Sarcoidosis: The Master of Disguise with Dr. Christine Jellis

Podcast Transcript

Francisco Alexandrino:

Hi everyone, my name is Francisco, and I’m a second-year internal medicine resident at Cleveland Clinic. Today I’m joined by Dr. Christine Jellis, Staff Cardiologist in the Cardiovascular Imaging Dept. and Vice Chair of Operations for the Heart, Vascular and Thoracic Institute.

Dr. Jellis trained in Australia before coming to Cleveland Clinic in 2015 for advanced imaging fellowship, and after that never left. Welcome, Dr. Jellis.

Dr. Christine Jellis:

Thank you, Francisco, pleasure to be here.

Francisco Alexandrino:

Pleasure to have you. So, Dr. Jellis and I share a passion for cardiology but most importantly for medicine and for complex medical decision-making. Today we are bringing you a case on one of the great masqueraders in clinical medicine. Let’s get started.

Dr. Christine Jellis:

Let’s hear this exciting case

Francisco Alexandrino:

A 40-year-old African American woman presents to cardiology clinic with dyspnea on exertion. Over the last six months, she has had worsening fatigue, dyspnea on exertion, dry cough, blurry vision, distal neuropathy, arthralgias, painful purple nodules over the anterior legs, and several episodes of unexplained syncope.

CT chest shows bilateral hilar lymphadenopathy with a peri-lymphatic micronodular pattern. Labs show normocytic anemia, hypercalcemia, elevated CRP, and NT-proBNP of 500. EBUS demonstrates noncaseating granulomas. 

Dr. Jellis, at this point, what are you thinking?

Dr. Christine Jellis: 

This is a classic systemic sarcoidosis presentation. The key is not anchoring on one symptom. However, we must do our due diligence and exclude infections such as histoplasmosis, tuberculosis and also lymphoma.

Sarcoidosis is a multisystem inflammatory disease characterized by noncaseating granulomas. Commonly involves lungs, lymph nodes, skin, and eyes such as in this patient. That’s the leading hypothesis for sure. 

With the syncope, we always wonder about cardiac involvement of the systemic inflammatory process that is happening. 

Francisco Alexandrino:

Before we tackle the heart, let’s define the disease. What is sarcoidosis? Also known as one of the great masqueraders of modern medicine since its initial description in the XIX century

Dr. Christine Jellis:

Multisystem inflammatory disease of unknown cause. It has genetic and environmental triggers and it-s most prevalent in northern Europeans and Africans. Characterized by noncaseating granulomas. Can involve almost any organ. Most common sites: lungs, lymphatic system, skin, eyes.  Cardiac involvement is less common clinically. While 90% have lung involvement only 20% have cardiac disease however it is the second causes of death. It often affects young and middle-aged adults. 

Francisco Alexandrino:

So sarcoidosis affects any organ and the heart is not an exception. Otherwise, we wouldn’t be talking about it. Now our patient has syncope and dyspnea that seems out of proportion to lung disease. Along with elevated NT-proBNP. Echo shows LVEF 40%, some wall motion abnormalities in the bases and EKG reveals intermittent 2:1 AV block. What should make us suspect cardiac sarcoidosis?

Dr. Christine Jellis: 

Red flags include Unexplained high-grade AV block, especially in patients younger than 60; unexplained ventricular arrhythmias; unexplained reduced LVEF; regional wall motion abnormalities not explained by coronary disease; basal septal thinning or aneurysm, Syncope in a patient with known or suspected systemic sarcoidosis. 

Basal septal involvement frequently presents with conduction disease. More extensive fibrosis can present with ventricular dysfunction, heart failure, or ventricular arrhythmias. 

The 2024 AHA scientific statement emphasizes that cardiac sarcoidosis should be considered as a probability spectrum rather than a simple yes/no diagnosis, and that ECG, echo, CMR, and FDG-PET all play complementary roles. 

Francisco Alexandrino:

So the practical teaching point is: young patient, unexplained heart block. We need to think about infiltrative, inflammatory, genetic CMP, and in the right context, cardiac sarcoid. How do we establish the diagnosis?

Dr. Christine Jellis:

Definitive diagnosis requires myocardial tissue showing noncaseating granulomas. 

But endomyocardial biopsy has low sensitivity because the disease is patchy; only 20% of patients have a positive endomyocardial biopsy. A negative biopsy does not exclude cardiac sarcoidosis. Extracardiac biopsy plus compatible cardiac findings is often how the diagnosis is made clinically. 

Diagnostic frameworks include Heart Rhythm Society, Japanese Circulation Society, and WASOG criteria. 

WASOG defines sarcoidosis in different categories: definite, highly probable, probable, and possible/low probability 

Francisco Alexandrino:

This is exciting because we can have both structural and conduction heart disease. 

So cardiac sarcoidosis is one of those diseases where pathology is the gold standard. We have a significant clinical suspicion, but now we need the last pillar, imaging. This is where cardiovascular imaging enters the chat. What tools do we have?

Dr. Christine Jellis: 

Echo is often the first clue: LVEF, regional wall motion abnormalities, RV involvement, basal septal thinning. 

CMR is excellent for scar/fibrosis using LGE. FDG-PET identifies active inflammation. PET can also assess extracardiac inflammatory activity. CMR and PET are complementary, but sometimes are discordant. 

Francisco Alexandrino:

Tell us about cardiac FDG-PET. This test has a diet prep that patients never forget; what should a general clinician and a resident know about this tool?

Dr. Christine Jellis: 

FDG is a glucose analog taken up by metabolically active inflammatory cells. The goal is to suppress normal myocardial glucose uptake. Patients usually need a high-fat, low-carbohydrate diet before the scan. Often followed by fasting. If physiologic myocardial uptake is not suppressed, the study can become nondiagnostic. Proper patient preparation is critical. 

FDG-PET identifies metabolically active inflammation, whereas CMR identifies myocardial injury/fibrosis, the tests are often used together when clinical suspicion is high. 

Francisco Alexandrino:

Great to know. I think that if we were as strict with the Mediterranean diet for cardiovascular prevention as we are with sarcoidosis PET diets, we’d probably be out of jobs.

Now, in this particular case, how do you distinguish cardiac sarcoidosis from myocarditis, genetic cardiomyopathy, or ARVC?

Dr. Christine Jellis: 

Start with the clinical context: systemic sarcoidosis, pulmonary findings, skin, eye, neurologic symptoms. 

Sarcoid often involves basal septum, subepicardial or mid-myocardial regions, and can be multifocal. 

RV septal involvement can mimic ARVC. 

Myocarditis…

Genetic cardiomyopathy…

Francisco Alexandrino:

So the answer is not “imaging says sarcoid.” The answer is a combination of: clinical story, ECG, echo, CMR, PET, pathology when available. Now we have systemic sarcoidosis, high-grade AV block, reduced EF, and imaging consistent with active cardiac involvement. How do we treat?

Dr. Christine Jellis: 

Treatment is usually started when there are clinical manifestations and active inflammation. Corticosteroids are first-line therapy. 

When to think about ICD…

Imaging can help monitor treatment response…

Francisco Alexandrino:

This is beautiful, a single condition makes us have a very thorough understanding of not just cardiology but medicine overall. And then within cardiology we need to manage immunosuppressants, heart failure therapies, devices, imaging, etc. 

One thing I also love about cardiac sarcoidosis is how multidisciplinary it is. Pulmonary, cardiology, imaging, EP, rheumatology, ophthalmology, dermatology, everyone gets invited. How are these patients managed at Cleveland Clinic?

Dr. Christine Jellis: 

Importance of a coordinated multidisciplinary pathway. 

Pulmonary/rheumatology often guide systemic immunosuppression. 

Imaging helps establish diagnosis and monitor disease activity. 

EP is crucial for conduction disease, ventricular arrhythmias, and device decisions. 

Ophthalmology/dermatology/neurology as needed for extracardiac involvement. 

Communication prevents fragmented care. 

Francisco Alexandrino:

In these situations, I like to evoke the 4 Cs: collaboration, communication, consensus, and consistency, well in cardiac sarcoidosis maybe a 5^th C, corticosteroids

Francisco Alexandrino:

To close, what are the major take-home points?

Dr. Christine Jellis: 

Think of cardiac sarcoidosis in young or middle-aged patients with unexplained high-grade AV block, VT, syncope, or cardiomyopathy. 

Diagnosis is probabilistic and requires integration of clinical, pathology, and imaging data. 

CMR and FDG-PET are complementary. 

PET detects active inflammation; CMR detects scar/fibrosis. 

Treatment requires immunosuppression plus standard cardiac management. 

Multidisciplinary care is essential. 

Francisco Alexandrino:

Perfect, so from now on, when it’s not lupus, think about sarcoidosis. It has been a pleasure as always, Dr. Jellis.

Dr. Christine Jellis:

Thank you so much.