By JOSEPH JUSTIN MULVEY
There is an inexorable mantra among physicians confronted with autoimmune disease: that autoimmunity has both genetic and environmental components. Physicians point to cases of identical twins and to family history to illustrate the validity of this aphorism. However, the immune system, like any other, obeys cellular mechanisms and can be analyzed logically; there is a specific cause, or combination of causes, however veiled, for each patient. It is time we begin identifying and addressing these causes on an individual level.
The immune system, or some aspects of it, is the newest system in the human body from an evolutionary standpoint. It involves the interplay of a myriad of cell types, extracellular matrices, cytokines, integrating centers, co-inhabitants and even gene splicing. Why then should such a comprehensive, vital system have no home in medicine? Sure, it is a $35 billion and growing market for medications according to Reuters, and we all know someone being treated for an autoimmune disease, but by whom are they being treated? A psoriasis, vitiligo or alopecia areata patient will see a dermatologist. If you have remitting seronegative symmetrical synovitis with pitting edema, you are off to see a rheumatologist. Infectious disease handles the worm with which your eosinophils are having trouble. “Immunologists” deal with allergy medicine in the Th2 wing, and gastroenterologists handle Crohn’s disease, microbiome dysregulation and ulcerative colitis. I believe this system is flawed.
Alopecia and psoriasis are less closely linked by the location in which they manifest (the skin) than they are by their elaboration through T-cell infiltrates. These conditions are closer even to ulcerative colitis than ulcerative colitis is to gastroesophageal reflux disease. Superseding the physical organs in which diseases manifest, the common mechanisms underlying seemingly diverse autoimmunities demands a devoted service. I propose a clinical immunology department.
As a lifetime patient with a unique global immune diathesis ranging from manifestations of RA to TTP to UC and several other acronyms, I have seen few changes in the way these diseases are treated now compared to how they were 20 years ago. There are more drugs, ever more DMARDs, and more treatment options. There are more epidemiological studies that document better responses to one dosing regimen or another which guide specialists to adjust their treatment plans, but rarely is anything decided on an individual scale.
Currently, for example, when a rheumatologist treats a patient with rheumatoid arthritis, the disease is referred to as a singular entity. A well-equipped clinic may list that the patient is positive for rheumatoid factor or anti-nuclear antibodies, however, the disease is generally treated the same way: empirically. Nearly every patient presenting with moderate rheumatoid arthritis will be started on a COX-2 inhibitor, followed by methotrexate if the condition persists. If this too fails to control the symptoms then a biologic agent such as a TNF-alpha decoy receptor may be considered. Such uniformity is not the quality of medicine to which we should aspire. Patients may spend years losing micron after micron of tissue before an acceptable drug balance is found through trial and error.
Getting into medical school is competitive to say the least. All young doctors today understand advanced science, research and drug mechanisms. It is time the medical community started employing that knowledge. One place this has been successful is oncology. Compared to immune disorders, oncologists rely more on clinical trials and bench to bedside medications in their work, demanding them to look outside of established protocols. In oncology, tumor biopsies are taken and examined for biomarkers, which predict treatment, and for the presence of targetable receptors. Cancers of the same tissue, and even with the same histological appearance, are not all treated the same way. For this reason, as a scientist and soon to be physician, I deeply respect the field of oncology, and I want the same for immunology.
I am a proponent of a “clinical immunology” consult service, with its own residency program, and which outside of consults, sees the cross-system cases that baffle other physicians. Cases that affect the skin and intestine with cellular infiltrates may not be cross-system at all. They share an overlooked system: the immune system.
One day a visit to a rheumatologist will not be limited to joint manipulation, function tests, and blood work identifying factors that rarely affect the treatment plan, but instead will include draining synovial fluid sample for immunology specialists. These experts will then determine that because the fluid shows t-cells producing large amounts of IL-6, as opposed to macrophages pumping out TNF-alpha, that maybe a tailored combination tocilizumab and ultra-low-dose cyclosporine with a touch of fecal bacteriotherapy would be more appropriate than MTX and adalimumab. One sample in the right hands could save a patient years of suffering and lasting damage.
This week Illumina advertised that it could analyze a human genome for $1,000, a procedure that cost Steve Jobs one-hundred times that amount only a few years ago. Less than a decade ago, James Watson was sequenced at 7.4 fold coverage for an extraordinary amount of money. Last year, for $3,000 I sequenced my genome at approximately 46 fold coverage revealed a hitherto unseen HLADRB1 mutation, a possible cause for my disease that convinced my physicians to treat my disorder with the drug abatacept. Things got better. Twenty nine years, and millions of dollars in treatment expenses later I had something concrete to go on.
Joseph Justin Mulvey is the Class of 2016 for the Tri-Institutional MD/PhD Program through Weill Cornell Medical College. Comments and reactions can be sent to [email protected] What’s Up, Doc? appears alternate Fridays this semester.