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Effective intravenous immunoglobulin therapy for Churg-Strauss syndrome (allergic granulomatous angiitis) complicated by neuropathy of the eighth cranial nerve: a case report

  • Yoshio Ozaki1Email author,
  • Akihiro Tanaka2,
  • Keiko Shimamoto1,
  • Hideki Amuro2,
  • Yonsu Son1,
  • Tomoki Ito2 and
  • Shosaku Nomura2
Journal of Medical Case Reports20126:310

https://doi.org/10.1186/1752-1947-6-310

Received: 9 March 2012

Accepted: 31 July 2012

Published: 18 September 2012

Abstract

Introduction

We report the case of a patient with Churg-Strauss syndrome with eighth cranial nerve palsy. Vestibulocochlear nerve palsy is extremely rare in Churg-Strauss syndrome. To the best of our knowledge, only one case of complicated neuropathy of the eighth cranial nerve has been described in a previous report presenting an aggregate calculation, but no differentiation between polyarteritis nodosa and Churg-Strauss syndrome was made. High-dose immunoglobulin was administered to our patient, and her neuropathy of the eighth cranial nerve showed improvement.

Case presentation

At the age of 46, a Japanese woman developed Churg-Strauss syndrome that later became stable with low-dose prednisolone treatment. At the age of 52, she developed sudden difficulty of hearing in her left ear, persistent severe rotary vertigo, and mononeuritis multiplex. At admission, bilateral perceptive deafness of about 80dB and eosinophilia of 4123/μL in peripheral blood were found. A diagnosis of cranial neuropathy of the eighth cranial nerve associated with exacerbated Churg-Strauss syndrome was made. Although high doses of steroid therapy alleviated the inflammatory symptoms and markers, the vertigo and bilateral hearing loss remained. Addition of a high-dose immunoglobulin finally resulted in marked alleviation of the symptoms associated with neuropathy of the eighth cranial nerve.

Conclusions

A high dose of immunoglobulin therapy shows favorable effects in neuropathy of the eighth cranial nerve, but no reports regarding its efficacy in cranial neuropathy have been published.

Keywords

Churg-Strauss syndrome Cranial neuropathy Intravenous immunoglobulin

Introduction

Churg-Strauss syndrome (CSS), also known as allergic granulomatous angiitis, is a syndrome consisting of angiitis in the systemic small vessels, bronchial asthma, eosinophilia, fever, and vasculitis of various organ systems [1]. Mononeuritis multiplex is seen in 36.1% to 71.8% of cases of CSS [25]. However, cranial neuropathy is rare in CSS, and neuropathy of the eighth cranial nerve is extremely rare. Although a case of complicated neuropathy of the eighth cranial nerve was described in a previous report presenting an aggregate calculation without differentiating between polyarteritis nodosa and CSS [6], no cases that could be definitively diagnosed as CSS have been reported.

Intravenous infusion therapy with high doses of immunoglobulin (intravenous immunoglobulin, or IVIg) has been shown to be efficacious in Kawasaki disease and idiopathic thrombocytopenia. Also, IVIg was reported to be effective in cases of new-onset CSS [7] and in pregnant women with CSS in whom immunosuppressants cannot be administered [8]. In Japan, IVIg has been approved for neuropathy of the peripheral nerves in CSS as coverage under the national health insurance scheme. Although IVIg shows favorable effects in neuropathy of the peripheral nerves, no reports regarding its efficacy in cranial neuropathy have been published. Here, we report a case of CSS complicated by neuropathy of the eighth cranial nerve in which IVIg was effective.

Case presentation

A 35-year-old Japanese woman with no notable medical or family histories developed bronchial asthma. Treatment was initiated, and the course of bronchial asthma had been favorable. After 11 years, rotary vertigo, difficulty of hearing in the right ear, and palsies of the left lower extremity and right forearm occurred. A diagnosis of CSS was made on the basis of bronchial asthma, neuropathy of the peroneal nerve and ulnar nerve, findings of angiitis by biopsy of the left sural nerve, increased eosinophil counts, and positivity for myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). The pathological conditions were alleviated by prednisolone (PSL) treatment with a tapering schedule from a dose of 1mg/kg and methyl-prednisolone pulse therapy (mPSL). Three years later, owing to another increase in MPO-ANCA and exacerbation of peripheral nerve neuropathy during PSL treatment at a dose of 10mg/day, mPSL pulse therapy was administered again and the dose of PSL was increased to 50mg/day (1mg/kg). However, because the neuropathy was not alleviated, intravenous cyclophosphamide (IVCY) pulse therapy (750mg/body) was administered six times every four weeks. The IVCY therapy stabilized our patient’s condition. Subsequently, the dose of PSL was decreased to 10mg/dL gradually.

More than three years later (when our patient was 52 years old), she was hospitalized again because of the recurrence of bilateral hearing difficulty and rotary vertigo. At admission, physical findings included a body temperature of 36.2°C, a blood pressure of 132/74mmHg, a pulse of 66 beats per minute, and a respiratory rate of 18 per minute. No abnormal cardiac sounds were noted, and mild wheezing sounds were present in the lung field. Spontaneous leftward horizontally rotary mixed nystagmus was present, and owing to strong vertigo our patient had difficulty being in a sitting position. A hearing test revealed average hearing thresholds of 86.3dB in the right ear and 78.8dB in the left ear, which indicated severe perceptive deafness (sensorineural hearing impairment). She did not have tinnitus or recruitment phenomenon. Neurological findings included neuropathies of the right ulnar, left peroneal, and right tibial nerves, and left foot drop. Chest radiography and head magnetic resonance imaging did not show any abnormalities, and examination findings included a leukocyte count of 13,300/μL, an eosinophil count of 31.0% (4123/μL), a C-reactive protein (CRP) level of 6.408mg/dL, and an MPO-ANCA of 226EU (Table 1). The results of serum cytokine measurements by the cytometric bead array method were as follows: interleukin-4 (IL-4) of 3.3pg/mL (normal is less than 1.4), IL-5 of 11pg/mL (normal is less than 1.1), IL-6 of 6.9pg/mL (normal is less than 1.6), IL-10 of 4.9pg/mL (normal is less than 0.13), IL-13 of 7.4pg/mL (normal is less than 0.6), and interferon-gamma (IFNγ) of 0.1pg/mL (normal is less than 1.8).
Table 1

Laboratory findings of the patient on admission

Parameter

Value

Normal range

White blood cell count, ×102/μL

133

35-85

Neutrophil, percentage

63.0

42.0-77.0

Basophil, percentage

0.5

0.1-2.0

Eosinophil, percentage

31.0

0.5-6.0

Lymphocyte, percentage

3.5

18.0-49

Monocyte, percentage

2.0

3.0-9.0

Red blood cell count, ×104/μL

413

370-510

Hemoglobin, g/dL

14.5

11.3-15.4

Hematocrit, percentage

41.9

34 - 46

Platelet, 104/μL

18.1

14 - 34

Glucose, mg/dL

98

60-100

Hemoglobin A1c, percentage

5.7

4.0-6.0

Sodium, mEq/L

144

138-146

Potassium, mEq/L

3.7

3.5-5.0

Chloride, mEq/L

102

100-110

Blood urea nitrogen, mg/dL

8

8-20

Creatinine, mg/dL

0.55

0.4-0.8

Uric acid, mg/dL

3.1

2.5-5.5

Calcium, mg/dL

8.8

8.5-10.3

Total protein, g/dL

6.2

6.5-8.2

Albumin, g/dL

3.9

3.8-5.0

Aspartate aminotransferase, U/L

17

13-35

Alanine aminotransferase, U/L

5

5-35

Total bilirubin, mg/dL

0.6

0.2-1.2

Alkaline phosphatase , U/L

115

107-340

γ-Glutamyl transpeptidase, U/L

36

8-45

Lactate dehydrogenase, U/L

226

112-230

Creatine kinase, U/L

36

45-165

Amylase, U/L

61

37-125

C-reactive protein, mg/dL

6.408

<0.3

IgG, mg/dL

883

870-1700

IgA, mg/dL

112

110-410

IgM, mg/dL

82

46-260

IgE, IU/mL

421

<320

MPO-ANCA, EU

226

<20

PR3-ANCA, U/mL

0

<3.5

Rheumatoid factor, IU/mL

5

<20

Anti-nuclear antibody

×20

<×40

Ig: immunoglobulin; MPO-ANCA: myeloperoxidase anti-neutorophil cytoplasmic antibody; PR3-ANCA: proteinase 3 anti-neutorophil cytoplasmic antibody.

The diagnosis was neuropathy of the eighth cranial nerve associated with exacerbation of allergic granulomatous angiitis, and mPSL pulse therapy and subsequent oral PSL at a dose of 55mg/day (1mg/kg per day) were begun. This treatment resulted in gradual alleviation of bronchial asthma, eosinophilia, CRP level, and mononeuritis multiplex but not of the foot drop. Also, the hearing difficulty and vertigo were not alleviated. Although reinforced treatment by IVCY was planned initially, our patient refused because of the severe nausea that occurred in the previous IVCY treatment. Therefore, IVIg (400mg/kg per day for five days) was combined from day 14. From around day 20, the hearing ability and foot drop began to improve gradually. On day 42, a hearing test revealed average hearing thresholds of 70.0 and 61.7dB in the right and left ears, respectively, and the vertigo had disappeared. After our patient was discharged from the hospital, the dose of PSL was decreased to 10mg/day and her condition is currently stable.

Discussion

Because the vertigo continued for a long period of time and recruitment phenomenon and tinnitus were not present, we ruled out atypical sudden deafness in our patient. Since auditory brain-stem response was not performed, the cause of her hearing loss was not identified. Her vertigo and deafness were likely the results of CSS exacerbation or late flare-up, which was evidenced by rising titers of MPO-ANCA and inflammatory markers. Thus, the presumptive diagnosis of CSS-associated cranial neuropathy involving the eighth cranial nerve was made, and the condition subsequently resolved with immunoglobulin therapy.

Conclusions

CSS accompanying cranial neuropathy is relatively rare. Guillevin et al. [9] reported that only four out of 96 CSS cases were complicated by cranial neuropathy. In the present case, the perceptive deafness with vertigo corresponded to pathological conditions of CSS, such as increased MPO-ANCA and some inflammatory markers and exacerbated neuropathy of the peripheral nerves. With regard to serum cytokine concentrations in CSS, increases in Th2 cytokines IL-4 [10], IL-5 [11], IL-10 [12], and IL-13 [10, , 13] have been reported, although there are reports showing no apparent increases in IL-4 [13], IL-5, and IL-10 [10]. In the present case, increases in serum level of inflammatory cytokine IL-6 and IL-4, IL-5, IL-10, and IL-13, but not Th1 cytokine IFNγ, were found.

As a disease complicated by angiitis and perceptive deafness, Cogan syndrome in aortitis syndrome is well known. However, the pathogenesis of perceptive deafness with Cogan syndrome remains unclear. Meanwhile, the etiology of neuropathies in CSS has been suggested to be involved in damage by feeding vessels of the peripheral nerves.

It is speculated that the effect of IVIg is due to the blockade of Fc receptors, adjustment of complement activities with idiotype network [14], or inhibition of damage to myelin or axons as an antigen [15]. In the present case, as for mononeuritis multiplex of the sensory nerves, mPSL pulse therapy was effective. The foot drop as a neuropathy of the motor nerve and the neuropathy of the eighth cranial nerve were resistant to the mPSL pulse therapy but were alleviated after administration of IVIg. We inferred that the effects of steroids were enhanced through some active mechanisms of IVIg as speculated above. Given our present case, IVIg could possibly be a useful treatment for cranial neuropathy associated with CSS and should be taken into consideration for cases in which the effects of mPSL pulse therapy are insufficient or administration of immunosuppressants is difficult.

Consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Abbreviations

CRP: 

C-reactive protein

CSS: 

Churg-Strauss syndrome

IFNγ: 

interferon-gamma

IL: 

interleukin

IVCY: 

intravenous cyclophosphamide

IVIg: 

intravenous immunoglobulin

MPO-ANCA: 

myeloperoxidase anti-neutrophil cytoplasmic antibody

mPSL: 

methyl-prednisolone pulse therapy

PSL: 

prednisolone.

Declarations

Acknowledgments

We are grateful to Kohei Kawamoto for his cooperation and advice.

Authors’ Affiliations

(1)
Department of Rheumatology and Clinical Immunology, Kansai Medical University Hirakata Hospital
(2)
First Department of Internal Medicine, Kansai Medical University

References

  1. Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, Calabrese LH, Edworthy SM, Fauci AS, Leavitt RY: The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990, 33: 1094-1100.View ArticlePubMedGoogle Scholar
  2. Sehgal M, Swanson JW, DeRemee RA, Colby TV: Neurologic manifestations of Churg-Strauss syndrome. Mayo Clin Proc. 1995, 70: 337-341. 10.4065/70.4.337.View ArticlePubMedGoogle Scholar
  3. Hattori N, Ichimura M, Nagamatsu M, Li M, Yamamoto K, Kumazawa K, Mitsuma T, Sobue G: Clinicopathological features of Churg-Strauss syndrome-associated neuropathy. Brain. 1999, 122: 427-439. 10.1093/brain/122.3.427.View ArticlePubMedGoogle Scholar
  4. Cattaneo L, Chierici E, Pavone L, Grasselli C, Manganelli P, Buzio C, Pavesi G: Peripheral neuropathy in Wegener's granulomatosis, Churg-Strauss syndrome and microscopic polyangiitis. J Neurol Neurosurg Psychiatry. 2007, 78: 1119-1123. 10.1136/jnnp.2006.111013.View ArticlePubMedPubMed CentralGoogle Scholar
  5. Hattori N, Mori K, Misu K, Koike H, Ichimura M, Sobue G: Mortality and morbidity in peripheral neuropathy associated Churg-Strauss syndrome and microscopic polyangiitis. J Rheumatol. 2002, 29: 1408-1414.PubMedGoogle Scholar
  6. Guillevin L, Le Thi Huong D, Godeau P, Jais P, Wechsler B: Clinical findings and prognosis of polyarteritis nodosa and Churg-Strauss angiitis: a study in 165 patients. Br J Rheumatol. 1988, 27: 258-264. 10.1093/rheumatology/27.4.258.View ArticlePubMedGoogle Scholar
  7. Danieli MG, Cappelli M, Malcangi G, Logullo F, Salvi A, Danieli G: Long term effectiveness of intravenous immunoglobulin in Churg-Strauss syndrome. Ann Rheum Dis. 2004, 63: 1649-1654. 10.1136/ard.2003.015453.View ArticlePubMedPubMed CentralGoogle Scholar
  8. Hot A, Perard L, Coppere B, Simon M, Bouhour F, Ninet J: Marked improvement of Churg-Strauss vasculitis with intravenous gamma globulins during pregnancy. Clin Rheumatol. 2007, 26: 2149-2151. 10.1007/s10067-007-0628-8.View ArticlePubMedGoogle Scholar
  9. Guillevin L, Cohen P, Gayraud M, Lhote F, Jarrousse B, Casassus P: Churg-Strauss syndrome. Clinical study and long-term follow-up of 96 patients. Medicine (Baltimore). 1999, 78: 26-37. 10.1097/00005792-199901000-00003.View ArticleGoogle Scholar
  10. Kiene M, Csernok E, Müller A, Metzler C, Trabandt A, Gross WL: Elevated interleukin-4 and interleukin-13 production by T cell lines from patients with Churg-Strauss syndrome. Arthritis Rheum. 2001, 44: 469-473. 10.1002/1529-0131(200102)44:2<469::AID-ANR66>3.0.CO;2-0.View ArticlePubMedGoogle Scholar
  11. Tsukadaira A, Okubo Y, Kitano K, Horie S, Momose T, Takashi S, Suzuki J, Isobe M, Sekiguchi M: Eosinophil active cytokines and surface analysis of eosinophils in Churg-Strauss syndrome. Allergy Asthma Proc. 1999, 20: 39-44. 10.2500/108854199778681486.View ArticlePubMedGoogle Scholar
  12. Schönermarck U, Csernok E, Trabandt A, Hansen H, Gross WL: Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA-associated vasculitides. Clin Exp Rheumatol. 2000, 18: 457-463.PubMedGoogle Scholar
  13. Kurosawa M, Nakagami R, Morioka J, Inamura H, Mizushima Y, Sugawara N, Yamashita T, Yokoseki T, Kitamura S, Omura Y, Shibata M, Chihara J: Interleukins in Churg-Strauss syndrome. Allergy. 2000, 55: 785-787. 10.1034/j.1398-9995.2000.00720.x.View ArticlePubMedGoogle Scholar
  14. Levy Y, Sherer Y, George J, Langevitz P, Ahmed A, Bar-Dayan Y, Fabbrizzi F, Terryberry J, Peter J, Shoenfeld Y: Serologic and clinical response to treatment of systemic vasculitis and associated autoimmune disease with intravenous immunoglobulin. Int Arch Allergy Immunol. 1999, 119: 231-238. 10.1159/000024199.View ArticlePubMedGoogle Scholar
  15. Dalakas MC: Mechanisms of action of IVIg and therapeutic considerations in the treatment of acute and chronic demyelinating neuropathies. Neurology. 2002, 59 (Suppl 6): S13-S21.View ArticlePubMedGoogle Scholar

Copyright

© Ozaki et al.; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.