Washington Post – By Sandra G. Boodman -June 27, 2020 at 10:00 a.m. EDT-
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 general practitioner, who ordered blood tests that revealed an abnormally low iron level.
Several years later when he developed foot pain, Sipos saw a podiatrist who told him he had osteoarthritis, typically caused by wear and tear on joints. A few years later, a specialist diagnosed his painful wrists and ankles as rheumatoid arthritis, a serious autoimmune disease. That was followed by the diagnosis of a rare blood condition that a hematologist monitored, but did not treat.
It wasn’t until 2018 — nearly 17 years to the day after he first saw a doctor for fatigue — that Sipos learned he had none of those illnesses.
The news was delivered by a specialist whose gentle, measured tone belied the shocking message that galvanized Sipos: Without treatment, which was long overdue, he could die.
“We both started crying,” Sipos recalled of his reaction and that of his wife, Tami. “It felt like the oxygen had been sucked out of the room.”
He credits his survival to the expertise and compassion of that specialist, who continues to oversee his treatment.
Sipos trusted the family physician, who had delivered his sons. 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.
The pills seemed to work. “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. For a while, they quelled the pain.
By 2015, the foot pain was considerably worse and had engulfed his ankles, putting an end to his participation in extreme sports. Sipos’s 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.
“He said I should have it looked at because someone 46 years old should not have neuropathy,” Sipos remembers being told. Peripheral neuropathy can be caused by a variety of ailments, among them diabetes, liver disease and bone marrow disorders.
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, hydroxychloraquine, an anti-malaria drug used to treat autoimmune disorders. Neither worked.
At that point, Sipos recalled, the pain was so intense “the weight of the [bed] sheets would feel like my feet were being crushed.” He wore braces on his wrists and ankles in a mostly failed attempt to deaden the pain, and took the opioid pain killer hydrocodone to make it through the day.
In 2016, Sipos consulted a second rheumatologist. She agreed it was odd that neither drug had been effective and prescribed other medications. When they failed, 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, who by then was suffering from frequent night sweats, to a specialist who treats blood disorders.
The hematologist immediately ordered urine and blood tests. On the basis of those, Sipos said, she assured him he did not have cancer, but rather a precancerous condition called MGUS, short for monoclonal gammopathy of undetermined significance.
MGUS is often found incidentally, when doctors are looking for other things. It frequently causes no symptoms but must be watched closely because in about 1 percent 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.
“She said the standard of care was watch and wait,” Sipos recalled. That meant appointments every three months to check his blood and urine.
Sipos said the doctor also performed several bone marrow biopsies but the results were inconclusive.
When he asked the doctor about the unrelenting burning pain in his hands and feet, she offered no explanation.
In early 2018, he said, he confronted her. “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.’ ” His IgM level, she told him, was not sufficiently elevated to warrant the risks of treatment, which would involve chemotherapy. Watchful waiting was the safest course.
The hematologist told Sipos he was free to seek a second opinion. He was initially hesitant. Even though she was routinely an hour or two late for scheduled appointments, the doctor “seemed so knowledgeable and wise and would speak with such authority,” he said. But at his wife’s urging, Sipos decided it was time for another expert to weigh in.
What he didn’t know was that getting a second opinion would possibly save his life.
A dramatic reversal
Sipos and his wife waited six weeks for the consultation with Muhammad Omair Kamal, an assistant professor of medical oncology at Loma Linda University Cancer Center.
Transferring his records to Kamal in preparation for the appointment was a struggle, Sipos said, requiring multiple phone calls by him as well as Kamal’s staff.
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.” Then he handed the couple treatment guidelines from the National Cancer Institute.
Although he still didn’t have all of Sipos’s records, Kamal said he strongly suspected the principal 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 to 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. There is no cure. Treatment typically consists of chemotherapy and targeted treatments that kill only cancer cells. 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. “He was seeing the right doctor,” Kamal noted, referring to the proper specialty.
When he received Sipos’s complete records, 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, unsure about what to do, 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 and testing to rule out amyloidosis, a rare disease caused by the accumulation of a protein that can result in organ failure. 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 to treat Waldenstrom’s. 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’s 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.”