CIDP in an Adolescent After Pfizer-BioNTech COVID-19 Vaccination

Clinical Presentation

A teenager who had no significant medical history presented with sensory changes and weakness that began 2 weeks after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. The patient began to have difficulty walking, prompting the evaluation. In retrospect, the patient recalled experiencing transient sensory symptoms in the hands and feet after receiving the first dose of the vaccine, which resolved without medical attention. The examination upon presentation was notable for lower-extremity areflexia with distal greater than proximal weakness, sensory changes in the hands and feet, and an unsteady gait. A review of systems was unremarkable. There was no family history of neuromuscular, autoimmune, or other neurologic disease. The patient denied any recent illnesses, COVID-19 exposures, or previous adverse reactions to vaccinations. The patient’s identical twin sibling received the vaccine without complications. Initial EMG/nerve conduction study (NCS) showed evidence of a demyelinating motor greater than sensory polyneuropathy (Figure 1). Laboratory study results were unremarkable. The patient was diagnosed with acute inflammatory demyelinating polyradiculoneuropathy and received 2 g/kg of intravenous immunoglobulin (IVIg). The patient was prescribed gabapentin for neuropathic pain and trazodone as a sleep aid. The condition worsened over the next 2 months and the individual required hospital readmission. Additional evaluation included lumbar spine MRI, lumbar puncture, additional laboratory studies, and repeat EMG/NCS.

Diagnostic Process

The initial EMG/NCS showed evidence of a demyelinating motor greater than sensory polyneuropathy with reduced motor and sensory nerve action potential amplitudes, temporal dispersion, and conduction block (Figure 1). The initial serum laboratory workup included normal erythrocyte sedimentation rate and creatine kinase, C-reactive protein, ferritin, vitamin B12, lactate dehydrogenase, and aldosterone levels. When the patient was readmitted, lumbar spine MRI (Figure 2) demonstrated abnormal enhancement and thickening of the cauda equina nerve roots. Cerebrospinal fluid (CSF) studies were consistent with albuminocytologic dissociation, with an elevated protein level of 204 mg/dL and normal cell count. Ganglioside antibody and paraneoplastic panels were negative. Additional serum studies were notable for mildly decreased white blood cell count and elevated erythrocyte sedimentation rate. Normal results were noted on comprehensive metabolic panel, antinuclear antibody testing, antiphospholipid antibody panel, thyroid profile, antineutrophil cytoplasmic antibodies testing, serum immunofixation, CSF cytology, and CSF IgG index; urine amino acids testing; and in serum and urine porphyrin, C-reactive protein, creatine kinase, vitamin E, vitamin B12, and lead levels. Repeat EMG/NCS (Figure 1) demonstrated absent F-waves, conduction block, temporal dispersion, and reduced conduction velocities. Values were obtained with supramaximal stimulation of nerves. Needle EMG showed motor unit dropout in a length-dependent distribution.

Case Resolution

Lumbar spine MRI (Figure 2) showed nerve root enhancement consistent with an inflammatory demyelinating polyradiculopathy. CSF studies were consistent with albuminocytologic dissociation. Serum studies were nondiagnostic. Repeat EMG/NCS (Figure 1) findings met the European Federation of Neurological Societies/Peripheral Nerve Society criteria for a diagnosis of chronic inflammatory demyelinating polyradiculopathy (CIDP).¹

The patient was treated with plasmapheresis but was readmitted 1 month later for continued worsening of symptoms, severe neuropathic pain, and inability to ambulate independently. The patient was started on rituximab. After treatment with rituximab, there was improvement in the patient’s ability to stand and reduced pain severity. The patient continued on monthly IVIg treatments, with slow improvement in symptoms and function.

After returning to school in person approximately 15 months after initial symptom onset, the patient contracted COVID-19 and had significant worsening of CIDP. The patient was readmitted for another dose of rituximab, after which the symptoms improved greatly, with gains in strength in both arms and legs. The patient had reemergence of deep tendon reflexes, no longer had complaints of neuropathic pain, and began to be able to take steps while wearing knee ankle-foot orthosis bracing support. The patient believed the greatest response followed rituximab treatment. The treatment plan is to continue IVIg and solumedrol every 3 weeks and consider additional doses of rituximab.

Discussion

The relationship between COVID-19 vaccination and Guillain-Barré syndrome (GBS) is unclear, especially as pertains to children and adolescents. As more children are vaccinated, it will be important to establish an accurate assessment of the risk of neuropathy. We report a case of pediatric CIDP temporally related to the COVID-19 vaccination.

GBS is a postinfectious autoimmune disorder that affects 0.5 to 1.5 per 100,000 children.² In rare cases, individuals have developed GBS after vaccination. GBS after vaccination was first reported in the United States in 1976 during the H1N1 swine influenza pandemic.³ In total, 362 patients developed GBS during the 6 weeks after vaccination out of a total of 45 million vaccinated.⁴ Further analysis of the influenza vaccine found that, although the vaccine increased the incidence of GBS, the risk remained much higher with primary influenza infection compared to after vaccination.^3-5 The incidence of GBS from current influenza vaccines is estimated to be 1 extra case of GBS per 1 million vaccinated individuals.⁴ Additional studies looking at common childhood vaccines showed that none of these vaccines were associated with an increased risk of GBS.^6-8

At the time of this publication, the Pfizer-BioNTech and Moderna COVID-19 vaccines are the only COVID-19 vaccines approved for children age 6 months and older. Although GBS is listed on the Food and Drug Administration (FDA) fact sheet as an adverse reaction to the Janssen (Johnson & Johnson) vaccine,⁹ the risk of SARS-CoV-2 infection far exceeds the risk of developing acute inflammatory demyelinating polyradiculoneuropathy or CIDP, as shown by data from the FDA and the US Vaccine Adverse Event Reporting System.¹⁰ GBS was not reported in a large observational study examining the adverse effects of the Pfizer-BioNTech COVID-19 vaccine, although a substantially increased risk of myocarditis after vaccination was found. Although there was a potential small increase in the risk of Bell palsy after vaccination, the absolute effect was minimal, with up to 8 excess events per 100,000 persons. The risk of myocarditis, as well as other serious adverse events, was substantially increased after COVID-19 infection.¹¹

Malamud et al¹² reported GBS in an adolescent after receipt of the second dose of the Pfizer-BioNTech COVID-19 vaccine. We report a case of pediatric CIDP temporally related to Pfizer-BioNTech COVID-19 vaccination. It is unclear whether the vaccine caused the development of CIDP; however, other potential etiologies were not identified. The incidence of GBS after COVID-19 vaccination does not exceed the natural expected case rates in the population.¹² As more children are vaccinated, it will be imperative to report cases of GBS to better understand this risk and compare it with the risk associated with primary SARS-CoV-2 infection. Regardless of whether COVID-19 vaccination slightly increases a child’s chances of developing GBS, the benefits of vaccination clearly outweigh the risks of COVID-19 infection.