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    Nobody Has My Condition But Me


    In early 2021, Dr. Michael Ombrello, an investigator at the National Institutes of Health, received a message from doctors at Yale about a patient with a novel genetic mutation—the first of its kind ever seen. A specialist in rare inflammatory and immune disorders, Ombrello was concerned by what first-round genetic tests showed: a disabling mutation in a gene, known as PLCG2, that’s crucial for proper immune functioning. It was hard to discern how the patient, a forty-eight-year-old woman, had survived for so long without serious infections. Even more puzzling was the sudden onset of severe joint pain and swelling she was experiencing after years of excellent health. He decided to bring her to the N.I.H. campus, in Bethesda, Maryland, to study her case first hand.

    That’s how I ended up as a patient in his clinic on a sweet, warming day in April, 2021, just as the cherry blossoms in the Washington area were in full bloom. As a historian and a biographer, I am used to conducting research, examining other people’s lives in search of patterns and insights. That spring, I became the research subject. At the N.I.H., Ombrello’s team took twenty-one vials of my blood and stored a few of them in liquid nitrogen for future use. Scientists outside the N.I.H. began to study me, too. In the past few years, my case has been examined by specialists at Yale, Harvard, Columbia, and the University of Pennsylvania—by immunologists, rheumatologists, dermatologists, pulmonologists, and experts in infectious disease. It has been debated at hospital grand rounds and global medical conferences, and in high-powered conference calls. There are PowerPoint decks about it.

    All of which makes me lucky, in one respect. Far too often, women who present with hard-to-diagnose illnesses are told that the symptoms are no big deal, that the problem is in their head. They spend years going from doctor to doctor, in a desperate search for someone, anyone, who’s willing to help. This has not been my experience. From the first, doctors took my condition seriously, sometimes more seriously than I did. They pushed me along to the nation’s greatest experts, at the finest medical institutions. My insurance paid large sums for tests and treatments; my family and friends were patient and supportive. All the while, I was able to keep doing what needed to be done: write a book, raise a child, teach my classes.

    But none of this gets around a single, stubborn fact. “You are the only person known to have this exact mutation,” Ombrello explains. “I haven’t seen any reports in reference populations of this mutation, and I don’t have anyone that I’ve had referred to me or that I’ve seen in my patient cohort that has this mutation.” In other words, I am one of a kind, and therefore a medical curiosity. Doctors often blurt out that my situation is “fascinating” before catching themselves; they’re aware that nobody really wants to be fascinating in quite this way. Thanks to advances in genetic sequencing, though, researchers are increasingly able to identify one-offs like me.

    That leaves them engaged in a process not so different from what I do as a biographer, trying to understand a life and its meaning based on deep research but incomplete information. My historical training pushes me to think in chronological terms: Where do we stand in the great saga of human history? How do grand structural forces and ideas and technologies shape what it’s like for an individual to live a life, day to day? But nothing has rooted me in history quite like the experience of getting sick. Though illness and death may be the universals of earthly existence, the way that we get sick—and, sometimes, get better—has everything to do with the luck of the moment.

    Like any good historical narrative, mine has a day when it all began. On September 1, 2019, I went for a mile-long swim in the Long Island Sound, along a thin strip of Connecticut beach where distance swimmers like to gather. A few minutes in, I brushed up against a strange aquatic plant; it scratched my forearm and left me with angry welts that disappeared about an hour later. That night, my ankles started to itch—really itch, the maddening kind of sensation that blots out all thought and reason. By the next day, a hivelike rash was creeping up my calves and thighs, and I could barely turn my neck or open my jaw. By the following week, the symptoms had colonized the rest of my body, with the rash moving north along my trunk and arms while the pain in my neck and jaw descended south into my arms and shoulders.

    As a chronically healthy person, I assumed that these were temporary annoyances, perhaps reactions to that odd plant. My doctors initially thought more or less the same thing. As a professor at Yale, I receive my medical care through the university’s health center, a private bastion of socialized medicine for faculty, students, and staff. After five or six days of worsening symptoms, I made an appointment with an advanced-practice registered nurse, who sent me to a dermatologist, who prescribed a steroid cream and told me that things would clear up in a few weeks.

    The cream did the trick; the rash disappeared, never to return. But the joint pain stayed and grew steadily worse, soon accompanied by bouts of dramatic swelling as it migrated into my hands and ankles and knees. When the inflammation visited my shoulders, I could not raise my arms without yelping in pain. When it stopped off in a knee, I aged thirty years in a day, a hobbled old woman daunted by a flight of stairs. When it visited my hand, I suddenly had a thick, swollen paw.

    Based on these symptoms, I was sent to a rheumatologist. At first, I was charmed by the specialty’s anachronistic name, with its nod to an age when “rheums” and “vapors” and “humors” constituted the height of medical practice. Though scientific knowledge has advanced a good deal since then, rheumatology still relies on intuition and pattern recognition, as well as on definitive tests and cutting-edge therapies. Today’s rheumatologists deal regularly with autoimmune diseases, in which the body’s immune system attacks healthy cells and tissue. So perhaps it should have been no surprise when my first diagnosis fell into the autoimmune category. At our initial visit, the rheumatologist suggested that I might have serum sickness, a temporary allergic reaction (maybe to that plant in the Sound). Six weeks later, when the pain and swelling persisted, she switched to a diagnosis of seronegative rheumatoid arthritis, a chronic and incurable autoimmune disease that tends to afflict middle-aged women.

    Already, though, there were aspects of my condition that did not quite make sense. I did not test positive for the usual markers of autoimmune disease. Nor did the pattern of my symptoms—random, asymmetric pain that moved from joint to joint; swelling of the tissues rather than of the joints themselves—follow the usual rheumatoid-arthritis course. And the frontline treatment for the disease, a powerful immune suppressant known as methotrexate, seemed to have no effect. We spent months cycling through other standard R.A. medications: Humira, Xeljanz, Actemra—many of them vaguely familiar from prime-time TV commercials.

    The only drug that controlled my symptoms was the steroid prednisone, in substantial doses. The trouble is that prednisone has side effects dire enough to put even the most alarmist F.D.A.-mandated voice-over to shame. In the short term, the drug can cause mood swings, anxiety, sleep disruption, and even psychosis. In the medium term, it leads to weight gain and fat cheeks, also known as Cushingoid features, or moon face. In the long term, it rots your bones and teeth, thins out your skin, degrades your vision, and increases your susceptibility to diabetes. Plus, the longer you stay on it the harder it becomes to stop. Prednisone is sometimes referred to as “the Devil’s Tic Tac”: cheap and available and effective, but at potentially scorching long-term costs.

    Cartoon by Roz Chast

    I got off easy, at least at first. I gained about ten pounds and my face puffed up a bit. My lower teeth started to chip after a lifetime of solidity. These developments bothered me, but they were nothing compared with the prospect of life without prednisone. On a high enough dose, I could function reasonably well; once, I even played basketball with a band of teen-age boys. Dip below a certain threshold, though, and the simplest activities became impossible; there was no more bending of knees, chewing of food, lifting of arms.

    A few months into this back-and-forth, I began to keep a record of my symptoms and sensations, hoping to uncover clues that would break the steroid loop. I tried to be scientific, dispassionately recording dosage, symptoms, and external conditions such as food intake, exercise, and weather. Mostly, though, I complained. Entries included “oof,” “omg ouch,” “can barely move,” and “this sucks”—accurate depictions of my inner state, if not shining displays of literary merit. There were days, sometimes several in a row, when things seemed to improve. “Hooray. Gratitude + joy,” I wrote in February, 2020, after a largely pain-free day. Inevitably, though, the highs turned low. Even a single day could bring wild variation. “Bad in morn,” I wrote on January 14th. “Felt stoic + accepting midday. Eve am kinda miserable but have been worse.”

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