Seeking a Second, More Specialized,
Opinion for a Rare Genetic Disease

Guest post, by Ricki Lewis

Ricki Lewis is a geneticist and science writer. St. Martin’s Press just published “The Forever Fix: Gene Therapy and the Boy Who Saved It.” Ricki’s textbook Human Genetics: Concepts and Applications, from McGraw-Hill Higher Education, is in its 10th edition.

A challenge of living with a genetic disease, especially a very rare one, is that the mutation may affect different body parts. A health care practitioner may not consider a patient’s inherited condition, especially if the most recognizable symptoms don’t fall into his or her specialty.

Shirley Banks discovered the importance of seeking a second, specialized opinion when the doctor she’d been seeing for many years had a disturbing reaction to a question.

The Long Road to a Diagnosis

The Banks family has  osteogenesis imperfecta (OI) which affects 1 in 20,000 live births. Shirley, now 73, can trace the “brittle bone disease” back to her grandmother and a great uncle, who were two of seven children. They had type I OI, which is autosomal dominant, affecting each generation and both sexes.

Shirley remembers the disease appearing in first one brother, then another, when she was a child in upstate New York. “When my first brother was growing up he had many fractures, and the doctors told him to eat high calcium foods. We lived on a farm! All the dairy made no difference because of the mutation, but nobody knew.” Several cousins easily broke bones too, and Shirley had it but didn’t realize it. Years later, her son Todd inherited the family legacy.

“Todd was a very active kid. He had his first fracture at 2, when he tripped and broke his leg. I became suspicious because my brother’s child broke bones too. Finally, a doctor who had come across this disease as an intern explained it, and we were diagnosed. It wasn’t until the early 1960s that we recognized we had a disease,” Shirley says.

More Than Brittle Bones

Shirley’s OI is, thankfully, mild. “The only bones I’ve broken are in my toes from when I ran into furniture,” she explains. Like many with OI she has other symptoms. She wears digital hearing aids and the whites of her eyes (sclerae) have a bluish cast, a hallmark of the disease. The disease can also cause discolored brittle teeth, muscle weakness, fatigue, and loose joints.

Even a mild case of OI can lead to problems, which Shirley learned when she had a hysterectomy in 1983. She’d taken aspirin beforehand, and informed the medical staff of her OI, but “when they got in there everywhere they touched, I bled. And when the doctor went to sew me up, the tissue kept ripping.” She nearly died. OI makes many tissues fragile – but the medical staff had been unaware of this.

The Banks family has a mutation in a major gene for the connective tissue protein collagen. Their type I is usually manageable, with 1-100 fractures in a lifetime; other forms begin to break bones before birth, proving lethal in infancy. Before genetic testing for OI became possible, some parents of children with broken bones were falsely accused of
child abuse
. The other types began to be described when parents accused of child abuse “failed” the genetic test for type I. Eight forms of OI are now recognized.

Only a few cases of OI are known from history. An Egyptian mummy from 1000 B.C. had it, as did 9th century Viking “Ivan the Boneless,” who was reportedly comported into battle aboard a shield and whose remains were exhumed and burnt by King William I, forever obscuring the true diagnosis.

An OI Eye is Not a Normal Eye

People with OI are at higher risk for developing glaucoma, which results from high pressure in the eyeball. The corneas of people with OI are abnormally thin, which makes the pressure read as lower than it actually is, which can delay preventive treatment if a physician is unfamiliar with this and other effects of OI on the eye. That’s what happened to Shirley, who was diagnosed with glaucoma at 38.

Patients with osteogenesis imperfecta may have high intraocular pressure and glaucoma.

A few months ago, the ophthalmologist who’d been prescribing Shirley’s glaucoma drugs for many years told her she needed cataract surgery. “So I asked him if my OI would complicate anything. He looked at me and said no, it’s the same procedure.”

Had the doctor also been treating her glaucoma without considering her OI? Shirley grew concerned.

Todd had just had surgery to drain the fluid (aqueous humor) that was building up the pressure in his eyes. Would his doctor provide a second opinion, on Shirley’s glaucoma and cataracts? She sought a second, more experienced opinion from another ophthalmologist.

“I learned so much more in his exam, I took tests I’d never had with the other eye doctor, who wasn’t looking at the special condition of osteogenesis imperfecta,” Shirley says. The good news: the cataract surgery could wait. The disturbing news: She hadn’t been getting high enough doses of the glaucoma medicine, and the pressure in her eyes had already damaged her optic nerves.

“The other physician wasn’t looking at your special condition. You and your son are a whole different ballgame,” said the second doctor. OI can directly harm the optic nerve and the tissues that support it, plus the spongy tissue that normally drains fluid from the eye. “I might have ended up blind in 3 years,” Shirley says.

Lesson learned, according to Shirley Banks: “It pays to go to a specialist. People procrastinate, say ‘oh you don’t need a specialist for something as common as glaucoma.’ But it’s different if there’s a genetic disease.”

MR Imaging, Electronic Test Ordering Creates Waste

Waste is what you get with rampant, uncritical use of MRI and health information technology, according to two papers out this week.  The authors of a companion editorial to one of the papers even go so far as to suggest we should make waste a quality of care measure. I applaud them.

MRI Use Soaring for Stroke Care

James F. Burke, MD, department of neurology, and colleagues from the University of Michigan Medical School, Ann Arbor, MI, take a look at neuroimaging for the evaluation of acute stroke in a paper in the February Annals of Neurology. A companion editorial by S. Claiborne Johnston, MD, PhD, and Stephen L. Hauser, MD, neurologists at the University of California San Francisco, has the provocative title: “Modern Care for Neurological Problems Must Address Waste.”  Tame, yet critical at the same time.

Burke and colleagues acknowledge that imaging is a fundamental part of acute stroke evaluation and that it is more accurate than computed tomography (CT) for stroke diagnosis. However, they also point out that no data has shown that stroke patients undergoing MRI do any better than those who do not. They also note that the most recent American Heart Association Scientific Statement advises the routine use of MRI or CT angiography for stroke (not both). The American Academy of Neurology guideline states that MRI use should be limited to the first 12 hours of stroke onset.

What they found, in a study of neuroimaging for stroke in 11 states between 1999 and 2008, is an astronomical increase in MRI use.  In absolute terms, it is up 38%, relative utilization rose 235% (from use in 28% of strokes to two-thirds in 2008). At first glance, the numbers might seem like a reasonable jump, given the change in clinical practice guidelines.

Delving deeper, they show:

  •     95% of patients getting MRIs also had a CT;
  •    there was striking geographic variation in MRI utilization.
  •    MRI utilization was highest in Arizona (79%), lowest in Oregon (55%).
  •    Diagnostic imaging was the second leading cost center in percentage increase, outpaced only by room and board.
  •    MRI costs rose faster (up 413%), from 1999 to 2007, than overall diagnostic imaging.
  •   In 2008, in this analysis, MRI costs contributed 10% and CT 8% of total hospital costs.
  •    In states with the highest use of MRI, use has leveled off so that just about all eligible patients are getting MRIs.
  •     Head CT use was stable over the same time period.

Doctors order these tests, yet they don’t know yet whether they improve outcomes, according to the paper. Do patients need both tests? Doubtful. Also, all that variation reflects the uncertainty in the standard of care.

“No question, it is very satisfying to see that infarction on the MRI, but does it matter in terms of patient care?,” write Johnston and Hauser, in a companion editorial. “More importantly,” they continue, “would the ca. $700 be better spent focusing on maintaining better secondary prevention, a major problem after stroke that could be addressed with more aggressive disease management.”

When Health Information Technology Jacks Up the Bill

In a separate paper in the March Health Affairs, Danny McCormick, MD, assistant professor of medicine at Harvard Medical School, and director of social and community medicine at Cambridge Health Alliance, and coauthors, challenge the contemporary mantra that health information technology will cure so many ills in our healthcare system.

Here, they demonstrate how the ease of access to electronic test results led to a 40% to 70% jump in ordering imaging studies. when doctors had access to computerized imaging. They argue electronic access to test results alone may offer enticements to additional ordering.

“What we’ve got are computer systems that are essentially built around the bill,” said David Himmelstein, MD, the paper’s senior author, and professor of CUNY School of Public Health at Hunter College, New York, NY, in an interview with Patient POV. “People are buying systems that  jack up the bill. These systems, with rare exception, are not built by clinicians on the ground, and so they tend to overlook clinical information, improving care, and saving dollars.”

I loved this part of the study: even though women received more imaging studies than men, they didn’t get more advanced imaging. Hey girls, I guess these docs just don’t find visualization of us as that interesting or worthwhile. The authors didn’t pursue this, but I wonder whether this reflects that doctors take illness less seriously in women. It’s not as if I want access to the same waste that men get, but don’t you think it’s a finding worth looking at further? It’s got to be hypothesis generating.

Himmelstein was hard on the purchase and dissemination of many off-the-shelf systems. “We keep hearing that we are going to save dollars by computerizing,” he said.“Yet there is not an iota of evidence that this is true.” Importantly, the paper looked at electronic test ordering, not electronic health records. In the paper, they point out that predictions of cost savings as high as $8.3 billion with computerization were based on data from a few stellar systems: the VA, Latter Day Saints, Regenstrief, and Brigham and Women’s Hospital. These systems are not representative of what doctors are buying.

Together, these papers shine a light on how easy it is to order imaging tests and how imaging is the gee-whiz technology of our age. If we really ever get serious about waste and want to work on it equitably, we will have to invite patients to the table from the outset.

Bring the public in early and often in medical technology assessment discussions.

 Don’t say you are committed to “patient-centered care” if you don’t bring patients to the table. Warning: If you leave patients out, the public sees it as  smacking of benefits denied, arbitrariness, and cheapness.

But the other thing is that until we stop rewarding doctors based on volume, and instead, inspire outcomes, we are going to drown in the morass of waste.