Medical mystery: What caused active man’s searing hand and foot pain for nearly a decade?

Jeff Sipos wasn’t used to feeling wiped out.

At 31, the California elementary school principal was an endurance athlete in exceptional condition. Even though he had asthma, Sipos had climbed Mount Whitney, the tallest mountain in the contiguous United States, completed a rim-to-rim hike in the Grand Canyon in a mere 10 hours — at least two hours less than average — and thought nothing of clocking 100-mile bike rides on weekends.

But in May 2001, his energy was flagging. Sipos, who lived in Riverside, consulted his longtime family physician. The doctor told Sipos his fatigue was the result of anemia and could be easily treated with an over-the-counter iron supplement that he should take when he felt unusually tired.

“For the next 10 years I would pop iron pills every so often and notice a bump” in energy, Sipos said.

In 2007 a new problem arose: The soles of his feet ached and burned. He consulted a podiatrist, who told Sipos he had “fallen arches” — flat feet that develop in adulthood. The doctor prescribed orthotics.

By 2015, the foot pain was considerably worse and had engulfed his ankles, putting an end to his participation in extreme sports. Sipos’ hands felt tingly and numb and he was referred to a neurologist and a rheumatologist.

The neurologist told Sipos he was suffering from carpal tunnel syndrome — numbness or tingling in the hands caused by a compressed nerve — as well as peripheral neuropathy, damage to the nerves outside the brain and spinal cord.

The rheumatologist ordered blood tests and diagnosed “seronegative” rheumatoid arthritis. Although testing did not show antibodies to the disease, his joint pain, the doctor said, strongly suggested it.

The rheumatologist prescribed two drugs: methotrexate, a chemotherapy drug used to treat rheumatoid arthritis, and when that didn’t help, hydroxychloroquine, an anti-malaria drug used to treat autoimmune disorders. Neither worked.

At that point, Sipos recalled, the pain was so intense that “the weight of the [bed] sheets would feel like my feet were being crushed.” He took the opioid pain killer hydrocodone to make it through the day.

In 2016, Sipos consulted a second rheumatologist. She ordered a test for immunoglobulin M (IgM) antibodies, which can assess immune function. The test showed an “m spike,” an indication that Sipos might have a precancerous condition or possibly multiple myeloma, an uncommon cancer.

In early 2017 she referred Sipos to a hematologist, who immediately ordered urine and blood tests. On the basis of those, Sipos said, she decided he had a precancerous condition called MGUS, short for monoclonal gammopathy of undetermined significance.

MGUS must be watched closely because in about 1% of patients annually it can progress to multiple myeloma, a cancer of plasma cells, or another malignancy. If there is no progression, treatment is usually not required.

In early 2018, he confronted the doctor about the unrelenting burning pain in his hands and feet. “I’m getting worse,” he remembered saying. Her reply was stark. “She said, ‘Yes, you may be in a wheelchair, but we would never treat this.’”

At his wife’s urging, Sipos decided it was time for another expert to weigh in.

Sipos and his wife waited six weeks for a consultation with Muhammad Omair Kamal, an assistant professor of medical oncology at Loma Linda University Cancer Center.

Both Jeff and Tami Sipos say that details of the May 14, 2018, meeting are seared into their memories.

“I remember Dr. Kamal leaned forward and in his soft, sweet voice full of concern said, ‘Mr. Sipos, has anyone told you you have cancer? How come you’re not getting treated for this?’” Sipos recalled.

The stunned couple repeated what the hematologist had been saying for more than a year: that Sipos did not have cancer and that monitoring was the best course of action.

Kamal strenuously disagreed. “You have cancer,” Sipos remembers him saying. “If you were my patient, you’d be started on chemotherapy tomorrow.”

Kamal said he strongly suspected the patient had a rare, slow-growing form of B cell lymphoma called Waldenstrom macroglobulinemia, also known as Waldenstrom’s or lymphoplasmacytic lymphoma. Kamal had seen four other cases in his career. MGUS can be a precursor of multiple myeloma or Waldenstrom’s. Sipos later learned that a January 2017 pathology report mentioned it as a possible cause of his symptoms.

About 1,500 cases are diagnosed annually in the United States, compared with about 32,000 cases of multiple myeloma.

Waldenstrom’s occurs mostly in men over 60 when lymphoma cells in bone marrow proliferate, crowding out normal red and white blood cells. Anemia is common and symptoms include fatigue, neuropathy and night sweats, all of which he had. There is no cure. Treatment typically consists of chemotherapy. The disease is diagnosed through blood tests and a bone marrow biopsy and can be confirmed by a test for a genetic mutation.

Kamal said he cannot fathom why Sipos went undiagnosed for so long.

When he he finally received Sipos’ complete records after considerable effort, Kamal said, “lab after lab after lab” showed results that warranted treatment. “There are not many diseases [other than Waldenstrom’s] where you see high IgM and neuropathy. Most patients are diagnosed within a year or two.”

Sipos said that when he told the first hematologist what Kamal had recommended, she balked and insisted that her diagnosis was correct. Switching doctors was problematic; Kamal was outside his insurance network.

So another month elapsed while Sipos obtained another opinion. The third cancer specialist strongly sided with Kamal. “If you don’t have chemo, you’re going to expire,” Sipos remembers her saying.

Sipos called his insurance company and requested a transfer to Kamal; it was quickly approved.

He then underwent another bone marrow biopsy. A positive test for the MYD88 L265P mutation linked to Waldenstrom’s clinched the diagnosis. (The mutation is not passed on to offspring.)

In mid-August 2018, Sipos began a grueling chemotherapy regimen. He wore a Superman T-shirt that one of his kindergarten students had given him to every session as a sort of talisman. By January 2019, his cancer was in remission.

But the agonizing nerve damage to his hands and feet continues to plague him. Kamal said the damage is probably irreversible and may have occurred because his cancer went untreated for so long.

Sipos, who sees a pain specialist, said he has been prescribed methadone, which “takes the zing out of it.”

He said he has learned through bitter experience to ask questions.

“No healthy adult male should be anemic,” he said. “I wish I’d had the foresight to ask, ‘What would cause this?’”

Sipos also wishes he had sought a second opinion sooner. “I was afraid I was going to offend her,” he said, referring to the first hematologist.

To Kamal, Sipos’ case illustrates the necessity for doctors to keep looking and not brush off what patients tell them. “Don’t just ignore neuropathy, or any symptoms, in young patients. Even if they’re young, they can have cancer.”