by William Schwalbe
More than three years ago, I came down with a mysterious illness I thought might be a flu, but turned out to be something entirely different.
My blizzard of symptoms began innocuously in November 2016 with terribly cold feet. So cold that even when I got under the covers with a hot water bottle between them, and they were warm to the touch, they still felt like painful ice-blocks. At other times, I had the equally unpleasant sensation that my feet and shins were burning or already burnt.
A few weeks later, I started to experience intense throbbing pain in all my toes, as if someone had seconds before stomped on them with heavy boots, which made walking or standing difficult. Often my legs were so heavy that I could barely move them. Occasionally, my feet turned bright red. And every few hours came shooting pains, electric shocks that traveled up my legs. In my 55 years on earth, I’d never felt pain like that — except when a dentist drilled without Novocain.
All the symptoms increased at night, so sleep became elusive. I wound up sticking my feet outside the covers because even a sheet brushing against them proved too painful to bear. Before long, the same panoply of pains had moved to my hands and then arms — and occasionally my face and stomach.
Heat made the symptoms worse; cold and damp made them much worse. But often these pains flared for no discernible reason.
Totally unrelated, or so I thought, were other things that began to go wrong with me over the next few months: I often found myself pouring with sweat from my forehead, but became unable to sweat on my legs and arms; I lost all the hair on my lower legs; I was increasingly faint and dizzy, with my heart racing whenever I changed position or had a shower; and I was experiencing a fatigue and bone-pain so profound that every few hours I needed to stop whatever I was doing and lie down on the floor.
The exhaustion, which feels like the start of the flu, was particularly severe a day or two after I exercised.
Then, in early spring, I started getting vertigo after eating a full meal and hours later would vomit up undigested food. For someone who lives to eat, and frequently edits cookbooks for my job as an editor at a publishing house, that was worst of all.
Even though my problems had been multiplying, I kept delaying a checkup. I was almost constantly on the road to promote a book I’d written while working hard to keep up with my day job. Given that, I was certain that I just needed to rest. When I finally saw my internist, four months after the symptoms began, he suggested I see a cardiologist, a vascular specialist, and a neurologist, whom I approached in that order.
The first two told me that my heart and veins were in great shape; they didn’t know what was wrong with me. But in May 2017, when I started rattling off my crazy, random symptoms to Teena Shetty, a neurologist at Hospital for Special Surgery in New York, she wasn’t puzzled at all.
“I think I know what you have,” she said. “Small fiber neuropathy.”
Small fibers are the body’s temperature and pain sensors. (Large nerve fibers control muscles, feel vibration and let you know where your limbs are in space). Small fibers also work behind the scenes as part of what is called the autonomic (think: automatic) nervous system, influencing your circulation, breathing, digestion, and immune and glandular functions. That is why small fiber neuropathy typically causes such a diverse range of symptoms across almost every part of your body.
When you have small fiber neuropathy, the small fibers within the nerve bundles become damaged and start misfiring — causing pain and, often, systemic chaos. It’s at their tips that nerve fibers usually start to malfunction and can eventually shrink back, which is why peripheral neuropathies so often begin in the feet. It’s not the dead bits at the end that hurt; pain signals come from the more central ailing parts sending out an alarm.
Small fiber neuropathy is one of many kinds of peripheral neuropathy — that is, problems that affect the nerves that extend beyond your central nervous system. (Basically, any nerve that isn’t inside your brain or spinal cord.)
These days, small fiber neuropathy can be diagnosed with about 90 percent certainty by using a painless skin biopsy. Any doctor or nurse can take a pencil-eraser-sized sample from the side of your lower leg and then send it to an accredited lab to count the nerve fiber density within your skin’s surface and compare it to densities from skin biopsies of healthy people of your sex, race and age. It can also be diagnosed by testing sweat gland function. Unlike most more common neuropathies, small fiber neuropathy cannot be diagnosed by tests that use electrical impulses on the muscles and nerves.
Many cases of small fiber neuropathy cases are caused by diabetes. Other causes include some autoimmune disorders, such as Sjogren’s syndrome, some cancers and chemotherapies, HIV and certain HIV drugs, alcohol abuse, vitamin B6 toxicity, Celiac disease and several rare genetic disorders.
But in at least 40 percent of cases, including mine, no cause has yet been found, so doctors use the placeholder diagnosis of idiopathic small fiber neuropathy. Idiopathic means of unknown origin.
It’s unclear how many people have small fiber neuropathy. A 2013 study suggested about 175,000 people in the United States and 4 million worldwide might have it. But recent research indicates that as many as 50 percent of people diagnosed with another condition, fibromyalgia, which causes widespread musculoskeletal pain, have reduced nerve density consistent with small fiber neuropathy.
Small fiber neuropathy can develop at all ages, including in previously healthy children, although more commonly it begins in adolescence to mid-adulthood.
Although the skin biopsy test for it was introduced in the 1990s, the condition isn’t on the radar of most primary care doctors. And the varied symptoms make it challenging for generalists to spot.
Even neurologists who routinely diagnose the related large and mixed fiber peripheral neuropathies, which affect as many as 20 million people in the United States, will often miss small fiber neuropathy.
David Simpson, director of the Neuromuscular Diseases Division at the Icahn School of Medicine at Mount Sinai, says that “if a patient comes in with symptoms that might be neuropathic, when they get a normal result on the electrodiagnostic tests, the neurologist will often say, ‘Well, it’s not neuropathy, so who knows what it is?’ Most physicians are not knowledgeable about the role of skin biopsy in diagnosis. And so outside of the neuromuscular specialists, I would say most neurologists are not pursuing the diagnosis.”
As a result, many patients suffer for years or even decades with doctors who don’t know what tests to run — or who may not believe their symptoms.
“The main importance is to screen patients for the treatable causes of it,” says Louis Weimer, a professor of neurology at Columbia University Medical Center (who is also treating me), “so that for the majority — meaning more than 50 percent — the cause can be addressed before the damage is more severe. Sometimes it’s just as simple as behavioral modification. For example, neuropathy can be a red flag that brings a patient’s attention to diabetes before they develop a full-blown case of it.”
Depending on the cause, prompt treatment can even reverse the disease’s progression and allow symptoms to resolve.
After I got an abnormal skin biopsy that proved my neurologist was right, I found my way to NeuropathyCommons.org, a website created by neurologist Anne Louise Oaklander, director of the Nerve Unit at Massachusetts General Hospital. (She is the most widely-cited scientist in the field and her lecture “Small Fibers, Big Pain,” part of a Radcliffe Institute series on epidemics, has been viewed more than 25,500 times on YouTube.) The site includes a checklist of blood tests for all common treatable causes of small fiber neuropathy.
Since my blood didn’t reveal any of them — which is why my condition is classified as “idiopathic”— all I can do for now is try to treat the symptoms with medicine approved to reduce these symptoms in other neuropathic diseases.
Every four hours while I’m awake, I use pyridostigmine, a drug approved for myasthenia gravis — an autoimmune neuromuscular disease that causes weakness in skeletal muscles. It helps me digest food and gives me a bit more stamina. Before bed, I take the anticonvulsant Gabapentin, a sleep inducer that dulls the shooting pains I feel.
I have better days and worse days. I often need to cancel plans when I’m in too much pain or too nauseated and dizzy. Thanks to the Family and Medical Leave Act, an understanding employer and my profession, I’m lucky to be able to work from home on those two or so days a week. (And now that my office had to go largely virtual in the wake of covid-19, working remotely when I’m feeling ill is even less of an issue.) I’ve also found helpful advice at the website of the Foundation for Peripheral Neuropathy.
But I have a lot of hope. There is exciting new research into causes and treatments.
Oaklander presented promising findings about treating young patients who have evidence of immune causes of their small fiber neuropathy with corticosteroids or intravenous immune globulin (IVIG), a human blood product. IVIG is expensive (as much as $10,000 per month or more) and insurers will approve it only if there is evidence that an immune disorder is the cause. Unfortunately, since there’s no evidence that anything is wrong with my immune system, it’s not right for me.
Several biotech companies are working on new drugs to treat all kinds of pain based on what has been learned from studying genetic mutations that affect the way our small fibers function. People like me are potential subjects for these trials. The hope is that pain medicines that are more targeted and not addictive will help doctors fight the opioid epidemic without depriving people of the pain relief they need.
And other trials, funded by the National Institutes of Health, of other medicines and approaches are underway.
Walter J. Koroshetz, director of the National Institute of Neurological Disorders and Stroke at NIH, considers small fiber neuropathy to be “a vexing problem. It causes a lot of disability; and we don’t feel we have good treatments. So, anything that works would be fine with me. But what we’d like to do is prevent it.”