Your child with frequent fevers: is it autoinflammatory?

When I was little, I used to get a lot of fevers.  With my fevers, I would develop pain in one or both of my ears, and I felt so drained that I just wanted to be left alone to watch TV (or play Atari).  If my fever spiked in the middle of the night, my parents would soak me in a tub of lukewarm water to lower my temperature (how I hated those baths!).  On the following day, I would visit my pediatrician, who would invariably diagnose me with an ear infection.  He prescribed a delicious bubble-gum flavored antibiotic that my parents kept at the top shelf in the refrigerator (out of my reach so I wouldn’t overdose).  I’m not sure if it was the taste or the active ingredient, but this antibiotic always made me feel better.  After what seemed like the millionth episode of fever, my pediatrician recommended that I get tubes in my ears, and the episodes of fever and ear pain subsided.

Recurrent infections, like those I had when I was a child, are the most common cause of frequent fevers in children.  Usually, these infections are due to viruses, such as the ones that cause the common cold.  Children with colds often develop symptoms attributable to the virus, including a runny nose, nasal congestion, or cough.  Multiple infections, one after the other, are especially common in children attending daycare or school, where they trade viruses like I used to trade baseball cards with my friends.  When I see these the worried parents of these children in my office, I have to remind them that it is normal for a child to have 9-12 colds every year.  Fortunately, these children continue to grow and gain weight without difficulty, and they are healthy between episodes. “As your child grows,” I tell the parents, “her immune system will become better at fighting infections, and the frequency and severity of fevers will diminish.”  Aside from stressing the importance of hand washing among all family members, there is not much that can (or needs) to be done about these episodes. 

However, if the episodes do not clearly match the above description, other diagnoses should be considered.  In this post, I will provide some tips that may help parents and physicians recognize a rare cause of fever in children: autoinflammatory diseases.  The most common autoinflammatory disease in children is called PFAPA, which stands for Periodic Fevers, Aphthous stomatitis (canker sores or oral ulcers), Pharyngitis (sore throat) and Adenitis (enlarged glands in the neck).   This disease usually presents in children less than 5 years of age, and causes episodes of fevers in addition to the features that make up the name of the disease (oral ulcers, sore throat, enlarged glands in the neck).  The fever usually lasts about 4 days, and it recurs at regular intervals, usually every month.  What is unique about PFAPA is that parents can usually predict when the child is “due” to get ill.  The episodes of fever are so regular as to be predictable.  This regularity is rare in most other diseases.  PFAPA is commonly misdiagnosed as frequent Strep infections, and testing for Strep throat is usually negative.  Patients do not readily respond to antibiotics, although their symptoms can disappear with one dose of steroids.

Another clue that the child may have an autoinflammatory disease is that all of the episodes of fever look alike.  For example, if the child always develops abdominal and joint pain with the fevers, then he may have familial Mediterranean fever (FMF).  If, in addition to fever, she always develops a painful rash, muscle pain, and red eyes, then she may have TNF-receptor associated periodic fever (TRAPS).  If he develops fevers, rashes, and joint pain after exposure to cold weather, then the child may have familial cold-induced autoinflammatory syndrome (FCAS).

The length and frequency of fever, associated symptoms, and age at which the fevers began can help differentiate between these (and other) autoinflammatory diseases.   Thus, it is very helpful to keep a fever diary,  specifying the characteristics of each episode.  Because many of these autoinflammatory diseases are inherited (genetic), there is often a history of other family members having similar symptoms.  In addition, it is important to note that some autoinflammatory diseases are more common in people of certain ethnic backgrounds, such as FMF in Sephardic Jews, Turks, and Armenians.

In addition to autoinflammatory diseases, there are some features of recurrent fevers that should warrant a closer look by a child’s  pediatrician.  These include prolonged episodes of fever (more than one week), recurrent fever without symptoms attributable to a viral infection, difficulty growing or gaining weight, or if the child does not return to his baseline between episodes.  Other causes of fever that should be considered in these instances include:

  • Immunodeficiencies: problems in the immune system that makes the child more susceptible to infections
  • Anatomic and metabolic abnormalities: abnormalities in certain organs that make them more prone to infections (like my ears), or diseases such as cystic fibrosis
  • Inflammatory bowel disease: inflammation of the intestines
  • Cancer: such as leukemia or lymphoma

With this knowledge, parents and pediatricians alike can help distinguish between the majority of children that develop recurrent fevers because of frequent viruses, from causes which may require additional workup or treatment.

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 Ph.D. 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 of 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 in 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.

 

Some links provided are affiliate links, which means that I earn a small commission at no cost to you if you decide to purchase a product. Your purchase of these products helps to keep this site running. Please visit my disclosures for further information.

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?

Uncovering the mysteries of autoinflammatory diseases and other rheumatic illnesses.

%d bloggers like this: