Anti-Neutrophil Cytoplasmic Antibody Vasculitis in Pediatric Patients: Is the Incidence Rising?

Objectives: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease usually seen in middle-aged and older adults but which is rare in children and adolescents. We sought to determine if there has been a change in the incidence of this disorder. Methods: Single-center, retrospective review. Results: Over the last 2 years, we have encountered a striking increase in the frequency of this disease in pediatric patients. All eight patients seen during this period had renal involvement and 5 patients rapidly progressed to end stage kidney disease. The prognosis was worse in younger patients, those with microscopic polyangiitis, and those with chronic kidney damage in the diagnostic renal biopsy. Conclusions: We report these observations to highlight this change in the epidemiology of ANCA-associated vasculitis and to promote earlier recognition and treatment of this severe form of glomerulonephritis.

耳鼻受累首发的肉芽肿性血管炎1例

1临床资料患者,女,57岁,既往体健,因“右耳不适1个月”于2022-01-03收治入院。1个月前患者因右耳耳闷伴轻度听力下降反复就诊于当地医院,考虑分泌性中耳炎,经口服抗生素、激素等药物保守治疗后未能完全缓解,收治于我科。专科查体:右耳耳道湿润可见淡黄色脓液,稍黏稠,量稍多,鼓膜充血肿胀,标志欠清,鼓室可见积液(图1A)。

Eosinophilic granulomatosis with polyangiitis,asthma as the first symptom,and subsequent Loeffler endocarditis:A case report

BACKGROUND Eosinophilic granulomatosis with polyangiitis(EGPA),formerly known as Churg-Strauss syndrome,is a rare form of anti-neutrophil cytoplasmic antibodyassociated vasculitis characterized by asthma,vasculitis,and eosinophilia.CASE SUMMARY We report an atypical case of EGPA in a 20-year-old female patient.Unlike previously reported cases of EGPA,this patient’s initial symptom was asthma associated with a respiratory infection.This was followed by Loeffler endocarditis and cardiac insufficiency.She received treatment with methylprednisolone sodium succinate,low molecular weight heparin,recombinant human brain natriuretic peptide,furosemide,cefoperazone sodium/sulbactam sodium,and acyclovir.Despite prophylactic anticoagulation,she developed a large right ventricular thrombus.EGPA diagnosis was confirmed based on ancillary test results and specialty consultations.Subsequent treatment included mycophenolate mofetil.Her overall condition improved significantly after treatment,as evidenced by decreased peripheral blood eosinophils and cardiac markers.She was discharged after 17 d.Her most recent follow-up showed normal peripheral blood eosinophil levels,restored cardiac function,and a reduced cardiac mural thrombus size.CONCLUSION This case illustrates the swift progression of EGPA and underscores the significance of early detection and immediate intervention to ensure a favorable prognosis.

Triple hit to the kidney-dual pathological crescentic glomerulonephritis and diffuse proliferative immune complexmediated glomerulonephritis: A case report

BACKGROUND Anti-glomerular basement membrane(GBM)disease is a rare rapidly progressive glomerulonephritis,frequently associated with alveolar hemorrhage in the lungs and involving the kidney by crescentic glomerulonephritis.It has been described in association with other glomerulonephritides[such as anti-neutrophilic antibody(ANCA)-glomerulonephritis,membranous nephropathy,and immunoglobulin(Ig)A nephropathy].CASE SUMMARY Herein we present an unusual case of concurrent anti-GBM disease,ANCAassociated crescentic glomerulonephritis and diffuse proliferative immune complex mediated glomerulonephritis with predominant staining for IgA and C3 by immunofluorescence.The patient is a 46-year-old Caucasian male who presented to the emergency department with acute onset of flank pain and was found to have high serum creatinine levels of 15 mg/dL,proteinuria,and hematuria.He rapidly deteriorated and became anuric.He was found to have high anti-GBM antibodies titers(151 units)and high anti-neutrophil cytoplasmic-ANCA.Despite prompt and early treatment,the patient’s condition worsened,and he succumbed to his illness.CONCLUSION Our case emphasizes the importance of a renal biopsy in anti-GBM disease,even in the presence of positive serum anti-GBM antibodies,to identify other potential causes of rapidly progressive glomerulonephritis.The challenge in treating such cases lies in the different therapy modalities.

Inflammatory bowel disease serology in Asia and the West

AIM:To study serological antibodies in Caucasians and Asians,in health and inflammatory bowel disease(IBD),in Australia and Hong Kong(HK).METHODS:Anti-glycan antibodies[anti-chitobioside(ACCA),anti-laminaribioside(ALCA)],and anti-mannobioside(AMCA),anti-Saccharomyces cervisiae(gASCA);and atypical perinuclear anti-neutrophil cytoplasmic antibody(pANCA)were tested in IBD patients,their unaffected relatives,and healthy controls in Australia and HK(China).Antibody status(positive or negative)and titre was compared between subjects of different geography,ethnicity and disease state.RESULTS:Ninety subjects were evaluated:21 Crohn’s disease(CD),32 ulcerative colitis(UC),29 healthy controls,and 8 IBD patient relatives.Forty eight subjects were Australian(29 Caucasian and 19 ethnic Han Chinese)and 42 were from HK(all Han Chinese).Caucasian CD patients had a significantly higher antibody prevalence of gASCA(67%vs 3%,P<0.001),ALCA(44%vs 6%,P=0.005),and AMCA(67%vs 15%,P=0.002),whereas HK CD patients had a higher prevalence of only AMCA(58%vs 25%,P=0.035),when compared with UC and healthy subjects in both countries.Caucasian CD had significantly higher gASCA prevalence(67%vs 0%,P<0.001)and titre(median59 vs 9,P=0.002)than HK CD patients.Prevalence and titres of ALCA,ACCA and AMCA did not differ between CD in the two countries.Presence of at least one antibody was higher in Caucasian than HK CD patients(100%vs 58%,P=0.045).pANCA did not differ between countries or ethnicity.CONCLUSION:Serologic CD responses differ between HK Asian and Australian Caucasian patients.Different genetic,environmental or disease pathogenic factors may account for these differences.

Crohn's disease with gastroduodenal involvement: Diagnostic approach

Crohn's disease(CD) is a chronic idiopathic inflammatory disease of gastrointestinal tract characterizedby segmental and transmural involvement of gastrointestinal tract. Ileocolonic and colonic/anorectal is a most common and account for 40% of cases and involvement of small intestine is about 30%. Isolated involvement of stomach is an extremely unusual presentation of the disease accounting for less than 0.07% of all gastrointestinal CD. To date there are only a few documented case reports of adults with isolated gastric CD and no reports in the pediatric population. The diagnosis is difficult to establish in such cases with atypical presentation. In the absence of any other source of disease and in the presence of nonspecific upper gastrointestinal endoscopy and histological findings, serological testing can play a vital role in the diagnosis of atypical CD. Recent studies have suggested that perinuclear anti-neutrophil cytoplasmic antibody and anti-Saccharomycescervisia antibody may be used as additional diagnostic tools. The effectiveness of infliximab in isolated gastric CD is limited to only a few case reports of adult patients and the long-term outcome is unknown.

Serologic and laboratory markers in prediction of the disease course in inflammatory bowel disease

The search for biologic markers that can assess the natural history and perhaps predict the course of individual's disease including response to treatments over time has become an important focus of inflammatory bowel disease research.The knowledge of an individual's prognosis can help physicians and patients make important management decisions and aid communication on risk and benefits of disease and treatment.

Polyarteritis nodosa clinically mimicking nonocclusive mesenteric ischemia

Here, we present the case of a 74-year-old Japanese man with segmental intestinal necrosis, which developed after treatment with pulsed methylprednisolone for mononeuritis multiplex. The patient was weakly positive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA). Computed tomography and surgical findings were compatible with nonocclusive mesenteric ischemia (NOMI). He underwent small intestinal resection by emergency surgery and an intestinal fistula was made. Pathologically, necrotizing vasculitis with fibrinoid necrosis was present in medium to small-sized arteries, which was equivalent to Arkin's classification Ⅱ-Ⅳ. Most of the arteries had fibrous intimal thickening, which was considered to obstruct the arteries and thus cause segmental intestinal necrosis. A diagnosis of polyarteritis nodosa (PAN) was made, and intravenous cyclophosphamide pulse therapy was added to the therapeutic regimen. This patient was successfully treated with these multidisciplinary therapies and his stoma was finally closed. This is a very rare and indicative case of PAN weakly positive for MPO-ANCA and clinically mimicking NOMI, which occurred even after treatment with pulsed methylprednisolone.

Relapsing polychondritis with p-ANCA associated vasculitis: Which triggers the other?

Relapsing polychondritis(RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody(ANCA) associated vasculitis(AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia,which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.

Isolated gastric Crohn's disease

Crohn's disease(CD) is a chronic idiopathic inflammatory disease of gastrointestinal tract characterized by segmental and transmural involvement of gastrointestinal tract. Ileocolonic and colonic/anorectal is a most common and account for 40% of cases and involvement of small intestine in about 30%. The stomach is rarely the sole or predominant site of CD. To date there are only a few documented case reports of adults with isolated gastric CD and no reports in the pediatric population. Isolated stomach involvement is very unusual presentation accounting for less than 0.07% of all gastrointestinal CD. The diagnosis is difficult to establish in cases of atypical presentation as in isolated gastroduodenal disease. In the absence of any other source of disease and in the presence of nonspecific upper GI endoscopy and histological findings, serological testing can play a vital role in the diagnosis of atypical CD. Recent stud-ies have suggested that perinuclear anti-neutrophil cytoplasmic antibody and anti-Saccharomycescervisia antibody may be used as additional diagnostic tools. The effectiveness of infliximab in isolated gastric CD is limited to only a few case reports of adult patients and the long-term outcome is unknown.

"Triple-positive" renal limited vasculitis presenting with rapidly progressive glomerulonephritis: A case report

Rationale:Coexistence of anti-glomerular basement membrane(anti-GBM)disease with anti-neutrophil cytoplasmic antibody(ANCA)in a case of glomerulonephritis is often identified as a"double-positive"disease.Interestingly,the majority of"double positive"ANCA is myeloperoxidase(MPO)-ANCA and some of the MPO-ANCA positive cases showed intrarenal arteritis,suggesting an ANCA-associated kidney lesion.Proteinase 3-ANCA positive diseases are also rarely reported.Patients positive for all three antibodies,i.e.,triple-positive patients,are extremely rare.Patient's Concern:A 53 year-old female presented with anasarca and oliguria of 2 months'duration.Diagnosis:Pauci-immune type renal limited crescentic glomerulonephritis positive for MPO-ANCA,proteinase 3-ANCA,and anti-GBM antibody(triple-positive).Interventions:Intravenous high dose cyclophosphamide,oral azathioprine,intravenous methylprednisolone,and plasma exchange as per British Health Professionals in Rheumatology Guidelines.Outcomes:After one-month follow-up,anasarca and proteinuria were lessened,serum creatinine was normalized,titers of MPO-ANCA levels were decreased,and anti-GBM antibody levels were normalized.Lessons:Triple-positive renal limited vasculitis is rare and response to combined immunosuppressive therapy and plasma exchange can contribute to successful remission.

Renal Amyloidosis Secondary to ANCA-Associated Vasculitis:A Case Report

Renal amyloidosis secondary to anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis is extremely rare.Here,we reported a 77-year-old woman with ANCA-associated vasculitis.Renal biopsy with Masson trichrome staining showed pauci-immune crescentic glomerulonephritis,and electron microscopy showed amyloid deposition in the mesangial area.Immunofluorescence revealed kappa light chain and lambda light chain negative.Bone marrow biopsy revealed no clonal plasma cell.Finally,she was diagnosed as ANCA-associated vasculitis with secondary renal amyloid A amyloidosis.

ANCA-Associated Vasculitides—An Update

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are characterized by destruction of small vessels, granulomatous inflammation of the respiratory tract and necrotizing glomerulonephritis. This review describes the clinical diagnosis and therapy as well as the patho-physiology of ANCA-associated vasculitides with a specific focus on the interplay of ANCAs with activated neutrophils and the deleterious pathophysiological consequences of neutrophil-endothelium interaction.

Classification,diagnosis and treatment of ANCA-associated vasculitis

Diagnosis of anti-neutrophil cytoplasmic antibodies(ANCA)-associated vasculitis is usually not difficult in patient with systemic disease, including lung and kidneys involvement, and laboratory signs of inflammation. The presence of ANCA and the results of histological investigation confirm diagnosis of ANCAassociated vasculitis. Cyclophosphamide/azathioprine in combination with high dose steroids are used to induce and maintain remission of systemic vasculitis. The clinical trials also showed efficacy of rituximab that induces depletion of B-cells. Our understanding and management of ANCA-associated vasculitis improved significantly over the last decades but there is still a lot of debate over its classification, diagnostic criteria, assessment of activity and optimum treatment.

Epidemiology of Biopsy Proven Glomerular Disorders and Effect of Severe Cyclone on Its Incidence in Central Queensland Region of Australia

Aim: The objectives of this study are to determine the epidemiology of biopsy-proven glomerular disease (GD) in Central Queensland and the effect of a severe cyclone on its incidence and clinical phenotype. Background: Central Queensland (CQ) has a relatively high incidence of kidney disease. Since its biopsy service commenced in 2005, there have been no data on biopsy-proven GD. It has been suggested that GD incidence changes around times of natural disasters. In February 2015, the CQ region was affected by a category 5 Cyclone Marcia. This provides an opportunity to explore possible environmental triggers of GD. Methods: This was a single-centre retrospective observational study on biopsy-proven kidney disease in CQ. All kidney biopsies performed between January 2005 and December 2019 were included. Patients with biopsy-proven GD during 3 years before and after Cyclone Marcia (from 2012 to 2018) were analysed. Results: 170 native kidney biopsies occurred during the 15 years. The number of annual biopsies steadily increased from 7 to 16. The most common biopsy-proven kidney disease was IgA Nephropathy (27%) followed by diabetic nephropathy (20%). GD comprised 64% of biopsies. Unlike other GD, the incidence of ANCA-associated vasculitis (AAV) significantly increased after cyclone (one pre- and eight post-cyclone, P value = 0.039). The majority of AAV cases occurred in the first year after the cyclone. Conclusion: Kidney biopsies in CQ provide important epidemiological data on biopsy-proven kidney disease. Cyclones have a possible effect on the incidence and clinical phenotype of ANCA associated vasculitis.

Urological manifestations and treatment of the primary systemic vasculitides

The primary systemic vasculitides(PSV) are a group of rare inflammatory disorders affecting blood vessels of varying size and multiple organs. Urological manifestations of PSV are uncommon. Testicular vasculitis is the most commonly reported finding and is associated with Polyarteritis Nodosa(PAN), Henoch-Sch?nleinPurpura(HSP), anti-neutrophil cytoplasm antibody associated Vasculitides(AAV), Giant Cell Arteritis(GCA) and Kawasaki disease. Prostatic vasculitis has been reported in association with GCA and AAV. Ureteric involvement has been noted in PAN, HSP and AAV. Other urogenital manifestations of PSV include genital ulceration and bladder dysfunction in Beh?ets Disease and haematuria which is commonly seen in many of the PSV. Finally, therapies used to treat the PSV, especially cyclophosphamide, are associated with urological sideeffects including haemorrhagic cystitis and urothelial malignancy. The aim of this review is to examine how the urological system is involved in the PSV. Each PSV is examined in turn, with a brief clinical description of the disease followed by a description of the urological manifestations and management. Identification of urological manifestations of PSV is important as in many cases symptoms may improve with immunosuppressive therapy, avoiding the need for invasive surgery. Additionally, patients who present with isolated urogenital PSV are at higher risk of developing subsequent systemic vasculitis and will need to be followed up closely.

Drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis

Objective:In recent years,an increasing number of drugs have been proved to be associated with the induction of anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV).This article reviews the latest research progress on drug-induced AAV.Data sources:We conducted a comprehensive and detailed search of the PubMed database.The search terms mainly included druginduced,ANCA,and vasculitis.Study selection:We summarized the original articles and reviews on drug-induced AAV in recent years.The extracted information included the definition,epidemiology,associated drugs,pathogenesis,clinical features,diagnosis,treatment,and prognosis of druginduced AAV.We also focused on the differences between drug-induced AAV and primary vasculitis.Results:The offending drugs leading to drug-induced AAV are almost from pharmacologic categories and we need to be vigilant when using these drugs.The pathogenesis of drug-induced AAV might be multifactorial.The formation of neutrophil extracellular traps is an important mechanism for the development of drug-induced AAV.The clinical features of drug-induced AAV are similar to those of primary AAV.Understanding the difference between drug-induced AAV and primary AAV is helpful to identify druginduced AAV.Stopping the offending drug at once after diagnosis may be sufficient for those patients with mild symptoms.Immunosuppressive therapy should only be used in patients with vital organs involvement.Conclusions:Patients with drug-induced AAV usually have a good prognosis if they stop using the offending drug immediately.Recent advances in research on AAV are expected to help us better understand the pathogenesis of drug-induced AAV.

Dynamically changing antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis:A case report

BACKGROUND Granulomatosis with polyangiitis(GPA)is one of the most prevalent forms of the antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis.GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis.The diagnosis of GPA depends on clinical presentation,serological evidence of a positive ANCA,and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation.Cytoplasmic ANCA(c-ANCA)is positive in 65%-75% of GPA patients,accompanied by proteinase 3(PR3),the main target antigen of c-ANCA,another 5% of GPA patients had negative ANCA.CASE SUMMARY The patient,a 52-year-old male,presented with unexplained nasal congestion,tinnitus,and hearing loss.After a duration of 4 months experiencing these symptoms,the patient subsequently developed fever and headache.The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis,and the ANCA results were negative.The anti-infective therapy proved to be ineffective,but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day.However,after continuous use of methylprednisolone tablets for 3 months,the patient experienced a recurrence of fever accompanied by right-sided migraine,positive c-ANCA and PR3,and increased total protein in cerebrospinal fluid.The and cyclophosphamide 0.8 g monthly,the patient experienced alleviation of fever and headache.Additionally,the ANCA levels became negative and there has been no recurrence.CONCLUSION For GPA patients with negative ANCA,there is a potential for early missed diagnosis.The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

Association between follistatin-related protein 1 and the functional status of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Background:Follistatin-like 1(FSTL1)plays both pro-inflammatory and anti-inflammatory roles in the inflammatory processes.We investigated whether serum FSTL1 could predict the current anti-neutrophil cytoplasmic antibody-associated vasculitis(AAV)-specific indices.Methods:We randomly selected 74 patients with AAV from a prospective and observational cohort of Korean patients with AAV.Clinical and laboratory data and AAV-specific indices were recorded.FSTL1 concentration was determined using the stored sera.The lowest tertile of the short-form 36-item health survey(SF-36)was defined as the current low SF-36.The cutoffs of serum FSTL1 for the current low SF-36 physical component summary(PCS)and SF-36 mental component summary(MCS)were extrapolated by the receiver operator characteristic curve.Results:The median age was 62.5 years(55.4%were women).Serum FSTL1 was significantly correlated with SF-36 PCS(r=-0.374),SF-36 MCS(r=-0.377),and C-reactive protein(CRP)(r=0.307),but not with Birmingham vasculitis activity score(BVAS).In the multivariable linear regression analyses,BVAS,CRP,and serum FSTL1 were independently associated with the current SF-36 PCS(β=-0.255,β=-0.430,andβ=-0.266,respectively)and the current SF-36 MCS(β=-0.234,β=-0.229,andβ=-0.296,respectively).Patients with serum FSTL1≥779.8 pg/mL and those with serum FSTL1≥841.6 pg/mL exhibited a significantly higher risk of having the current low SF-36 PCS and SF-36 MCS than those without(relative risk 7.583 and 6.200,respectively).Conclusion:Serum FSTL1 could predict the current functional status in AAV patients.

Analysis of clinical features and prognosis of anti-glomerular basement membrane antibody positive patients with anti-neutrophil cytoplasmic antibodies

Objective To investigate the characteristics and outcome of glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody.Methods The sera of 23 antiGBM glomerulonephritis patients were collected and were tested for ANCA respectively.Characteristics and outcome of patients with coexisting anti-GBM antibody