Tuesday, January 2, 2018

A rare disease? Or no disease at all?

One afternoon in 2013, after swimming and playing outside, 9-year-old Taylor Johnson, from outside Atlanta, began sneezing incessantly. The fit lasted days before stopping abruptly, only to return months later. For a year, her violent sneezing fits came and went, to the bewilderment of a series of doctors.

For families, the diagnosis can seem like an answer to their prayers. But there’s a catch: Most doctors won’t treat the diseases — and many don’t believe they even exist.

“She was making this noise with her mouth at times 140 to 150 times a minute,” said her mother, Lori Johnson. “She was frantic, she couldn’t eat, she couldn’t sleep.” And “when she wasn’t sneezing, she was very depressed… She lost all interest in anything. Her whole personality just dissolved into nothing.”

Then an otolaryngologist (an ear, nose, and throat doctor) realized Taylor wasn’t sneezing at all — the behavior was a repetitive, sneeze-like tic. That prompted a round of visits to neurologists, psychologists, and other specialists, until an allergist finally suggested a set of diagnoses unfamiliar to the Johnsons: PANS and PANDAS.

These disorders, a specialist told them, can arise in certain predisposed children when the immune system responds to an infection like strep throat by attacking the brain. The resulting inflammation can lead to violent body tics and OCD-like symptoms.

For confused and frustrated families like the Johnsons, these diagnoses can seem like an answer to their prayers, because they at least point a way to treatment. (Lori Johnson says Taylor has now had almost three years of antibiotics and a restricted diet, though she still has flare-ups and began IV treatment in March.)

But there’s a catch: Most doctors won’t treat the diseases — and many don’t believe they even exist. They believe standard treatments like Taylor’s lengthy rounds of antibiotics are unhelpful at best, and could have negative side effects and contribute to antibiotic resistance at worst.

“There clearly are children who have abrupt onset — and flare-ups — of a variety of behavioral abnormalities. That clearly happens,” said Dr. Stanford Shulman, an infectious disease specialist at Lurie Children’s Hospital and Northwestern University, in Chicago. “What’s unclear is whether there are any specific infectious triggers that are responsible for that — either strep or some other kinds of infections.”…

But the diagnoses have long been controversial. Shulman wrote in 2016 that “the great preponderance of scientific evidence” on PANDAS “has been nonsupportive.” In an earlier paper, he suggested another explanation: that many childhood stressors can exacerbate underlying OCD and tics, and that strep infection “contributes to this to a relatively minor degree.” In an interview, he emphasized that there is no proof for the idea that infections act as a trigger for these symptoms.

Donald Gilbert, a neurologist at Cincinnati Children’s Hospital Medical Center, told The Wall Street Journal in 2015 that children who suddenly develop OCD — even following an infection — should be treated with standard OCD therapies, not the antibiotics and physical treatments advocated by PANDAS doctors.

And UpToDate, a resource used by doctors to aid diagnosis, is decidedly cautious on PANDAS. (It doesn’t have a separate entry for PANS.) It states that while most physicians agree that strep throat can exacerbate OCD or tic disorder in a subset of patients, PANDAS remains a controversial diagnosis.

“Because it’s not seen in every pediatric practice,” said Dr. Paul Grant, Susan Swedo’s colleague at NIMH, many pediatricians “don’t accept that it’s a real thing. But my experience is, when you see it, you say, ‘I don’t see how anybody could doubt that this is a real thing.’”…

In 2010, a group of researchers and experts gathered at NIMH to discuss how to treat children with PANDAS-like symptoms who test negative for strep throat. Swedo supported keeping PANDAS, but adding PANS as a broader category. Another prominent researcher, Dr. Harvey Singer, published a dissenting paper advocating the replacement of PANDAS with CANS — a new, broad category of sudden-onset symptoms without an emphasis on infectious triggers or treatment with antibiotics…

The two disorders are often described as rare, but PANDAS Network, a parent-created national support group, estimates that upwards of 1 in 200 children are affected. Dr. Rosario Trifiletti, a neurologist in Ramsey, New Jersey, told Cosmopolitan in 2014 that there is “probably one PANDAS kid in every kindergarten class.” He said he treated 3,000 cases in the preceding five years.

While Trifiletti may be in the spotlight, he is hardly in the mainstream. In 2012, when a bewildering epidemic of mysterious tics descended on a group of high school girls in western New York, he examined some of the victims and announced on HLN’s “Dr. Drew” show that PANS or PANDAS was the likely culprit. That diagnosis did not convince other doctors, including NIMH’s Swedo, and the medical community eventually settled on conversion disorder (in which psychological stress is manifested physically) and mass psychogenic illness (in which the appearance of symptoms in others causes anxiety, triggering conversion disorder).

Lori Johnson says the uncertainty surrounding the disease makes pediatricians unwilling to diagnose or treat, and drives up the cost of care. The first PANDAS/PANS specialist she contacted charged $1,200 for a first appointment. All four specialists in her area “don’t want to deal with insurance companies, so they just say, ‘No, if you want to see me, you will pay me,’” she said. “They know they’re highly specialized, they’re one of a few that treat it … and some of them are, I hate to say it, exorbitant.”…

Perhaps as a result of cost, the disease seems to be more often diagnosed in wealthy children, Johnson says. Cases of PANDAS in Bethesda, Maryland — Time magazine’s “top earning town” and home to NIMH — prompted a feature on the disease in a local magazine, which reported that it tends to affect children who are “smart, popular, active and well behaved.”…

No physician wants to see a child suffer. Yet different doctors look at the same body of PANDAS/PANS research and come to drastically different conclusions, and — in the face of uncertainty — whether to err on the side of caution or action.

For Dr. Shulman, the infectious disease specialist in Chicago, the answer is caution.

“Every treatment has potential downsides and toxicities and side effects,” he said. “Taking antibiotics for very prolonged periods of time, IVIG on a repetitive basis, or plasma exchange or plasmapheresis — everything has side effects. So I think we want to be judicious in recommending therapy when we really think it’s going to be beneficial, when the benefit would outweigh the risk.”

Dr. Grant of NIMH, despite falling on the opposite side of the debate, expressed similar concerns. “Long-term use of antibiotics has any number of adverse effects,” he said. “It has side effects in the individual who is taking them, but it also has sort of population effects, because it predisposes to the overgrowth of resistant bacteria, so you don’t want to do that casually.”

Still, “all those things are considerations. You balance that with the severity of the symptoms in the individual child,” he said. “The role of a scientist, I think, is to be an inquirer, and to try to answer questions. You can be skeptical, sure, but until proven otherwise, you should keep an open mind.”

For her part, Lori Johnson agreed that “there’s just going to have to be a lot more research.”

In the meantime, every day, she sees more parents reaching out for help on PANDAS/PANS message boards and Facebook groups, desperately describing their children’s erratic and frightening behavior and hoping for answers.

https://undark.org/article/doctors-divide-on-pandas/ 

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