Adam’s Amazing Journey
words by Maryann Brinley / photograph by Pete Byron
Harumi Jyonouchi, MD,
associate professor, pediatrics,
UMDNJ-New Jersey Medical School.
(Left)
Harumi Jyonouchi and her patient, Adam, who has a history
of complex medical issues
|
t age 15 months, our patient Adam, the youngest of three siblings, suddenly became very sick, according to his mother, Deborah Darnley-Fisch, MD, an ophthalmologist at the Henry Ford Hospital in Detroit, MI. Now 13, he has been sick ever since. This mom, who provided many of the details about our dramatic case, is an experienced healthcare professional, a glaucoma specialist and eye surgeon. She’s kept the kind of diligent medical records that rule out guess-work — which is why she knows the exact point when her toddler’s life changed forever.
“The only way in which our youngest, beautiful boy differed early on from his sister, Lindsey, 22, and brother, Daniel, 20, was in how many food allergies he had,” she recalls. Daniel had some eczema and an allergy to cow’s milk as a baby, but Adam, who also had bouts of eczema, was allergic to multiple foods and became sensitized to many of them while on breast milk alone. Because he was growing, developing normally and not prone to ear or other serious infections, they did not consider the implications of these clinical hints, which indicated that his immune system was maturing more slowly than normal. “We avoided the allergenic foods and he thrived,” she says…until he was 15 months old.
What followed were nightmare years of slowly progressive, systemic, medical issues: chronic diarrhea — alternating with constipation; recurrent ear infections requiring 19 courses of antibiotics over 26 months before tubes were placed in his ears; the development of allergies to three main groups of antibiotics; and escalating epilepsy. He was up every two hours, every single night for two years and fell off his growth curve in both height and weight – dropping from the 25th percentile in weight and 50th percentile in height to a tiny 1.5th percentile. More importantly, he regressed developmentally, ultimately losing all speech and comprehension of spoken language.
“A psychiatrist-friend once told me that people are only as happy as their least-happy child,” this mother says. “This has been a wild ride.”
The Fisch family tried everything to help their son, even re-mortgaging their home in a Detroit suburb to buy a second one 160 miles away in Kalamazoo so Adam could be placed in a school providing one-on-one attention 30 hours a week. The couple split their time to divide the parental responsibilities between Kalamazoo and Detroit. “I would drive the little guy to Kalamazoo on Sunday evenings or Monday mornings and spend the first part of the week there until Wednesday night. While he was at school, I’d glue myself to the computer searching PubMed for parallel situations because I realized we were in trouble. He wasn’t in the books.”
Adam’s dad would take the second half of the week away from their home. Eventually, however, Darnley-Fisch had to give up her busy glaucoma practice because trying to squeeze her patients and surgery into 12-hour schedules on Thursday, Friday and Saturday didn’t work. Because she’s the parent with the medical background, she is “the one responsible for medicines, shots, diet, nutritional supplements, and trying to coordinate it all,” she says. “My husband helps Adam in other ways."
“Our daughter Lindsey once tapped me on the shoulder while I was surfing PubMed and said, ‘Mom, the first step to recovery is recognizing that you have a problem.’ I laughed. ‘What problem? I’m on a mission.’ As hard as it was on the older kids, how could I just give up? What kind of message would that send to Lindsey and Daniel?’”
Eight neurologists in Detroit, Cleveland, Chicago, Omaha. Elevengastroenterologists in Detroit, Chicago, Cincinnati, New York. Four specialists in allergy / immunology in the Detroit area and southern California. The list was long.
Adam had ear tubes inserted five times. Because of the intractable seizures, he underwent a PET scan, which showed severe abnormalities on both sides of the brain. He’s had a lumbar puncture, a brain biopsy, and epilepsy surgery as well as multiple doses of intravenous immunoglobulin (IVIG). Yet, the epilepsy failed to respond.
This often uncontrolled, aggressive epilepsy would last close to seven years. An electroencephalogram (EEG) at age 3 was read as normal. Unfortunately, in spite of his language difficulties, another was not obtained until Adam had a clinical seizure at age 6. By that time, the EEG demonstrated complex partial epilepsy involving critical language areas of the brain. Surgery was performed, and initially, it seemed like a miracle. A few weeks after the procedure, Adam gave his mom a precious gift: “A 17 word sentence – slowly and with effort – accompanied by a huge grin. He was bright-eyed, happy, learning and trying to use language. He was still in there.” But improvements lasted only a few months.
“Evidence of inflammation was obvious at the time of surgery. No one knew exactly how to address it, so it was never addressed. Unfortunately, inflammation cannot be ignored.” In hindsight, Darnley-Fisch believes that Depakote, prescribed as an anticonvulsant, may have exacerbated the epilepsy. “While on Depakote, Adam’s epilepsy became worse. Later I found reports indicating that Depakote can increase the replication of a variety of viruses – one or more of which were probably playing a role in his inflammatory epilepsy,” Darnley-Fisch explains.
Meanwhile, the diagnoses kept coming in…from at least 12 major medical institutions and the verdicts varied from Landau-Kleffner Variant, benign rolandic epilepsy, lymphoid nodular hyperplasia of the terminal ileum, non-infectious gastroenteritis, small intestinal bacterial overgrowth, metabolic bone disease, and pituitary-based adrenocortical insufficiency. “When Adam first became sick and showed signs of developmental regression, we were told that his only chance for improvement lay in education, speech therapy, and occupational therapy — a course we pursued with intensity, only to watch him fall further and further behind. Now I know better. With a child like this, significant developmental progress is impossible unless underlying brain, gastrointestinal and systemic inflammation are managed.”
The alternative and complementary routes they took on this journey went in every direction: Adam was put on a gluten-free, dairy-free and eventually soy-free diet and took numerous vitamin and mineral combinations, DHA/EPA, n-acetylglucosamine, a derivative of glucose, and probiotics. Yet, they were still lost in a medical maze.
Darnley-Fisch first crossed paths with our expert, Harumi Jyonouchi, MD, at a conference in Minnesota in November 2001 when Adam had just turned 6. “I was impressed by Dr. Jyonouchi’s scientific curiosity, her genuine concern for sick children and her research showing abnormal cytokine responses to dietary protein antigens,” says this mother. “This could explain his food intolerances.” Jyonouchi, who was recruited in July 2002 to NJMS from the University of Minnesota, was the physician who had first tested Adam and found the dietary soy allergy.
A graduate of the Yokohama City University School of Medicine, this quiet scientist smiles shyly when she is compared to the “Dr. House” on television. Yes, she knows all about the TV character so skilled in the art of diagnosing. And while she hasn’t watched the show, she knows she isn’t as mean-spirited. Jyonouchi was in her 20s when she began training under the late Robert Good at the University of South Florida in how to treat very complex pediatric cases.
“All of my cases in the PCRCD program are rare, difficult, time-consuming but very rewarding,” says Jyonouchi. Like Adam, the other children in her files have diseases with no single name. There are no medical protocols for dealing with symptoms that can’t easily be categorized, and there are no commercially available tests for diagnosing. To treat her young patients, she explains, “You have to think about every adaptive mechanism in the body, how each organ affects another as well as the whole child. Many genes interact with many others, as well as the environment, triggering the immune system. One system compensates for another, affecting multiple organs, causing different and complex health issues. Clinical features can be disparate and deceiving.”
She describes her patients as “the children who will never have a clear diagnosis. There are no medical specialties or subspecialties to care
specifically for them” — which is exactly why Darnley- Fisch finally turned to Jyonouchi for help.
Adam was not growing and had been found to have adrenocortical insufficiency, multiple antibiotic allergies, and progressively decreasing white blood and neutrophil counts. “The epilepsy was back with a vengeance, his gut was a mess and he was obviously sick, but simply too systemically complex, even for good doctors. But how could we just let him suffer? I could still see the normal, bright-eyed toddler he had once been, and on a good day, that glint and sense of humor was there. Everyone was inclined to give up and let ‘nature’ take its course, which meant progressive brain injury from the epilepsy. I couldn’t do it. I am a glaucoma specialist, after all, and we fight for the last vision fiber! It struck me that we needed a brilliant immunologist who could think of his whole body as one large, complex, interacting system. I thought of Dr. J, found she had moved to New Jersey and emailed her, explaining, ‘We have lots more data than we had three years ago. Can I come see you and share his records?’”
That was in May 2004. She flew to New York by herself, navigated her way to Newark, and spent an hour over lunch with Jyonouchi. Darnley-Fisch remembers, “She listened carefully, asked pertinent questions and considered everything before saying, ‘I think I can help him.’
“Even though many institutions proclaim that they treat each patient first and foremost, Dr. J. was one of the very few who looked at my child as an individual, didn’t just lump him into a category and then give up when he failed to respond to standard treatment. To me, she is a true scientist and a doctor’s doctor. I cannot express the relief I felt at having found someone who would not shove my little square-peg boy into a round hole.”
Back in Michigan, Adam’s neurologist had requested a 48-hour EEG. The news was not good. The EEG recorded 301 seizures in two days’ time. Later that week, the family drove to Newark to begin the hard work of healing with Jyonouchi.
First, Jyonouchi put Adam on the drug thalidomide to try to inhibit the activity in his brain and intestines. She also recommended intestinal cleansing to eradicate the bacterial overgrowth in his gut. And she looked for immune modulators.“Initially, we made progress slowly,” the doctor recalls. “We implemented antagonists, based on different lab tests. We designed our own tests specifically for him. He had many complex diseases.” Within a week, his condition began to stabilize. The diarrhea and accidents stopped. He started to grow, gaining nine pounds and growing two and a half inches in the next nine months. After six months, a repeat EEG recorded only three seizures in 48 hours. At home, he was less hyperactive, understanding more of what was said to him, and was trying to talk.
“Dr. J. kept thinking about Adam, what else we needed to test, and what we could do to control his systemic inflammation,” Darnley-Fisch recalls. Jyonouchi discovered that his body’s own interleukin-1-beta was one of Adam’s biggest enemies. When thalidomide caused unwanted side effects after nine months, she switched to Kineret, which is used for rheumatoid arthritis and can block the impact of interleukin-1 beta. He also receives regular IVIG to maintain adequate antibodies and prevent infections.
Cooperative and happy, Adam has made cognitive and social gains at school and loves to help at home. His epilepsy hasn’t completely disappeared but is much improved. Not so long ago, he went tubing, a family excursion that once would have been impossible. Three to four times a year, this family makes the trek to Newark for continuing care and fine-tuning treatment.
Because all chronic disease involves some genetic susceptibility, Darnley-Fisch thinks back to what may have sent her son’s life off the cliff of normalcy. “If I had an undo button, I would have delayed his measles, mumps and rubella (MMR) vaccination,” she says, “at least until he turned 2. I think his immune system was not mature enough to handle it.” Even though recent research has dismissed this vaccination fear and its connection to autism or systemic immune diseases like Adam’s, this medically well-versed mother still points to the MMR shot.
According to Jyonouchi, live vaccines like MMR create an immune activation that can mimic systemic infection, albeit mild. In exceptional cases like Adam’s where there are underlying immune problems, such immune activation can induce abnormal reactions and trigger or aggravate fundamental (yet to be diagnosed) medical conditions. Such hazardous effects of live viral vaccines for patients with primary immunodeficiency have been appreciated and documented by the medical community. However, it is often difficult to assess the risk of immunization in apparently healthy babies because many mild immunodeficiency conditions don’t manifest themselves until after infancy.
“I don’t think Adam was destined to have all these health issues,” says his mother. “Adam is unique in our family. Gene abnormalities associated with developmental disorders were ruled out. We’ve had him tested for every gene known to cause developmental or regressive issues. I now know that babies with multiple food allergies and eczema share a pattern of delayed immune maturation.” Jyonouchi believes that very subtle changes in multiple immune system genes combined at a time of increased vulnerability with an environmental insult (in Adam’s case, the MMR), prompted this unfortunate cascade.
Meanwhile, the Fisch family “feels fortunate to have found Dr. J. to allow Adam — and all of us — to have the best life possible. It has been a long slog but Adam’s smiles, hugs and improvements are so worth it.”