Eosinophilic Granulomatosis with Polyangiitis and Spinal Subdural Hematoma: A Case Report and Review of the Literature

AUTHORS

Saeedeh Shenavandeh 1 , * , Mehdi Eazadnegahdar 2 , Mohammad Ali Nazarinia 3 , Shiva Najafzadeh 4 , Fariba Zarei 5

1 Division of Rheumatology, Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Shiraz Geriatric Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

4 School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

5 Department of Radiology, Shiraz University of Medical Sciences, Shiraz, Iran

How to Cite: Shenavandeh S, Eazadnegahdar M, Nazarinia M A, Najafzadeh S, Zarei F. Eosinophilic Granulomatosis with Polyangiitis and Spinal Subdural Hematoma: A Case Report and Review of the Literature, Iran Red Crescent Med J. 2018 ; 20(11):e13058. doi: 10.5812/ircmj.13058.

ARTICLE INFORMATION

Iranian Red Crescent Medical Journal: 20 (11); e13058
Published Online: February 12, 2018
Article Type: Case Report
Received: May 12, 2017
Revised: July 11, 2017
Accepted: September 5, 2017
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Abstract

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic vasculitis. Central nervous system (CNS) involvement is described in rare cases. Acute spinal subdural hematoma (SSDH) is an uncommon condition presented with acute severe, radiating pain in the back area, and symptoms of spinal cord compression. The association of these two rare entities has been rarely reported so far.

Case Presentation: A 32-year-old female known case of limited scleroderma for 12 years and EGPA for six years with the presentation of eosinophilia, high P-ANCA, and skin vasculitis was admitted to the rheumatology ward of Faghihi hospital related to Shiraz University of Medical Science in Iran (May 2016) due to new necrotizing vasculitis lesions on her hands, dyspnea, bilateral crackles, and eosinophilia. During this hospital admission, while receiving methylprednisolone, low dose aspirin, and prophylactic heparin, she developed severe upper back pain and neck rigidity and in her imaging studies, thoracic spinal subdural hematoma was seen.

Conclusions: This article describes a case of EPGA presented with a non-traumatic acute subdural thoracic hematoma in addition to her classic symptoms along with limited scleroderma. This suggests that non-traumatic spontaneous acute spinal subdural hematomas should be considered in manifestations of EPGA and early recognition could be helpful for appropriate management.

Keywords

Churg-Strauss Syndrome Eosinophilic Granulomatosis with Polyangiitis Hematoma Scleroderma Spinal Subdural

Copyright © 2018, Iranian Red Crescent Medical Journal. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited

1. Introduction

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic small vessel vasculitis (1). Asthma, eosinophilia, chronic paranasal sinusitis, nasal polyposis, non-fixed pulmonary infiltrates, and myocarditis are the most common manifestations of EGPA (2). Neurologic involvement mostly involving the peripheral nervous system (PNS) is reported in 59% to 86% of patients, mainly in the form of peripheral neuropathy (3). On the contrary, central nervous system (CNS) involvement is described in less than 10% of cases (3). The most common CNS manifestations are cerebral infarction, diffuse encephalopathy, and rare cases of cerebral hemorrhages (4). Only four cases of spinal subarachnoid hemorrhage have been reported so far in association with this disease (5-8).

Acute non-traumatic spontaneous spinal subdural hematoma (SSDH) is an exceedingly uncommon condition. In some reports of subdural hematoma, blood dyscrasias and arteriovenous malformation, have been the predisposing factors (9, 10). Also, anticoagulant therapy (therapeutic doses of warfarin, dabigatran, etc.) and diseases with bleeding tendency, have been reported as risk factors for rapid spinal cord or cauda equina compression due to SSDH (11). Kreppel et al. identified 613 cases during 170 years until year 2003 (12). The classic presentation of SSDH is an acute, severe, radiating pain in the back area and then symptoms of spinal cord compression, sensorimotor deficits, and sphincter disturbance as typical clinical manifestations, which develop minutes to days later (12, 13). Physical findings could be different based on the level of spinal lesion and could be without motor or sensory loss. The spontaneous spinal subdural hematoma is very rare usually with no previous cause (14). This report describes a patient with EGPA and limited scleroderma on low dose aspirin and a prophylactic dose of low molecular weight heparin presented with non-traumatic spontaneous SSDH that has been very rare till now.

2. Case Presentation

The case was a 32-year-old female, known case of limited systemic sclerosis lasting for 12 years with presentation of sclerodactyly, Raynaud’s phenomenon, the telangiectasia, active scleroderma pattern of capillaroscopy and mild bilateral lung fibrosis and ground glass radiological features in both lower lungs. After six years, EGPA was diagnosed, presented with new onset of asthma, wheezing, eosinophilia (15%), positive p-ANCA, Esr:74, and vasculitic skin lesions with a biopsy-proven diagnosis of eosinophilic vasculitis compatible with EGPA, and the patient was admitted to the hospital due to recent necrotizing vasculitis lesions on her hands and increasing dyspnea and lung infiltration. She was on prednisolone 5 mg daily and ongoing cyclophosphamide (CTX) since one year ago due to her interstitial lung disease that was detected on her high resolution CT scan (Figure 1A); she received six doses of monthly CTX and then every three months. The last dose was 3 months ago. Another drug history of the patient was Aspirin 80 mg per day, prednisolone 5 mg per day, amlodipine 2.5 mg per day, and losartan 25 mg per day.

A, Chest high resolution computerized tomography scan showing bilateral lung infiltration and ground glass appearance; B, Thoracic MRI showing upper thoracic subdural hematoma; C, both hands’ small necrotizing palpable vasculitic lesions.
Figure 1. A, Chest high resolution computerized tomography scan showing bilateral lung infiltration and ground glass appearance; B, Thoracic MRI showing upper thoracic subdural hematoma; C, both hands’ small necrotizing palpable vasculitic lesions.

In the physical exam, she had normal vital signs apart from bilateral crackles in the lower 1/3 of lungs and multiple palpable purpuric lesions on her hands, one of which was ulcerated with the necrotizing pattern (Figure 1C). Neurologic exam was completely normal on arrival. She did not have neuropathy in her nerve study and no signs of sinusitis.

Chemistry lab tests including blood sugar, liver function, kidney function, urine analysis, and 24-hour urine protein were in the normal range.

Other clinical and laboratory tests are listed in Table 1.

Table 1. Main Clinical and Laboratory Data
VariablesOn ArrivalHematomaDischarge Day
Physical examination
weight63 kg
Height159 cm
Temperature37.2
Pulse rate78/min
Respiratory rate16/min
Blood pressure110/75
Lung examBilateral lower 1/2 of lung crackles
ExtremitiesSclerodactyly of both hands and multiple small round protruded purplish necrotizing lesions on both hands
CapillaroscopyLate scleroderma pattern
WBC, per mm3125601490013050
Eosinophil, per mm3423224430
ANA, u/mL6.3 (0 - 10)
Anti ds DNA, u/mL1.4 (0 - 18)
C3, g/L1.2 (0.89 - 1.87)
C4, g/L0.26 (0.16 - 0.38)
Anti-myeloperoxidase, u/mL2.2 (< 3.1)
Anti-proteinase 3, u/mL0.1 (< 0.4)
Anti jo1, unit2 (< 12)
Anti scl-70, unit2.4 (< 12)
Anti RO, unit2.7 (< 12)
Anti LA, unit2.5 (< 12)
Anti SMITH, unit2.8 (< 12)
Anti U1RNP, unit2.2 (< 12)
Anti B2 Glycoprotein(IgM), U/mL2.5 (< 12)
Anti B2 Glycoprotein(IgG), U/mL5.9 (< 12)
RF, IU/mLNegative
ESR, mm/hour37 (0 - 20)
CRP, mg/L12 (< 6)
PT(INR), s11.5 (1.1)
PTT, s31
Table 2. Characteristic Findings of Eosinophilic Granulomatosis with Polyangiitis Cases with Subdural Hemorrhage
Ref/ Published YearAgeSexMedications Before SSDHClinical ManifestationANCA TiterEosinophil CountTreatmentFollow-Up
1/198539FemaleSteroids and cyclophosphamideSevere back pain, paralysis of the left leg from the hip downwards; also weakness of the right leg; vibration sense was totally absent below T12Not availableNot available80 mg prednisolone and cyclophosphamideWas stable for 4 years on a low dose of prednisolone and cyclophosphamide then died with acute subarachnoid hemorrhage
2/201240FemaleHigh dose steroidUrinary incontinence and an inability to move her legs, complete paraplegiaLow titer p-ANCA150001 g of methylprednisolone intravenously for Three daysEmergency decompression laminectomy was done. After six months, she still had the paraplegia and urinary retention
3/201351FemaleNo treatment beforeBilateral hand numbness decreased grip strength and hyperreflexia in her lower extremitiesPositive (anti-MPO 40 U/mL (normal range 020 U/mL))Not availablePrednisolone and cyclophosphamideRecovered well
4/201431FemaleMethylprednisolone 1 mg/kg/Day i.v.A headache and neck stiffnessPositive p-ANCA13230Intravenous steroid (methylprednisolone 1 mg/kg/day i.v. For 6 days) and after 5 months rituximabRecovered well
5/2016 (our case)32FemaleAspirin 80, enoxaparin 40/day, prednisolone 10 mg/daySevere neck rigidity, upper thoracic painNegative4232Azathioprine, Rituximab, methylprednisolone 500Recovered well

Skin biopsy of purpuric lesions of the extremities revealed complete epidermal and superficial dermal necrosis with acute inflammatory infiltration in the superficial dermis as well as fibrinoid necrosis of the blood vessels. There was also eosinophilic infiltration in the mid dermis.

The patient’s plan was to receive an increasing dose of steroid and rituximab to be effective for her vasculitis and interstitial lung disease. After admission to the rheumatology ward of Faghihi hospital (which is a general hospital related to the Shiraz University of Medical Science in Iran with multiple special departments including specialized referral rheumatology ward that our patient was admitted in May 2016), prednisolone was increased to 10 mg per day along with omeprazole 20 mg per day for her reflux complaints, and due to Raynaud’s disease amlodipine was increased to 5 mg per day. For her vasculitic skin lesions, 50 mg azathioprine was started twice daily. Since her admission, subcutaneous 40 mg enoxaparin sodium per day was added to her medications as a prophylactic dose. Also, two doses of 250 mg IV methyl prednisolone were used for her. On the 6th day of her admission, she developed severe neck rigidity, back pain, and headache, thus enoxaparin sodium and aspirin were discontinued and a cervicothoracic MRI was performed, which revealed linear hypersignality in the central part of the thoracic cord at the level of T3-T4 to T6-T7. There was a sign of associated extramedullary intradural hematoma overlying the right side of the thoracic cord at this level, causing minimal pressure over the thoracic cord. It was about 6.5 cm in length. The diagnosis was a thoracic spinal subdural hematoma (Figure 1B). Due to a headache and neck rigidity, brain MRI was done to rule out intracranial hemorrhage (ICH); it was normal and there was no evidence of mass, hemorrhage or acute ischemic infarction.

A neurosurgical consultation was done for her and since the patient had no neurological symptoms, besides neck rigidity, no surgical therapy was recommended.

After seven days, when her headache and neck rigidity decreased, 1 gram Rituximab was prescribed and she was discharged with follow-up of a neurosurgeon and rheumatologist. During the follow-up after three weeks, her symptoms were completely relieved.

3. Discussion

Eosinophilic granulomatosis with polyangiitis is an eosinophil-rich necrotizing vasculitis of small-to-medium size blood vessels; diagnostic criteria require the presence of any four or more of the following, asthma, eosinophilia greater than 10%, neuropathy, pulmonary infiltrates, paranasal sinus abnormality, or extravascular eosinophils (2). The presentation of non-traumatic acute spinal subdural hematoma is rare, and it typically presents with sharp, intense back pain in the region of the hemorrhage (15). Most patients usually present myelopathy, including motor, sensory and autonomic dysfunctions after back pain (12). It is usually related to anticoagulation (in therapeutic doses), blood dyscrasia, spinal arteriovenous malformations, or is idiopathic (10). There has been no association between low-dose aspirin or prophylactic dose of heparin and subdural hematoma except for cases related to post-spinal anesthesia (16, 17). The current case had no history of back trauma.

In scleroderma, there is a case report for the association of renal crisis and subdural hematoma and one case of overlap syndrome and at the same time idiopathic thrombocytopenic purpura (ITP) with very low platelet, which developed spinal hematoma yet with no other associations (18, 19). Although in our case her limited scleroderma manifestations were very mild, her eosinophilic and necrotizing vasculitis was much more prominent.

In reviewing the literature, there were four cases of EGPA with the manifestation of subdural hematoma (5-8) (Table 2). All of the patients on presentation had active disease and were on a high dose of steroid treatment.

Central nervous system involvement is very rare in patients with EGPA yet can be presented as ataxia, paraplegia, optic neuritis, hemiplegia-hemiparesis, spasmodic quadriplegia, seizures, meningitis, cerebral infarction, organic psycho-syndrome, other mental changes, stroke, temporal arteritis, leptomeningeal dissemination, memory deficits, and dysarthria (20).

There are case reports of associations of this presentation with lupus. In a previous study on nine reported cases, hematomas were observed in the thoracic spine in three cases and in the cervical spine in four cases. Six of the 9 reported cases had a high level of disease activity of their systemic lupus. Vasculitis at the bleeding site was pathologically documented in three of the six active cases. However, there was one case of lupus without disease activity and in the last presented case, hematoma was presented on the ninth day of admission after receiving three methylprednisolone pulses and 15000 units of heparin therapy (21). Four cases of granulomatosis with polyangiitis (GPA) were presented with subdural hematoma of the spine as a vasculitis activity pattern of the disease, which mostly responded to cyclophosphamide and a high dose of prednisolone (22).

The patient presented symptoms on the 6th day of admission after receiving two doses of 250 mg methylprednisolone and five days of therapy with azathioprine and at the same time aspirin low dose (80 mg) and enoxaparin prophylactic dose 40 mg/day with normal coagulation profiles, and still had eosinophilia, dyspnea, and necrotizing skin lesions on both hands. After this presentation, aspirin and enoxaparin were discontinued and she received 1 gram rituximab and was discharged. On her follow-up, two weeks later, her symptoms decreased significantly.

This report presents a patient with EPGA and limited scleroderma manifestations, who was admitted with manifestations of necrotizing vasculitis and eosinophilia along with an acute subdural hematoma. Presentation of these two rare manifestations together with three previously reported cases before and multiple reports of associations with other vasculitic diseases may indicate the importance of this manifestation as a vasculitic manifestation in EPGA. However, other background causes, such as a low dose of aspirin and a low dose of heparin along with disease activity, should be considered.

3.1. Conclusion

This article describes a case of EPGA, who presented a non-traumatic acute subdural thoracic hematoma in addition to her classic symptoms along with limited scleroderma. This suggests that non-traumatic acute spinal subdural hematomas should be considered in manifestations of EPGA and early recognition could be helpful for appropriate management.

Acknowledgements

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