This week’s blog features another of the fantastic entries we received to our 2018 Student Voice essay competition. Here, Sarah-Ethel (Sally) Justus from Harvard Medical School explores what future doctors can learn from rare disease patients.
When Elizabeth, a thirty-five-year-old immigrant living in the US, woke up one morning with crusty, red eyes, her first thought was that she had conjunctivitis. It posed a mild inconvenience in her otherwise happy, bustling life. A self-described adventurer, she moved from her sleepy hometown in rural Greece to study in America, where she met Neil, a fellow Greek immigrant who won her heart and hand in marriage. They stayed in the US and became citizens, established careers, and started a family. Between preparing breakfast and packing lunch, driving their two children to school, and managing her full-time job as a teacher, Elizabeth could hardly make time for the appointment to get her eyes checked. She wasn’t too concerned though. After all, it was just conjunctivitis.
Destiny has a funny way of dispensing life-changing moments when they’re least expected. I have spoken with many patients about their D-day, or diagnosis day. It is a visceral memory for most. The journey can often feel like a game of human pinball, with patients flung from one uncertain provider to the next. Even when the appropriate specialist is consulted, the relief of finally getting an answer is often tarred by the way it’s delivered. According to one patient: “I was at a teaching hospital, so fifteen people lined up to examine me. As they talked, I overheard them whispering a word I presumed might be my diagnosis, but no one would say for sure until my labs came back. It wasn’t until two weeks later that a nurse called to confirm the doctors’ suspicions and my fears.”
For Elizabeth, her doctor was perhaps a bit too direct.
“You do have conjunctivitis, but there’s something odd—can you even see anything?”
Puzzled, she replied, “Yes, I can see just fine. Why do you ask?”
“Well, I don’t know what you have, but…you’re going blind.”
For the next several years, Elizabeth would undergo numerous tests administered by multiple specialists before she was finally diagnosed with Stargardt Disease, a rare genetic condition that causes blindness (1,2). The disease preferentially takes the centermost vision first, then compromises the periphery. Morphological changes to the retina often precede symptom onset, as in Elizabeth’s case.
Tommy and Reed, two cousins and best friends, had a slightly different experience. “I remember looking across the room to see if the answering machine light was on and realizing that sometimes it was there and sometimes it wasn’t. Then one day, I was staring off in the distance and suddenly realized that my entire central vision was only in black and white,” Reed recalled. Tommy still remembers when Reed told the family he had Stargardt: “I just remember thinking, ‘Gosh that’s horrible, I’m glad that’s not me!’ ” But, a few months later, Tommy drove out of his driveway and was almost hit by a car that seemingly came out of nowhere. “That’s when I knew something was up,” he said.
Patients with rare diseases often have severely debilitating conditions that impact every aspect of their lives, yet they receive little attention in the medical school curriculum. While I am only in my second year of training, there has thus far been no mention of conditions like Stargardt, mal de débarquement syndrome, or alkaptonuria, and I can understand why. Medical school is often likened to sipping from a fire hydrant: the amount of material coming at you far surpasses your ability to take it all in. Some would argue that learning about the most common diseases should take precedence to lessons on rare conditions. Yet, after working with patients with congenital blinding disorders for two years, I believe that these patients have just as much, if not more, to teach future doctors.
At the very least, patients with rare conditions are a precious resource for better understanding the body, and they may be the key to unlocking the next frontier: personalized medicine. With the completion of the Human Genome Project in 2003, great strides have been made in gene mapping, but our understanding of the function of these genes and the consequences of mutations is still in its infancy. Many rare conditions have a genetic component, in part or in whole, and they provide a case study for modeling congenital diseases that may otherwise be difficult to replicate in model organisms. These findings could ultimately have implications for common conditions as well. For example, the discovery of bisphosphonates, drugs used in the treatment of osteoporosis and multiple myeloma, can largely be attributed to the study of hypophosphatasia, a rare disease of defective bone mineralization (3,4). This is one of many examples where rare conditions serve as fundamental diseases that are gateways to broadly applicable treatments (5).
In my opinion, however, a far more important lesson from the rare diseases community is what to do once we’ve reached the limits of medicine: advocate. “One doctor told me to come back in ten years, since ‘There might be some treatments in the pipeline by then.’ That was twenty years ago,” Reed confided. Elizabeth refuses to wait idly for that day to come and speaks publicly about her condition to raise awareness. Even though she is now legally blind in one eye and can no longer drive, she is resilient and insistent that “with the right support, we can be unstoppable in achieving all we desire.”
Providing the right support is exactly where physicians can help. We can play an important role in empowering patients to advocate for themselves. There are several ways to do this. We can start by providing educational materials outside of Dr. Google for patients to learn about their conditions. Second, we can inform patients of alternative therapeutic options while a definitive cure is still in development. From dietary modifications, to acupuncture, to holistic medicine, there are other options that should be explored that can alter the patient’s experience and provide them a sense of control over their disease progression. Finally, doctors should provide patients with information about support and advocacy groups. Patient organizations have accomplished more in the way of advancing rare disease awareness, research, and policy than could be achieved through any other means (6). One example comes from the National Organization for Rare Disorders (NORD, USA), which actively lobbied for legislation that ultimately became the Orphan Drug Act of 1983, a monumental policy that incentivized pharmaceuticals to pursue drug development for rare conditions at a time when they were completely forsaken (6). As physicians, we must remind our patients of their own power to change the course of their disease for themselves and their posterity. As one anthropologist, Dr. Margaret Mead, put it, “Never doubt that a small group of thoughtful, committed citizens can change the world; indeed, it’s the only thing that ever has.”
Ultimately, the greatest lesson patients with rare conditions can teach is the essence of what it means to be a doctor. This population is uniquely poised to serve as a mirror for the medical profession to reflect on its identity and purpose. When I was a little girl, I dreamed of the day when I could draw lab work, identify a pathogen, give medications, and cure a patient. But what is the doctor’s role when there is neither pathogen nor cure? What do we have to offer patients fighting their own bodies? Many doctors may have an identity crisis when a patient with a rare condition walks into their office. After years invested in our education and development as clinicians, it is uncomfortable not to have answers to patients’ questions. The temptation comes to pass these patients off to yet another specialist, avoid corresponding with the rest of their care providers for fear of appearing ignorant before our peers, or worse, jumping to a diagnosis that may be inaccurate.
Becoming comfortable with our insecurities regarding the limits of our knowledge begins with recognizing the true experts: the patients themselves. With a lifetime of experience in their own unique conditions, our patients must be encouraged to actively participate in their own care, and we must create a safe space for them to do so. This involves delivering a diagnosis in a compassionate way, refraining from treating patients as medical marvels rather than human beings, and facilitating a multidisciplinary conversation so that their care is not fragmented across providers. Reed’s suggestion? “Put the pride aside.” Elizabeth would agree: “Everyone is different, and everyone has something to teach you.” Our role as physicians, then, is to build a partnership with our patients, one based on mutual respect, equally balanced decision-making, and companionship for the journey ahead. No longer should we feel the need to try and lead our patients when we ourselves are often blinder than we would like to admit. Instead, we must take Elizabeth, Reed, Tommy, and all of our patients by the hand and walk through the darkness with them, side by side, until we findacure.
1. Tanna, P., Strauss, R. W., Fujinami, K. & Michaelides, M. Stargardt disease: Clinical features, molecular genetics, animal models and therapeutic options. British Journal of Ophthalmology (2017). doi:10.1136/bjophthalmol-2016-308823
2. DiCarlo, J. E., Mahajan, V. B. & Tsang, S. H. Gene therapy and genome surgery in the retina. Journal of Clinical Investigation (2018). doi:10.1172/JCI120429
3. Gallagher, J. A., Ranganath, L. R. & Boyde, A. Lessons from rare diseases of cartilage and bone. Curr. Opin. Pharmacol. (2015). doi:10.1016/j.coph.2015.04.002
4. Whyte, M. P. Physiological role of alkaline phosphatase explored in hypophosphatasia. in Annals of the New York Academy of Sciences (2010). doi:10.1111/j.1749-6632.2010.05387.x
5. Gallagher, J. A., Dillon, J. P., Sireau, N., Timmis, O. & Ranganath, L. R. Alkaptonuria: An example of a ‘fundamental disease’-A rare disease with important lessons for more common disorders. Seminars in Cell and Developmental Biology (2016). doi:10.1016/j.semcdb.2016.02.020
6. Aymé, S., Kole, A. & Groft, S. Empowerment of patients: lessons from the rare diseases community. The Lancet (2008). doi:10.1016/S0140-6736(08)60875-2