Surprise Attack

Sometimes the immune system turns on its host

By Tony Dajer|Saturday, December 01, 2001
Mrs. Wong opened her mouth and moved her tongue to the side. Along its edge, I saw a huge ulcer, pearly bordered and angry as a brazier's mark. She spoke only Cantonese. "Veddy pain," she said, "veddy pain."

Her daughter took over. "She saw the doctor yesterday. He gave her medicine here," she said, cradling her mother's right hand to show the vein where the IV had gone in. "But the bumps on her legs keep getting bigger." She lifted her mother's skirt. A half dozen red, raised lesions the size of small grapes studded Mrs. Wong's thighs. I pressed gently to confirm the soft give of an abscess. I felt none.

"Fever?" I asked.

"Sometimes," the daughter replied.

"The bumps. How long?"

"Two, three weeks." She pointed again to her mother's mouth. "She cannot eat."

"The sores in the mouth and the bumps on the legs, they came together?"

"Yes."

"Have the bumps been getting bigger? Are they painful too?"

"Yes, yes." Now the daughter smiled eagerly. Was the doctor onto something?

Nobody really understands diagnosis. With puzzling cases, it's a matter of connecting the dots: You gather as many points—symptoms, time course, physical findings, and lab tests—as possible, then assemble them in your mind until a picture emerges. The trick is to order them in a way that matches one of the disease patterns stored in your head.

I ran my fingers along Mrs. Wong's legs one more time. Mouth ulcers and skin abscesses equals what? Simultaneous infection of the tongue and legs? Disseminated staph infection? Could be. But for three weeks?

"We'll give her more antibiotics, the first dose by vein," I said to her daughter. "The bumps on the legs look infected. But the most important thing is that I see her again in two days to make sure she is getting better. We will also give her something for pain, for the tongue. She must eat." She bowed her head in thanks.

Two days later, at the appointed minute, Mrs. Wong and her daughter returned. At the triage station, I immediately checked the woman's legs. The bumps had changed. Their middles had gone soft and black, the skin over them bubbling up like cellophane. But there was still no sign of pus.

I grabbed Lincoln, my fellow attending physician.

"Got an odd case. Want to take a look?"

"Sure," he smiled.

"Forty-eight-year-old woman complaining of a tongue ulcer and raised lesions on her legs," I began. "Two days ago, they looked like abscesses. Maybe. But now they're just necrotic. No pus. It's as if her oral mucosa and her skin ..." Just then the dots assembled. "She has Behcet's," I blurted out.

In 1937, Hulusi Behcet, a Turkish dermatologist, described a cluster of patients with recurrent mouth ulcers, genital ulcers, and eye inflammation. That he was Turkish was no accident: The disease, mysteriously, has been found to be much more common in the Middle and Far East than around the Atlantic.

Like lupus, multiple sclerosis, and other autoimmune diseases, Behcet's occurs when an individual's antibodies mistakenly attack the body's healthy tissues. Behcet's can attack virtually any system, including the eyes, the brain, the joints, the heart, the kidneys, and the skin. But its most distinctive trait is lesions in the mouth and genitals.

"Has she ever had problems down below?" I asked her daughter, gesturing vaguely toward my own crotch.

"Yes, yes. Painful too."

"How long?"

"Same." Why hadn't I asked that the first time?

We wheeled the patient into the gynecologic exam room. Teri, one of our nurses, asked Mrs. Wong to undress, then helped her into position for an exam. When I gently pushed her thighs apart, I saw two nickel-sized sores along her labia.

"I wonder how long she's been putting up with this?" said Teri.

The immune system is a fantastically complex instrument of attack. In most people, pathogens are targeted, and healthy "self" tissue remains untouched. In autoimmune diseases, the defense response goes awry and rogue antibodies directly attack proteins in normal, healthy tissue. Certain trends in Beh?et's patients suggest how this system goes wrong. First, certain genetic markers frequently show up in patients with Beh?et's, so an inborn predisposition is likely. Second, a misguided reaction to infection may trigger the outbreak: Herpes viruses and certain species of streptococcus bacteria—which colonize tissues in the mouth or genitals—occur at above-normal rates in Behcet's sufferers. Third, the misguided immune response initiates the production of immune complexes—antibodies bound to their favored target, or antigen. Whether immune complexes in Behcet's patients stem from a direct response to infection or an immune-system overreaction, or both, remains unclear.

Without immune complexes, we would die of infections. But if the body overreacts to a small amount of foreign protein, say, some protein shed from a tooth infection, the system can spin out of control, releasing a steady flow of immune complexes that evade normal destruction by scavenger cells. These immune complexes can then lodge in small blood vessels.

There the trouble begins. Immune complexes signal for help to roving white blood cells called neutrophils. When neutrophils charge in, they disgorge powerful enzymes and inflammatory proteins that can dissolve blood vessels. Unless the attack is called off by the immune system, surrounding tissue will die from lack of blood flow and nutrients.

"This is vasculitis," I said to Teri, pointing to one of the ulcers on the patient's legs. "The body attacks its own blood vessels, and the tissue around them dies."

Teri grimaced. "How do you treat it?"

"First we need an exact diagnosis. Other diseases can cause similar signs. There's no definitive test for Behcet's, although a biopsy can rule out other things."

Teri thought a moment. "There's this other funny thing. I went to put in another IV," she said, picking up Mrs. Wong's hand, "and she had this bump where the other IV had gone in."

On the back of Mrs. Wong's hand, marbled red and white like a tiny scoop of peppermint ice cream, was a pimple the size of a BB. I clapped Teri on the back. "You made the diagnosis, Teri! This little bump is called pathergy. It's the reaction Behcet's patients get to needle sticks. That, plus the mouth and genital ulcers, makes the diagnosis."

As we were talking, a horde of dermatologists, rheumatologists, and residents came in.

"Please tell your mother she is helping young doctors learn," I explained to the daughter. A Western dermatologist can go 10 years without ever seeing a case of Behcet's.

After a few days on immunosuppressants, Mrs. Wong's immune system quieted down. Her tongue felt so much better that she was able to eat again. Still, there were more worries. When Behcet first described the disease, he had noted pus cells behind the cornea and red, painful, light-sensitive eyes in some of his original patients. This is the worst complication of Behcet's. Once an immune response gets going in this part of the eye, it's hard to stop. Even with aggressive immunosuppression, many patients eventually lose their sight.

But an ophthalmology exam told us Mrs. Wong's eyes were fine. A month later, I ran into the resident who was handling the follow-up.

"She's doing great," she said. Mrs. Wong's leg ulcers were healing.

The resident thought a moment. "It's funny, really. We're still not sure what causes Behcet's, we make the diagnosis on clinical grounds, and the drugs we're using have been around for decades." Then she smiled. "But, boy, is she a new woman now."
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