Aug. 13, 2015

How Do We Think About Lupus and Why Does it Matter?

By: Joan T. Merrill, MD, Medical Director for the Lupus Foundation of America

After the first microscopes were devised in the late 1500's, it became clear that our universe is made up of tiny wheels within wheels comprising the underlying structure of all that we see.  As time went by, we began to understand that most human ailments are caused by disorders arising in structures that are smaller than the eye can see.  An idea began to emerge that optimal treatments should be specifically targeted to certain miniscule proteins and cells that are the actual culprits in disease instead of aiming at (and potentially damaging) major areas of healthy tissue. 

A significant setback to this understanding came in the 19th century when the science of taxonomy emerged.  Major advances were made in naming and organizing hierarchies out of everything that could be found on the planet from different families of plants and animals to different types of medical diseases.  Some diseases, such as lupus, were clearly complex in origin.  It was understood that lupus affects different organs in different people in a way that isn't predictable using an understanding based on the major visible organs that are most commonly involved.  Still, two centuries later, it is still true that the medical school training of the doctors who take care of you, and all the sub-specialties in medicine around the world remain a bit stuck in this (not entirely correct) organ-based view of disease.  If you have something wrong in your digestive tract, you are sent to a gastroenterologist.  If something is wrong with your lungs, you are sent to a pulmonologist.  If it is your heart, you see a cardiologist.  What if you have lupus, and you could, at a given time, develop all three of those disorders?  You are sent to a rheumatologist, a sub-specialty that developed to provide expertise in illnesses of the joints (e.g., arthritis) and connective tissues (e.g., muscles and tendons), but not all of these other things. 

Somehow, all by itself, and without the support of any medical board, a very specialized (sub-sub-specialty) of doctors began to evolve who spend most of their time studying lupus and/or taking care of lupus patients.  It is becoming clearer that lupus is not a disease of one organ more than others.  However, as time went by, it was better appreciated that all patients with lupus do share an overlapping spectrum of symptoms, and an overlapping spectrum of molecular disorders in the immune system. But there is not a one to one correspondence of the symptoms and the immune disorders and all treatment strategies do not work for everyone.  Let’s use arthritis, one of the most common symptoms of lupus, as an example:

  • There may be another person with similar arthritis, but who has low levels of BLyS, and very strong signals from immune cells called myeloid cells, and may be more likely to respond to mycophenolate mofetil (CellCept®).
  • One person may have a high level of "interferon alpha" signals in the immune system and have severe arthritis and a rash.
  • Another person with the same interferon alpha finding may have no rash, only the mildest arthritis, and severe kidney involvement.
  • Another patient may have both myeloid and inteferon alpha involvement and have very severe kidney involvement.

Not all patients who share a certain organ involvement are going to be optimally treated with the same medicine at the same dose.  Some may need a combination of treatments; others may not need so much.  A better understanding of those variables can be made, in part, by an improved classification of lupus. This would allow better results for more patients and avoid unnecessary toxic combination therapies for others. This is exactly where the field of lupus needs to go.  Thinking of lupus as a subset of arthritis isn't going to get us there. The time has come for a more rational approach to selection of therapy than treating lupus by the organ.

Dr. Merrill’s commentary on this subject was recently published in Nature Reviews Rheumatology , a leading international scientific journal. Learn more about the work the Lupus Foundation of America and Dr. Merrill is performing to improve lupus treatment and clinical trial design.