Eosinophilic Granulomatosis with Polyangiitis Manifested by Cholecystitis and Mononeuritis Multiplex: A Case Report.
Eosinophilic granulomatosis with polyangiitis or Churg--Strauss syndrome (CSS) is a systemic vasculitis characterized by bronchial asthma, hypereosinophilia, and systemic vasculitis. (1) The prevalence of this disorder is estimated at 10.7 to 13 cases per million. (2) The histopathological features include necrotizing vasculitis in both veins and arteries with eosinophilic infiltration in the vessels and the surrounding tissues. In up to 50% of the patients, gastrointestinal involvement may occur with such symptoms as abdominal pain, vomiting, and diarrhea. (3) Gallbladder involvement is a very rare comorbid condition in CSS. (4,5) There are some reports of acute cholecystitis alone or in combination with other manifestations in this disorder. (4-11) We herein introduce a patient suffering from CSS with cholecystitis and peripheral neuropathy, treated with cholecystectomy and carpal tunnel syndrome surgery.
A 50-year-old woman referred to a rheumatologist with a complaint of hand deformity and difficulty in walking, in August 2016. The patient had suffered from bronchial asthma and sinusitis for the previous 8 years. Eight months earlier, she was evaluated for abdominal pain via sonography and magnetic resonance cholangiopancreatography, and a dilated gallbladder with thickened walls was detected. The lab data at the time included while blood cells of 20100 (26.9% eosinophil), erythrocyte sedimentation rate of 104 mm/h, C-reactive protein of 32 mg/L (up to 10), alkaline phosphatase of 599 IU/L (up to 306), and gamma-glutamyl transferase of 75 U/L (up to 32). A diagnosis of acalculous cholecystitis was made, and she underwent a cholecystectomy. The gallbladder biopsy specimen showed mild flattening and sloughing of the mucosal folding with marked eosinophilic, neutrophilic, and lymphoplasmacytic infiltration in the stroma. Eosinophils filled the blood vessels and infiltrated across the wall (figure 1).
Two months later, left-hand surgery was done for carpal tunnel syndrome. Despite releasing the median nerve, the atrophy and disability of the left hand progressed and difficulty in walking was added because of right-foot pes cavus.
Physical examination was negative for rash, lymphadenopathy, crackle over both lung fields, and cardiac murmurs. Her abdomen was soft and flat, and the scar of the cholecystectomy could be seen. On neurological examination, the patient was alert and oriented with normal cranial nerve functions. Atrophy of the interosseous muscles was found in both hands, with more severity in the left hand and the right foot (figure 2). The laboratory tests are shown in table 1.
Electrodiagnostic study showed confluent sensory motor axonal mononeuropathy multiplex. Echocardiography demonstrated normal chamber size and left ventricular ejection fraction. Lung computed tomography (CT) scan showed patchy ground-glass opacity with a mosaic pattern. CT scan of the abdomen and pelvis did not show any pathological findings in the liver, pancreas, gastrointestinal tract, and colon. Sural nerve biopsy demonstrated mononuclear cell infiltration, especially around the vessels and the perineurium.
On the basis of her clinical features, including history of sinusitis and bronchial asthma, pulmonary infiltration, eosinophilia, and mononeuropathy multiplex, as well as her histopathological findings of eosinophilic vasculitis, a diagnosis of CSS was established.
Treatment was started with 60 mg of prednisolone daily and because of rapid neurological deterioration, cyclophosphamide (1000 mg monthly) was added to the glucocorticoid.
Two weeks later, she noted significant improvements in the upper and lower respiratory tract symptoms, including mucopurulent drainage and nasal obstruction. Leukocytosis and acute-phase reactants also declined. Informed consent was obtained from the patient for the publication of this case report and the accompanying images.
CSS is a small-vessel vasculitis with different manifestations in the upper and lower respiratory system, skin, nervous system, heart, kidney, and gastrointestinal system. (12) The gastrointestinal manifestations of CSS include gastroenteritis, ileal or colonic ulcers with subsequent bleeding, ischemia, and perforation. Cholecystitis is a rare manifestation of CSS. (4,5) In this patient, eosinophilic infiltration of the gallbladder wall and blood vessels helped us diagnose cholecystitis.
The classification criteria for CSS comprise asthma, eosinophilia (>10% on differential), mononeuropathy, non-fixed pulmonary infiltrates, paranasal sinusitis, and biopsy containing a blood vessel with extravascular eosinophils. The presence of 4 or more of these 6 criteria yields a sensitivity of 85% and a specificity of 99.7%. (1) Our patient exhibited all the described features.
Coarse granular and perinuclear antineutrophil cytoplasmic antibodies (ANCAs) can be detected in 38% to 50% of the patients. (6) There are some hypotheses about the existence of 2 types of CSS based on the presence or absence of ANCAs. Renal involvement, neuropathy, alveolar hemorrhage, and vasculitis with purpura are the predominant manifestations in ANCA-positive patients, while cardiac and pulmonary involvements are the predominant complaints in ANCA-negative patients. (12) In this case, C- and P-ANCA, anti-proteinase 3 (anti PR3), and anti-myeloperoxidase (anti MPO) were negative similar to some other cases (table 2).
Limited, non-severe CSS can initially be treated with glucocorticoids alone; nonetheless, patients with life-threatening manifestations and/or major organ involvement should receive a combination of glucocorticoids and an immunosuppressant, mainly cyclophosphamide. (13) In this case, cyclophosphamide was added because of gastrointestinal involvement and progressive and disabling confluent mononeuritis multiplex.
This case highlights a common surgical presentation resulting from a much less common systemic disorder. Surgeons should be aware that the gastrointestinal and neurological manifestations of CSS can occur. Marked peripheral eosinophilia, especially in patients with asthma, should alert the clinician to the possibility of this rare disorder.
The authors wish to acknowledge the patient and her family, whose cooperation aided in the completion of this study.
Conflict of Interest: None declared.
(1.) Masi AT, Hunder GG, Lie JT, Michel BA, Bloch DA, Arend WP, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990;33:1094-100. PubMed PMID: 2202307.
(2.) Mouthon L, Dunogue B, Guillevin L. Diagnosis and classification of eosinophilic granulomatosis with polyangiitis (formerly named Churg-Strauss syndrome). J Autoimmun. 2014;48-49:99-103. doi: 10.1016/j.jaut.2014.01.018. PubMed PMID: 24530234.
(3.) Franco DL, Ruff K, Mertz L, Lam-Himlin DM, Heigh R. Eosinophilic granulomatosis with polyangiitis and diffuse gastrointestinal involvement. Case Rep Gastroenterol. 2014;8:329-36. doi: 10.1159/000369129. PubMed PMID: 25473392; PubMed Central PMCID: PMCPMC4250003.
(4.) Ye L, Lu X, Xue J. Eosinophilic granulomatosis with polyangiitis complicated by cholecystitis: A case report and review of the literature. Clin Rheumatol. 2016;35:259-63. doi: 10.1007/s10067-014-2521-6. PubMed PMID: 24515868.
(5.) Tatsukawa H, Nagano S, Umeno Y, Oribe M. Churg-strauss syndrome with cholecystitis and renal involvement. Intern Med. 2003;42:893-6. PubMed PMID: 14518684.
(6.) Francescutti V, Ellis AK, Bourgeois JM, Ward C. Acute acalculous cholecystitis: An unusual presenting feature of Churg-Strauss vasculitis. Can J Surg. 2008;51:E129-30. PubMed PMID: 19057725; PubMed Central PMCID: PMCPMC2592564.
(7.) Lenders G, Goethals M, Verstreken S, Dierckx R, Vanderheyden M. Acalculous cholecystitis and tamponade: An unusual combination? Acta Cardiol. 2011;66:383-5. doi: 10.2143/AC.66.3.2114142. PubMed PMID: 21744712.
(8.) Nishie M, Tomiyama M, Kamijo M, Kannari K, Tanosaki M, Baba M, et al. Acute cholecystitis and duodenitis associated with Churg-Strauss syndrome. Hepatogastroenterology. 2003;50:998-1002. PubMed PMID: 12845966.
(9.) Sironen RK, Seppa A, Kosma VM, Kuopio T. Churg-Strauss syndrome manifested by appendicitis, cholecystitis and superficial micronodular liver lesions--an unusual clinicopathological presentation. J Clin Pathol. 2010;63:848-50. doi: 10.1136/jcp.2010.078279. PubMed PMID: 20671044.
(10.) Suzuki M, Nabeshima K, Miyazaki M, Yoshimura H, Tagawa S, Shiraki K. Churg-Strauss syndrome complicated by colon erosion, acalculous cholecystitis and liver abscesses. World J Gastroenterol. 2005;11:5248-50. PubMed PMID: 16127765; PubMed Central PMCID: PMCPMC4320408.
(11.) Yuksel I, Ataseven H, Basar O, Koklu S, Ertugrul I, Ibis M, et al. Churg-Strauss syndrome associated with acalculous cholecystitis and liver involvement. Acta Gastroenterol Belg. 2008;71:330-2. PubMed PMID: 19198581.
(12.) Sinico RA, Di Toma L, Maggiore U, Bottero P, Radice A, Tosoni C, et al. Prevalence and clinical significance of antineutrophil cytoplasmic antibodies in Churg-Strauss syndrome. Arthritis Rheum. 2005;52:2926-35. doi: 10.1002/art.21250. PubMed PMID: 16142760.
(13.) Pagnoux C, Groh M. Optimal therapy and prospects for new medicines in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Expert Rev Clin Immunol. 2016;12:1059-67. doi: 10.1080/1744666X.2016.1191352. PubMed PMID: 27191665.
Maryam Mobini (1), MD;
Hamed Cheraghmakani (2), MD;
Zhila Torabizadeh (3), MD;
Omid Emadian (3), MD;
Fatemeh Nezhadi Kelarijani (4), MD
(1) Diabetes Research Center, Department of Internal Medicine, Mazandaran University of Medical Sciences, Sari, Iran;
(2) Department of Neurology, Bu Ali Sina Hospital, Mazandaran University of Medical Sciences, Sari, Iran;
(3) Department of Pathology, Mazandaran University of Medical Sciences, Sari, Iran;
(4) Resident in Internal Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Correspondence: Maryam Mobini, MD; Diabetes Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Tel: +98 11 33350672
Fax: +98 11 33264044
Received: 02 January 2017
Accepted: 05 February 2017
* Churg--Strauss syndrome (CSS) is a systemic disorder characterized by bronchial asthma, hypereosinophilia, and systemic vasculitis.
* Gallbladder involvement is a very rare comorbid condition in CSS. There are some reports of acute cholecystitis alone or in combination with other manifestations in this disorder.
* This case highlights a common surgical presentation resulting from a much less common systemic disorder.
* Surgeons should be aware that gastrointestinal and neurological manifestations of CSS can occur and marked peripheral eosinophilia, especially in patients with asthma, should alert the clinician to the possibility of this rare disorder.
Table 1: Laboratory test results of the patient Laboratory tests Results CBC WBC: 14250 (45.2% eosinophil), Hg: 12.1, Plt: 402000 Acute-phase reactants ESR: 42 mm/h, CRP: 3 mg/L (up to 10) Biochemical tests FBS: 100 mg/dL, creatinine: 0.7 mg/dL, ALT: 13 IU/L, ALP: 185 IU/L, calcium: 9.7 mg/dL Rheumatologic tests: result and (normal range) ANA: 1/100 (up to 1/100), anti-dsDNA: 10 IU/mL (up to 100), anti Ro: 0.22 (up to 1.1), anti La: 0.3 (up to 1.1), C3: 105 mg/dL (90-80), C4: 30 mg/dL (10-40), CH50: 39 units (23-46), ACE level: 43 U/L (8-65), C-ANCA: 1 U/mL (up to 10), P-ANCA: 1.3 U/mL (up to 5), anti MPO: 2.7 RU/mL (up to 20), anti PR3: 3.6 RU/mL (up to 20), IgE: 49.8 KIU/L (up to 150) Urine analysis 4-5 WBC, 0-1 RBC, protein of 24 h urine: 32 (up to 150) Stool examination WBC and RBC: many, negative for ova or cyst of parasites Endocrinology: result FBS: 100, HgA1C: 5.6, TSH: 6.75 mIU/L and (normal range) (0.5-5.5) Virology HBs Ag (ECLIA): Neg, HCV Ab (ELISA): Neg Table 2: Summary of the case reports on cholecystitis in Churg--Strauss syndrome Author Age/Sex Asthma Eosinophilia Mononeuritis (Reference (% or/[mm.sup.3]) No) Tatsukawa (5) 50/F + 35% + Nishie (8) 36/M - 17000 + Suzuki (10) 21/F + 56% - Yuksel (11) 65/M - 39% - Francescutti (6) 38/F + 12000 - Lenders (7) 31/F + 8300 - Ye (4) 49/M - 57.2% + Curent case 50/F + 45.2% + Author ANCA Other Treatment (Reference test manifestations No) Tatsukawa (5) Anti MPO Glomerulonephritis Prednisolone Nishie (8) Duodenitis Prednisolone Suzuki (10) - Liver abscess Prednisolone Yuksel (11) Active interface Prednisolone hepatitis Francescutti (6) - - Prednisolone Lenders (7) - Cardiac Prednisolone tamponade Ye (4) - Gastric ulcers Prednisolone Curent case - - Prednisolone and cyclophosphamide
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||Case Report|
|Author:||Mobini, Maryam; Cheraghmakani, Hamed; Torabizadeh, Zhila; Emadian, Omid; Kelarijani, Fatemeh Nezhadi|
|Publication:||Iranian Journal of Medical Sciences|
|Article Type:||Case study|
|Date:||May 1, 2018|
|Previous Article:||Neonatal Presentation of Unremitting Inflammatory Bowel Disease.|
|Next Article:||Masson's Hemangioma of the Urethra: A Case Report.|