Daniel L. Kastner, M.D., Ph.D.

Within a few months of starting as a fellow at the National Institutes of Health, Dr. Daniel Kastner cared for an adult patient with an undiagnosed form of recurring arthritis who had endured high fevers nearly every month since he was an infant. Attempting to solve this mystery set Kastner on a path to identifying an entire new class of rare genetic diseases, along with treatments to alleviate pain and suffering of thousands of patients.

Kastner has worked like a shoe-leather detective piecing together patients’ information to understand the causes of numerous rare disorders involving unexplained inflammation and fevers that result in disabling conditions and even death.

Kastner defined this new class of rare illnesses as autoinflammatory diseases and uncovered the genetic causes of seven of them—the latest in 2016. He identified 14 other previously unrecognized disorders and has found effective treatments for 12 of them—improving the quality of patients’ lives, and in many cases, saving their lives.

The disorders include DADA2, a genetic disease that usually starts in childhood and can cause recurrent strokes, severe systemic inflammation, immune deficiency and damage to many of the body’s tissues and organs. NOMID, an autoinflammatory disease characterized by fevers and inflamed tissues lining the brain, can result in blindness and hearing loss, and if the disorder starts early, can cause death in the teenage years.

“Dan is indisputably the father of the field of autoinflammation and is its intellectual driver,” said Dr. Eric Green, director of the National Human Genome Research Institute.

Autoinflammatory diseases refer to problems with the immune system, which usually fights off viruses, bacteria and infection. These diseases result in high temperatures, rashes, swollen joints and serious buildup of a blood protein in the organs. Autoinflammatory diseases are caused by genetic mutations, but because of their rarity, knowledge of these conditions and treatment options typically are limited.

The condition Kastner encountered as a rheumatology fellow in 1985 turned out to be familial Mediterranean fever, an inherited disease that primarily affects people of Jewish descent as well as individuals of Arab, Armenian and Turkish ancestry.

Two years later, as his interest peaked in finding out more about familial Mediterranean fever and whether he could find the genetic cause, Kastner tried to locate other patients in the Washington, D.C., area suffering from the same condition. Cases were too limited to launch a viable study not just locally, but also throughout the U.S.

This prompted Kastner to contact a medical center in Israel where a physician was researching patients with the same ailment. It took a decade of research that included examining patients in Israel and the U.S., before the doctors—in collaboration with an NIH research group Kastner created and other experts—identified the problem gene and a new treatment for the debilitating disease.

Now that the full human genome has been mapped, the process of determining the genetic cause of such illnesses is faster, and greater numbers of patients with these rare, unexplained diseases are being helped as a result of Kastner’s research and findings.

In a recent case, Kastner and his team compared the genes of a New Jersey child to a Texas youngster with similar symptoms of recurring fevers and repeated strokes. They found a gene in common and experimented with a biologic medicine used to treat severe rheumatoid arthritis. Since beginning this treatment, 21 children who previously had strokes now have had no strokes at all, and they have been freed of many of the debilitating effects of the disease.

Evan Luton, the mother of the Texas child, said her daughter Hallie was born in 2005 and had suffered seven strokes by 2012, which created temporary paralysis and altered her vision. The child experienced high fevers daily and unrelenting pain, and could not go to school.  In addition, her growth was stunted due to chemotherapy and steroid treatments that proved unsuccessful. After years searching desperately for help, Kastner diagnosed Hallie’s disease as DADA2 and prescribed the biologic medicine to alleviate her suffering.

“It’s been a miracle. Hallie is walking, going to school and growing normally. She does not have pain or a fever and has not had a stroke since 2012,” Luton said. “I will forever be grateful to Dr. Kastner and his team. He had the passion to find out what was happening, and he didn’t stop until he found the answer and a treatment. My daughter’s life is so much better because of him.”

Dr. James Balow, a NIH clinical director, said Kastner has “really advanced the autoinflammatory field in a way that stands out nationally and internationally.”

Many of the illnesses Kastner has studied attack patients very early in life and can devastate them, Balow said, so Kastner’s ability to find individualized treatment plans has been crucial.

Green and other colleagues said Kastner is a world-class scientist and a mentor to others, and he excels at patient care.

“He’s a Renaissance physician. He’s deeply empathetic and committed to these patients,” Balow said. “He is one of the world’s leaders, but still has this humility, which is absolutely breathtaking.”