Chronic inflammatory demyelinating polyradiculoneuropathy, or CIDP, is a rare immune-mediated nerve disorder characterized by progressive weakness and sensory impairment in the arms and legs, the result of an autoimmune attack on myelin.
Though some clustering of cases may occur in families, and susceptibility genes have been found, it is not considered a genetic disease. It can strike patients of either sex at any age, though most cases will occur in or after midlife.
Complicating matters further, CIDP has several variants whose symptoms differ from classical presentations.
Many patients who do not have CIDP end up being treated for it, and many CIDP patients experience delays to diagnosis and treatment that can potentially result in greater nerve damage and worse outcomes.
The good news, CIDP experts say, is that the last few years have seen important advances in diagnosis and treatment – including comprehensive new clinical guidelines and the June 2024 approval by the Food and Drug Administration of a new treatment, efgartigimod alfa and hyaluronidase-qvfc (Vyvgart, argenx). This antibody fragment represents the first non-steroid, non-immunoglobulin option for CIDP.
Despite the difficulties of recruiting patients with a tough-to-confirm disease that affects between 2 and 9 of every 100,000 people, according to the GPS-CIDP Foundation clinical trials have been successfully carried out in CIDP, and new ones continue to recruit. The experimental therapies being explored are based on a wide range of proposed disease pathways.
courtesy University of Minnesota
Dr. Jeffrey Allen
“It’s a very exciting time,” said Jeffrey Allen, MD, a neurologist at the University of Minnesota, Minneapolis, one of three CIDP experts who spoke about this challenging but treatable syndrome, its diagnosis and management, and the research questions that they hope to see answered.
Refining Diagnosis
In classical or typical CIDP, which accounts for most cases, patients present with progressive weakness and numbness that affects the arms and legs symmetrically, with the weakness being both proximal and distal. The disease usually evolves over a period of months, which helps distinguish it from Gullain-Barré syndrome, whose onset is more sudden and progression is less than 4 weeks.
CIDP was first described in the 1970s, and since that time more than a dozen sets of diagnostic criteria have been published. Starting about a decade ago, Dr. Allen and neurologist Richard Lewis, MD, of Cedars-Sinai Medical Center in Los Angeles, California, helped launch an effort to improve them.
“Experts in the field who were seeing patients with CIDP recognized that a lot of referrals coming to them were of people who actually didn’t have it, or they had the disease and were treated for it but didn’t need to be on treatment, or their treatment was very unconventional,” Dr. Allen said. “We wanted to try to put some data behind that.” In 2015 Dr. Allen and Dr. Lewis published a paper that found that nearly half of patients referred with a diagnosis of CIDP failed to meet basic diagnostic requirements.
courtesy Cedars-Sinai Medical Center
Dr. Richard Lewis
Erroneous interpretation of nerve conduction studies “was a significant factor” contributing to the misdiagnoses, Dr. Lewis said. And another major problem was that patients’ response to standard treatment with intravenous immunoglobulins (current treatments have also come to include subcutaneous immunoglobulins) was not being measured objectively. Instead of evaluating patients using grip strength, walking tests, or other objective instruments, clinicians asked patients whether they felt better. “The problem is that IVIg makes people feel good,” Dr. Lewis said, “possibly by reducing normal inflammatory agents in the body.”
The 2015 paper caught the attention of neurologists and neuromuscular specialists worldwide, who reported similar problems with misdiagnosis. “And from there we did other work to try to dissect out what the more specific issues are,” Dr. Allen said. “The electrophysiology was a big one.”
courtesy University of Buffalo
Dr. Nicholas Silvestri
Neurologist Nicholas Silvestri, MD, of the University at Buffalo in New York, one of the centers of excellence recognized by the CIDP-GBS Foundation, affirmed that nerve conduction studies, which essential to diagnosing CIDP, “are not as objective as we think they are. They’re very prone to user error and overinterpretation error. If they’re not performed appropriately, things can look like CIDP when they’re not. Very common forms of neuropathy, like diabetic neuropathy, can be misinterpreted as CIDP.”