A case of microscopic polyangiitis associated with aortic valve insufficiency

Microscopic polyangiitis (MPA) is an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterized by inflammation of small-sized vessels. Although there have been some reports of ANCA-associated vasculitis presenting as aortitis syndrome, MPA rarely involves large-sized vessels such as the aorta. We report an unusual case of MPA combined with severe acute aortic valve insufficiency in a 56-year-old man. He initially presented with prolonged fever, skin rash, and rapidly progressive glomerulonephritis. P-ANCA and anti-myeloperoxidase (MPO) antibodies were positive, but the c-ANCA and anti-proteinase-3 antibodies were negative. Skin biopsy of the lower leg showed necrotizing arteritis. Kidney biopsy was also performed, which revealed diffuse necrotizing and crescentic glomerulonephritis (GN) consistent with pauci-immune ANCA-associated GN. Serial echocardiographic evaluations revealed aortic valve changes and worsening acute aortic valve insufficiency over a two-month period. Despite intensive treatment, our patient developed sudden cardiac arrest and died. Our patient demonstrated typical clinical features and histopathologic findings for systemic vasculitis and had a positive anti-MPO antibody, all of which were consistent with the diagnosis of MPA. Thus, MPA may have been the cause of acute aortic valve insufficiency in this case.     

Two patients with microscopic polyangiitis and unusual pulmonary manifestation

We encountered two patients with microscopic polyangiitis (MPA) associated with unusual pulmonary manifestations. The first patient was a 45-year-old man who had worked in amine for 3 years when he was young. On admission, chest X-rays showed long-standing silicosis and a new patchy infiltration. The second patient was a 52-year-old female. On admission, chest X-rays showed bilateral patchy infiltrations. Since then, variable patterns of patchy infiltration have waxed and waned repeatedly. The renal biopsy revealed that both patients had glomerulonephritis associated with small vessel vasculitis but with few or no immune deposits. There was neither granulomatous inflammation nor eosinophilic infiltration. Myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA) was positive in both patients. After treatment with glucocorticoids and cyclophosphamide, radiological findings were minimal and stable. These two cases show that patients with MPA have a wide spectrum of radiological findings.     

Wegener’s granulomatosis—a rare presentation

Wegener’s granulomatosis (WG) is a necrotizing granulomatous vasculitis involving the nose, paranasal sinuses, lungs, and kidneys. There are two types of WG—systemic, which is characterized by focal segmental necrotizing glomerulonephritis and limited in which the kidneys are spared. Without proper immunosuppression, WG can be aggressive and often fatal. There are very few reports on WG presenting as parotitis and lacrimal gland involvement. We report a lady who presented recurrent parotitis, focal segmental glomerulosclerosis, and orbital cellulitis, in whom the final diagnosis was revealed after an open lung biopsy.     

Microscopic polyangiitis histologically confirmed by biopsy from nasal cavity and paranasal sinuses: a case report

Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis affecting small vessels without necrotizing granulomatous inflammation and is commonly associated with necrotizing glomerulonephritis. Diagnosis is based on typical clinical features, the presence of antimyeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA), and histopathologic findings. Cases of pathologically proven small-vessel vasculitis in nasal biopsy specimens are sparse. Here we report a patient with MPA that was histopathologically confirmed by nasal and paranasal biopsy. A 67-year-old man presented with fever and general fatigue. Laboratory examinations showed severe inflammation and acute progressive renal failure. The serum MPO-ANCA level was elevated. The patient also had nasal polyps that seemed to be nonspecific chronic sinusitis. To obtain a pathologic diagnosis, bilateral ethmoidectomy and nasal polypectomy were performed. Pathological findings revealed vasculitis of small vessels in the mucosal surface. MPA was diagnosed on the basis of clinical symptoms, elevated MPO-ANCA and the pathological findings of the nasal and paranasal surgical specimen.     

The lung in systemic vasculitis

Pulmonary vasculitis is usually caused by one of three disorders: (1) Wegener's granulomatosis (WG); (2) Churg-Strauss syndrome (CSS), or allergic angiitis and granulomatosis; or (3) a nonspecific small vessel systemic necrotizing vasculitis (SNV), or microscopic polyarteritis. WG, the most common cause of lung vasculitis, has features of a granulomatous vasculitis of the upper airway and lung and widespread small vessel vasculitis involving the kidneys and other organs. The features of pulmonary WG overlap with those of malignancy and infectious granulomatous lung disease; accurate diagnosis generally requires open lung biopsy. CSS is defined by the triad of asthma, eosinophilia, and systemic vasculitis. Easily accessible tissues should be biopsied, but the clinical features are so distinctive that tissue biopsy is not invariably required for diagnosis. CSS must be differentiated from other diseases that cause pulmonary infiltrates with eosinophilia, including infections. Nonspecific SNV causes diffuse alveolar hemorrhage due to pulmonary capillaritis. Concomitant segmental necrotizing glomerulonephritis is almost always present. Diagnosis is made by renal biopsy, compatible extrarenal features, exclusion of nonimmune causes of lung hemorrhage, and exclusion of WG to the extent possible.     

Microscopic polyangiitis (microscopic polyarteritis) with late emergence of generalised Wegener's granulomatosis.

OBJECTIVES: Recent proposals for the nomenclature of systemic vasculitis have focused on a distinction between (classic) polyarteritis nodosa (PAN) and microscopic polyangiitis or polyarteritis (MPA). Thus, MPA may cause necrotising vasculitis of medium sized or small arteries but, unlike PAN, involvement of "microscopic" vessels must always be present in the former. This study aimed to show that the term "MPA" may represent a source of misinterpretation and to help illustrate difficulties of applying diagnostic criteria/definitions for conditions of unknown aetiology or variable clinical presentation and course. METHODS: Among 1250 consecutive patients screened for antineutrophil cytoplasmic antibodies (ANCA), 59 had been found to have idiopathic necrotising and crescentic glomerulonephritis plus ANCA while five had been found to have isolated pulmonary haemorrhage with biopsy verified necrotising alveolar capillaritis plus ANCA. None of these patients had clinical or histological evidence of Wegener's granulomatosis (WG) or evidence of biopsy verified vasculitis involving vessels other than glomerular or pulmonary capillaries at the time of presentation. RESULTS: Six of the 64 patients who met definition criteria for MPA at the time of initial diagnoses had entered into complete clinical remission upon appropriate corticosteroid and cyclophosphamide treatment between two weeks and three months, though subsequently (20 to 72 months; mean time: 42.3 months) developed characteristic clinical and histological features of overt WG. CONCLUSIONS: Microscopic polyangiitis/polyarteritis may be a dynamic condition with clinical and histopathological features evolving over time to other forms of small vessel vasculitis, mainly WG, thereby meaning that follow up would be necessary not only to control a given patient but also to make a final diagnosis. This follow up should be for a long time as there may be a long interval between initial presentation and subsequent development of WG lesions.     

Wegener’s granulomatosis presenting as multiple bilateral renal masses: case report and literature review

Wegener's granulomatosis (WG) is a disease of unknown etiology characterized by necrotizing granulomatous vascularitis. The upper and lower respiratory tract and kidney involvements are very common; however, its presentation as bilateral renal masses is unusual. We report a case of a 59-year-old female patient who presented with multiple bilateral renal masses. The patient presented with sinusal and ocular symptoms suggestive of WG, and positive antineutrophil cytoplasmic antibodies (c-ANCA) with an anti-PR3 pattern. Histopathologic examination of the renal biopsy specimen revealed granulomatous inflammation with vasculitis and fibrinoid necrosis. The patient management, including prednisone and cyclophosphamid, induced a marked improvement of the renal masses. This case illustrates that WG should be considered in the differential diagnosis of renal masses.     

Malignancy is increased in ANCA-associated vasculitis

OBJECTIVE: In the light of previous reports of an association between malignancy and renal vasculitis, we aimed to investigate the association of malignancy in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, either Wegener's granulomatosis (WG) or microscopic polyangiitis (MPA), and compare it with the general population and disease control groups comprising patients with systemic lupus erythematosus (SLE) or Henoch-Schonlein purpura (HSP). METHODS: A retrospective review of 200 consecutive patients with WG or MPA was performed. Malignancies preceding or concurrent with vasculitis were recorded and the incidence of malignancy was compared with those in a population of 129 patients with HSP, 333 patients with SLE and a normal population in the West Midlands of the UK. RESULTS: Twenty patients had a diagnosis of malignancy, 14 had MPA and six had WG. Patients with ANCA-associated vasculitis had an increased risk of malignancy compared with HSP patients, of whom six patients had malignancy (relative risk 0.85, confidence interval 0.69-1.05; P = 0.034), or SLE patients, of whom five patients had malignancy (relative risk 0.31, 95% confidence interval 0.14-0.7; P<0.0001). The rate of malignancy compared with an age-matched control group was increased in patients with ANCA-associated vasculitis and HSP (ANCA-associated vasculitis, relative risk 6.02, 95% confidence interval 3.72-9.74; HSP, relative risk 5.25, 95% confidence interval 2.4-11.5). The presence of ANCA was not predictive of malignancy. CONCLUSION: In conclusion, patients with ANCA-associated vasculitis have an increased risk of preceding or concurrent malignancy.     

A case of Wegener's granulomatosis with necrotizing granuloma limited to intraorbital lesions]

A patient of Wegener's granulomatosis (WG) who developed intraorbital tumor without pulmonary and renal involvement was reported. A 52-year-old male has suffered from visual disturbance and right proptosis. Administration of betamethasone resulted in a temporary relief of his symptoms. However, following the reduction of steroid dosage, severe recurrence of ocular symptom occurred and his right sight was completely lost. On admission to our hospital, there were swollen eyelids and saddle nose. The CT scan demonstrated intraorbital tumors bilaterally associated with chronic sinusitis. The repeated biopsies of nasal mucosal lesions disclosed presence of a giant cell granuloma with necrotizing vasculitis. A diagnosis of WG had been made, so intermittent high-dose intravenous cyclophosphamide therapy were initiated. The size of the bilateral intraorbital tumors reduced with continuous cyclophosphamide therapy. At the last observation during 22 months after the initiation of cytotoxic therapy, there was no evidence of clinical and radiological recurrence. Three cases of WG with intracranial tumors in our hospital showed multiple cranial nerve palsy and poor response to corticosteroid therapy. The "limited form" without renal involvement has been known as a subset of WG with a relatively good prognosis. This report suggest the existence of further limited form with intracranial granuloma as a cardinal presentation of WG. Although the extent of granulomatous lesions are limited and progression is slow, the treatment by corticosteroid alone is not sufficient and as the systems form of WG, combined therapy with cyclophosphamide appeared to be indicated.     

ANCA-associated vasculitis: diagnostic and therapeutic strategy.

Among small-vessel vasculitides, microscopic polyangiitis (MPA), Wegener's granulomatosis (WG), and allergic granulomatous angiitis (AGA) are known collectively as ANCA-associated vasculitis (AAV) because of the involvement of anti-neutrophil cytoplasmic antibodies (ANCA) as the common pathogenesis. Major target antigens of ANCA associated with vasculitis are myeloperoxidase (MPO) and proteinase 3 (PR3). MPO-ANCA is related to MPA and AGA, and PR3-ANCA is the marker antibody in WG. MPO-ANCA-associated vasculitis is more frequent in Japan, whereas PR3-ANCA-associated vasculitis is more common in Europe and USA. ANCA appears to induce vasculitis by directly activating neutrophils. Therefore, no immunoglobulins or complement components are detected in the vasculitis lesions; hence, AAV is called pauci-immune vasculitis (pauci = few/little). Untreated patients with severe AAV with multi-organ involvement have a poor prognosis, which is improved by combination therapy with cyclophosphamide and high-dose corticosteroid. Randomized controlled trials (RCT) regarding induction and maintenance of remission of AAV indicated that the rate of remission induction by the standard regimen is approximately 90% in 6 months, that maintenance of remission can be achieved with oral azathioprine as well as cyclophosphamide, and that methotrexate can be used only for non-renal mild AAV. As these data were obtained mostly in patients positive for PR3-ANCA, caution must be taken in applying these findings to Japanese patients, most of whom are positive for MPO-ANCA. A prospective study is now underway to clarify the effectiveness of the standard regimen in Japanese patients with MPO-ANCA-associated vasculitis. This article describes the diagnostic criteria and the recent evidence-based therapeutic strategy of AAV.     

Esophageal involvement in wegener's granulomatosis

Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis, renal disease, and upper and lower respiratory tract disease. Although most organ systems can be involved, gastrointestinal (GI) manifestations are notably uncommon. We describe a patient with WG whose presentation was unique for the prominence of odynophagia. Esophagoscopy revealed erosive esophagitis, which on biopsy was shown to be due to direct involvement by the underlying vasculitis. This is first antemortem documentation of esophageal disease secondary to WG. The GI manifestations of WG are reviewed.     

Systemic sclerosis associated with microscopic polyangitis presenting with high myeloperoxidase (MPO) titer and necrotizing angitis: a case report]

We herein report a case of systemic sclerosis associated with microscopic polyangitis. The patient was a 54-year-old woman, who was diagnosed to have systemic sclerosis at a hospital in 1992, but she did not receive any medical treatment. She had been suffering from pyrexia, paresthesia and muscle weakness of both lower limbs since the beginning of 2001, and was introduced to our hospital. She showed hardened skin extending from her fingers to upper arms, weakness in both lower limbs and livedo reticularis. Her laboratory test showed WBC 11, 600/microliter, CRP 6.63 mg/dl, CH 50 24 U/ml, anti Scl-70 antibody 90.1 index, and MPO-ANCA 281 EU, but no impaired renal function was recognized. Chest computed tomography showed interstitial pneumonia while necrotising vasculitis of the right sural nerve was found in a biopsy specimen. Based on these findings, we diagnosed her to have systemic sclerosis accompanied with microscopic polyangitis (MPA). She received steroid treatment after the diagnosis was made, and her symptoms and the laboratory findings thereafter immediately improved. Many cases have been reported to have ANCA positive systemic sclerosis among patients with systemic sclerosis that are complicated MPO-ANCA-related vasculitis. However, since our patient demonstrated necrotising vasculitis in a sural nerve biopsy and no evidence of an impaired renal function, we diagnosed her to have systemic sclerosis complicated with MPA instead of ANCA positive systemic sclerosis. The pathological state of this patient thus seemed to be different from that of ANCA-positive systemic sclerosis. We concluded that this patient had both systemic sclerosis and MPA. It is therefore important to note that some patients who have been reported to have ANCA-positive systemic sclerosis may also have systemic sclerosis complicated with MPA.     

A case of granuloma in the occipital lobe of a patient with Wegener’s granulomatosis

We report a case of Wegener's granulomatosis (WG) with central nervous system (CNS) involvement in a woman who complained of bilateral visual disturbance. The intracranial necrotizing granulomatous lesion was confirmed by MR imaging and brain biopsy. After high-dose oral corticosteroid treatment, not only clinical manifestations but also laboratory tests improved. Moreover, the CNS lesion completely regressed. This suggests that high-dose corticosteroid alone might be effective in treating WG with CNS involvement.     

Polyarteritis nodosa presenting with clinical and radiologic features suggestive of polymyositis

We report a patient who presented with clinical and MRI findings suggestive of polymyositis but, in whom, muscle biopsy disclosed a strikingly different diagnosis. A 65-year-old woman presented with 3-week history of bilateral proximal muscle pain and weakness. Laboratory investigations showed markedly elevated inflammatory markers and mildly elevated muscle enzymes. MRI scans of lower limbs showed features suggestive of polymyositis. However, muscle biopsy showed features of a polyarteritis-type vasculitis affecting an intramuscular blood vessel. Our reports highlight the critical role of muscle biopsy in establishing the correct diagnosis in patients with suspected myositis.     

Orbital Wegener’s granulomatosis: a case report and review of the literature

Wegener's granulomatosis (WG) is a multisystem granulomatous, necrotizing vasculitis of presumed autoimmune origin that affects small- to medium-sized blood vessels. The respiratory tract and kidneys are typically involved (Gross and Reinhold-Keller, "Clinical features of primary ANCA-associated vasculitis" in Oxford textbook of rheumatology, third edition, 2004). The limited form usually involves the head and neck, lacks renal involvement, and may not progress to generalized disease (Cassan et al., Am. J. Med. 49:366-379, 1970). Ocular involvement, which may be the initial manifestation, is often encountered and can result in significant morbidity and possibly blindness (Pakrou et al., Semin. Arthritis Rheum. 35:284-292, 2006). We report an unusual case of WG presenting as an orbital mass. The diagnostic triad of granulomatous inflammation with multinucleated giant cells, vasculitis, and necrosis was discovered on histopathology (McDonald and Edwards, JAMA 173:1205-1209, 1960).     

A case of recurrent bilateral pneumonia with fever. Diagnosis: microscopic polyangiitis

Microscopic polyangiitis (MPA) is a rare systemic disease that usually presents as a pulmonary-renal syndrome. We describe 35-year-old men who presented with hemoptysis and bilateral alveolar opacities of the upper part of both lungs. The CT scan showed alveolar and round-glass opacities with a "mosaic-like" pattern. Bronchoalveolar lavage confirmed pulmonary hemorrhage. Renal biopsy was indicated because proteinuria revealed extracapillary glomerulonephritis. Laboratory tests showed a high level of serum antimyeloperoxidase-antineutrophil cytoplasmic antibody. We made a diagnosis of MPA. Cyclophosphamide and corticosteroid therapy was instituted and remission achieved. Through this case report, we discuss the diversity of the radio-clinical features of MPA.     

Pathology of pulmonary vasculitis

There are three major vasculitis syndromes that affect the lung: Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS), and microscopic polyangiitis (MPA). The pathology of pulmonary vasculitis is complicated because it requires correlation with clinical, laboratory, and radiological features; there is overlap in some histological features among the vasculitis syndromes; biopsies early in the course of disease or after therapy may show atypical or incomplete histological features; the differential diagnosis is complex and includes infection that should not be treated with corticosteriods or immunosupressive agents; and few pathologists have much experience with these cases. Major histological features of necrosis, granulomatous inflammation, and vasculitis characterize WG. The inflammatory consolidation consists of a mixture of neutrophils, lymphocytes, plasma cells, macrophages, giant cells, and eosinophils. Necrosis may take the form of neutrophil microabscesses or geographic necrosis. Granulomas may take several forms, including scattered or loose clusters of giant cells, palisading histiocytes or giant cells lining the border of geographic necrosis or microabscesses, and palisading microgranulomas. Sarcoidal granulomas are very rare. CSS may show eosinophilic pneumonia, allergic granulomas, and eosinophilic vasculitis. Asthmatic bronchitis may also be present. Biopsies from CSS patients are rare because this syndrome is usually diagnosed clinically. Microscopic polyangiitis demonstrates neutrophilic capillaritis and diffuse alveolar hemorrhage.     

A case of Wegener's granulomatosis presenting with jaw claudication

The major manifestations of Wegener's granulomatosis have been well described. Jaw claudication has not been recognized as one of the symptoms associated with this disease. We report the first case of Wegener's granulomatosis presenting with jaw claudication. Documentation of different histological types of vasculitis producing similar symptoms broadens our concepts of systemic vasculitis and emphasizes the need for tissue biopsy for diagnosis.     

Churg–Strauss syndrome confined to calf muscles

A 42‐year‐old Caucasian man presented with spontaneous bilateral calf pain. Past history included asthma for 8 months and sinusitis for 1 month. Investigations revealed eosinophilia, raised ESR, CRP, IgE and antimyeloperoxidase antibodies. Ethmoid sinus tissue excised during otolaryngological surgery showed non‐specific mixed inflammatory infiltrate including eosinophilia. A calf muscle biopsy demonstrated vasculitis with extravascular eosinophilia. He responded promptly to treatment with prednisone which was eventually stopped after 6 months. There is no recurrence at 6‐year follow up. It is important to recognize this presentation because prompt treatment might prevent progression of localized vasculitis to more widespread and life‐threatening vasculitis.     

Microscopic polyangiitis with diffuse peribronchovascular nodular involvement: Case report

Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis that affects small vessels with no immune deposits. MPA is a rare disease. The incidence of MPA is approximately 1:100.000 per year. The etiology of this disease is unknown. Pulmonary involvement is mainly characterized with ground-glass attenuation, consolidation, thickening of bronchovascular bundles, and honeycombing on computerized tomography (CT). We report a patient with an atypical pattern of pulmonary involvement which is diffuse peribronchovascular nodular infiltration. A 59-year-old male patient presented with symptoms of shortness of breath, cough, purulent sputum, back pain and hemoptysis. Laboratory studies depicted increased serum creatinine levels, hematuria and proteinuria. His chest X-ray and CT of thorax showed bilateral diffuse peribronchovascular nodular infiltrations. Circulating myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (p-ANCA) was positive. Renal biopsy was obtained because of hematuria, proteinuria and increased creatinine level and revealed crescentic glomerulonephritis associated with small vesel vasculitis which was consistent with MPA. He was treated with corticosteroid and cyclophosphamide. At the end of two months of treatment, renal function and other pulmonary symptoms improved.