Positive Antineutrophil Cytoplasmic Antibodies Research Articles

Simultaneous automated screening and confirmatory testing for vasculitis-specific ANCA.

Anti-neutrophil cytoplasmic antibodies (ANCA) are the serological hallmark of small vessel vasculitis, so called ANCA-associated vasculitis. The international consensus requires testing by indirect immunofluorescence (IIF) on human ethanol-fixed neutrophils (ethN) as screening followed by confirmation with enzyme-linked immunosorbent assays (ELISAs). This study evaluates the combination of cell- and microbead-based digital IIF analysis of ANCA in one reaction environment by the novel multiplexing CytoBead technology for simultaneous screening and confirmatory ANCA testing. Sera of 592 individuals including 118 patients with ANCA-associated vasculitis, 133 with rheumatoid arthritis, 49 with infectious diseases, 77 with inflammatory bowel syndrome, 20 with autoimmune liver diseases, 70 with primary sclerosing cholangitis and 125 blood donors were tested for cytoplasmic ANCA (C-ANCA) and perinuclear ANCA (P-ANCA) by classical IIF and ANCA to proteinase 3 (PR3) and myeloperoxidase (MPO) by ELISA. These findings were compared to respective ANCA results determined by automated multiplex CytoBead technology using ethN and antigen-coated microbeads for microbead immunoassays. There was a good agreement for PR3- and MPO-ANCA and a very good one for P-ANCA and C-ANCA by classical and multiplex analysis (Cohen's kappa [κ] = 0.775, 0.720, 0.876, 0.820, respectively). The differences between classical testing and CytoBead analysis were not significant for PR3-ANCA, P-ANCA, and C-ANCA (p<0.05, respectively). The prevalence of confirmed positive ANCA findings by classical testing (IIF and ELISA) compared with multiplex CytoBead analysis (IIF and microbead immunoassay positive) resulted in a very good agreement (κ = 0.831) with no significant difference of both methods (p = 0.735). Automated endpoint-ANCA titer detection in one dilution demonstrated a very good agreement with classical analysis requiring dilution of samples (κ = 0.985). Multiplexing by CytoBead technology can be employed for simultaneous screening and quantitative confirmation of ANCA. This novel technique provides fast and cost-effective ANCA analysis by automated digital IIF for the first time.

ASSOCIATING AUTOANTIBODIES WITH CLINICAL FEATURES IN MS

<h3>Background</h3> A higher prevalence of autoimmune disease and non-CNS autoreactive antibodies in multiple sclerosis (MS) patients has long been established. It remains unclear, however, if this is associated with particular disease characteristics. <h3>Aim</h3> This study investigates the association of non-CNS autoreactive antibodies with the clinical features of MS. <h3>Methods</h3> A cohort of 200 patients with relapsing-remitting and secondary-progressive MS were tested for common autoantibodies. Multivariate analysis was used to look for associations with clinical and radiological parameters. <h3>Results</h3> 30% of patients were positive for one or more autoantibodies, primarily anti-neutrophil cytoplasmic antibody (ANCA), anti-nuclear antibody (ANA) and/or anti-thyroid peroxidase antibody (anti-TPA). Multivariate analysis demonstrated that a model with age at assessment, presence of oligoclonal bands, relapses in the last year, ANCA and anti-TPA positivity was a significant predictor of the Multiple Sclerosis Severity Score (MSSS) (p&lt;0.02), explaining 7% of the variability(R2=0.07). In this model, relapse number in the last year (p&lt;0.05) and ANCA positivity (p&lt;0.01) were significant factors. Radiological parameters were not significant. <h3>Conclusions</h3> ANCA positivity in MS patients may impact disability progression in MS, thus affecting the MSSS. ANCA positivity has the potential to help classify subsets of patients based on their ‘autoantibody fingerprint,’ with possible implications on management.

Antineutrophil Cytoplasm Antibody: Positivity and Clinical Correlation

ObjectiveTo determine positivity and clinical correlation of anti-neutrophil cytoplasmic antibodies (ANCA), taking into account the interference of antinuclear antibodies (ANA). Material and methodsA prospective study was conducted in the Laboratory of Immunology of the National Cuban Center of Medical Genetic during one year. Two hounded sixty-seven patients with indication for ANCA determination were included. ANCA and ANA determinations with different cut off points and assays were determined by indirect immunofluorescense. Anti proteinase 3 and antimyeloperoxidase antibodies were determined by ELISA. ResultsMost positivity for ANCA was seen in patients with ANCA associated, primary small-vessel vasculitides, rheumatoid arthritis and systemic lupus erythematosus. Presence of ANCA without positivity for proteinase 3 and myeloperoxidase was higher in patients with ANA and little relation was observed between the perinuclear pattern confirmed in formalin and specificity by myeloperoxidase. Highest sensibility and specificity values for vasculitides diagnostic were achieved by ANCA determination using indirect immunofluorescense with a cut off 1/80 and confirming antigenic specificities with ELISA. ConclusionANCA can be present in a great number of chronic inflammatory or autoimmune disorders in the population studied. This determination using indirect immunofluorescence and following by ELISA had a great value for vasculitis diagnosis. Anti mieloperoxidasa assay has a higher utility than the formalin assay when ANA is present.

Anticuerpos contra el citoplasma del neutrófilo: positividad y correlación clínica

ObjectiveTo determine positivity and clinical correlation of anti-neutrophil cytoplasmic antibodies (ANCA), taking into account the interference of antinuclear antibodies (ANA). Material and methodsA prospective study was conducted in the Laboratory of Immunology of the National Cuban Center of Medical Genetic during one year. Two hounded sixty-seven patients with indication for ANCA determination were included. ANCA and ANA determinations with different cut off points and assays were determined by indirect immunofluorescense. Anti proteinase 3 and antimyeloperoxidase antibodies were determined by ELISA. ResultsMost positivity for ANCA was seen in patients with ANCA associated, primary small-vessel vasculitides, rheumatoid arthritis and systemic lupus erythematosus. Presence of ANCA without positivity for proteinase 3 and myeloperoxidase was higher in patients with ANA and little relation was observed between the perinuclear pattern confirmed in formalin and specificity by myeloperoxidase. Highest sensibility and specificity values for vasculitides diagnostic were achieved by ANCA determination using indirect immunofluorescense with a cut off 1/80 and confirming antigenic specificities with ELISA. ConclusionANCA can be present in a great number of chronic inflammatory or autoimmune disorders in the population studied. This determination using indirect immunofluorescence and following by ELISA had a great value for vasculitis diagnosis. Anti mieloperoxidasa assay has a higher utility than the formalin assay when ANA is present.

Concomitant presentation of myocarditis and non-bacterial thrombotic endocarditis in a patient with granulomatosis with polyangiitis

Granulomatosis with polyangiitis (GPA) is a necrotizing vasculitis. The etiology of the disease is not completely known. In this report, we describe a 47-year-old male who presented with ongoing dyspnea. He is a known case of GPA for 3 years based on skin biopsy and positive antineutrophil cytoplasmic antibody. The electrocardiogram showed changes suggestive for myocarditis. A transthoracic and trans esophageal echocardiogram revealed left ventricular systolic dysfunction, thickened left atrial and ventricular wall and vegetation on mitral valve. Blood cultures were negative. Myocarditis and nonbacterial thrombotic endocarditis (NBTE) were diagnosed. As far as we know, NBTE is a rare manifestation of GPA and its presentation with myocarditis is not reported to date. This case indicates the uncommon manifestations of GPA and notifies the importance of performing echocardiography in order to prevent life threatening cardiac complications of the disease.

AB0534 Does the Presence of ANCA in Patients with Lupus Nephritis (LN) Help to Distinguish A Subset?

BackgroundAntineutrophil cytoplasm antibodies (ANCA) are known to occur in some patients with systemic lupus erythematosus (SLE), with a prevalence of 15 to 20% [1]. The perinuclear pattern (pANCA) predominates in...

Cocaine induced midline destructive lesions.

Review of the literature concerning cocaine induced midline destructive lesions (CIMDL). We reviewed the English literature regarding CIMDL involving the nose and its surrounding structures. The review is based on a search of the US National Library of Medicine (PubMed) online database from January 1st, 1982 to March 31st, 2013. CIMDL is a pathology that mimics systemic diseases with positive anti-neutrophil cytoplasmic antibodies (ANCA). The prevalence of CIMDL is considered to be about 4.8% among cocaine users. Clinical manifestations include hyposmia, facial pain, crusting, ulcers, nasal septal perforation, palatal perforation, sinus wall destruction, orbital erosion and damage of the anterior skull base. The presence of ANCA directed against human neutrophil elastase (HNE) is the most distinguishing feature of CIMDL. Toxicological tests, indirect immunofluorescence microscopy, antigen specific solid assay testing, histopathological analysis, apoptosis assay and MRI imaging concur in the clinical identification of CIMDL. The pathogenesis of CIMDL is poorly understood and implicates inflammatory, infective, proapoptotic and autoimmune mechanisms. CIMDL must be readily recognized by clinicians to provide appropriate treatment. Immunosuppressive therapy has no role in the treatment of CIMDL. Only abstinence can interrupt the progression of the disease.

Brief Report: Prevalence of Antineutrophil Cytoplasmic Antibodies in Infective Endocarditis

Infective endocarditis (IE) mimics primary systemic vasculitis, and there are sporadic reports of positivity for antineutrophil cytoplasmic antibodies (ANCAs) among patients with IE. Because the frequency of ANCAs in IE is unknown, this study was undertaken to assess the seroprevalence of ANCAs in a large number of patients with IE. The study was conducted in the framework of a single-center prospective cohort study of incident IE cases. Demographic, clinical, laboratory, and microbiologic data were collected, and magnetic resonance imaging of the brain was performed at diagnosis. For those patients whose serum had been stored at diagnosis, ANCAs were assessed by indirect immunofluorescence assay in ethanol-, formalin-, and methanol-fixed neutrophils. In addition, ANCA specificity for proteinase 3 (PR3) and myeloperoxidase (MPO) was assessed by enzyme-linked immunosorbent assay. Rheumatoid factor (RF), antinuclear antibodies (ANAs), anticardiolipin antibodies (aCL), and serum Ig levels were also measured. Comparisons between groups were made using Wilcoxon's rank sum and chi-square or Fisher's exact tests. Among 109 patients with IE, 18% had cytoplasmic ANCAs (cANCA) and/or perinuclear ANCAs (pANCA) and 8% had PR3-ANCAs or MPO-ANCAs, some with very high titers. Positivity for both cANCA or pANCA and PR3-ANCAs or MPO-ANCAs was found in 6% of patients, and RF, ANAs, and aCL were detected in 35%, 16%, and 23% of samples, respectively. No consistent clinical pattern of IE was observed in the anti-PR3/anti-MPO-positive IE patients, whereas positivity for cANCA/pANCA was associated with younger age (P = 0.022), more frequent occurrence of echocardiographic vegetations (P = 0.043), and above-normal serum IgG levels (P = 0.017). ANCAs, including PR3- and MPO-ANCAs, occur in a substantial proportion of patients with IE. The link between cANCA/pANCA and specific features of IE requires further study.

Association ofHLA-DRB1alleles and anti-neutrophil cytoplasmic antibodies in Han and Uyghur patients with ulcerative colitis in China

We aimed to study the association between HLA-DRB1 alleles and anti-neutrophil cytoplasmic antibodies (ANCA) among Uyghur and Han patients with ulcerative colitis (UC) in China. Altogether 160 UC patients and 466 healthy controls of Uyghur and Han groups residing in the Xinjiang Uyghur Autonomous Region of China were included. HLA-DRB1 variants were identified from genomic DNA using polymerase chain reaction and gene sequencing. Serum ANCA were determined by indirect immunofluorescence assay. Among the Uyghur populations, the HLA-DRB1*08 gene frequency was lower in the UC patients than in the control group (P = 0.012, OR 0.12, 95% CI 0.02-0.91); however, that of HLA-DRB1*13 was much higher in the UC patients than in the controls (P = 0.001, OR 4.32, 95% CI 1.92-9.74). In Han patients with UC, there was no significant difference in HLA-DRB1 frequency between UC patients and healthy controls. The positive rate of ANCA in Uyghur patients with UC was significantly higher than in Han UC patients (P = 0.026), and ANCA positivity was associated with an increased frequency of HLA-DRB1*13 in Uyghur UC patients, but no such difference was observed in the Han patients. Genetic polymorphisms of the HLA-DRB1*08 and *13 may contribute to the clinical heterogeneity of UC between Uyghur and Han UC patients in China. In Uyghur UC patients, HLA-DRB1*13 may be correlated with ANCA positivity.

Pulmonary Manifestations of Granulomatosis With Polyangiitis

ObjectiveTo describe the clinical and laboratory data, with special emphasis on thoracic imaging findings, in 14 patients with a definitive diagnosis of granulomatosis with polyangiitis (GPA). MethodsThe clinical and tomographic data of 14patients with a definitive diagnosis of GPA are presented. Patients with thoracic manifestations suggestive of GPA were evaluated in 3 hospitals from 2000 to 2012. All patients had a sputum analysis and bronchoalveolar lavage for bacterial, mycobacterial and fungal stains and cultures; antineutrophil cytoplasmic antibodies, antinuclear-antibodies, rheumatoid factor, and a biopsy of involved organs. ResultsA total of 13 patients had at least two organs involved. The most frequent thoracic findings were pulmonary nodules, ground glass opacities and patches of consolidation; other abnormalities were tracheal stenosis, diffuse alveolar hemorrhage, lung masses with organized pneumonia. More than three-quarters (78%) of patients had positive antineutrophil cytoplasmic antibodies (ANCA). Ten patients had respiratory tissue biopsy (8 open lung, one tracheal, and one nasal). In 4 patients the diagnosis was made with the classic organ involvement in GPA, positive ANCA, and renal or skin biopsy, and response to treatment on follow-up. At 6–12months all patients showed clinical and radiological improvement, with 54% showing a recurrence of disease. DiscussionThe majority of thoracic findings described in GPA are presented in this study. A complete diagnostic approach with invasive diagnostic procedures to rule out other more prevalent respiratory diseases with similar thoracic manifestations must be performed. The positivity of ANCA in this study was high, and the recurrence of the disease was frequent.

Purpura, petechiae, and bullae as first signs of juvenile granulomatosis with polyangiitis

We present a case of a 14-year-old girl who had a severe form of granulomatosis with polyangiitis (GPA) with extensive dermatological involvement, whose initial presentation was nonspecific leading to diagnostic confusion and initial consideration of infectious and other vasculitis causes. The patient presented with fever, congestion, malaise, and sinus pain. She was diagnosed with bacterial sinusitis and treated with antibiotics. Within weeks, she developed abdominal pain, hematuria, migratory arthritis, and palpable purpura and was diagnosed with Henoch-Schonlein purpura. She went on to develop hemoptysis and progression of the rash into erosive bullae. Investigations revealed that she was ANCA positive and had pauci-immune glomerulonephritis. Given her upper airway, pulmonary and renal involvement, and antineutrophil cytoplasmic antibodies positivity, a definitive diagnosis of a severe form of GPA was made. GPA is a chronic relapsing, life threatening vasculitis that predominantly affects small vessels. Our case demonstrates that GPA can present initially with nonspecific symptoms, including extensive dermatological involvement, leading to diagnostic confusion, and delays in treatment. In the case of a severe peripheral rash in the juvenile population and/or resistant upper airway symptoms, it is vital to consider a diagnosis of GPA to avoid serious organ or life threatening consequences.

Antineutrophil Cytoplasmic Antibodies in Patients with Idiopathic Inflammatory-Demyelinating Diseases

Objective: We assessed the clinical significance of antineutrophil cytoplasm antibodies (ANCA) in patients with idiopathic inflammatory-demyelinating disease (IIDD). Methods: A consecutive cohort of 269 subjects with IIDD and 595 controls was analyzed retrospectively. Results: Among all subjects, ANCA positivity rates were low [9.5% in a perinuclear pattern (pANCA) and 2.3% in a cytoplasmic pattern (cANCA)]. One of the 117 patients with multiple sclerosis (MS) had cANCA and 2 had pANCA. Ten patients with neuromyelitis optica (NMO; 13.9%) had pANCA and 3 (4.2%) had cANCA. Four patients with recurrent longitudinal extensive transverse myelitis (RLETM; 19.0%) had pANCA and 1 (4.8%) had cANCA. In monophasic TM, 22.9% were pANCA seropositive. Among patients with brainstem syndromes, 14.3% were pANCA seropositive. Patients with NMO, RLETM or monophasic TM had higher pANCA levels than patients with MS. There was a positive association between spinal cord (SC) lesions and ANCA, and especially between longitudinal extensive transverse myelitis and ANCA. Among anti-aquaporin 4 antibody-positive patients, ANCA-positive patients (n = 16) were older and had higher Expanded Disability Status Scale scores, more antinuclear antibodies, longer SC lesions and fewer brain abnormalities than the ANCA-negative patients (n = 68). In the NMO subgroup, ANCA-positive patients were older and had more antinuclear antibodies and longer SC lesions than ANCA-negative patients. Conclusion: Among the IIDDs, we found a higher occurrence of ANCA in patients with NMO spectrum disorders than in patients with MS. Therefore, ANCA is another interesting marker of autoimmunity in IIDD patients, especially those with anti-aquaporin 4 antibody.

Infective Endocarditis with Antineutrophil Cytoplasmic Antibody: Report of 13 Cases and Literature Review

ObjectiveChronic infections tend to induce the production of antineutrophil cytoplasmic antibody (ANCA). Infective endocarditis (IE) has been reported to exhibit positive ANCA tests and to mimic ANCA-associated vasculitis, which may lead to a misdiagnosis and inappropriate treatment. The aim of this study was to clarify whether there is any difference in the clinical features between ANCA-positive IE and ANCA-negative IE.MethodsA retrospective study was carried out on 39 IE patients whose proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA levels were measured. After dividing the patients into ANCA-positive and ANCA-negative IE, we compared their clinical features.Resultswe compared 13 ANCA-positive IE patients with 26 ANCA-negative IE patients. All 13 ANCA-positive IE patients were proteinase-3-ANCA positive. Compared with the ANCA-negative IE group, the prevalence of edema of the lower extremities, the serum lactate dehydrogenase (LDH) level and positive blood cultures rate were higher in ANCA-positive IE group, but there was no significant difference in other clinical features.ConclusionTherefore, if a patient presents with fever, arthralgia, skin rash and is ANCA-positive, appropriate steps should be taken to exclude infection (especially IE) before confirming the diagnosis of ANCA-associated vasculitis and embarking on long-term immunosuppressive therapy.

Manifestaciones pulmonares de la granulomatosis con poliangitis

ObjectiveTo describe the clinical and laboratory data, with special emphasis on thoracic imaging findings, in 14patients with a definitive diagnosis of granulomatosis with polyangiitis (GPA). MethodsThe clinical and tomographic data of 14patients with a definitive diagnosis of GPA are presented. Patients with thoracic manifestations suggestive of GPA were evaluated in 3hospitals from 2000 to 2012. All patients had a sputum analysis and bronchoalveolar lavage for bacterial, mycobacterial and fungal stains and cultures; antineutrophil cytoplasmic antibodies, antinuclear-antibodies, rheumatoid factor, and a biopsy of involved organs. ResultsA total of 13patients had at least two organs involved. The most frequent thoracic findings were pulmonary nodules, ground glass opacities and patches of consolidation; other abnormalities were tracheal stenosis, diffuse alveolar hemorrhage, lung masses with organized pneumonia. More than three-quarters (78%) of patients had positive antineutrophil cytoplasmic antibodies (ANCA). Ten patients had respiratory tissue biopsy (8 open lung, one tracheal, and one nasal). In 4patients the diagnosis was made with the classic organ involvement in GPA, positive ANCA, and renal or skin biopsy, and response to treatment on follow-up. At 6-12months all patients showed clinical and radiological improvement, with 54% showing a recurrence of disease. DiscussionThe majority of thoracic findings described in GPA are presented in this study. A complete diagnostic approach with invasive diagnostic procedures to rule out other more prevalent respiratory diseases with similar thoracic manifestations must be performed. The positivity of ANCA in this study was high, and the recurrence of the disease was frequent.

Human Bartonella Infective Endocarditis is Associated with High Frequency of Antiproteinase 3 Antibodies

To the Editor: Bartonella henselae and B. quintana are the 2 Bartonella species most commonly involved in human disease and are associated with the formation of vasoproliferative tumors1. Chronic infections are bacteremia (particularly affecting homeless patients), endocarditis, bacillary angiomatosis, and liver peliosis2. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are a group of diseases characterized by necrotizing vasculitis of small vessels and associated with autoantibodies against neutrophil constituents such as myeloperoxidase (MPO) and proteinase 3 (PR3)3. Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MP), and Churg-Strauss syndrome (CSS) are all forms of vasculitis associated with anti-PR3. Several chronic infectious diseases (mycobacterial infections, chronic hepatitis C virus infection, and amoebic liver abscess) have been reported to be associated with a positive ANCA by immunofluorescence, but the specificity was not always defined by ELISA-testing specificity4. A few cases of subacute endocarditis have been reported to be associated with ANCA positivity, mainly anti-PR3. A 40-year-old … Address correspondence to Dr. E. Aslangul, Internal Medicine Department, Hôtel Dieu 1, Place du Parvis Notre Dame, 75004 Paris, France. E-mail: elisabeth.aslangul{at}htd.aphp.fr

Diagnosis and classification of granulomatosis with polyangiitis (aka Wegener's granulomatosis)

Granulomatosis with polyangiitis (GPA, formerly known as Wegener's Granulomatosis) is an autoimmune small vessel vasculitis which is highly associated with anti-neutrophil cytoplasmic antibodies (ANCA). The hallmarks of this condition are systemic necrotising vasculitis, necrotising granulomatous inflammation, and necrotising glomerulonephritis. The aetiology of granulomatosis with polyangiitis is linked to environmental and infectious triggers inciting onset of disease in genetically predisposed individuals. Anti-neutrophil cytoplasmic antibodies are pathogenic and play an important role in the pathogenesis of this disease, although ANCA positivity is not essential for a clinical diagnosis of granulomatosis with polyangiitis. Granulomatosis with polyangiitis is diagnosed based on clinical manifestations of systemic vasculitis and histological evidence of necrotising vasculitis or granulomatous inflammation. This small vessel vasculitis may present as limited disease of the ears, nose and upper airways or mild, moderate or severe systemic disease. Immunosuppression and adjuvant therapies have contributed to the improved prognosis of granulomatosis with polyangiitis over the past decades. Treatment strategies are tailored to the severity of the disease. They are based on published evidence of the efficacy and safety of the immunosuppressive drugs indicated to manage active vasculitis and maintain clinical remission. This review will summarise the history, aetiology, pathogenesis, classification, diagnosis and management of granulomatosis with polyangiitis.

Wegener's granulomatosis simulates pulmonary adenocarcinoma

Wegener's granulomatosis is a rare systemic granulomatous necrotizing vasculitis that characteristically involves the upper airways, lungs, and kidneys. Pulmonary Wegener's granulomatosis can present with multifocal lung involvement or solitary lung lesions. Diagnosing Wegener's granulomatosis on the basis of cytological material from sputum may be challenging for pathologists. A wrong diagnosis may lead to inappropriate treatment. We report a case of Wegener's granulomatosis in a patient who first presented with hemoptysis, poor appetite, and weight loss. Multifocal pulmonary nodules were seen on a chest radiograph and the features seen on sputum cytology were similar to those of lung adenocarcinoma. A lung biopsy sample proved granulomatous inflammation. Wegener's granulomatosis was diagnosed based on the biopsy sample and a positive cytoplasmic antineutrophil cytoplasmic antibody titer (1:1280). After treatment with prednisone and cyclophosphamide, the lung lesions resolved. We recommend measuring the cytoplasmic antineutrophil cytoplasmic antibody titer in patients with bilateral pulmonary lesions. A lung biopsy sample should always be obtained, even when the cytology findings suggest a malignancy.

Touch not the cat bot a glove*: ANCA-positive pauci-immune necrotizing glomerulonephritis secondary to Bartonella henselae.

A 36-year-old male presented with a secondary, but anti-neutrophil cytoplasmic antibody (ANCA) (proteinase-3) positive, vasculitis with renal insufficiency due to a pauci-immune necrotizing glomerulonephritis. An infective process was initially excluded by blood cultures and an echocardiogram prior to immunosuppression. The patient's condition failed to improve and re-evaluation confirmed infective endocarditis requiring valve replacement. Subsequent tissue cultures identified Bartonella henselae. Antibiotic treatment led to full resolution of physical, biochemical and immunological markers. This is the first case of B. henselae endocarditis-associated ANCA positivity with a pauci-immune glomerulonephritis. It demonstrates the importance of revisiting standard investigations in patients not improving expectantly on conventional therapy.

Outcome after Discontinuation of Immunosuppression in Children with Autoimmune Hepatitis: A Population-Based Study

To assess sustained immunosuppression-free remission (SIFR) in children with autoimmune hepatitis (AIH). We retrospectively reviewed all children with AIH in the region between 1986 and 2011 using a population-based methodology. We identified 56 children with AIH (62.5% females; median age, 11.1years [IQR, 5.7-14.4years], followed for a median of 5.6years [IQR, 2.8-8.6years]). Liver disease was characterized by type II AIH in 8.9%, cirrhosis in 14.0%, and primary sclerosing cholangitis in 21.4%. Coexisting nonhepatic immune-mediated diseases occurred in 37.5%. Biochemical remission on immunosuppressive therapy was achieved in 76.4% of all patients with AIH at a median of 1.2years (IQR, 0.4-3.6years); 23.1% of these patients experienced a subsequent relapse. Discontinuation of all immunosuppressive medications was attempted in 16 patients and was successful in 14 patients (87.5%) with type 1 AIH (median age at discontinuation, 8.9years [IQR, 3.5-17.9years], treated for a median of 2.0years [IQR, 1.3-3.5years] after diagnosis), with SIFR occurring at a median of 3.4years (IQR, 2.6-5.8years) of follow-up. Excluding patients with inflammatory bowel disease who received immunosuppressive therapy independent of their liver disease, the probability of achieving SIFR within 5years of diagnosis of AIH was 41.6% (95% CI, 25.3%-62.9%). Baseline patient characteristics associated with an inability to achieve biochemical remission on immunosuppression or SIFR were elevated international normalized ratio, positive antineutrophil cytoplasmic antibody titer, cirrhosis, and a nonhepatic autoimmune disorder. We found a high rate of successful discontinuation of all immunosuppressive medications in carefully selected patients with AIH in a population-based cohort. SIFR is an achievable goal for children with AIH, particularly those with type I disease in stable biochemical remission on immunosuppressive therapy.

Mediastinal Fibrosis and Positive Antineutrophil Cytoplasmic Antibodies: Coincidence or Common Etiology?

Retroperitoneal fibrosis (RPF) with positive antineutrophil cytoplasmic antibodies (ANCA) has been reported in several cases. We herein present the case of a 52-year-old woman who was diagnosed with mediastinal fibrosis (MF) on a thoracoscopic surgical biopsy. The patient had positive myeloperoxidase ANCA and thereafter developed crescentic glomerulonephritis, which was considered to be a form of ANCA-related nephritis. Both the MF and crescentic glomerulonephritis favorably responded to immunosuppressive therapy. These findings suggest a common pathogenesis of these disorders involving ANCA positivity, as reported in patients with RPF.