Rheumatology Rheumatol Int DOI 10.1007/s00296-016-3424-4 INTERNATIONAL CASE BASED REVIEW - CASES WITH A MESSAGE Microscopic polyangiitis complicated with bilateral brachial plexopathy: a case report and review of the literature Seyed Ahmad Naseri Alavi1 · Mohammad Meshkini1 · Tala Pourlak1 · Alireza Khabbazi1 Received: 10 October 2015 / Accepted: 5 January 2016 © Springer-Verlag Berlin Heidelberg 2016 Abstract Microscopic polyangiitis is a small-vessel necrotizing vasculitis associated with anti-neutrophil cytoplasmic antibodies and presents itself with glomerulonephritis and hemorrhagic pulmonary capillaritis. Peripheral nervous system involvement is common in anti-neutrophil cytoplasmic antibodies-associated vasculitis, but brachial plexopathy is unusual. We present the case of a 22-year-old man with known microscopic polyangiitis who was under maintenance therapy with prednisolone and cyclophosphamide and developed cough, dyspnea, and hemoptysis which increased in 6 days accompanying pain and paresthesia in the upper limbs. His physical examination revealed hypoesthesia, absence of deep tendon reflexes, and decreased muscle strength in the upper limbs. His chest computed tomography scan showed ground glass pattern in the lower and middle lobes. Electromyography and nerve conduction study showed bilateral brachial plexopathy with involvement of all of the cervical roots that were more severe in the lower roots and left side. antibodies (ANCA) and presents itself with glomerulonephritis and hemorrhagic pulmonary capillaritis. MPA can involve any organ, but the most commonly involved organs are kidneys and lungs. The involvement of joints, skin, upper airways, and peripheral nervous system is also common [1]. Renal involvement can be seen in 80–100 % of patients and present itself by rapidly progressive glomerulonephritis [1]. The hallmark pathologic finding of MPA is pauci-immune, focal, segmental and necrotizing glomerulonephritis, which causes crescent formation in 90 % of patients [1]. The classic pulmonary involvement of MPA is diffuse alveolar hemorrhage which is reported in 12–55 % of patients [2]. ANCA is not a fixed laboratory finding and can be detected in only 50–75 % of MPA patients [1]. Peripheral nervous system involvement is common in antineutrophil cytoplasmic antibodies-associated vasculitis, but brachial plexopathy is unusual. To the best of our knowledge, no report exists about brachial plexus involvement in MPA. In what follows we present a case of MPA complicated with bilateral brachial plexopathy. Keywords Microscopic polyangiitis · Vasculitis · Brachial plexopathy Case report Introduction Microscopic polyangiitis (MPA) is a small-vessel necrotizing vasculitis associated with anti-neutrophil cytoplasmic * Alireza Khabbazi dr.khabazi@gmail.com; dr_khabbazi@yahoo.com; khabbazia@tbzmed.ac.ir 1 Connective Tissue Diseases Research Center, Emam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran A 22-year-old man with known microscopic polyangiitis (MPA) was admitted with dyspnea and hemoptysis in March 2015. He had sought medical attention 18 months prior to his admission because of cough, dyspnea, and hemoptysis. Abdominal pain, bloody diarrhea, polyarthritis, and palpable purpura in the lower extremities were the other manifestations of his disease at the time. Table 1 shows his basic laboratory data. Blood cultures were negative. Echocardiography was normal. Chest CT scan showed ground glass pattern in the right middle lobe and lower lobes of lungs (Fig. 1). Bronchoscopy revealed bright hemorrhage 13 Rheumatol Int Table 1  Laboratory values of the patient Laboratory parameters Blood Hemoglobin (mg/dL) WBC (×103/μL) PLT (×103/μL) ESR (mm/h) Urine Protein Blood RBC (count/μL) WBC (count/μL) Dysmorphic RBC (%) 24-h urine protein (mg) Serum Creatinine (mg/dL) C-reactive protein (mg/dL) SGOT SGPT Albumin (g/dL) Globulin (g/dL) Electrolytes Immunological tests C-ANCA (U/mL) P-ANCA (U/mL) C3 (mg/dL) C4 (mg/dL) Cryoglobulin Other auto antibodies (RF, ANA, anti-dsDNA, anti-CCP, LA, acL, antiSSA, anti-SSB, anti-GBM) Antibody against CMV, EBV, hepatitis B, hepatitis C, and HIV viruses Normal range Baseline (January 2014) On admission (March 2015) 13–17 4–10 100–300 10–20 9.5 12.3 346 37 7.9 5.4 135 39 (−) (−) 0–3 0–3 0 100–300 2+ 2+ 12–15 5–6 60 % 1500 (−) (−) 2 0 0 126 0.8–1.2 <10 0–35 0–35 3.5–5 2.5–3.5 1.2 35 32 28 4.2 3.1 Normal 1.1 42.8 30 24 3.9 3.4 Normal <18 <18 80–120 10–40 4.2 6.3 92 34 (−) (−) 5.9 8.2 85 27 (−) (−) (−) (−) WBC white blood cells, PLT platelets, ESR erythrocyte sedimentation rate, RBC red blood cells, CRP C-reactive protein, C-ANCA cytoplasmic anti-neutrophil cytoplasmic antibody, P-ANCA perinuclear anti-neutrophil cytoplasmic antibodies, C3 complement C3, C4 complement C4, RF rheumatoid factor, ANA autoantibody to nuclear antigen, anti-dsDNA anti-double-stranded DNA, anti-CCP anti-citrullinated C peptide, LA lupus anticoagulant, acL anticardiolipin, anti-GBM anti-glomerular basement membrane, CMV cytomegalovirus, EBV Epstein–Barr virus, HIV human immunodeficiency virus, (−) negative or not detectable Fig. 1  Diffuse bilateral alveolar hemorrhage 13 in the right middle lobe and lower lobes. Broncho alveolar lavage (BAL) was performed. Microbiologic examination of BAL fluid was negative for microorganisms. BAL fluid cytology showed hemosiderin-filled macrophages. Biopsy of the skin lesions showed leukocytoclastic vasculitis (Fig. 2). He was treated with methylprednisolone pulse, plasmapheresis and prednisolone 60 mg/d and cyclophosphamide 100 mg/d. His clinical symptoms were resolved and repeated CT scan after 14 days showed resolution of ground glass pattern. He was diagnosed with MPA for the following reasons: multiorgan involvement (nephritis, alveolar hemorrhage, arthritis, enteritis, and purpura), absence of autoantibodies, ruling out of infectious diseases, and leukocytoclastic vasculitis on the skin biopsy. He was Rheumatol Int hemosiderin-laden macrophages. Microbiologic examination of his bronchial washing was negative for pathogenic organisms. Electromyography and nerve conduction study (EMG–NCV) showed bilateral brachial plexopathy with involvement of all of the cervical roots that were more severe in the lower roots and left side. After 16 days and 15 sessions of plasmapheresis, his symptoms improved and control chest CT scan demonstrated resolution of ground glass pattern. Therefore, mechanical ventilation and plasmapheresis were discontinued and he was extubated. Magnetic resonance imaging (MRI) of brain and cervical spine were normal. Finally, the patient was discharged with good pulmonary function, while he had severe hypoesthesia and weakness in the proximal and distal of both upper limbs, which were more severe in the left side, and atrophy of thenar and interosseous hand muscles. Discussion Fig. 2  Skin biopsy. a Leukocytoclastic vasculitis, b infiltration of vessel wall by fragmented neutrophils nuclei (arrow and curved arrow) followed in the vasculitis clinic of Tabriz University of Medical Sciences. He had a severe flare up of the disease presented with alveolar hemorrhage 11 months ago. Up to 6 days before the admission his disease was in remission and he was on prednisolone 10 mg/d and cyclophosphamide 100 mg/d. However, he developed cough, dyspnea, and hemoptysis which increased in 6 days and had pain and paresthesia in both upper limbs. He was admitted in the ICU. On admission, he was ill and in respiratory distress. His respiratory rate was 32, and his other vital signs were in normal range. In his chest examination, coarse crackles existed in both lung fields. Neurologic examination revealed hypoesthesia, absence of deep tendon reflexes, and decreased muscle strength in the upper limbs. Because of hypoxemia and respiratory distress, he was intubated and mechanical ventilation was started. Table 1 shows his laboratory data. His chest CT scan showed ground glass pattern in the middle and lower lobes. Bronchoscopy showed previous evidence of hemorrhage without any active bleedings in the right middle and lower lobes. Treatment with imipenem, vancomycin, methylprednisolone pulse and plasmapheresis with fresh frozen plasma was started. Methylprednisolone pulse continued for 3 days and after that prednisolone 75 mg/d was started. Cytological examination of his bronchial washing material showed multiple Nervous system is involved in 37–72 % of patients with MPA [2]. Peripheral nervous system involves more than central nervous system [2]. Mononeuritis multiplex and distal asymmetrical polyneuropathy are the main peripheral nervous system involvements [3]. Peripheral neuropathy usually occurs 2–16 months after the onset of vasculitis [4]. Brachial plexopathy presents itself with pain and paresthesia, sensory loss, weakness, and loss of tendon reflexes in the regions innervated by nerves in the C5-T1 segmental distribution. Trauma is the most common cause of brachial plexopathy [5]. Other causes of brachial plexopathy are paralytic brachial neuritis (Parsonage–Turner syndrome) [6], hereditary brachial plexopathy (hereditary neuralgic amyotrophy) [7], neoplasms especially small cell lung cancer, breast cancer, and lymphoma [8], radiation-induced brachial plexopathy [8], thoracic outlet syndrome [9], diabetes [10], and iatrogenic brachial plexopathies [5]. Rarely inflammatory and autoimmune diseases cause brachial plexopathy. Plexopathy in vasculitis was also observed, but it was an unusual symptom. To the best of our knowledge, we identified all the studies on brachial plexopathy in patients with systemic vasculitis by a systematic search and hand search of the literature and electronic databases, including MEDLINE, EMBASE and Google scholar for studies published between 1990 and December 2015. The search terms were: “brachial plexopathy” OR “brachial neuritis”, AND “vasculitis” OR “Microscopic polyangiitis”. The search resulted in 13 case reports of brachial plexopathy in systemic vasculitis. Brachial plexopathy was reported in polyarteritis nodosa, Behcet’s disease, giant cell arteritis (GCA), hypersensitivity vasculitis and HenochSchönlein purpura [12–23]. GCA is the most common vasculitis reported as a cause of brachial plexopathy. The 13 13 Behcet’s disease Yoo et al. [23] GI system gastrointestinal system Behcet’s disease Lee et al. [22] 39 38 Male Male Male 12 Henoch-Schönlein purpura Agras et al. [21] – 2 years – – – – – 3 days Female 6 weeks Female Male Female Female Male Giant cell arteritis Giant cell arteritis Giant cell arteritis Giant cell arteritis Henoch-Schönlein purpura Blaise et al. [16] Saidha et al. [17] Shapiro et al. [18] Rivest et al. [19] Yilmaz et al. [20] 2 days 7 days 18 months Disease duration before plexopathy Male – Female – Male Male Male Sex 67 59 64 53 11 73 46 Giant cell arteritis Hypersensitivity vasculitis Raz et al. [12] 78 Dierckx et al. [15] Polyarteritis nodosa Allian et al. [11] 22 66 64 Microscopic polyangiitis Naseri Alavi et al. Age (years) Chowdhry et al. [13] Giant cell arteritis London et al. [14] Giant cell arteritis Type of vasculitis References Table 2  Summary of published cases of brachial neuritis in systemic vasculitis Type of brachial neuritis Unilateral Unilateral Unilateral Bilateral Unilateral Unilateral Bilateral Unilateral Unilateral Bilateral Mucosa, skin, GI tract Unilateral Mucosa, GI tract Skin, joints, GI tract Large arteries Large arteries Large arteries Large arteries Skin, GI tract, joints, kidney Large arteries Large arteries Large arteries Small and medium Bilateral size arteries Respiratory tract, skin, Bilateral GI tract Lung, kidney, skin, GI Bilateral tract, joints Other involved organs At the course of disease At the course of disease At the course of disease Initial presentation Initial presentation Initial presentation Initial presentation At the course of disease At the course of disease Initial presentation Initial presentation At the course of disease Initial presentation At the course of disease Time of brachial neuritis Pressure of subclavian artery aneurysm Pressure of subclavian artery aneurysm Undetermined Undetermined Dissection of aorta Undetermined Undetermined Undetermined Undetermined Ischemia secondary to inflammatory thickening of the intima of the subclavian and brachial vessels Undetermined Arteritis of the epineurial vessels Undetermined Undetermined Mechanism Rheumatol Int Rheumatol Int brachial plexopathy in GCA is usually unilateral and occurs early in the course of disease. Table 2 shows the features of the described patient and the other cases of brachial plexopathy in the systemic vasculitis. The most acceptable explanation for the involvement of brachial plexus in vasculitis is ischemia of the subclavian artery or brachial vessels leading to plexus ischemia [16]. The other potential mechanism is direct pressure of arterial aneurysm on brachial plexus. To the best of our knowledge, brachial plexopathy has not been reported in MPA and other ANCAassociated vasculitis. Conclusion Peripheral nervous system involvement is common in ANCA-associated vasculitis, but brachial plexopathy is unusual. In this article, we reported a case of brachial plexopathy associated with MPA. Acknowledgments We are grateful to Dr. L. Khabbazi for editing this manuscript. Compliance with ethical standards Conflict of interest The authors declare that they have no potential conflict of interest. References 1. Chung SA, Seo P (2010) Microscopic Polyangiitis. 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