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Defining and Diagnosing Chronic Inflammatory Demyelinating Polyneuropathy

April 15, 2024
in Health
Defining and Diagnosing Chronic Inflammatory Demyelinating Polyneuropathy
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Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common chronic immune-mediated neuropathy. It affects peripheral nerves and roots.

CIDP has no biomarkers. It may be monophasic or recurrent, has multiple clinical manifestations, and often results in serious cumulative disability despite some improvement in most patients with first-line therapies of corticosteroids, intravenous immunoglobulin (IVIG), or plasmapheresis.

In recent years, CIDP has received increasing attention due to its high misdiagnosis rate, along with the publication of new diagnostic and treatment criteria from the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) in 2021 and the possibility of novel maintenance therapies.

Early this year, the FDA approved hyaluronidase-facilitated subcutaneous immunoglobulin (SCIG) 10% (Hyqvia) for maintenance therapy to prevent relapses in CIDP. Promising phase II results have been presented recently for efgartigimod combined with hyaluronidase (Vyvgart Hytrulo), which inhibits recycling of circulating immunoglobulin G, and the investigational agent riliprubart, a complement C1s inhibitor.

CIDP Variants

“CIDP is a syndrome that is heterogeneous in clinical presentation and is without a diagnostic biomarker,” said Jeffrey Allen, MD, of the University of Minnesota in Minneapolis.

“Although tools like spinal fluid, imaging, nerve biopsy, and tests-of-treatment can be helpful to increase or decrease diagnostic confidence, none of these tools are diagnostic of CIDP in isolation and all can be misleading if interpreted in the wrong clinical and electrophysiologic context,” Allen noted.

“We know that CIDP misdiagnosis is very common,” he said. “At least half of patients who carry a diagnosis of CIDP actually do not have that condition.” This leads to unnecessary treatment and exposes patients to adverse effects without benefit, he added.

Since CIDP was first described in the 1970s, over 15 sets of diagnostic criteria have been proposed. The 2021 EAN/PNS guideline now recognizes six types of CIDP: typical CIDP (symmetric proximal and distal limb involvement), and five variants: multifocal, focal, distal, motor, and sensory CIDP.

“Typical CIDP is the most common CIDP form,” said Peter Van den Bergh, MD, PhD, of University Hospital Saint-Luc in Brussels, who led the joint task force that prepared the 2021 guideline.

In the past, other forms were labeled predominantly distal, asymmetric, pure motor, and pure sensory CIDP, Van den Bergh pointed out.

“We used to call these forms atypical CIDP, but they really are CIDP variants because each of these has well-defined characteristics,” he said. “They are hosted under the CIDP umbrella because of a common denominator of inflammation and demyelination.”

Diagnosing CIDP

CIDP should be considered with any progressive polyradiculoneuropathy regardless of symmetry or asymmetry when symptoms recur or worsen within 2 months, the guideline states. Symptoms suggesting CIDP include limb paresis, absent tendon reflexes, and sensory dysfunction including vibration.

The next step, in the absence of established biomarkers, is electrophysiologic evaluation with nerve conduction studies and electromyography.

Nerve conduction studies should include at least four peripheral nerves, with stimulation of median, ulnar, peroneal, and sural nerves performed on the same side. If criteria are not met, the same nerves should be studied on the other side.

Definite and possible CIDP are distinguished by electrodiagnostic evidence for demyelination, according to the EAN/PNS guideline. A possible diagnosis can become definite by meeting two supportive criteria from cerebrospinal fluid (CSF) studies; MRI imaging of nerves, roots, or plexuses; nerve biopsy; or objective response to treatment.

In a 2022 review of CIDP diagnosis, Allen and co-author Richard Lewis, MD, of Cedars-Sinai Medical Center in Los Angeles, cited a peak prevalence of CIDP at ages 70 to 79 with typical onset when patients are in their 40s. They also emphasized that delays or misdiagnosis can result in accumulating axonal injury and disability.

“Although even in this setting electrophysiological studies are important to provide evidence of peripheral nerve demyelination, a diagnosis of ‘typical’ CIDP can confidently be made provided there is no serum paraprotein, suspicion for a genetic abnormality, or other apparent explanation for the symptoms,” they wrote. “When demyelination is present, but the clinical features are unusual for CIDP, an alternative explanation for the demyelinating polyneuropathy should be pursued.”

Additional clinical features that may be prominent include fatigue, pain, tremor, or dysfunction of the autonomic or cranial nerves.

“From a management perspective, these symptoms should not be dismissed, but from a diagnostic perspective caution is needed because an overreliance on any of these features introduces a possible misdiagnosis,” Lewis and Allen observed.

Misdiagnosis of CIDP mainly occurs in variants other than typical CIDP, Van den Bergh pointed out.

“Clinical research has shown that there are four main pitfalls: clinical criteria and differential diagnostic exclusions are not respected, electrodiagnostic testing is not correctly performed or criteria are not adhered to, over-reliance on spinal fluid protein levels, and non-objective treatment response,” Van den Bergh explained. “Therefore, we paid a lot of attention to adjusting criteria for other than typical CIDP forms to try to improve their specificity.”

The EAN/PNS 2021 guideline is highly specific and sensitive for CIDP, Allen noted. “It was developed for daily clinical practice, not just clinical trials,” he said. “It is free to use and in the public domain.”

“Although parts of the guideline can be complex, it is an excellent resource when trying to balance and proportionally integrate all the bits of data that are collected during the diagnostic journey,” Allen added. “The guideline also provides important alternative diagnosis to consider, which can be especially helpful when encountering a patient that potentially has one of the CIDP variants.”

Disclosures

The 2021 EAN/PNS guideline task force was supported by the European Academy of Neurology, the Peripheral Nerve Society, the GBS/CIDP Foundation International, and the GAIN Charity U.K.

Allen reported relationships with Argenx, CSL Behring, Takeda, Grifols, and Alexion.

Van den Bergh reported relationships with Pfizer, Genzyme, CSL Behring, LFB, Natus, UCB Pharma, and Alnylam Pharmaceuticals.

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Copyright for syndicated content belongs to the linked Source : MedPageToday – https://www.medpagetoday.com/spotlight/aan-cipd/109652

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