Eosinophilic granulomatosis with polyangiitis presenting with myositis: case based review.

Eosinophilic granulomatosis with polyangitis (EGPA) is a systemic necrotizing small-vessel vasculitis that presents heterogeneously as a multi-organ disease. EGPA evolves through three phases: (1) prodromic phase with asthma, atopy and sinusitis, (2) eosinophilic phase characterized by peripheral eosinophilia and eosinophilic infiltration without necrosis, and (3) vasculitic phase involving organ damage. EGPA often presents with asthma, mononeuritis multiplex, lung infiltrates, sinusitis and constitutional symptoms. Although myalgias are common, EGPA rarely presents with true weakness with elevated creatinine kinase (CK). We describe a rare case of a patient presenting with eosinophilic myositis, who subsequently developed fulminant EGPA. The patient's diagnosis was supported by an initial clinical presentation of weakness and elevated CK, followed by fleeting pulmonary infiltrates and mononeuritis multiplex, peripheral eosinophilia, and strongly positive myeloperoxidase anti-cytoplasmic antibody (MPO-ANCA). Muscle biopsy revealed eosinophilic myositis. The patient responded well to high-dose glucocorticoids and cyclophosphamide with improved symptoms and biochemical markers. Based on our literature review, there are only seven similar cases reported of EGPA presenting with myositis and confirmatory muscle biopsies. There is significant heterogeneity in their clinical findings, histopathology and treatments that were used. Our case report and literature review highlights the importance of recognizing myositis as an initial presenting symptom of EGPA, providing an opportunity for early diagnosis and treatment to reduce risk of further disease progression and morbidity.

Kidney transplantation for a patient with refractory childhood-onset ANCA-associated vasculitis.

A 14-year-old Japanese girl was admitted to our institution for the evaluation of renal dysfunction. Her serum creatinine was 1.1 mg/dL, proteinuria was 1.5 g/day, the urine sediment contained numerous erythrocytes per high-power field, and she was positive for myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). Proteinuria was first noted at the age of 12 years. Renal biopsy showed crescentic glomerulonephritis with slight immunoglobulin A (IgA) deposition. A diagnosis of ANCA-associated vasculitis was made. Immunosuppressive therapy was initiated, including steroid pulse therapy and intravenous cyclophosphamide pulse therapy, but hemodialysis was required after 6 years. Eight months after the patient became anuric and her MPO-ANCA titer became negative, living-related donor kidney transplantation was done from her mother. ANCA became slightly positive 2 years later, but the patient remains stable without proteinuria or hematuria at 4 years after surgery. This case suggests that kidney transplantation can be performed successfully for a patient with refractory childhood-onset ANCA-associated vasculitis, and that remission of vasculitis associated with ANCA negativity at transplantation may contribute to a better renal prognosis in this patient.

Four cases of MPO-ANCA-positive vasculitis with otitis media, and review of the literature.

Otitis media is one of the common organ injuries that appear during the course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We experienced four patients with myeloperoxidase (MPO)-ANCA-positive AAV with otitis media. All were elderly Japanese women. MPO-ANCA in our patients was reminiscent of microscopic polyangiitis (MPA), although chest computed tomography (CT) scans revealed characteristics of both granulomatosis with polyangiitis (GPA), showing bronchial lesions and nodule formation, and MPA, showing interstitial changes. Whether our cases should be classified as GPA or MPA is a matter of discussion. We detail their profiles, and review previous literature on MPO-ANCA-positive AAV with otitis media.

[A case of Churg-Strauss syndrome with short duration from the onset of asthma to diagnosis of vasculitis].

A 68-year-old woman was hospitalized because of bronchial asthma and a high myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) level. She had suffered from rhinitis from one year before hospitalization, body weight loss from three months before, and asthma from one month before. On admission, she complained of dyspnea and body weight loss of over 6 kg. On laboratory tests, high MPO-ANCA and urinary abnormalities were found. On the next day, a renal biopsy was performed and histology showed necrotizing vasculitis with cellular crescents. Churg-Strauss syndrome (CSS) was diagnosed on the basis of the clinical course and histological findings. Prednisolone therapy induced rapid symptom remission, which was achieved within one month from the onset of asthma to the diagnosis of CSS. Early diagnosis and early care led to a good prognosis.

Improvement in health-related quality of life in MPO-ANCA-associated vasculitis patients treated with cyclophosphamide plus prednisolone: an analysis of 18 months of follow-up data from the JMAAV study.

OBJECTIVES: To examine the improvement in health-related quality of life (HRQOL) in association with disease activity in myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis patients treated with cyclophosphamide plus prednisolone. METHODS: According to the Japanese Patients with MPO-ANCA-Associated Vasculitis (JMAAV) study protocol, a total of 48 patients with newly diagnosed MPO-ANCA-associated vasculitis received a standardized cyclophosphamide plus prednisolone regimen, and their clinical courses were followed for 18 months following their entry into the study. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS) 2003. HRQOL was assessed using MOS Short-Form 36 (SF-36) v2. BVAS new/worse, BVAS persistent, and SF-36 domain scores (norm-based) were calculated for the 32 eligible patients. RESULTS: The mean SF-36 domain scores were significantly lower than the Japanese general population norm. Stepwise multiple linear regression analysis showed that the presence of new or worsening features of the nervous system was significantly associated with a deterioration in physical function. During the 18 months of follow-up, there were significant improvements in BVAS new/worse and all SF-36 domains except for general health and role emotional. CONCLUSION: MPO-ANCA-associated vasculitis patients experienced a considerable deterioration in HRQOL. The standardized cyclophosphamide plus prednisolone regimen of the JMAAV study induced remission in the majority of patients, and the induction of remission accompanied a recovery in HRQOL.

[Case of MPO-ANCA-positive Wegener's granulomatosis with hepatitis C virus infection].

A 77-year-old Japanese man was referred to our hospital because of the progression of renal dysfunction. Two months prior to the admission he had been diagnosed with otitis media. Urinalysis showed proteinuria and microscopic hematuria. Blood examination revealed renal dysfunction, hepatitis C virus (HCV)infection and positive myeloperoxidase (MPO)-ANCA. A chest CT revealed small infiltrates in the right middle lobe. The renal biopsy demonstrated crescentic glomerulonephritis with tubulitis. He was diagnosed as having Wegener's granulomatosis according to the American College of Rheumatology classification criteria. Methylprednisolone pulse therapy followed by oral prednisolone improved all of the otitis media, lung infiltrates and renal function. Recently, a high prevalence of ANCA has been reported in patients with HCV. It has also been reported that the prevalence of HCV infection is high in patients with Wegener's granulomatosis. Therefore, our case points to the clinical significance of HCV infection in ANCA-associated systemic vasculitis including Wegener's granulomatosis.

Successful early introduction of mepolizumab for peripheral neuropathy with a peripheral circulatory disorder in a patient with myeloperoxidase anti-neutrophil cytoplasmic antibody-negative eosinophilic granulomatosis with polyangiitis.

A 26-year-old woman presented with abdominal pain, diarrhoea, vomiting, fever, and progressive paralysis in the lower limbs. She had a history of bronchial asthma and experienced sinusitis, progressive peripheral neuropathy, polyarthritis, and leukocytosis with prominent eosinophilia. The patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA). Abdominal pain was considered to be an ischaemic enteritis associated with EGPA. She was administered 1,000 mg/day of methylprednisolone for 3 days and intravenous immunoglobulin (400 mg/kg/day of γ-globulin for 5 days) followed by 50 mg (1 mg/kg)/day of oral prednisolone due to rapidly progressing peripheral neuropathy. Her symptoms temporarily improved; however, peripheral neuropathy recurred after a week, and the eosinophil count increased. Eighteen days after following the resumed treatment, 300 mg of mepolizumab, a humanised monoclonal antibody, was administered. Subjective symptoms, nerve conduction velocity, and skin perfusion pressure (an index of peripheral circulation in the lower extremities) improved after 4 weeks. Although mepolizumab has been approved for EGPA, there is no evidence of its efficacy against peripheral neuropathy. Early introduction of mepolizumab may contribute to an the early improved progressive peripheral neuropathy with eosinophilia.

Microscopic polyangiitis initiated with liver dysfunction, calf pain and fever of unknown origin.

We report herein a case of microscopic polyangiitis (MPA), presenting onset with a spiking fever, liver/biliary dysfunction without jaundice and calf pain without elevation of serum creatine phosphokinase. During 1 month of careful examinations for initial diagnosis, the patient developed renal dysfunction and pulmonary hemorrhage. Based on the results of positive MPO-ANCA, renal and pulmonary involvements, the patient was diagnosed with MPA and treated with high-dose prednisolone and oral cyclophosphamide. Soon after initiation of the treatment, symptoms such as fever, calf pain, liver/biliary dysfunction and renal dysfunction disappeared with decrease of MPO-ANCA titer to the normal level.

Improvement of rapidly progressive lupus nephritis associated MPO-ANCA with tacrolimus.

A 43-year-old Japanese woman with systemic lupus erythematosus (SLE) developed rapidly progressive renal failure and nephritic syndrome with a high titer of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). Methylprednisolone pulse therapy did not suppress the progression of renal failure. Intravenous cyclophosphamide pulse therapy and administration of azathioprine was abandoned due to adverse effects. Tacrolimus was employed as an alternative immunosuppressive therapy and was well tolerated, effectively preventing renal failure. Oral prednisolone dosage was successfully tapered without recurrence, along with decreasing titer of MPO-ANCA. Renal biopsy showed diffuse proliferative lupus nephritis (International Society of Nephrology/Renal Pathology Society class IV-G A/C) with crescent formation. These findings indicate that in addition to lupus nephritis, which usually results from deposition of circulating or locally formed immune complexes, MPO-ANCA may be involved in the pathogenesis of crescentic glomerulonephritis. Furthermore, we propose that tacrolimus is an effective immunosuppressant for MPO-ANCA-related renal crisis in diffuse proliferative lupus nephritis.

Development of myeloperoxidase-antineutrophil cytoplasmic antibody-associated renal vasculitis in a patient receiving treatment with anti-tumor necrosis factor-α.

We report on a 33-year-old woman who presented with positive myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) during rheumatoid arthritis treatment with infliximab. She had a history of worsening arthralgia, and urinalysis showed the new occurrence of hematuria and proteinuria. Renal biopsy showed necrotizing crescentic glomerulonephritis. Immunosuppressive therapy and discontinuation of the infliximab therapy alleviated her arthralgia and improved the urinalysis results. We report this rare case in which an anti-tumor necrosis factor-α (TNF-α) agent for ANCA-associated systemic vasculitis was studied.

A case of anti-neutrophil cytoplasmic antibody-associated vasculitis with anti-glomerular basement membrane antibodies that was successfully treated with mizoribine as a safe and effective remission maintenance therapy with prednisolone and plasma exchange.

We herein report the case of myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis with anti-glomerular basement membrane (anti-GBM) antibody positivity that successfully treated with mizoribine (MZR) as an immunosuppressive drug for remission maintenance therapy after the initiation of dialysis in addition to plasma exchange (PE) and glucocorticoid treatment to control the disease condition. A 79-year-old woman developed serious renal dysfunction and pulmonary alveolar hemorrhaging due to MPO-ANCA and anti-GBM antibody double-positive vasculitis. She was started on hemodialysis and was treated with methylprednisolone (m-PSL) pulse therapy with PE, followed by oral prednisolone (PSL). The pulmonary alveolar hemorrhaging disappeared, and both antibody titers immediately decreased but then rose again. Thus, m-PSL pulse therapy performed again in combination with combined with MZR treatment. Her poor renal function was irreversible; however, this therapy decreased both antibody titers, and they did not increase again. The patient developed pancytopenia and hyperuricemia. It was considered likely that these conditions developed in association with MZR treatment. We, therefore, measured the patient's blood concentration of MZR, and the maintenance dose was finally set at 50 mg after each dialysis session. The patient's pancytopenia and hyperuricemia improved and PSL could be smoothly tapered. This is the first case report of the use of MZR for remission maintenance therapy in a patient on hemodialysis who was positive for both ANCA and anti-GBM antibodies. The findings suggest that MZR can be used safely and effectively in such cases.

[MPO-ANCA-associated hypertrophic pachymeningitis with monoclonal gammopathy of undetermined significance: a case report].

A 66-year-old woman presented with dysesthesia over the right side of her face, hypoglossal nerve dysfunction, dysphagia, and dysgeusia of the right side. A MRI scan of the brain revealed cerebral dural thickening on the right side of the skull base, and histopathological examination revealed granulomatous inflammation of the dura. Based on paranasal sinusitis, bronchodilatation, laboratory tests showing weakly positive MPO-ANCA, intact renal function, and the patient's favorable response to steroids, we diagnosed the patient with limited granulomatosis with polyangiitis (GPA). Reportedly, autoimmune disease might occur in patients with exacerbation of monoclonal gammopathy of undetermined significance, which was observed in this case. This suggests the utility of immunoelectrophoresis.

[Case of rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibody in the course of MPO-ANCA-associated pachymeningitis].

A 56-year-old female developed rapidly progressive glomerulonephritis in the course of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated pachymeningitis that had been found four years previously. On admission, her serum creatinine increased from 0.8 mg dL to 1.84 mg dL and to 3.66 mg dL every 3 to 4 weeks. Urinalysis revealed that urinary protein excretion was 1.25 g day and 3+ hematuria. MPO-ANCA titer was found to be 50 EU and anti-glomerular basement membrane (GBM) antibody was also elevated to as high as 174 EU. Renal pathology revealed cellular to fibrocellular crescents in 21 out of 23 glomeruli with interstitial inflammation and fibrosis. Immunohistochemistry with anti IgG antibody showed linear staining along the glomerular capillary walls. Following plasma exchange and methylprednisolone pulse therapy, oral prednisolone at a dose of 50 mg day was instituted, but without significant effect. Subsequent cyclophosphamide pulse therapy was effective, resulting in the stabilization of serum creatinine at 2 mg dL and disappearance of urine abnormalities. In addition, the MPO-ANCA titer and anti-GBM antibody titer of the patient decreased to within the normal range in one month and three months, respectively. Pulmonary lesions were not found throughout the course. Recently the emergence of anti-GBM antibody-associated crescentic glomemrulonephritis in the course of MPO-ANCA-associated vasculitis has increasingly been reported. Accumulation of such cases may unravel the pathogenesis of these diseases. one month and three months, respectively. Pulmonary lesions were not found throughout the course. Recently the emergence of anti-GBM antibody-associated crescentic glomemrulonephritis in the course of MPO-ANCA-associated vasculitis has increasingly been reported. Accumulation of such cases may unravel the pathogenesis of these diseases.

Manifest interstitial and vascular pathology in anti-neutrophil cytoplasmic antibody-associated renal disease.

Rapidly progressive renal failure in anti-neutrophil cytoplasmic antibody (ANCA)- associated renal disease customarily implies crescentic glomerulonephritis with approximately 50% of the glomeruli will have crescents. The tubulointerstitial inflammation is often proportionate to the glomerular inflammation and may have granulomatous pattern adjacent to the glomeruli or an inflamed vessel. A 77-year-old male with rapidly progressive renal failure was myeloperoxidase-ANCA positive, and renal histopathology revealed thrombotic microangio-pathy, significant interstitial inflammation, interstitial granulomas, and arteritis. Pathology is unique for the paucity of the classical crescents and the myriad of extraglomerular features. His renal function improved and stabilized after induction with cyclophosphamide and maintenance with azathioprine.

[Case of ANCA associated vasculitis induced by interferon therapy for HCV infection].

A 50-year-old man with chronic HCV infection had been received the injections of 12MU of Consensus-Interferon (C-IFN) three times a week in a previous hospital. Six months later, C-IFN therapy was terminated because of fever and massive ascites. Diuretics and antibiotics had not been effective against these symptoms. In the meantime, skin symptoms of purpura and giant ulcers in the extremities developed, and he was transferred to our hospital. Because skin biopsy revealed vasculitis and serum MPO-ANCA was positive, the diagnosis of ANCA associated vasculitis was made. Methylpredonizoron pulse therapy improved skin symptoms and massive ascites, and the skin ulcers eventually disappeared. ANCA is suggested to be responsible for this rare complication.

Tacrolimus as a reinforcement therapy for a patient with MPO-ANCA-associated diffuse alveolar hemorrhage.

A 67-year-old woman, suffering from continuous hemoptysis, was admitted to our hospital where she was managed with mechanical ventilation. Computed tomography of the chest demonstrated bilateral massive alveolar hemorrhage without evidence of infectious disease. She was diagnosed with anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated diffuse alveolar hemorrhage because a high titer of MPO-ANCA was found in the serum. Plasmapheresis as well as methylprednisolone pulse therapy were initiated, followed by intravenous administration of cyclophosphamide. Tacrolimus was employed for the maintenance therapy, and the oral prednisolone dosage could successfully be tapered without recurrence, along with the decrement of the titer of MPO-ANCA.

[Case of myeloperoxidase-antineutrophil cytoplasmic antibody-associated pulmonary alveolar hemorrhage caused by propylthiouracil].

We reported the case of pulmonary alveolar hemorrhage caused by propylthiouracil (PTU) with severe respiratory failure and anemia, who improved with PTU discontinuance and steroid therapy. A 35-year-old woman presented with pyrexia, shortness of breath, and arthralgia. Her chest radiograph and CT showed diffuse ground-glass opacities, and her arterial blood gas analysis revealed severe respiratory failure. Laboratory results included a hemoglobin level of 5.2 g/dl, and a myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) level of 203 EU (normal range <9.0 EU). As bronchoalveolar lavage (BAL) fluid showed fresh blood-like fluid containing hemosiderin-laden macrophages, pulmonary alveolar hemorrhage was diagnosed. Since she had been taking PTU for 4 years, PTU was immediately discontinued. Steroid pulse therapy was performed, followed by oral prednisolone 30 mg per day, and her symptoms and chest radiograph findings rapidly improved. Based on the time-course changes, MPO-ANCA may have been involved in the development of pulmonary alveolar hemorrhage.

A case of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated hypertrophic pachymeningitis presenting with multiple cranial nerve palsies and diabetes insipidus.

A 61-year-old woman developed hearing difficulties and became thirsty after experiencing cold symptoms. A neurological examination revealed a loss of odor sensation, facial palsy, dysphasia, and dysarthria. Vocal cord palsy was observed during pharyngoscopy. Brain magnetic resonance imaging (MRI) showed a thickened pituitary stalk and swelling of the pituitary gland, but no high signal intensity regions were seen in the posterior portion of the pituitary gland. Gadolinium-enhanced MRI demonstrated a thickened dura mater over the anterior cranial fossa. A biopsy specimen of the thickened dura mater showed fibrosis, granulomatous inflammation, and necrotic foci. Blood tests detected myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA). The patient's urine osmolarity was low even though she exhibited hypernatremia. We diagnosed her with hypertrophic pachymeningitis associated with MPO-ANCA and diabetes insipidus. The patient received two courses of 5-day high-dose intravenous methylprednisolone (1.0 g/day), and was subsequently administered oral prednisolone, which gradually relieved her symptoms. However, the patient's symptoms recurred despite the high-dose prednisolone treatment. It was difficult to control the patient's symptoms in this case with oral prednisolone monotherapy, but combined treatment with cyclosporine resulted in sustained remission. It is considered that patients with MPO-ANCA-positive hypertrophic pachymeningitis require combination therapy with prednisolone and immunosuppressive agents at an early stage.