All posts by Jonathan Hausmann

I am a pediatric and adult rheumatologist at Boston Children’s Hospital and Beth Israel Deaconess Medical Center. I have an interest in autoinflammatory diseases, medical education, and the role of social media and technology in healthcare.

What the heck is a connective tissue disease?

This week, I was called to evaluate a young man with several aneurysms (ballooning of his blood vessels) and a dilated (widened) aorta.  The medical team thought he had a “connective tissue disease” because a family member also had a connective tissue disease–she had lupus.  Unfortunately, doctors can mean very different things when they talk about a “connective tissue disease;” this is a common source of confusion for doctors and patients alike.  After reading this post, I hope you’ll be able understand the difference.

Connective tissue is the “stuff” that holds your body together.  That is, the bones, ligaments, tendons, cartilage, fat, and “glue” that keeps all your organs in place.  Two very different types of diseases can affect these tissues–you can have problems in MAKING the connective tissues, or these tissues can be ATTACKED by the body’s own immune system.

In the first type of “connective tissue disease,” the body is unable to produce strong connective tissues.  It’s like trying to build a house with weak materials.   If the materials are weak, the house is likely to develop cracks on the walls, holes in the roof, and the whole structure may fall down.  There are many genetic (heritable) diseases that prevent the body from making high-quality building blocks.  Marfan syndrome, for example, is a disease where the body is unable to make high-quality fibrillin (a protein present in many types of connective tissues).  This causes weakness of various parts of the body including the eye (causing lens dislocation), the aorta (causing dilation and potential to rupture), and lungs (causing pneumothorax, or collapse of a lung).   Ehlers-Danlos is another group of diseases where patients have difficulties making collagen, another protein necessary for high-quality connective tissues.  In this disease, patients have loose joints that often dislocate, fragile skin that is unusually “stretchy,” and have difficulties healing after injuries.  In the most severe cases of Ehlers-Danlos, the blood vessels are also weak, making them prone to breaking and causing internal bleeding.  Because these types of connective tissue diseases are genetic (hereditary), medical geneticists are the experts in this field.

The second type of “connective tissue disease” does not involve problems in making the building blocks of the body.  In fact, the body is able to make all of the connective tissues without a problem.  However, once these tissues are made, they are attacked by the body’s own immune system (and thus they are autoimmune diseases).  The body’s own immune cells (white blood cells) are tricked into thinking that the connective tissue is abnormal, and thus they  attacking those tissues.  In a sense, the body can build a house with high-quality materials, but the house is invaded by wild animals that can damage the structure of the house.  In Sjogren syndrome, for example, the glands that make tears and saliva are attacked.  In scleroderma, the skin and internal organs are attacked.  In lupus, many organs can be attacked, including the kidneys, skin, and lung.  To date, we have very little idea what causes these diseases.  Because these types of diseases are autoimmune and often involve inflammation, rheumatologists are the experts in these types of illnesses.

Don’t you think we should change the name that we use to refer to these two very different types of diseases?  What names do you propose?

After reading this post, what kind of disease do you think my patient had? Genetic or autoimmune?

What the heck is rheumatology?

When I meet someone for the first time and tell them that I’m a rheumatologist,  I usually get blank stares, as if I had spoken to them in a foreign language.  It doesn’t matter if they are a medical student, family member,  or even an immigration officer.  It doesn’t matter if they have a PhD or they are a high school dropout.  I even see patients in my rheumatology clinic who have no idea what rheumatology is, nor how I’m supposed to help them.

I can’t blame them.  Rheumatology is a weird field.  Just look at the origin of the word “rheumatology.”  The prefix “rheuma,” meaning “to flow,” was first used by a Greek physician 2000 years ago,  referring to the phlegm that flows from the nose when a person is ill.   But rheumatology, as it is practiced today, has nothing to do with phlegm (talk about false advertising!).  Cardiologists don’t have this identity problem because they, of course, manage the heart.   Dermatologists treat your skin.  Proctologists…well, you get the picture.  

A quick web search about rheumatology is not fruitful either.  Rheumatology is defined as: “the medical specialty that manages rheumatic diseases.”  My rheumatology textbook doesn’t even try to define what field is all about.

In addition, we’re not a popular specialty.  I don’t know of one famous rheumatologist.  We’re not usually in the news.  We’re not  the heroes in any movie.  In fact, I don’t  think I’ve ever seen a TV character who is a rheumatologist (even though there is at least one paleontologist on TV!).   The TV character that most closely approximates what a rheumatologist does is my hero Dr. House (no relation, unfortunately) on the TV show House, MD.  He is actually board certified in nephrology and infectious diseases, but he gets consulted on very complicated cases, much like rheumatologists often do.  However, he’d make a lousy rheumatologist because, according to him, “it’s never lupus!”

As I see it, rheumatology is the study of inflammation (swelling, redness, warmth, and pain) occurring in the structures that hold up the body, such as the bones, muscles, and joints.  Arthritis, or inflammation of the joints, is the most common disease that we see, both in children and adults (kids get arthritis too!).  Arthritis comes in a variety of flavors, including juvenile, rheumatic, psoriatic, gouty, osteoarthritis, etc..

We also take care of complex diseases such as systemic lupus erythematosus, systemic sclerosis,  and dermatomyositis, in which the immune system attacks various different organs.  Vasculitis, or inflammation within a blood vessel, is another disease which we treat.  Other strange illnesses (with even stranger names) such as Kawasaki disease, Sjögren syndrome, and relapsing polychondritis are all within the field of rheumatology.

Most of the above-mentioned diseases are considered autoimmune, in which the immune system loses the ability to recognize self from non-self.  When a cell of the immune system passes through the kidney, it should be able to recognize it and say: “Hello! You are my kidney, I will protect you against infections!” However, in autoimmune diseases, the immune cell gets confused and says: “Whoa! What is this bean-shaped organ doing here? You look foreign, I will fight you to the death!”   As a result, the immune cell begins a process of inflammation that causes organ damage.  Many different organs can be affected in autoimmune diseases, and the name of the disease depends on which organ is affected.

At the other end of the rheumatology spectrum are autoinflammatory diseases (my favorite!).  These diseases occur when the machine that produces inflammation goes awry.   Immune cells are tightly regulated to produce inflammation only when needed (such as in response to a microbe or to damaged tissue).  However, in most autoinflammatory diseases, there is a mutation within the inflammation machine that causes it to produce inflammation at inappropriate times.  The immune cell in autoinflammatory diseases says: “Darn, I’m leaking inflammatory fluid yet again!”  Thus, the patient develops episodes of fevers, rashes, and joint pain without any other explanation.

As you can see, rheumatologists manage a wide variety of illnesses that affect many different organs.  Most of these diseases do not have clear causes, which makes rheumatology a fascinating field to study.  At least until a smart marketing team comes up with a better name for our specialty (I vote for “inflammatology!”), you won’t have to look at me weird when I tell you what I do for a living.

301 patients with PFAPA–what do they look like?

This month, an interesting article about PFAPA appeared in the journal Rheumatology.  PFAPA (periodic fevers, aphthous stomatitis, pharyngitis, and adenitis) is an autoinflammatory disease that affects children.  It is manifested by episodes of fevers lasting a few days, in addition to the features that make up the name of the disease.  Unlike other autoinflammatory diseases, episodes of fever occur at very specific intervals (parents mention that the fevers occur “like clockwork,” and they can predict when the next episode will occur on a calendar).  Fortunately, most patients respond well to steroids during fever episodes, and the disease usually resolves within a few years without sequellae.

This study represents the largest group of patients with PFAPA ever published.  They found that the average age of onset of symptoms was about 2 years of age, and it often took several years to make the diagnosis of PFAPA.  Most patients were diagnosed before age 6.  On average, episodes of fever lasted 4 days, and recurred every 4 weeks.  Only 44% of patients with PFAPA had the classic triad of apthous ulcers (oral ulcers), adenitis (swollen, tender lymph nodes in the neck), and pharyngitis (sore throat); the rest had only one or two of these symptoms.   Interestingly, children often complained of abdominal pain, joint pain, muscle pain, and headaches during episodes.  

This study highlights one of the biggest difficulties of PFAPA–making an accurate diagnosis.  Patients don’t need to have the classic triad of symptoms to be diagnosed with PFAPA, and many children complain of additional symptoms during episodes that are likely underrecognized.  Perhaps it is time to create new diagnostic criteria for this disease!

What do you think?  Have you or a loved one been diagnosed with PFAPA?  How long did it take for your doctors to make the diagnosis?

It’s in your genes, or is it? The genetics of autoinflammatory diseases

Autoinflammatory diseases have a variety of causes.  Some are clearly genetic–they are caused by single mutations in specific genes.  These abnormal genes produce abnormal proteins that cause unprovoked episodes of inflammation.  If you have the abnormal gene (for the most part) you develop the disease.  If you don’t have the gene, you don’t develop the disease.  Familial Mediterranean Fever (MEFV), cryopyrin associated periodic syndrome (NLRP3), and the TNF-receptor associated periodic syndrome (TNFRSF1A), are examples of autoinflammatory diseases associated with mutations in single genes.  These diseases are often called hereditary periodic fever syndromes, although they are not always “hereditary” (passed down from parent to child); many are caused by new mutations that arise in the embryo.

Some types of autoinflammatory diseases have associations with specific genes, such as Behcet’s disease with the gene HLA-B51.  Behcet’s is characterized by recurrent oral and genital ulcers, rash, and episodes of eye inflammation (uveitis).  Unlike the genetic diseases above, having the gene HLA-B51 is not sufficient to have the disease.  This complex disease is likely caused by interplay between HLA-B51, other genes, and the environment (it is interesting to note that patients with Behcet’s that live in the Middle East have a more severe disease than patients with Behcet’s that live in the United States).

Finally,  some autoinflammatory diseases do not appear to be associated with any specific gene.  PFAPA (periodic fevers, aphthous stomatitis, pharyngitis, and adenitits), is such an example.  This is an autoinflammatory disease that commonly affects children, and it is characterized by periodic episodes of fever and the associated symptoms that give it its name.  To date, no specific gene has been associated with the development of this disease.  The fact that removal of the tonsils appears to be curative for many patients suggests that perhaps an infection that resides in the tonsils contributes to the expression of this disease.

We are still just beginning to understand the causes of these fascinating autoinflammatory diseases.  It is still unclear what makes patients with the same genetic mutation have mild or severe disease. We also don’t know how the environment plays a role in the expression of this disease.  Further research over the next few years should be able to give us better answers to these important questions.

To review the wide variety of autoinflammatory syndromes (and their specific causes), please refer to this comparison chart by the Autoinflammatory Alliance, by far the most complete chart of autoinflammatory diseases I’ve seen.