RESUMEN

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises a spectrum of autoimmune diseases, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Studies have shown that avacopan and mepolizumab are promising therapeutics for partial or complete replacement of glucocorticoids (GC), with sustained remission while completely weaning off GC. Avacopan inhibits C5aR in the complement pathway, preventing neutrophil migration, while mepolizumab targets IL-5R, reducing eosinophil activity. Additionally, complement inhibition has not only contributed to the recovery of renal function and alleviation of physical symptoms but has also enhanced patients' overall quality of life and mental well-being. This systematic review explores the pathogenesis of AAV, traditional treatments, and the potential of emerging complement and interleukin antagonist therapies such as avacopan and mepolizumab in revolutionizing AAV management.

RESUMEN

Disease manifestations of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a small vessel vasculitis with multisystemic effects, include respiratory, renal, nervous, gastrointestinal, and skin implications. Muscle weakness and inflammatory myopathy are rare manifestations of AAV. We report the case of a 77-year-old female with a medical history of hypothyroidism and osteoarthritis who presented with a two-month history of worsening muscle weakness (mainly proximal). She endorsed dysphagia, a 40-lb unintentional weight loss, and persistent sinusitis with middle ear effusions, requiring bilateral tympanostomy. The physical examination was notable for 2/5 muscle strength in her hip flexors and extensors, with 4/5 strength in other extremities. Lower extremity MRI showed diffuse intramuscular edema between fat planes and intramuscular septal regions. Erythrocyte sedimentation rate (70 mm/hr), C-reactive protein (141 mg/L), creatine kinase (690 U/L), and anti-myeloperoxidase (MPO) antibodies (>999 AU/mL) were elevated. A thigh biopsy revealed fibrinoid necrosis of small intramuscular arteries, confluent circumferential granulomatous vessel wall inflammation, and associated mild chronic inflammation, including occasional eosinophils and a few plasma cells. She was diagnosed with MPO-positive AAV. The patient was started on high-dose steroids (prednisone), with a taper on a disease-modifying agent, azathioprine, with significant improvement in symptoms over the next four months and complete resolution at 16-month follow-up. This patient's clinical presentation of predominant lower extremity weakness due to inflammatory myositis is an unusual manifestation of AAV. Clinicians should keep a broad differential diagnosis and consider the possibility of AAV, especially in cases of muscle weakness presenting as inflammatory myositis, in the absence of other clinical manifestations of systemic vasculitis or specific myositis serologies.

RESUMEN

Antineutrophil cytoplasmic antibody-related vasculitis (AAV), is a group of diseases marked by systemic symptoms and severe small vessel inflammation. The three subtypes of AAV are eosinophilic GPA (EGPA), Microscopic Polyangiitis (MPA), and Granulomatosis with Polyangiitis (GPA). The organs that get involved in the disease process are the kidneys and the upper and lower respiratory tracts, with a spectrum of neurological manifestations. Here, we present a case report of a 68-year-old man who came with complaints of tingling and numbness over bilateral lower limbs for two months accompanied by difficulty in walking and bilateral foot drop without any respiratory complaints or involvement of sensory or autonomic system who was diagnosed with AAV (c-ANCA +) on further workup. A sural Nerve biopsy was done for confirmation which was suggestive of chronic, asymmetrical axonal neuropathy with perivascular inflammation, suggestive of vasculitic neuropathy. The patient had no other organ involvement. The patient was started on glucocorticoids and cyclophosphamide therapy for 6 cycles after which his symptoms and quality of life improved drastically.

RESUMEN

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic necrotizing vasculitis that affects small to medium-sized vessels. We describe two cases of patulous Eustachian tube (PET) in patients with otitis media with ANCA-associated vasculitis (OMAAV). The two cases presented in this paper had previously been diagnosed with Eustachian tube (ET) stenosis, and both presented with bilateral aural fullness, with one also experiencing postnasal drip and hearing loss. Both patients experienced positive myeloperoxidase (MPO)-ANCA and negative proteinase 3 (PR3)-ANCA, and treatment for ANCA-associated vasculitis (AAV) resulted in a diagnosis of PET. The patients were treated with transnasal self-installation of physiological saline into the pharyngeal orifice of the ET. This paper highlights the importance of considering PET in the differential diagnosis of OMAAV patients presenting with aural fullness.

RESUMEN

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotizing vasculitis accompanied by granulomas and eosinophilic inflammation, exhibiting marked peripheral blood eosinophiliaandasthma. Neuropathy is a difficult-to-treat common manifestation that frequently remains after achieving clinical remission with current therapy in a subpopulation of patients with EGPA with or without life-threatening organ involvement. Refractory neuropathy regularly reduces the quality of life and requires glucocorticoids (GCs) and/or immunosuppressants for a long time. Long-term immunosuppressive therapy is a factor associated with a high risk of adverse effects. Mepolizumab, at three times the dose for severe asthma, provides benefits to induce the remission of relapsing or refractory EGPA and to reduce the doses of GC. Here, we present a case of EGPA successfully treated with mepolizumab at the reference dose for severe asthma. In this case, mepolizumab resolved peripheral neuropathy resistant to corticosteroids, immunosuppressants, and intravenous immunoglobulin and contributed to the improvement of comorbid chronic pulmonary aspergillosis during GC dose reduction.

RESUMEN

Peripheral neuropathy is a common manifestation of Eosinophilic Granulomatosis with Polyangiitis (EGPA), a rare autoimmune disorder caused by eosinophilic infiltration of multiple organs including the nervous system. Recent research has shown an association between myelin oligodendrocyte glycoprotein (MOG) antibodies and various neurologic conditions. We present a unique case of EGPA with positive MOG antibodies in the cerebrospinal fluid (CSF) in a patient presenting with peripheral neuropathy. We also highlight a few diagnostic dilemmas with EGPA and the importance of early diagnosis and appropriate treatment. Clinical, laboratory, radiological, and electrophysiologic findings are discussed.

RESUMEN

Granulomatosis with polyangiitis (GPA), formerly Wegener's granulomatosis, is a small- and medium-vessel vasculitis with characteristic cutaneous morphologic presentation and systemic involvement. Most patients have palpable purpura at some point in their disease course, but this is not always the presenting manifestation. This autoimmune disorder can affect a range of organs, with the upper and lower respiratory tract, kidneys, and nervous system being commonly implicated, while gastrointestinal and cardiac involvement is less frequent. This is a 44-year-old female presenting to the emergency department (ED) with polyarthralgia and palpable purpura. Palpable purpura was distributed on the oral palate, elbow, and lower back, and a punch biopsy revealed leukocytoclastic vasculitis (LCV). While this was an atypical distribution for leukocytoclastic vasculitis, the skin biopsy provided the necessary evidence to diagnose GPA. This case characterizes non-specific and atypical signs and symptoms of GPA that all providers should be aware of in order to diagnose the condition early in its disease course.

RESUMEN

We describe a rare case of concurrent eosinophilic granulomatosis with polyangiitis and mixed connective tissue disease in a 27-year-old man who presented with pulmonary, renal, cardiac, and skin manifestations. We confirmed the diagnosis based on clinical, histopathological, and serological criteria. We treated the patient with corticosteroids, methotrexate, cyclophosphamide, and hydroxychloroquine, achieving early remission. The coexistence of both conditions in the same patient is extremely rare and has only been reported in a few cases worldwide. We also review the literature on these two rare autoimmune diseases' coexistence, pathogenesis, diagnosis, and management. Our case emphasizes recognizing overlapping autoimmune conditions in patients with complex clinical features and employing a comprehensive diagnostic approach and tailored treatment strategies. Further research is needed to understand these patients' epidemiology, prognosis, and optimal therapy. Early diagnosis and aggressive immunosuppression are crucial for achieving remission and preventing organ damage. We also identified the knowledge gaps and research needs in this field.

RESUMEN

Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated necrotizing vasculitis of small to medium-sized blood vessels. The typical presentation is the classic triad of upper airway, pulmonary, and renal involvement. However, it can rarely present with the involvement of a single organ system known as limited granulomatosis with polyangiitis. We present a case of a 53-year-old male with chronic rhinosinusitis as the only manifestation of limited GPA. The diagnosis was established incidentally based on biopsy findings from the paranasal sinuses obtained during functional endoscopic sinus surgery. Subsequent testing revealed a positive cytoplasmic antineutrophilic antibody. No evidence of systemic involvement was noted. Prednisone and azathioprine were initiated leading to significant improvement. Although upper respiratory tract involvement is common in GPA, it is rare for the condition to be limited to this organ system. Our case of limited GPA is distinct in that it represents a rare presentation of this already rare disease.

RESUMEN

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis is a systemic autoimmune disease that typically presents as a multi-organ manifesting disease of unclear etiology that can predispose to rapidly progressive glomerulonephritis (RPGN). If left untreated, ANCA-associated vasculitis can be fatal, and RPGN can progress to irreversible renal failure. Environmental and genetic factors have been implicated in the pathogenesis of this vasculitis. Coronavirus disease (COVID-19) has been noted to have various physiologic impacts on the body, with literature indicating possible autoimmune effects. We present a rare case of ANCA-associated vasculitis in an elderly male with no known autoimmune history after a recent illness with COVID-19. The patient had been seen as an outpatient with progressively declining renal function until he presented to the hospital with acute renal failure and pericarditis. Workup revealed elevated anti-myeloperoxidase antibody (MPO-AB) and perinuclear ANCA (p-ANCA) antibodies with a biopsy confirming focal cresenteric glomerulonephritis, and the patient was initiated on steroid therapy with notable improvement and a return to baseline kidney function.

RESUMEN

This case follows a 38-year-old Caucasian male with no known medical history who presented to the emergency department for syncope. He also endorsed a two-month history of fevers, weight loss, oral ulcers, rashes, joint swelling and arthralgias. After extensive workup, he was given a working diagnosis of granulomatosis with polyangiitis (GPA). Conflicting diagnostic evidence made it increasingly difficult to distinguish between GPA and eosinophilic granulomatosis with polyangiitis. In conclusion, we believe the patient may be better diagnosed with polyangiitis overlapping syndrome.

RESUMEN

Background: Double filtration plasmapheresis (DFPP) was initially used to facilitate the conduction of ABO-incompatible renal transplantation. The applicability of DFPP has recently expanded to cover the removal of various antibodies in adults with immune-mediated diseases. However, DFPP is seldom used in children, with few reports addressing its efficacy and safety in this population. This study aimed to explore the efficacy and adverse effects of DFPP for pediatric patients with renal indications. Methods: Children who received DFPP between December 2017 and December 2020 at Tongji Hospital were retrospectively studied, and sub-grouped for analysis according to the types of disease. All children received 3 to 6 DFPP sessions within 2 to 3 weeks, and were assessed for clinical outcomes according to glomerular filtration rate, proteinuria and extra-renal symptoms. Pre- and post-DFPP plasma were collected to measure the levels of pathogenic autoantibodies, immunoglobulins, fibrinogen, albumin, calcium, etc. In-hospital complications were also recorded. Results: Totally there were 10 children receiving 44 sessions of DFPP, including 2 males and 8 females, with a median age of 11.2 years old (5-13 years) and a median weight of 42.1 kg (20-59 kg). Five patients were treated for systemic lupus erythematosus (SLE), three patients for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), one for C3 glomerulopathy and one for ABO-incompatible renal transplantation. Plasma autoantibodies decreased substantially by 93% and 89% in those with SLE and AAV after the last session, respectively. Complete or partial responses were achieved in 80%, 33.3%, 100% and 100% of patients with SLE, AAV, C3 glomerulopathy, and ABO-incompatible renal transplantation, respectively. The proportion of cumulative IgG, fibrinogen, and albumin removal at the end of the last sessions were 58.8%, 67.69%, and 14.05% respectively. The removal of calcium, potassium and creatinine were not statistically significant. A few episodes (4.55%) of hypotension were observed when fresh frozen plasma was used as the replacement fluid, and no bleeding nor severe anaphylaxis was noted. Conclusions: The efficacy and safety of DFPP treatment in children with SLE, AAV, C3 glomerulopathy and ABO-incompatible renal transplantation were described in the present study. DFPP is proven to be a safe apheresis method for children weighing more than 20 kg.

RESUMEN

Co-occurrence of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and IgA nephropathy (IgAN) is extremely uncommon. To date, only a few case reports have described such patients. Here, we describe the clinical presentation, pathologic features, treatment response, and outcome data of five patients with the rare form of co-existing AAV and IgAN and compared the characteristics of these patients to AAV patients with pauci-immune glomerulonephritis (n = 10) and IgAN patients (n = 10) that were selected as controls by stratified random sampling. In addition, we summarize all the previously reported cases of AAV and IgAN. In total, including the current study, 16 AAV/IgAN overlap cases were reported. Our five patients with the coexistence of AAV and IgAN were younger than the ten AAV patients with pauci-immune glomerulonephritis (22.6 ± 8.2 years versus 48.9 ± 15.7 years, respectively, P = 0.004). Histologically, they had a significantly lower percentage of glomeruli with fibrous crescents compared with AAV patients (0.0% versus 4.0%, P = 0.038). Compared with ten IgAN patients, our five AAV/IgAN patients had higher levels of ESR (P = 0.032) and CRP (P = 0.031). After accepting treatment with a combination of steroid and immunosuppressants, all patients showed a positive response to therapy, except for one patient in our cohort and another previously reported patient. We described the clinical presentation, pathologic features, treatment response, and outcome data of five patients with overlapping AAV and IgAN. They had mild glomerular pathological lesions and a positive response to aggressive immunosuppressive therapy. They were quite similar to pauci-immune AAV patients in clinical features, except for younger age. They had a lower percentage of glomeruli with fibrous crescents compared with AAV patients. In contrast to IgAN patients, they had higher levels of ESR and CRP. The mechanism of the coexistence of IgAN and AAV needs further study.

Asunto(s)

RESUMEN

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) refers to a group of disorders characterized by inflammation and destruction of small- and medium-sized blood vessels. It can be classified into various clinical disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and renal-limited AAV or serologic subtypes, which are myeloperoxidase (MPO)-AAV and proteinase 3 (PR3)-AAV. Renal involvement is a common manifestation in these types of vasculitis. MPO-AAV usually involves the glomeruli causing membranous changes and presents with glomerulonephritis. However, MPO-AAV renal type without glomeruli involvement is much rarer, and very few case reports of this condition have been reported in the literature. Once the diagnosis is confirmed by renal biopsy, the treatment of AAV involves high-dose steroids and cyclophosphamide to induce remission. Rituximab, a chimeric monoclonal antibody that targets against the pan-B-cell marker CD20, was the first monoclonal antibody to be approved for the treatment of vasculitis. It is now considered first-line therapy for ANCA vasculitis with kidney involvement thanks to the higher remission rates associated with it. We report a unique and rare case of acute kidney injury due to MPO-AAV without glomeruli involvement, which was successfully treated with rituximab over a period of 12 months and led to the remission of the disease in the kidneys.

RESUMEN

Small-vessel vasculitis has a broad differential with similar clinical presentation and laboratory abnormalities, including petechial rashes, neurologic symptoms, glomerulonephritis, and abnormal inflammatory markers. Biopsy-based diagnosis is critical as the treatment varies by etiology. We report a case of a 41-year-old man with diagnosed cryoglobulinemia and hepatitis C presenting with a petechial rash, altered mental status, and acute kidney injury and ultimately found to have proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis secondary to infective endocarditis. Skin biopsy was consistent with resolving, but nonspecific vasculitis and MRI showed foci of hemosiderin deposition concerning vasculitic lesions. Blood cultures grew Enterococcus faecalis, and he was treated with IV antibiotics. Kidney biopsy showed pauci-immune necrotizing focal segmental glomerulonephritis (GN) and diffuse acute tubular necrosis (ATN). After blood cultures cleared, he was initially treated with mycophenolate for worsening renal function. When the patient stopped antibiotics unexpectedly, his kidney function worsened and improved only after immunosuppression was stopped and antibiotics were restarted. This case highlights the importance of renal biopsy in patients with multiple potential etiologies of GN. The case resolution also reinforces that patients with infective endocarditis causing ANCA-associated GN should be treated with antibiotics in addition to, and possibly instead of, immunosuppression.

RESUMEN

Lupus nephritis is typically associated with anti-nuclear antibodies and anti-double-stranded DNA antibodies resulting in the intrarenal immune complex deposition. Levels of anti-double-stranded DNA antibodies reflect disease activity in these patients. With negative anti-double-stranded DNA antibodies, establishing a diagnosis of lupus nephritis is difficult. Lupus nephritis overlapped with anti-neutrophil cytoplasmic antibody-associated vasculitis is both a diagnostic and therapeutic dilemma. Herein, we describe a case of an asymptomatic 41-year-old female who had incidental findings of low hemoglobin and elevated serum creatinine. Making a clinical diagnosis of lupus nephritis and anti-neutrophil cytoplasmic antibody-associated vasculitis in an asymptomatic patient can be challenging and must be made based on the interpretation of evolving serology, imaging studies, and histopathology. Based on extensive workup, the patient was diagnosed with concurrent lupus nephritis and anti-neutrophil cytoplasmic antibody-associated vasculitis overlap syndrome warranting immediate immunosuppressive therapy.

RESUMEN

Hydralazine is a vasodilator used in the treatment of resistant hypertension. It is a safe and widely used antihypertensive medicine. Its common adverse effects include headache, rebound tachycardia, fluid retention, and angina. It is a rare cause of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) with pulmonary and renal involvement. We report a case of a 74-year-old woman, with over eight years of use of hydralazine, who presented to the hospital with shortness of breath and cough. Blood work revealed deranged renal function with high creatinine levels. Serology workup was positive for anti-histone antibodies (AHA), anti-nuclear antibodies (ANA), myeloperoxidase (MPO) ANCA and proteinase-3 (PR-3) ANCA. Renal biopsy showed diffusely flattened tubular epithelium, focal micro vesicular degeneration, and focal loss of the brush border of the proximal tubular epithelium. Hydralazine was stopped and the patient was treated with corticosteroids, resulting in the resolution of her kidney injury.

RESUMEN

Vasculitis, by definition, causes changes in the walls of blood vessels, including thickening, weakening, narrowing, and scarring, leading to inflammation and necrosis of the blood vessel walls. Small-vessel vasculitis is commonly associated with anti-neutrophil cytoplasmic antibodies (ANCA), which activate cytokine-primed neutrophils and monocytes that express ANCA antigens proteinase 3 (PR3) and myeloperoxidase (MPO) on their surface. The continuous injury and inflammation of these small vessels characterized by circulating immune complexes and antinuclear antibodies result in clinical features standard in all types of vasculitis. When a 59-year-old male with a history of heart failure, hypertension (on hydralazine 100 mg every eight hours for more than ten years), diabetes mellitus, and dyslipidemia presented to the hospital, he was complaining of hematuria, intermittent periumbilical abdominal pain, and 40-lb weight loss over four months. Initial evaluation showed symptomatic anemia and large blood cells with proteinuria on urine analysis. During his clinical course, the patient developed a new diffuse purpuric rash. Imaging showed systemic involvement with ground-glass opacities, diffuse alveolar hemorrhage, and peripancreatic inflammatory changes, consistent with small-vessel vasculitis. Immunological tests confirmed ANCA-associated vasculitis, and kidney biopsy showed ANCA-mediated pauci-immune glomerulonephritis supported by the salvage technique used by pronase immunofluorescence, which provides evidence against the glomerular disease of the complex immune type in the setting of MPO-ANCA seropositivity. Despite the withdrawal of hydralazine and prompt initiation of immunosuppressive therapy and alternating sessions of plasmapheresis, the patient succumbed to acute massive pulmonary hemorrhage and subsequent demise. We recommend that patients on the common antihypertensive, hydralazine, should be monitored with non-specific inflammatory markers and, if warranted, with qualitative and quantitative assessment tools to measure inflammatory disease activity for possible complications of hydralazine drug-induced vasculitis or hydralazine ANCA-associated vasculitis (HAAV). Furthermore, cumulative dosages may be a predisposing factor for HAAV to present as a pulmonary-renal syndrome, which can be fulminant and fatal, despite aggressive efforts. Therefore, screening, revisiting therapy, early diagnosis, and prompt discontinuation of the drug are imperative.

RESUMEN

Autoimmune-associated vasculitis is related to conditions like granulomatosis with polyangiitis (GPA) and eosinophilic polyangiitis with granulomatosis (EGPA), among many others. An unlikely scenario is patients with the above conditions presenting with ischemic strokes before any renal or pulmonary pathology. These conditions are associated with increased antineutrophillic cytoplasmic antibodies (C-ANCA) levels in the blood, and its decline after treatment is directly proportional to the recovery of the patient. We present a case of a previously healthy 38-year-old male patient who presented with acute/subacute ischemic stroke with elevated C-ANCA levels; his MRI brain images revealed multiple posterior circulation infarcts with hemorrhagic transformation. With pulse steroid therapy, he had significant improvement in neurological functions. This case report highlights the importance of maintaining a high degree of suspicion and providing early treatment for autoimmune strokes in young patients with no clear etiology for such a presentation.

RESUMEN

Drug-induced autoimmunity occurs when exposure to a causative agent leads to serologic or clinical autoimmune responses. Syndromes that may be associated with drug-induced autoimmunity include antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) and drug-induced lupus (DIL). When drug-induced autoimmunity involves the kidney, histological patterns of injury include pauci-immune glomerulonephritis (GN), which occurs with AAV, and immune complex-mediated GN, which is associated with DIL. We present a case of hydralazine-induced dual ANCA-positive vasculitis and nephritis.