When Liam Schulze was four months old, he developed a fever of 103 to 104 that lasted about a week and then went away.

It was a pattern that would repeat every month and doctors would assure his parents Michelle and Chris Schulze that it was not uncommon for toddlers. They should treat the fever with Tylenol or Motrin and keep him comfortable. Schulze was a first-time mother and at first accepted what the doctors said. Her father told her something didn’t seem right and she soon agreed.

Liam had developed other symptoms. He seemed a bit jaundiced. He had developed a rash that looked like sunburn on his arms and legs. His belly looked distended, and his liver and spleen were enlarged. She pushed for a referral to a specialist.

The frequency of the fevers accelarated and their duration grew longer. Blood tests showed Liam was anemic, but otherwise didn’t provide a lot of insight. Schulze and her husband brought Liam to an infectious disease specialist. They brought him to a pediatric rheumatologist. They brought him to a pediatric hematologist/oncologist. A biopsy of his lymph nodes was inconclusive.   

When Liam grew lethargic, was sweating profusely, and wouldn’t eat, his parents brought him to Children’s Hospital in Aurora, Colorado, about 70 miles north from their home in Colorado Springs, Colorado. One of the doctors recognized Liam as possibly having a condition known as HLH. She had seen a case when she was a resident.  She wanted to do a bone marrow biopsy. “It could be cancer,” she said. “Pray it’s not HLH.”

It was.

HLH is hemophagocytic lymphohistiocytosis, a rare and life-threatening immune system disease. In HLH, the immune system becomes overactive and attacks healthy cells and tissues. He had battled the condition for ten months without a diagnosis, but the disease was taking its toll.

“We struggled to find a diagnosis for him.” Schulze said. “There’s no reason he should have gone that long without a diagnosis.”

Within weeks, Liam would be moved to the care of an HLH expert at Cincinnati Children’s Hospital. The plan was to do a bone marrow transplant, but a suitable match could not be found among the 13 million donors in the national database. In a last-ditch effort to save Liam, doctors decided to use an imperfect match of cord blood stem cells.

To do the procedure, doctors must knock out the immune system and then rebuild it with stem cells harvested from umbilical cord blood. The day of the transplant, though, Liam tested positive for adenoviral pneumonitis, a common virus that causes lung infection. With his immune system knocked out, Liam was unable to fight the virus. Even though the transplanted stem cells had a 93 percent engraftment, he died 41 days later on September 9, 2009 as a result of the infection. Nearly ten years later, Schulze keeps the Elmo doll Liam clung to throughout his life.

“I was a mom and I was taking care of my sick child. That’s what I did 24-7 and then there was nothing,” said Schulze, who shortly after Liam’s death launched Liam’s Lighthouse Foundation, which supports families affected by HLH, educates physicians about the disease, and funds research to develop better treatments. “I can’t show him how much I love him in person, so I felt like that was the way I was going to do it. I was going to make a difference for other people going through this and get more information out there and more awareness out there so people didn’t have to struggle to get the diagnosis.”

There are many reasons why the diagnostic odyssey is often long for rare disease patients. The symptoms of rare diseases often present like common diseases. Doctors are taught to think about common disease to explain a patient’s symptoms. But what is painful to consider in Liam’s case is that he hadn’t been diagnosed earlier because his doctors had never heard of HLH or thought to look for a rare disease as an explanation for Liam’s symptoms.

Individually a rare disease is rare by definition. Collectively, though, one in ten people in the United States have a rare disease. While there is much still to understand about these diseases, we are at a point where we have technology available to accurately diagnose a disease if a doctor knows to look for one. Given the prevalence of rare diseases collectively, it’s likely doctors will come upon many patients with rare diseases during their careers.

Perhaps it is time for medical schools to revise their old adage that instructs students, when they hear hoofbeats, to look for horses, not zebras.

It’s difficult to second guess doctors from a case that’s nearly ten years old, but what’s stunning about Liam’s story is how quickly a doctor, who had previously seen a patient with HLH, recognized the telltale signs of the disease—the fever, distended belly, rash, enlarged liver and spleen, and jaundice.

Doctors should think horses when they hear hoofbeats, but at some point they need to know enough to check if the horse has stripes.

Photo: Michelle Schulze

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