registry to help researchers do more observational studies about people with sarcoidosis. 

https://www.stopsarcoidosis.org/patient-registry-data/

Questions? Comments? Ideas for a future blog post? E-mail ebraley@stanfordhealthcare.org. 

Living with someone with sarcoidosis

As anyone living with sarcoidosis knows, having a great team behind you is important for your well-being. Besides a great medical team, having a supportive partner, friend, or family member can make a huge difference in navigating life with sarcoidosis. A new research article shows how a sarcoidosis diagnosis impacts the partners of people with sarcoidosis.

Researchers in the Netherlands studied couples where one partner had sarcoidosis, and healthy control couples in which neither partner had sarcoidosis. They found couples in which one partner had sarcoidosis, both partners reported lower quality of life than healthy controls. Some factors that contributed to the reported lower quality of life were fatigue, pain and anxiety. The authors note that sarcoidosis is a chronic, relapsing disease that can be very unpredictable and have variable symptoms.

Read the full article here: https://www.karger.com/Article/Pdf/501657

What does this mean?

Both patients AND their caregivers need psychosocial support to face a sarcoidosis diagnosis. Sarcoidosis symptoms are often invisible but debilitating to both the patient and their partner. Recognition of the burden of the disease and psychosocial support may mitigate some of the challenges patients and their partners face.

What can I do?

Support groups are not just for patients- meetings held online and in person are welcoming to anyone working through a sarcoidosis diagnosis as a patient or caregiver. In the Bay Area, we have a support group. E-mail ebraley@stanfordhealthcare.org to learn more. Online, groups like Inspire are a great place to get good information and support from your peers. Head to https://www.inspire.com/groups/stop-sarcoidosis/ to start talking to patients and family members. You are not alone in your diagnosis.

Questions? Comments? Have an idea for a future blog post?

E-mail ebraley@stanfordhealthcare.org