“A Case of Eosinophilic Granulomatosis With Polyangiitis Presenting as Quadriplegia”: A Clinical and Diagnostic Report

Abstract

An antineutrophil cytoplasmic antibody-associated small artery vasculitis that primarily affects the skin, lungs, and heart is called eosinophilic granulomatosis with polyangiitis (EGPA). It typically begins with initial respiratory symptoms like asthma and chronic sinusitis, and later progresses to systemic vasculitic issues that are linked to increased levels of eosinophils in the blood and tissues. While both central nervous system (CNS) and peripheral nervous systems can be affected, CNS involvement is rare. Nerve damage from vasculitis in EGPA usually appears as mononeuritis multiplex and is infrequently seen as polyradiculopathy. Here, we discuss an unusual case where a patient with EGPA presented with worsening asthma, a skin rash, and a sudden quadriplegia due to involvement of the cervical spine. After all relevant investigations and findings, the patient was treated with IV rituximab along with IV corticosteroids and oral azathioprine which improved the condition including the paralysis.

Introduction

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg–Strauss syndrome, is small-vessel vasculitis linked to antineutrophil cytoplasmic antibodies (ANCAs). ¹ Granulomatous inflammation of small- to medium-sized blood vessels along with eosinophilia, which causes organ failure, are the causes of this multisystem illness. There is a wide range of clinical manifestations associated with this illness, which most typically affects the skin and lungs. It can also impact the renal, cardiovascular, gastrointestinal, central, and peripheral neurological systems. ²

The American College of Rheumatology defined 6 distinct criteria for EGPA and established classifying criteria to distinguish between different kinds of vasculitis. These are asthma (rhonchi upon expiration, wheezing), >10% eosinophilia in peripheral blood, the paranasal sinusitis, pulmonary infiltrates (which could be temporary), histological evidence of mononeuritis multiplex, polyneuropathy, or vasculitis with extravascular eosinophils. A diagnosis of EGPA is considered likely if at least 4 of these criteria are met, which provides a sensitivity of 85% and a specificity of 99.7%. ³

While involvement of the peripheral nervous system is relatively common, affecting between 55% and 72% of patients, central nervous system (CNS) manifestations are far less frequent and less well known, occurring in only about 5% to 9% of cases. ⁴ Cardiac involvement, on the other hand, has been observed in 17% to 29% of patients. ⁵ In light of the rarity and potential severity of CNS involvement, this case aims to shed light on an unusual presentation of EGPA with CNS involvement resulting in quadriplegia.

Case

This case was reported in line with the CARE guidelines. ⁶

A male patient, aged 57, arrived at the outpatient department complaining of bodily pains, dyspnea, and quadriplegia. He had a history of asthma and was on treatment for that and had a nasal polypectomy 1.5 years ago. ¹ Over the past year, he had experienced a persistent productive cough without hemoptysis and had also lost 6 kg of weight in the last 3 to 4 months. The patient had shortness of breath for the last 2 months, which was gradual in onset and progressive in nature with no aggravating or relieving factor except inhalers. These respiratory symptoms were taken as respiratory tract infections and exacerbations of asthma and were treated locally by the General practitioner. At that moment, he presented with an unusual presentation of severe shortness of breath that had worsened in the last 5 days along with cough and high-grade fever and was associated with loss of appetite and drowsiness. Subsequently, he developed weakness of upper and lower limbs with some paresthesia and numbness in the hands and feet.

On examination, pulse was 88/minute, BP 110/70, and SpO₂ 96%, room air with RR 20/minute. For the last 2 weeks on lower limbs, the patient had multiple nonblanching, reddish-brown to purple macules and papules over the anterior aspects of both lower legs, more prominent on the left side, consistent with small vessel cutaneous vasculitis. The neurological exam of the patient showed spasticity, exaggerated deep tendon reflexes, and an upgoing plantar reflex. The power in the upper and lower limbs was 3/5 and 1/5, respectively; the patient was unable to move the lower limbs due to profound weakness, though minimal muscle contraction was still present. Because the sensations were also decreased in both upper and lower limbs that was why peripheral neuropathy along with that of CNS manifestation was obvious. Upon chest auscultation, bilateral crackles were heard up to the scapulae, with wheezing on the right side.

Blood workup showed leukocytosis with a count of 23.25 k/µL, with almost normal neutrophil and platelet counts and normal hemoglobin, while markedly high eosinophilia with a count of 13 k/µL. The peripheral smear showed MCV, MCH, MCHC, and RDW in the normal range, while leukocytosis and severe eosinophilia were detected. Inflammatory biomarkers, that is, CRP, were high (18.3 mg/L), and procalcitonin levels were normal. The liver profile reported normal total bilirubin but high ALT/GPT (56.1 U/L), ALP (144 U/L), and LDH (402 U/L). The renal profile showed an increase in BUN (80.4 mg/dL), while creatinine was in the normal range. However, urinalysis reported positive urine albumin, white blood cells 8 to 10/hpf, and 10 to 12 RBCs. Infectious work up including blood cultures, urine cultures, echocardiogram, and detailed skin exam were unrevealing of infectious source. An X-ray followed by HRCT was advised also, which showed mild bilateral perihilar bronchial thickening with patchy infiltrate and ground glass haze, suggesting small airway disease. Also, an MRI of the brain and spinal cord was carried out to look out for the pathology. The MRI of the brain showed scattered hyperintense signals bilaterally in the cortex and subcortex along with long-segment patchy high signals from C3 to C6 on the spinal cord MRI.

Differentials included CNS vasculitis, demyelinating disorders, transverse myelitis, and, less likely, neoplastic or compressive lesions. Demyelinating disorders and transverse myelitis were considered less likely due to the absence of typical symmetric cord involvement, lack of CSF pleocytosis, and the presence of systemic vasculitic features. Hyper eosinophilic syndrome was unlikely given the patient’s asthma, nasal polyposis, and ANCA positivity. Microscopic polyangiitis and polyarteritis nodosa were excluded due to marked eosinophilia and allergic features, while sarcoidosis was ruled out by imaging and absence of granulomas. c-ANCA and p-ANCA were sent, and to rule out other autoimmune diseases, other antibody profiles were done that included anti-dsDNA, anti-histones, anti-SM, anti-RNP, anti-PCNA, anti-SSA/RO, anti-SSB/La, anti-SCL-70, anti-Mi2, anti-jo-1, anti-PL7, anti-sp100, and F-Actin ab, and all were in the negative range except c-ANCA and p-ANCA, which came out positive in high titers.

Due to the overall picture, a working diagnosis of EGPA was felt to be most likely and therefore treatment was initiated.

After supportive treatment (including drugs for asthma relief, antibiotics, and others for symptomatic relief), the patient was given 2 doses of 1 g of IV rituximab along with IV corticosteroids and oral azathioprine. The definitive treatment that was Rituximab was started after ANCA antibodies came back positive, while the supportive treatment of steroids was started earlier, on strong clinical suspicions of vasculitis. Initially, a pulse steroid of 1 g once a day for 3 days and then an oral steroid of 1 mg/kg body weight for 4 weeks, then tapered gradually according to the protocol. Azathioprine was started 2 weeks after the second dose of Rituximab and increased over a month’s time to 200 mg/day.

Discussion

The clinical spectrum of EGPA is quite broad, ranging from respiratory symptoms such as asthma, cough, and shortness of breath to more severe multisystemic involvement, including skin, GI, cardiovascular, and neurological complications. ³ The classification criteria established by the American College of Rheumatology provide a valuable framework for identifying EGPA in clinical settings. ⁷

EGPA mainly affects patients with asthma, nasal polyposis, allergic rhinitis, and sinusitis. ⁸ The respiratory system constitutes one of the most commonly affected regions, ⁹ and pulmonary eosinophilic infiltrates may be evident. ¹⁰ The patient in our instance also had a history of patchy infiltrates on the HRCT chest, asthma, and nasal polypectomy (which was followed by an MRI that revealed pansinusitis). Our patient exhibited typical vasculitic-phase skin symptoms of EGPA, such as nonblanching, reddish brown to purple macules and papules over the anterior aspects of both lower legs and trunk. ¹¹ These manifestations reinforce the need for early diagnosis and monitoring in EGPA patients to manage complications effectively. An earlier diagnosis might have been facilitated by recognizing the constellation of asthma, eosinophilia, and evolving neuropathy, particularly in the presence of systemic symptoms such as weight loss, rash, and fever. The initial presentation was managed as asthma exacerbation, and key signs such as persistent eosinophilia, cutaneous vasculitis, and progressive neurological deficits were initially overlooked. Earlier consideration of vasculitic processes in the differential could have prompted timely autoimmune screening and immunosuppressive therapy. Several alternative diagnoses were considered: hypereosinophilic syndrome was less likely, given the presence of asthma, nasal polyposis, and ANCA positivity; microscopic polyangiitis and polyarteritis nodosa were unlikely due to prominent eosinophilia and allergic features; and sarcoidosis was excluded based on imaging and absence of granulomas. Parasitic or infectious causes were ruled out by negative cultures and lack of exposure history. Ultimately, the combination of multiorgan eosinophilic inflammation, asthma, sinusitis, and ANCA positivity supported EGPA as the most plausible diagnosis.

Neurological involvement occurs in about 70% of adult EGPA cases; however, the CNS is less frequently affected. ¹² CNS manifestations include ischemic lesions, hemorrhage, cranial nerve palsy, and vision loss, ¹³ often linked to cerebral vasculitis and eosinophilic infiltration. ⁷ The most common manifestation is ischemic lesions (52%), followed by intracranial/subarachnoid hemorrhage (24%), loss of visual acuity (33%), and cranial nerve palsies (21%). ¹³ In our instance, scattered hyperintense signals were seen bilaterally in the cortex and subcortex on brain MRI along with long segment patchy high signals from C3 to C6 on the spinal MRI more consistent with ischemic changes from CNS vasculitis rather than classic viral transverse myelitis, which typically presents as symmetric cord involvement with CSF pleocytosis not present in our case. Additionally, the absence of infectious markers, negative cultures, and serology, the context of systemic vasculitis, and concurrent cerebral cortical/subcortical changes support EGPA-related vasculitis as the most likely cause. This also likely reflects the commonest manifestation in CNS, that is, ischemic lesions as sequelae of CNS vasculitis. Long-term neurological sequelae are common, and intracerebral hemorrhage has the worst prognostic impact and has the highest mortality associated with it. ¹³ The presented case is noteworthy cause it is a rare manifestation of EGPA as quadriplegic presentation because of brain and cervical spine involvement substantiated by MRI brain showing vasculitic lesions in cortical and subcortical regions of both hemispheres along with focal involvement of the cervical cord. This could have led to permanent neurologic damage resulting in long-term disability that’s why CNS involvement mandates early and aggressive treatment. Along with this, our patient also reported symptoms of peripheral neuropathy, a rather common manifestation of this disease. This shows how the peripheral and CNS were both involved in EGPA simultaneously. Laboratory findings, including eosinophilia and elevated inflammatory markers, were consistent with EGPA. ⁹ Due to this overall picture a working diagnosis of EGPA was felt to be most likely and therefore treatment was initiated.

The French Vasculitis Study Group created the 5-Factor Score (FFS), which is primarily used to measure disease severity, organ involvement, and progression, in order to guide treatment for EGPA. ¹⁴ Systemic glucocorticoids remain the mainstay of treatment, effectively suppressing inflammation and managing symptoms. The regimen for patients with severe disease includes pulsed intravenous glucocorticoid treatment, typically administered as daily methylprednisolone pulses ranging from 500 to 1000 mg each over a 3-day period, with a maximum cumulative dose of 3 g. Thereafter, high-dose oral glucocorticoids should be prescribed, such as 0.75 to 1 mg/kg/day, to maintain effective therapy. Though there is no specific treatment aimed at the PNS/CNS manifestations of the disease, specifically given its poor prognostic impact, CNS involvement is included in the FFS to guide treatment decision as in severe cases like ours, particularly when the CNS, heart, kidneys, or digestive tract are affected, immunosuppressive agents such as cyclophosphamide, azathioprine, or methotrexate may be prescribed. These agents safeguard blood vessels and organs from further harm. ¹⁵ Based on this, we used steroids and azathioprine, resulting in the improvement of the patient’s quadriplegia and other symptoms. We preferred azathioprine over other agents because of its lower toxicity. Recent advances include targeted therapies like mepolizumab and rituximab, which have shown promise. ¹⁶ In our case, the addition of rituximab likely enhanced the patient’s prognosis, supporting existing evidence of its efficacy.

Conclusion

As EGPA often involves multiple systems, making early diagnosis is crucial to prevent complications. This case highlights how the patient’s chief complaints, symptoms, and investigations guided the diagnostic process. Given the potential for a severe course, especially with peripheral and CNS involvement in late-onset EGPA, early suspicion and aggressive treatment are essential. This case underscores the importance of a tailored therapeutic approach and timely intervention based on the patient’s clinical presentation. The positive outcome reinforces the need for a substantial level of concern for EGPA in patients with similar symptoms, emphasizing early and proactive care to improve patient outcomes.