blood test revealed a dangerously low platelet count. Doctors hospitalized her immediately and began transfusions to boost her blood count, which worked — but only briefly. Less than three days after her discharge she was rehospitalized, as doctors sought to determine what was destroying her platelets — cells that help blood to clot.
Stein, who lives in Arlington, said she kept telling doctors and nurses about an odd coincidence involving her oldest brother — one she increasingly believed was relevant to her medical problems — but no one seemed to pay much attention.
“They were all sort of scratching their heads about what might be wrong, and I was getting so frustrated,” recalled Stein, now 48.
Uncertain about how to make herself heard, she offered to arrange a call between the hematologist treating her and her brother, who is a physician.
“Doctors talk to doctors happily,” she said. “It’s sometimes hard to get them to listen to patients.” She hoped that such a conversation might lead to an answer that could help spring her from the hospital, or at least enable doctors to investigate — or to rule out — a potential disease and get to the bottom of her medical problem.
That phone call proved to be pivotal: It led to a diagnosis that explained Stein’s frightening symptoms as well as a string of recurring illnesses that had plagued her for decades. And it cemented a bond between siblings.
More than klutzy
At first Stein attributed her recurrent nosebleeds to allergies, winter dryness and chronically infected sinuses. The bruising was harder to explain, even for someone who describes herself as “a true klutz.” When she banged her arm on a post in a restaurant, it turned a ghastly shade of mauve. Then parts of her body that she didn’t remember bumping became bruised. After an episode of dizziness, she saw her internist, who ordered blood tests.
On Feb. 17, the internist called Stein. Her results looked fine, he said, except for one test that was probably a lab error and needed to be repeated. Her platelet count was in the low thousands — virtually nonexistent. A normal count ranges from 150,000 to 400,000 per microliter; people with counts below 10,000 are at risk for spontaneous bleeding that can be fatal.
Stein, who had just started an unusually heavy period, mentioned it to the doctor. He told her to go straight to a nearby emergency room to get her blood retested. Freaked, she telephoned her brother, a doctor, who concurred.
Arriving at the ER with her husband on a busy Friday evening, Stein said, she waited for several hours, bleeding so heavily that she soaked through blankets. Doctors ordered blood tests and quizzed her about her health; she told them that both her children, then 3 and 7, were sick — one with strep, another with a viral infection — and that she had had a headache and a mild sore throat.
After the blood test results came back, a nurse entered the cubicle and asked, “Did you not notice that you were tired?”
Stein, who had worked a full day as the Web site director at Washington’s Urban Institute before picking up her children at their schools, replied, “I’m the mother of young children — I’m always tired.”
The nurse told Stein that her platelet count was so low, a condition called severe thrombocytopenia, that she was at risk of a fatal brain hemorrhage. She was being admitted to the hospital for immediate transfusions of platelets to boost her count while doctors searched for the underlying cause. Among the possible culprits: cancer, lupus or a viral or a bacterial infection.
Stein remembers feeling too stunned to reply.
Around midnight, after her husband had gone home, the hematologist stopped by. “He was very calm, which made me feel better,” she recalled. “He said, ‘Something’s happening and we’re not really sure why.’ ”
“At that point I wasn’t too worried because I thought, ‘Well, they’ll figure this out,’ ” she recalled. Doctors suspected her low platelet count was probably the result of a condition called immune thrombocytopenia purpura (ITP), a clotting disorder that can occur when the body mounts a defense against an infection ranging in severity from a simple virus to hepatitis or HIV.
‘You can’t have it’
Stein’s brother was at first disbelieving: Several years earlier, he had been given a diagnosis of ITP. “He said, ‘That’s so weird — you can’t have it, because I have it.’ ” ITP was not known to be a genetic disorder and no one else in their family had a similar problem.
After two days in the hospital she was discharged: The nosebleeds had lessened, her period had nearly stopped and her platelet count was on the rise at 36,000. But a day later the hematologist found that her count had nosedived to 4,000. Stein was sent back to the hospital for more transfusions and tests. Leukemia or another blood cancer seemed increasingly unlikely; a bone marrow biopsy showed nothing amiss. An infectious-disease specialist wondered whether her body was mounting an overly aggressive immune response to a disease she had avoided as a child but had contracted from one of her children.
But after researching ITP online and talking to her brother, Stein kept circling back to his experience: His ITP had been the result of common variable immune deficiency (CVID), a disorder that affects one in 25,000 Americans. The disorder results from the failure of the body to produce sufficient antibodies to ward off disease, resulting in frequent infections. ITP can be one of its symptoms. Because this form of immune deficiency mimics other diseases and causes a variety of disparate ailments, it takes an average of six years for patients to receive a correct diagnosis. Most cases are diagnosed in people between the ages of 20 and 40, according to the Immune Deficiency Foundation.
“A weird little bell went off in my head,” Stein said, “and I thought maybe I had it, too.” Since childhood she had been a magnet for all kinds of respiratory problems: She had frequent colds, strep and sinus infections and seemingly every bug to which her children were exposed. When she contracted both strep throat and pinkeye after assisting at an elementary school party, her husband jokingly asked, “What did you do, lick the desk?”
At her brother’s suggestion, Stein said, she kept telling doctors about his CVID diagnosis, but no one seemed to follow up. “They’d say, ‘Yeah that’s interesting.’ ”
Frustrated, she decided to offer to arrange a call between her brother and the hematologist, figuring that they might speak the same language. The hematologist was receptive, and after the two men talked, “that’s when things started to click.” During her first hospitalization, testing had revealed that the levels of two key antibodies, IgG and IgA, were low, a key clue to possible immune deficiency.
The hematologist decided to treat her with an infusion of intravenous immunoglobulin (IVIG), a solution containing antibodies extracted from the plasma of multiple blood donors, to see if that would boost Stein’s immune system.
It worked. A few days later, after two more infusions that took about 12 hours each, Stein’s platelet count had jumped to more than 140,000. For the next six months, doctors monitored her counts and gradually weaned her off prednisone, a steroid that reduces the chance of platelet destruction. In May her ITP was found to be in remission.
While it appeared that Stein had CVID, a definitive diagnosis would rest with immunologist Shelby Josephs.
Prized by researchers
In October 2006 Stein saw Josephs, who practices in Montgomery County. To test her immune response, he administered a diphtheria and tetanus booster and a shot to prevent pneumococcal pneumonia, a vaccine Stein had never received. Several weeks later, he measured her production of antibodies.
“It wasn’t an open-and-shut case,” Josephs said, because Stein’s body did make some antibodies. But overall, her response to both vaccines was weak. Josephs decided that her history and hospitalizations, combined with the vaccine and other results, made her a candidate for continued IVIG therapy to prevent serious infections.
Josephs said there is no way to know when or why Stein developed CVID. “My assumption is that people are born with a tendency” to develop it, he said. The immune system weakens over time and an unknown trigger results in the disease.
The fact that Stein’s brother has the same disorder has attracted attention from researchers interested in exploring possible genetic underpinnings. Both siblings, as well as their brother, who has a normal immune system, have participated in studies at the National Institutes of Health. So far, neither of Stein’s children shows signs of an immune disorder.
Loath to receive infusions for the rest of her life and hoping that the CVID diagnosis was wrong, Stein sought a second opinion in 2007 at the University of Pennsylvania. “I didn’t want to believe I had CVID,” she said. “There is no cure for this and I’m potentially susceptible to lymphoma and all sorts of other nasty things.”
An immunologist at Penn retested her, confirmed the diagnosis and echoed Josephs’s recommendations.
Since then, Stein has received monthly infusions, which take about six hours and leave her with a headache and fever for several days afterward. She still gets sinus infections and colds, but has had no recurrence of the bleeding or low platelet count.
“I don’t want to live in a bubble and I’ve tried really hard to live a regular life,” she said. “It sucks to have this, but there’s power in knowing that I do.”
The diagnosis has resulted in an increased closeness with her brother, whom she credits with helping her discover what was wrong far more quickly than many people with CVID. “I know when weird stuff happens I can call him,” she said. “There’s something wonderful about knowing that he’s there and that he understands.”
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