When Modern Medicine Battles Genetics... and Loses

[Guest guest]

Vital Signs When Modern Medicine Battles Genetics... and Loses

Despite the best care, a patient succumbs to a genetically

predisposed disease.

by Panosian Dunavan

published online January 14, 2009

Discover Magazine - New York,NY,USA

http://discovermagazine.com/2009/feb/14-when-modern-medicine-battles-

genetics-loses/article_view?b_start:int=0 & -C=

After 30 years in the doctor trenches, every so often I think about

patients I desperately wanted to save—and didn't. At the top of my

list is Arthur . A quiet, well-mannered teenager,

developed a fungal infection that attacked multiple organs. Three

years and many treatments later, the fungus claimed his life.

Most infectious diseases are color-blind; their outcome has nothing

to do with their hosts' hue. But 's illness,

coccidioidomycosis, was different. His African American ancestry put

him at special risk for the battle he bravely fought and lost.

His struggle reminds me of a basic truth in medicine. Although

excellent care can tip the balance between life and death, in some

cases patients have genetic vulnerabilities that all the high-tech

care in the world simply cannot conquer. Genes aren't everything

when it comes to coccidioidomycosis, a rare soilborne illness that

can be acquired by inhaling dust. Other variables (like the dose of

inhaled organisms, underlying lung anatomy, and subtle or overt

immune problems) also influence the course of the illness. But genes

can gravely color the outcome. Some patients with acute

coccidioidomycosis experience a short-lived infection that takes no

more of a toll than the flu. In other cases, patients develop a

chronic hacking cough, unexplained rashes, and joint pain. Many

patients do not require specific treatment, but those who do can

have tragically different outcomes.

Before I tell 's story, I'll start with another man with the

same infection and racial risk—and a happier ending. The year was

1985; the place, Van Nuys, California. A lanky African American in

gym shorts and T-shirt practically bounded into the waiting room of

the clinic where I worked, his mood and dress worlds apart from our

usual clientele. Back then, most of our patients had HIV,

tuberculosis, or a complication from IV drug abuse. When we opened

our doors at 7:30 a.m., the AIDS sufferers were bundled in sweaters,

the TB folks (hard-working immigrants, for the most part) wore

everything from painters' pants to saris, and the drug addicts had

not yet arrived.

Through a window I peered at the lively newcomer and wondered: What

brings you here, stranger? During my time as the sole infectious-

diseases specialist at this small county outpost, no one ever

visited our weekly clinic unless they had to. Ten minutes later, in

an exam room, we learned Luke 's reason for coming.

The 34-year-old coach and substitute teacher told us that a month

earlier, he had noticed a small crusty patch, roughly the size of a

nickel, on his left flank. Lacking health insurance, he consulted

our county dermatologist. No, it wasn't cancer, he was told, and it

didn't look like eczema or psoriasis either. So agreed to a

standard skin biopsy that took five minutes from start to finish,

then forgot all about it.

Until a couple of weeks later, that is, when a dermatology clerk

called and referred him to me. Something surprising had shown up on

his biopsy. " I think she called them…spherules? " said,

wrinkling his brow. " ly, Doc, I began to feel like a pod person

from Invasion of the Body Snatchers. What the heck is a spherule? "

I imagined 's spherules—micro­scopic cysts stuffed with

endospores—and realized why the clerk had used this word from the

pathology lab report rather than the tongue-twisting term

Coccidiodes immitis, the fungus responsible for 's tiny

cluster bombs.

So far, so good. By the time they finished their rotation with me,

every resident at my hospital had seen one or two patients

with " cocci, " also known as valley fever—a label that harks back to

the disease's early discovery in California's San Joaquin Valley.

There, as in other semiarid pockets of the American Southwest,

inhaling spore-laced dust was the usual way that humans (and the

occasional pet dog) contracted C. immitis. Small outbreaks sometimes

followed windstorms or earthquakes. For example, Ventura County,

just north of Los Angeles, reported 203 cases of cocci, three of

them fatal, after the January 1994 earthquake centered in

Northridge. However, an earthquake was not to blame for 's

infection. As a jogger and trail biker, he was a perfect candidate

for ordinary exposure through dust inhalation.

The problem was that his case was far from the classic, quickly

forgotten flulike variety. On the contrary, his single skin lesion

teeming with cocci spherules confirmed a far more ominous scenario:

After silently proliferating in 's lungs, fungal spores had

traveled through his bloodstream and had been deposited in his skin.

Inwardly I shuddered. At that very moment, countless more spores

could be incubating and multiplying in his prostate, lymph nodes,

bones, or brain.

The unique susceptibility of certain dark-skinned people (Filipinos

and African Americans in particular) to disseminated cocci—for

reasons that are still not under­stood—has been common knowledge

among infectious-diseases specialists for decades. In 1940 a

landmark article in the American Journal of Public Health reported

that African Americans were 23 times more likely to die of

coccidioidomycosis than whites were. More recently, similar research

in two California counties confirmed that, compared with their

Caucasian counterparts, African American men stand a tenfold to

thirtyfold increased risk of falling victim to the disease.

In some cases, patients have genetic vulnerabilities that all the

high-tech care in the world simply cannot conquer.The day I met

, I asked myself: Do I really need to share these grim

statistics with him? The bottom line was that he needed treatment.

Once he grasped that fact, he quickly agreed to our best shot.

Amphotericin B, an antifungal drug privately called " ampho terrible "

by many former recipients, is just as noxious as its nickname

suggests, but it did its job. After two months of infusions,

was out of the woods. I still have the Betty Boop coffee cup he gave

me as his parting gift.

Now back to Arthur . Ten years after treating , I met

at the university medical center where I now work. A 17-year-

old high school student who had just been transferred from another

hospital, presented in far worse shape than : febrile,

emaciated, doubled over in pain. Not only did he have scattered

fungal scabs on his skin, but his scans showed multiple abscesses in

his liver and spleen. Even more discouraging was his record of prior

treatment. By the time I saw him, he had already received the same

total dose of amphotericin B that had cured .

Over the next week, wasn't dying, but he had little energy or

appetite and even less motivation to study the textbooks next to his

bed. Meanwhile, my team pushed his daily amphotericin dose while

adding newer antifungal drugs to his regimen. We also tried

immunologic therapies such as interferon and something called

granulocyte-monocyte colony stimulating factor, a bioengineered

molecule meant to boost 's ability to mount a strong immune-

cell attack against C. immitis. Eventually his body temperature

normalized, his pain abated, and he went home on long-term oral

treatment. We hadn't won the war, but we had made progress.

felt well enough to start college in a nearby state.

My contact with him was sketchy for a year or two until I received a

call from a doctor at his college. had never before complained

of headaches, but now he was having migraines. Or so his doctor

thought; I wasn't so sure. Soon after, a CT scan and a spinal tap

confirmed my worst fear. The fungal infection had invaded the base

of his brain, producing cocci meningitis.

Over the next year, received amphotericin directly into his

spinal fluid via a special injectable reservoir. The treatment

helped, but only for a while. In the last months of his life—like so

many patients with an incurable disease who continue to receive

maximal high-tech care— experienced one complication after

another, and he was in the ICU more than once. Finally he had a full-

blown cardiac arrest and was gone.

Toward the end knew he was dying. But one thing brought him

joy. While at school he had fathered a child. Despite his tragic

downward spiral, talking about his little girl always brought a

smile to his face.

In fact, a few months before he died, brought his gurgling

daughter—the image of health and hope—to my outpatient office. As I

sat her on my knee and gazed into her shining brown eyes, I couldn't

help but wonder what science might someday reveal about her father's

fateful genes—and perhaps her own.

[Guest guest]

Its just a fact of life that everybody is born with a different genetic mix.

At various points in our history, many of these SNPs were advantageous in

various situations and they may be again. Its just part of our genetic

diversity.

Someone who is predisposed to a disease won't necessarily get it.

It depends on their environment, toxins, oxidative and emotional/physical

stressors, and their access to care.

Also, every few million years, climate changes so rapidly that huge numbers

of species die off and typically,

then fungi take over for a few hundred or thousand years as the old stuff

rots...and new species evolve to take over.

On Wed, Jan 14, 2009 at 8:47 PM, tigerpaw2c <tigerpaw2c@...> wrote:

> Vital Signs When Modern Medicine Battles Genetics... and Loses

> Despite the best care, a patient succumbs to a genetically

> predisposed disease.

>

> by Panosian Dunavan

> published online January 14, 2009

> Discover Magazine - New York,NY,USA

>

> http://discovermagazine.com/2009/feb/14-when-modern-medicine-battles-

> genetics-loses/article_view?b_start:int=0 & -C=

>

> After 30 years in the doctor trenches, every so often I think about

> patients I desperately wanted to save—and didn't. At the top of my

> list is Arthur . A quiet, well-mannered teenager,

> developed a fungal infection that attacked multiple organs. Three

> years and many treatments later, the fungus claimed his life.

>

>