Subcutaneous Cheek Nodule Associated with Granulomatosis with Polyangiitis

We herein report an unusual case of granulomatosis with polyangiitis (GPA) in a 65-year-old man in whom relapsed disease manifested as an anterior cheek nodule. Magnetic resonance imaging indicated the differential diagnoses of the subcutaneous nodule in the patient''s anterior cheek to be inflammatory granulomatous lesions with GPA, malignancy, or infectious disease. A histopathological examination ruled out malignancy and infectious diseases, and necrotizing vasculitis was suspected. The subcutaneous nodule was successfully treated using rituximab, suggesting that it was associated with GPA, secondary to vasculitis. Clinicians should be aware of the possibility of such a rare manifestation of GPA.     

Development of Microscopic Polyangiitis in Patients with Chronic Airway Disease

Microscopic polyangiitis (MPA) is a rare systemic vasculitis syndrome, which is often accompanied by positive myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA). While pulmonary involvement of MPA consists mainly of diffuse alveolar hemorrhage and interstitial pneumonia, bronchiectasis has been reported as a pulmonary lesion in association with MPA. To investigate the clinical features of patients with MPA, focusing on the presence or the absence of preceding chronic airway diseases (CAD), we conducted a retrospective observational study of 26 patients in the last 13 years at Saga University Hospital. The clinical records and radiologic chest examinations were reviewed retrospectively. Pulmonary manifestations were alveolar hemorrhage in 3 patients (12%) and interstitial pneumonia in 5 (19%). Bronchiectasis, defined by the findings of chest radiograph and computed tomography, was found in 9 patients (35%). Four patients (15%) with bronchiectasis and one patient (4%) with chronic bronchitis had experienced chronic bronchial suppuration prior to the onset of MPA. Ten patients were classified as having chronic airway disease (CAD) before the onset of MPA. MPO-ANCA tended to be lower in the CAD group than in the non-CAD group. None of the patients in the CAD group had pulmonary hemorrhage or interstitial pneumonia. Only one patient (10%) in the CAD group died within 90 days of the onset of MPA, while 7 (43.8%) of the non-CAD group died. Our study suggests that MPA may result in part from CAD and that the clinical course of MPA with CAD may be different from MPA without CAD.     

Severe Asthma Where Eosinophilic Granulomatosis with Polyangiitis Became Apparent after the Discontinuation of Dupilumab

The use of biologic agents has enabled control of severe asthma, but there is a risk that eosinophilic granulomatosis with polyangiitis (EGPA) may be masked in some cases. We herein report a 71-year-old man who was administered dupilumab for 2 years to stabilize his asthma symptoms. A few months after discontinuation of dupilumab administration, an increase in the eosinophil count in peripheral blood, leg pain, and a rash appeared. Based on pathology, he was diagnosed with EGPA. EGPA in this case was considered to have become apparent due to the discontinuation of dupilumab administration.     

Successful Treatment with Rituximab for Granulomatosis with Polyangiitis and Multiple Cranial Neuropathies

We herein report a case of granulomatosis with polyangiitis in a 73-year-old man. He had experienced bilateral ptosis, redness of both eyes, right facial weakness, and hearing loss in the right ear for two months. Myeloperoxidase anti-neutrophil cytoplasmic antibody was positive. Corticosteroids and intravenous cyclophosphamide pulse therapy yielded a response. After the fourth pulse of cyclophosphamide, he developed headache, diplopia, restricted left eye movement, right facial palsy, and hearing loss in the right ear. A one-year remission period was achieved by increasing the steroid and rituximab doses. Rituximab was effective against the relapse of granulomatosis with polyangiitis and cranial neuropathy.     

Anti-MPO-ANCA-Positive Microscopic Polyangiitis following Subacute Bacterial Endocarditis

Although infectious agents such as Staphylococcus aureus have been implicated in the pathogenesis of Wegener’s granulomatosis, the role of bacterial infections in the pathogenesis of other types of small-vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA) is less clear. We describe a patient who developed a non-granulomatous necrotising small vessel vasculitis and perinuclear ANCA (p-ANCA) directed against myeloperoxidase (MPO) after recurrent episodes of bacterial endocarditis due to Staph. aureus. Although cytoplasmic ANCA (c-ANCA) directed against proteinase 3 have been reported in single patients with bacterial endocarditis, to our knowledge this patient is the first reported case of an anti-MPO-ANCA positive systemic vasculitis following bacterial endocarditis. Received: 2 February 2001 / Accepted: 6 June 2001     

The First Case of Eosinophilic Granulomatosis with Polyangiitis Simultaneously Demonstrating Various Clinical Manifestations with Retroperitoneal Fibrosis and Membranous Nephropathy

The first case of eosinophilic granulomatosis with polyangiitis (EGPA) simultaneously demonstrating various clinical manifestations, including retroperitoneal fibrosis (RPF) causing hydronephrosis and membranous nephropathy (MN) leading to nephrotic syndrome, is presented. There have been no previous case reports demonstrating the simultaneous onset of these three disease categories with significant complex pathologies. This case was successfully managed by providing adequate combination therapies according to each disease category, leading to complete remission (CR) of all three diseases. In conclusion, we believe this case is extremely rare and clinically suggestive, and that these findings can be applied to a future phenotype-tailored treatment strategy for EGPA.     

Plasma Exchange Therapy to Reduce Mortality in Japanese Patients With Diffuse Alveolar Hemorrhage and Microscopic Polyangiitis

Diffuse alveolar hemorrhage (DAH) is well known as a serious complication of microscopic polyangiitis (MPA). We examined the effectiveness of plasma exchange (PLEX) therapy to reduce mortality in Japanese DAH patients with MPA. This retrospective, double‐center, observational cohort study included 20 DAH patients with MPA who were admitted to Juntendo University Hospital or Juntendo Koto Geriatric Medical Center between April 1998 and March 2018. The primary outcome was non–disease‐specific mortality. The 1‐year survival rate of patients with PLEX therapy (N = 4) was higher than that of patients with conventional therapy (N = 16, 75% and 13%, respectively, P = 0.037). Higher values of the 1996 Five‐Factor Score (FFS) and 2009 FFS were associated with increased mortality, with hazard ratios of 2.29 (P = 0.040) and 2.41 (P = 0.043), respectively, by Cox univariate analysis. We investigated PLEX therapy for reducing mortality in DAH patients with MPA, and the 1996 FFS and 2009 FFS were both independent prognostic factors.     

Cerebral Infarction and Myalgia in a 75-year-old Man with Eosinophilic Granulomatosis with Polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare condition of systemic vasculitis of small to medium-sized blood vessels. We herein report the case of a 75-year-old man who presented with hemiplegia on his right side due to cerebral infarction following myalgia and a high fever. He had no history of asthma or allergic rhinitis. He was diagnosed with EGPA based on the presence of eosinophilia, sinusitis suggested by magnetic resonance imaging, and muscle pathology. His hemiplegia improved rapidly after corticosteroid therapy. This case suggests that EGPA should be a differential diagnosis of cerebral infarction with myalgia and eosinophilia.     

Eosinophilic Granulomatosis with Polyangiitis Presenting with Central Retinal Artery Occlusion During Treatment with Anti-interleukin-5 Receptor Monoclonal Antibody

Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophilic cytoplasm antibody (ANCA)-associated vasculitis characterized by asthma and eosinophilia. Although EGPA involves multiple organs, ocular involvement is infrequent and often carries a poor visual prognosis. We herein report a rare case of EGPA presenting with central retinal artery occlusion (CRAO) in which visual loss developed during treatment with anti-interleukin (IL)-5 receptor monoclonal antibody, and improvement in visual outcomes was attained after treatment combining high-dose oral corticosteroids, cyclophosphamide and an anticoagulant. Physicians should consider CRAO as an ophthalmic manifestation of EGPA in patients with severe eosinophilic asthma.     

Hypertrophic Pachymeningitis with Characteristics of Both IgG4-related Disorders and Granulomatosis with Polyangiitis

We herein report a 73-year-old man with isolated hypertrophic pachymeningitis (HP) showing serological and pathological characteristics of both IgG4-related disorders and granulomatosis with polyangiitis. The patient presented with chronic onset headaches and ophthalmalgia. Brain magnetic resonance imaging (MRI) revealed a hypertrophic enhanced dura mater. Serum IgG4 and myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) levels were elevated. A dura mater biopsy showed infiltration of numerous IgG4-positive plasma cells and granulomatous inflammation without apparent vasculitic lesions, storiform fibrosis, or obstructive phlebitis. Corticosteroid treatments improved his clinical symptoms and MRI findings. There have been reports of MPO-ANCA-positive IgG4-related HP presenting as granulomatous inflammation in the dura mater.     

Multiple Cerebral Infarctions Accompanied by Subcortical and Subarachnoid Hemorrhaging in Bilateral Border Zone Areas in a Patient with Eosinophilic Granulomatosis with Polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with peripheral neuropathy, but reports of central nervous system involvement are quite rare. We herein report a patient with EGPA first identified as having hypereosinophilia who later developed asthma, eosinophilic otitis media, sinusitis, and hemorrhagic colitis. She subsequently developed hemiparesis. Head magnetic resonance imaging revealed multiple cerebral infarctions with subcortical and subarachnoid hemorrhaging colocalized at the bilateral border zone areas. She was diagnosed with EGPA-induced stroke and successfully treated with oral prednisolone. Inflammation in the small cerebral arteries in EGPA may induce bilateral border zone infarction with colocalizing subcortical and subarachnoid hemorrhaging.     

A Young Patient with Microscopic Polyangiitis Requiring Hemodialysis with Complications of Repeated Episodes of Posterior Reversible Encephalopathy Syndrome Probably Due to Different Etiologies

A young woman with microscopic polyangiitis (MPA) requiring hemodialysis showed repeated posterior reversible encephalopathy syndrome (PRES) with spatiotemporal multiple lesions over a period of two months. The first PRES episode with confusion and the second PRES episode with vertigo and nausea were caused by MPA, hypertension and renal failure. These symptoms were improved by the reinforcement of MPA treatment and blood pressure management. The third PRES episode with nausea, headache, seizure and visual changes was induced by rituximab infusion and hypertension. The PRES was improved with blood pressure and convulsant management. These conditions are challenging to diagnose and treat.     

Clinical Significance of Neutrophil/lymphocyte Ratio in Patients With Granulomatosis With Polyangiitis

ObjectiveTo determine to neutrophil-to-lymphocyte ratio (NLR) in granulomatosis with polyangiitis (GPA) patients and to study its relation to disease manifestations and activity.MethodsThe study included 44 GPA patients and 44 matched age and sex controls. Full history taking, thorough clinical examination with more attention to ocular examination, laboratory and radiological investigations were considered. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS).ResultsThe patients (21 males and 23 females) had a mean age of 45.66 ± 7.24 years, disease duration 6.8 ± 3.6 years and BVAS 50.1 ± 14.3. All patients had a positive cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) while only 5 had a positive p-ANCA. The NLR was significantly increased in the GPA patients (5.1 ± 2.4) compared to the control (1.5 ± 0.8) (P < .0001). Ten patients with uveitis had a significantly higher NLR (6.5 ± 1.9) compared to those without (4.7 ± 2.4) (0.03) while those with proptosis (n = 10), cutaneous manifestations (n = 17) or ischemic heart disease (n = 9) had a significantly lower NLR than those without (P = .0001, P = .017 and P = .046 respectively). The NLR did not significantly correlate with any of the patients’ characteristics. The NLR inversely yet insignificantly correlated with the disease activity (r = -0.02, P = .93).ConclusionThe NLR may have a significant role in the pathogenesis of GPA, the development of uveitis or proptosis, cutaneous manifestations and ischemic heart disease. NLR may serve as a future potential companion to c-ANCA positivity in diagnosing and evaluating GPA and may play a role in the tissue-specific and clinical characteristics.     

Wegener-Granulomatose und mikroskopische Polyangiitis

Wegener’s granulomatosis (WG) and microscopic polyangiitis (MPA) are primary systemic small vessel vasculitides, associated with a positive C/PR3-ANCA in WG and P/MPO-ANCA in MPA. The most prominently involved organs are the upper (only in WG) and lower respiratory tract and the kidneys. The diagnostic work-up is an interdisciplinary approach assessing disease stage and extent. Treatment is adapted to disease stage and extent and relies on a combination of a cytotoxic plus a tapering regimen of corticosteroids. Induction of remission in “early systemic” disease can be achieved with low-dose methotrexate. In severe generalized vasculitis cyclophosphamide (CYC) is the mainstay of therapy, in rapidly progressive glomerulonephritis in combination with plasmapheresis. After 3–6 months of induction CYC is switched to a maintenance treatment with azathioprine. Alternatives are leflunomide, mycophenolate or methotrexate (creatinine < 150 µmol/l). Age ≥ 50 at diagnosis, renal dysfunction and pulmonary involvement are associated with higher mortality rates. The relapse rate is approximately 50% within 5 years, being higher in WG than MPA.     

Classification of vasculitis: From historical controversies to present day pragmatic consensus

The classification of the systemic vasculitides has been controversial for several decades. However, over the past twenty years there have been several major developments, which means that there is pragmatic consensus regarding classification. These include the American College of Rheumatology criteria first published in 1990, and the Chapel Hill Consensus Conference definitions originally promulgated in 1994, but revised and extended in 2012. More recently the classical division of the ANCA vasculitides using clinical phenotype has come under scrutiny with evidence from epidemiological, genetic and outcome studies that perhaps these conditions should be classified on the basis of ANCA specificity into PR3-ANCA positive and MPO-ANCA positive groups. There remains, however, a major need for validated classification and diagnostic criteria, a need which hopefully the DCVAS project will address.     

Granulomatosis with Polyangiitis in Childhood

Granulomatosis with polyangiitis (GPA) is a rare yet frequently organ- or life-threatening systemic vasculitis affecting small- to medium-sized arteries in multiple organs. It characteristically leads to alveolar hemorrhage and destructive, pauci-immune glomerulonephritis. GPA is also characterized by granulomas in the upper and lower respiratory tract causing erosive sinusitis and nodular or even cavitating lesions in the respiratory tract. Antineutrophil cytoplasmic antibodies, a hallmark of GPA, are likely integral to the pathogenesis and recently have become a therapeutic target. International collaborations in childhood vasculitis have led to the development and validation of childhood vasculitis classification criteria, advanced our understanding of the clinical phenotype at presentation of GPA, and improved our ability to capture disease activity and determine treatment choices. Treatment efficacy and safety data continue to be largely derived from adult GPA studies. This review focuses on the recent publications on epidemiology, pathogenesis, and treatment in childhood GPA and relevant publications from the adult GPA literature.