The Tides are Changing

If the idea that Meniere's disease could be caused through a pathogenic process which goes on to produce immune dysfunction is new to you, you might find this article about the practice of rheumatology very interesting.  Wouldn't it be great if the mystery surrounding these diseases of unknown origin could finally be solved and each of us went on to be treated by the appropriate medical specialist?

Is this the end of rheumatology as we know it?
JONATHAN S. HAUSMANN, MD | CONDITIONS | MAY 21, 2014

Recently, an international research team led by Xavier Rodó published a fascinating study in PNAS suggesting that Kawasaki disease is caused by an agent transported by wind from farms in Northeast China.  This agent, possibly a fungal toxin, is responsible for triggering an exuberant immune response in children, causing the typical manifestation of the disease: fevers, rash, conjunctivitis, “strawberry tongue,” enlarged lymph nodes, and swelling of the extremities.  Untreated, Kawasaki disease can cause aneurysms of the coronary arteries, premature heart disease, and even death.


What I find so fascinating about this article is that it sheds light on the possible etiology of a rheumatic illness.  As rheumatologists, one of the biggest challenges we face is not knowing the causes of most of the diseases we treat (that’s our dirty little secret!).  Even though we use state-of-the-art medicines, our understanding of disease is still in the Dark Ages.

Fortunately, we’ve had some progress.  Rheumatic fever, for example, was found to be caused by Streptococcus, the same bug that causes Strep throat.  We learned that treating Strep throat with antibiotics prevents rheumatic fever, likely the reason why rheumatic fever is now extremely rare in the United States.

In the 1970′s, an epidemic of arthritis struck Connecticut, affecting many children.  Detailed research showed that it was due to a bacteria, Borrelia burgdorferi, carried by a tick.  To prevent disease, we advise people to use repellents and avoid tick-infested areas.  If they develop Lyme, we offer effective treatments with antibiotics.

We have also made progress in understanding of some types of vasculitis (diseases that cause inflammation of blood vessels).  Polyarteritis nodosa is often caused by hepatitis B virus, and cryoglobulinemic vasculitis is due to hepatitis C virus.  Cures for these types of vasculitides can be achieved by eradicating the virus.

Is it a coincidence that several diseases that we considered to be “rheumatic” are now known to be caused by bacterial, viral (and perhaps) fungal elements?  Not really, especially if we understand evolutionary medicine.  This often-overlooked field of study helps explain why humans, despite millions of years of evolution, are still vulnerable to disease.   Two common reasons include pathogens (which are able to evolve faster than we can), and the mismatch between our bodies and our new environment (likely responsible for the obesity epidemic).

Unfortunately, most rheumatology research is conducted without an awareness of evolution.  It seeks to find abnormalities of the immune system that cause disease, without first asking why any abnormality would exist in the first place.  It tries to identify genes that make people susceptible for a disease, without asking how deleterious genes could be passed down through generations.

Fortunately, the winds of change may be near.  Interest in P. gingivalis as a cause for rheumatoid arthritis continues to grow, and the role of the microbiome in the development of rheumatic diseases shows promise.  With a better understanding of why we get sick, we may uncover other environmental triggers responsible for the rest of the rheumatic diseases that we treat.

Gary Hoffman, a rheumatologist who studies vasculitis at the Cleveland Clinic, has said that understanding the cause of a disease is the “most crucial element.”  He writes: “How empowering that knowledge is, especially when the etiological agent persists and perpetuates the process.  In that setting, given adequate therapeutic interventions, we can even affect cures.”

Scientific progress is said to occur through “paradigm shifts,” or radical changes in our way of thinking, which abruptly transforms the field.  Will a fungal toxin mark this change for rheumatology?

Jonathan S. Hausmann is a rheumatology fellow who blogs at Autoinflammatory diseases.

Gut Health Equals Immune Health

As you may have heard by now, the bacteria living in our MALT play a critical role in the function of the immune system. These bacteria either produce or stimulate our own bodies to produce specific types of substances that are absorbed into the bloodstream and go on to communicate directly with immune cells. 

A subset of the MALT is the GALT, or gut-associated lymphoid tissue. In my area of practice as a nutrition support dietitian, we have been talking about this for years in relation to our patients who are unable to obtain their nutrition through the gut and instead are dependent on IV nutrition. It had been something of an enigma for years that this population was far more prone to infections, especially bloodstream infections, aka sepsis. We now know that this is due to the growth of undesirable bacteria in the gut and the subsequent increased permeability of the intestinal walls. It is common practice now that we administer a fiber-containing tube feeding formula into the gut as what are known as trickle feeds for the sole purpose of preventing this from happening, which has resulted in fewer bloodstream infections. 

Along these lines, scientists have begun studying the make-up of the intestinal flora of healthy people. While the communities of microbes can vary widely in the healthy population, there are some common themes among them and studies have shown that even small changes in the diet, specifically the presence or absence of certain types of fiber, can have an impact on the profile of the microbial flora. In particular, diets containing prebiotics, in conjunction with probiotics, are believed to be particularly beneficial. Click here for a brief article that explains this in a little more detail. 

It is very important to note that some people have difficulty digesting something called FODMAPs, of which prebiotic fibers are included. Symptoms of this can be gas, bloating, diarrhea, constipation, nausea, and fatigue. Click here to learn more about these symptoms and what to do about them.

Here's a good way to start the day:

Place 1/3 cup of dry, old-fashioned oats and about 2/3 cup of water in a cereal or soup bowl and cook in the microwave for 90 seconds. Stir in 2 heaping tablespoons of whole milk plain Greek yogurt, 1/2 sliced banana, and 1 tsp honey (opt.). Eat with 10-12 dry roasted, unsalted almonds and a small orange.

How the Immune System Works

I apologize for the formatting.  When I copy and paste directly from the web and, in this case, even from Word, weird stuff happens.  If anyone knows a way around this, please share in the comments (I won't necessarily publish the comment, but will take any helpful advise for solving this problem).

How the Immune System Works

The immune system is designed to provide protection from invading organisms, including bacteria and viruses, tumor cells, dirt, pollen, and other foreign material. Normally, barriers—including the skin and the lining of the lungs and gastrointestinal and reproductive tracts—protect the underlying delicate tissues from the outside environment. However, when there is a breakdown in that protective lining, germs and other irritants can enter the body. The immune system’s function is to conquer these foreign molecules by engulfing them or by destroying them with enzymes or other detoxifying means. In addition to fighting off these foreign invaders, the immune system has evolved to destroy abnormal cells (such as tumor cells) but occasionally reacts against the body’s own normal tissues (autoimmunity).

Innate and Acquired Immunity

There are two principal types of immune response, innate and adaptive (or acquired) immunity, which are distinguished from one another by both their speed and specificity. The innate immune system, so called because it is present from birth, involves nonspecific responses that are the first line of defense against common infectious agents, including bacteria and viruses. This system is generally able to recognize foreign organisms but is unable to distinguish between particular invaders. Thus, an innate response does not require stimulation by sophisticated cell­to­cell interactions to remove bacteria or other foreign material and degrade it.

In contrast to the innate immune system, the more specific adaptive (acquired) immune system must be triggered by a specific virus, bacterium, or other foreign material, which stimulates lymphocytes (see below) to produce antibodies that can combat the foreign substance. At the next exposure, the preformed antibodies will allow the person to respond with an even stronger, more specific response. This is called immunological memory.

Cells of the Immune System

The immune system consists of white blood cells (leukocytes), which are produced in the bone marrow and mature there or in the thymus and other lymphoid organs. Leukocytes circulate in the blood along with oxygen­carrying red blood cells. Under normal conditions, leukocytes leave the circulation and migrate into organs, including the skin, lungs, intestine, and reproductive tract, as these are places where germs can appear. There, they can wait for infectious agents, or they can migrate back through the circulation to other organs. There are three major types of leukocytes.

Neutrophils are the most plentiful of the white blood cells in humans. They are the immune system’s first line of defense, as they contain an arsenal of preformed chemicals known as enzymes, which are capable of destroying bacteria. In addition, they are phagocytic, meaning that they can engulf viruses, bacteria, or other foreign material, protecting the host from further damage. Neutrophils are very short­lived and are often destroyed during the process of fighting infection.

Monocytes are leukocytes that, after migrating to tissues, mature into macrophages. Like neutrophils, macrophages are phagocytic and can remove foreign material and parts of dead cells from the tissues. They too contain enzymes that can destroy infectious material but live longer than neutrophils and do not tend to self­destruct as easily. The tissue macrophage in the liver is called the Kupffer cell.

Lymphocytes, the most selective cells of the immune system, are specialized white blood cells that can combat specific infectious agents. There are two types of lymphocyte: B cells and T cells. B cells, which are responsible for humoral immunity (so­called because it takes place in the body fluids, classically known as the humors), release specialized, soluble proteins known as antibodies into the blood and other body fluids. The antibodies recognize and bind to the surface of foreign substances (i.e., pathogens), immobilizing them and further labeling them as foreign so that they can be more readily taken up by phagocytic cells.

T cells, in contrast, act directly on other cells rather than manufacturing antibodies to combat infectious agents. Because of this direct interaction with other cells, T cells are responsible for cellular immunity. They can be further divided into helper T cells, which recognize foreign invaders and stimulate immune responses from other cells; and cytotoxic T cells, which destroy infected cells. Whereas some of these cells survive only briefly, others are extremely long­lived, including “memory cells,” which are capable of remembering certain features on the foreign molecules so that, if the organism encounters that foreign molecule in the future, it can quickly stimulate its response team.

Communication Between Immune Cells

One form of communication between immune cells is direct cell­to­cell contact, which can occur either as a loose, transient association or as a tighter, more long­lasting encounter. Either way, cells must make physical contact with one another.

In the second form of contact, cells release small proteins called cytokines, which bind to specific receptors on the surface of target cells. This enables cytokines to interact only with the appropriate target cell with no effect on surrounding cells. Although many of the effects of cytokines are local, they have been called the hormones of the immune system, because like hormones, they are transported by the circulating blood.

Cytokines can affect the same cell that produced them, a neighboring cell, or a cell far away. They stimulate or dampen cell proliferation (replication), production of other cytokines, killing of damaged cells or tumor cells (cytotoxicity), and cell migration (chemotaxis). The latter response is controlled by a subset of cytokines called chemokines. Just as there are cells that can stimulate or inhibit immune response, cytokines produced by those cells can regulate a variety of cell functions either positively or negatively.

— Elizabeth J. Kovacs and Kelly A.N. Messingham

http://pubs.niaaa.nih.gov/publications/arh26-4/257-263.htm