I was distressed to hear that Bernie Mac died last Saturday of pneumonia at the age of 50. I always thought he was pretty funny, and I was a big fan of the Ocean’s Eleven movies where he played a prominent part. I also raised an eyebrow when I heard that he was only 50 because 50-year-olds do not typically die of pneumonia unless they are in some way immunosuppressed — either from medications or from some condition like HIV.
Even though it wasn’t the immediate cause of his death, Mac fought a poorly understood disease called sarcoidosis which may explain why he would be particularly susceptible to lung infections. Sarcoidosis is not something that most people have heard of, so I thought I would spend a little bit talking about it.
What is sarcoidosis?
To a pathologist, sarcoidosis triggers the following phrase: a chronic noncaseating granulomatous disease of unknown etiology.
Since there are likely very few words in that sentence that most of you understand, let me unpack it. Granulomatoses are diseases where you get bundles of scar tissue (granulomas) that form in various tissue and organs from immune activation. That activation can be the result of a persistent infection (for example, tuberculosis forms granulomas when the body tries to wall off the bacteria in the lungs), or it can be an autoimmune disease where the cause is unclear. Noncaseating is a technical term for pathologists meaning that it lacks necrosis (dead cells) on the insides of the granulomas. (Pathologists — in a particularly disgusting turn of phrase — say that the necroses look like cheese — hence the term caseate. I know…gross. Nothing would make me cringe in school more than when the pathologists compared diseases to food.) Sarcoidosis particularly is characterized by granulomas that do not have dead cells inside them — as opposed to disease likely tuberculosis which often do. This pathological finding is critical for diagnosing the disease (see below).
The “chronic” and “unknown etiology” part suggest that people who have this disease have these granulomas growing in them for long periods, and we do not know exactly why. The bad parts of the disease are caused when the granulomas obstruct the normal functions of whatever organ they are in. Etiologically, we think that this is an autoimmune disease caused by an unnecessary immune response, but past that we really don’t know.
What is the presentation of sarcoidosis, and how is it diagnosed?
The granulomas in sarcoidosis can grow in basically any organ system, so a patient could come into the hospital complaining of a variety of different symptoms. For example, if the granulomas were growing in the brain, the patient might complain that they are having trouble seeing. Since the granulomas can be anywhere the presenting symptoms can be quite variable.
The most common presentation is someone coming in with trouble breathing or coughing up blood. This is because the most common organ that the granulomas grow inside is the lungs. The granulomas block airways and can break blood vessels. (Also, from time to time you can catch sarcoidosis before these symptoms appear because you can see the granulomas on a chest x-ray.)
If someone comes in coughing up blood, one of the first things you would do is order a chest x-ray. It is likely but not certain that you would see something funny going on there. Then in order to diagnose sarcoidosis, you would also have to rule out that there wasn’t some sort of infectious disease like pneumonia — usually by taking a culture of sputum. These are the types of tests you run preliminarily when someone comes into the ER with a lung complaint.
However, the gold standard test for sarcoidosis is a biopsy of the organ involved. A pathologist will take sections of that biopsy and look at them under a microscope. He/she is checking for the noncaseating granulomas that I talked about earlier. If they see them, then sarcoidosis is a likely diagnosis. (Off the top of my head I can’t think of other things with that pathologic finding, but someone else who knows might be able to tell you.)
What is the incidence and clinical course of sarcoidosis?
With autoimmune diseases, the course is always a crap shoot. Some people go into remission, and they never have trouble again. Some people have very serious complications very quickly. Some people fight it their entire lives. Death can be caused by organ failure such as when the lungs scar so much they don’t work anymore (pulmonary fibrosis). About 2/3 of people with sarcoidosis have it clear up spontaneously.
That being said, African Americans have about a four times greater risk of sarcoidosis. We think that this is because some African Americans have HLA types that place them at greater risk. (HLA genes are genes on the surface of cells that the immune system uses to distinguish self from non-self. If they are not working correctly, the immune system may confuse a self-cell with a foreign pathogen, causing an autoimmune disease. Some versions HLA genes are more prone to this than others.) Also, for reasons that are unclear, African Americans tend to have a more serious disease course than Caucasians.
The prevalence of sarcoidosis is pretty rare: about 10-40 cases in 100,000.
How is sarcoidosis treated, and what was the deal with Bernie Mac?
Because sarcoidosis is an autoimmune disease the go-to drugs are steroids (like prednisone) and immunosuppresants (like methotrexate). Both drugs will suppress the immune system and slow the formation of new granulomas.
Unfortunately whenever you are suppressing the immune system, it also renders the individual vulnerable to infections. Though I have no idea what medication Mac was on, I suspect that this was the problem. If he was on drugs like these, you can run the risk of getting serious infections like pneumonia. From what I understand too, his sarcoidosis had not been a problem recently, so the issue with his health was probably related to the drugs alone.
It is a difficult cost-benefit for anyone trying to treat this disease. On the one hand, you want to ensure against new flare-ups. On the other, you have to be very careful of infectious disease. Particularly when the disease hasn’t been active in a while, this is a tough line to walk.
Still a sad, sad end to a wonderful career.
Anyway, that is all that I can think of about sarcoidosis at the moment. If you would like more information, this site at eMedicine was the best I read. Feel free to add questions in the comments, and I will see if I can find answers.