It was bitterly cold in December 2008 when I set out to jog my favorite dirt road. My lungs stung and ached. I breathed more gingerly to no effect, presuming the pain was from frigid air winding its way down my lungs. Finishing in the dark, every breath felt like a dagger wedging deeper.
The next morning, with labored breath and persistent jags in my rib cage, I urged my family to take me to a hospital. The verdict was pleurisy, a medieval term for liquid in the lining of the lungs. I was prescribed Valium to keep my muscles from seizing over the anxiety induced by the breathlessness. Time seems to stop when you labor to breathe, in part, because you don’t know what will happen next, reprieve or the unknown — something far worse. It’s one of the most isolating physical sensations imaginable.
While my immediate condition improved, my lungs became increasingly susceptible to infections. Foreboding events came in succession. A longtime distance swimmer, I gasped and grabbed my sister while looping around a lake island we had swum dozens of times. When downhill skiing, my lungs jammed on the emergency brakes. My body would not, could not continue without pausing every few steep feet to catch a breath and use the impotent steroid inhaler. Willpower, a longtime ally, simply didn’t cut it anymore.
By the end of 2012, chest infections lasted a month, and I had ruptured my eardrum from heaving coughs. Having been a somewhat sickly child, my tolerance for illness was robust, yet my gut knew something was terribly wrong. I had given up on 20 years of running, now often struggled to breathe during sex, dragged when walking up my subway stairs, and wheezed in cold weather.
Convinced of pneumonia or whooping cough, then in resurgence, I went for a chest X-ray. To my astonishment, the radiologist muttered, “I haven’t seen this since medical school.” Her boss told me to see a pulmonologist immediately.
When the pulmonologist called about the X-ray, I asked off the bat if it was cancer, the obvious mortal threat. It wasn’t, but he thought it was serious, “extremely rare,” and “progressive,” and the treatment, “is no chicken soup.” He requested reports for all CT scans of my chest and abdomen, and then rang the next day, demanding why I never told him I had LAM?
“What?” I asked, assuming he wasn’t discussing a menu item.
In 2005, I had had a CT scan to find a cause for chronic night sweats. In that report, procured from my then-internist’s office, a radiologist had diagnosed me with an ultrarare progressive disease called Lymphangioleiomyomatosis or LAM. The report advised its recipient, my internist, to send me to a pulmonologist in haste. For some reason, the internist did not inform me of the diagnosis at the time or during the ensuing eight years during routine checkups.
Now in 2013, the pulmonologist was telling me to “come tomorrow, and don’t look it up online” — an unrealistic exhortation all physicians give at the first mention of a rare diagnosis, I have since learned. Of course I turned to Google only to be assaulted with descriptions of LAM debilitating women (it is estrogen sensitive) in the oft-repeated “prime of their lives.”
Even though a person’s chances of suffering from any one rare disease are small, often vanishingly small, rare diseases in aggregate make up a substantial group. Estimates of rare diseases range from 7,000 to 7,300, which translates to about 1 in 10 Americans. With such high numbers, physicians must entertain zebras as a matter of course. If they fail to do so, they perpetuate and prolong the average five to seven years it takes for a rare disease diagnosis, precious time that could be spent by a patient managing their disease, maintaining a vibrant life, and finding hope and agency by helping to advance science to treat the culprit.
LAM, which was diagnosed accidentally in 2005 and took another eight years to be formally acknowledged in my case, affects 1 in 2 million people, the same likelihood as getting struck by lightning or being killed by a tornado. The disease causes smooth muscle cells to proliferate, resulting in cystic growth throughout women’s lungs and abdomens.
More than half of the women I’ve met with LAM were diagnosed after lung collapse — sometimes double — during labor. Elevated estrogen levels over the course of pregnancy had riddled their lungs with new cystic growth, and the primal force of labor caused cysts to burst triggering pneumothorax. This is why women with LAM are often discouraged by clinicians to carry their own babies. (My 2008 troubles were spurred by a misdiagnosed lung collapse, occurring in 60 to 70 percent of LAM women.)
The treatment goal, at the very least, is to stave off progression, and to avoid double lung transplantation, the survival rate for which five years out is 50 percent due to infection rates.
Casting about for answers, I remembered the hormones I took to prime my reproductive system for egg freezing in 2010-2011. When my beloved father died in 2009, I was 34, heartbroken, single and needing to grieve without worrying about my biological clock, likely ticking fast as my mother had hit menopause at 40. At the time, I was among a handful of healthy early adopters; most women chose to harvest their eggs as protection from the scourge of cancer treatments. I visited my internist to ask whether there was any medical reason to not freeze my eggs, I was told no. But as it turned out, the very hormones I ingested for egg freezing triggered an active growth phase in LAM and a precipitous decline in my lung function, now at 41 percent. (Most people go on the transplant list at 30 percent.)
Paradoxically, LAM’s estrogen sensitivity precludes me from bearing children, and those eggs sit in a Manhattan freezer awaiting a new assignment.
Rare diseases are also called “orphan” diseases for their long abandonment by the pharmaceutical industry because of small patient populations and profit margins. Before the Orphan Drug Act in 1983, the pharmaceutical sector had developed fewer than 10 therapeutics for rare diseases, an FDA study found.
In the ensuing 35 years, the legislation has spawned more than 600 products approved by the Food and Drug Administration. In 2018 alone, the FDA approved 87 orphan drugs. Yet, rare diseases are still considered niche by most drug developers, and a paltry 5 percent of rare diseases have treatments today.
But Lammies, our Facebook moniker, are contextually lucky; we are among the fortunate 5 percent sliver of rare diseases with a treatment. Still, progressive debilitation and lung transplantation loom for many of us. Most Lammies use a cocktail of an immunosuppressant to slow the cystic growth; supplemental oxygen for sleep, cardio, flying and high altitudes; estrogen blockers and stabilizers; and, in some cases, anti-inflammatory, low-dairy, low-phytoestrogenic diets.
When I chose my LAM specialist, I sought a clinician and researcher so I could better understand my disorder and how research gets initiated.
In 2013, when I learned of my diagnosis, there weren’t — and still aren’t — treatments to eradicate cysts from the lungs besides a double lung transplant, which I wanted to avoid because of the low survival rate. So I found a lab for which I could fundraise to seed early-stage research for potential LAM treatments.
During my first evaluation, she homed in on my family’s melanoma history — my paternal grandmother, my father and I all had the skin cancer, which killed my father. Melanoma and LAM cells share several biomarkers, including some of the same proteins, and my physician’s LAM Lab at Columbia University had proved that, in addition to melanoma and colon cancer, the HMGA2 protein was active in LAM.
These findings were a revelation: one lab for a single rare disease had demonstrated the potential of rare disease research to shed light on the pathology of seemingly unrelated illnesses with much larger patient populations.
The foundational research in rare disease labs on proteins, enzymes, chromosomes and genes holds myriad insights into diseases affecting many of us. Rare diseases may seem esoteric to the general population — they were to me before LAM bracketed my daily life — but 1 in 10 Americans stand afflicted.
With so much at stake, and so much hidden potential, physicians, researchers and the biomedical complex should keep their eyes on the zebras.
Sarah Hogate Bacon is a writer and rare-disease advocate in New York City.