Myeloperoxidase-antineutrophil Cytoplasmic Antibody Research Articles

Chest High-Resolution CT Findings of Microscopic Polyangiitis: A Japanese First Nationwide Prospective Cohort Study.

OBJECTIVE. The lung is one of the organs possibly involved in microscopic polyangiitis (MPA), and myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA) is commonly found in patients with MPA. The aim of this study was to assess pulmonary lesions in Japanese patients with MPA. SUBJECTS AND METHODS. This prospective study was based on 144 patients with MPA who were enrolled in the Remission Induction Therapy in Japanese Patients With ANCA-Associated Vasculitis and Rapidly Progressive Glomerulonephritis Study and who underwent chest high-resolution CT (HRCT) imaging at the time of diagnosis during 2011-2014. We reviewed the electronic case report forms of patients with MPA who did and did not have interstitial pneumonia (IP), and the clinical features and laboratory findings of these groups were compared. RESULTS. Abnormal HRCT findings were noted in 134 of the 144 patients (93%). Chest HRCT findings included ground-glass opacity (n = 72; 50%), reticulation (n = 69; 48%), traction bronchiectasis (n = 57; 42%), honeycombing (n = 44; 31%), and emphysema (n = 32; 22%). IP was diagnosed radiologically in 74 patients (51%), 38% of whom had the usual IP (UIP) pattern. Ground-glass opacity, reticulation, traction bronchiectasis, honeycombing, and interlobular septal thickening were frequent in patients with IP (p < 0.05). Patients with MPA with the UIP or possible UIP pattern also had minor findings, such as bronchial wall thickening, consolidation, increased attenuation around honeycombing, and traction bronchiectasis. CONCLUSION. IP (51%) was most commonly observed in Japanese patients with MPA, and 38% of these patients exhibited a UIP pattern. Increased attenuation around honeycombing or traction bronchiectasis was also found.

Prognostic nutritional index is associated with disease severity and relapse in ANCA-associated vasculitis.

The prognostic nutritional index (PNI), calculated by serum albumin and peripheral blood lymphocyte count, is considered to reflect immune-related nutritional status. In this study, we first investigated the clinical significance of PNI in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Medical records of 160 patients classified as AAV from October 2000 to September 2017 were reviewed. We calculated the Birmingham vasculitis activity score (BVAS) and collected laboratory data including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, white blood cell, lymphocyte, and platelet counts, and serum albumin, aspartate aminotransferase, and alanine aminotransferase levels at diagnosis. PNI at diagnosis was calculated as (10×serum albumin [g/dL] + 0.005×lymphocyte count [/mm3 ]). Associations between laboratory variables, PNI, and BVAS were assessed by linear regression analyses, and Cox proportional hazard analysis was used to evaluate factors associated with disease relapse. The mean age was 55.2years and 48 patients (30.0%) were male. In univariable linear regression analysis, BVAS was positively correlated with ESR and CRP and negatively with lymphocyte count, serum albumin, and PNI (r=-0.307). In multivariable linear regression analysis, among ESR, CRP, and PNI, PNI was associated with BVAS (β=-0.299). PNI also significantly correlated with the included laboratory data. In Cox proportional hazard analysis, myeloperoxidase-antineutrophil cytoplasmic antibody positivity (odds ratio [OR] 2.875, P=0.003) and PNI ≤36.75 (OR 2.066, P=0.042) revealed to be independent predictors of disease relapse during the follow-up period. Prognostic nutritional index at diagnosis might be useful for assessing disease severity and predicting the prognosis of AAV patients.

Epipharyngeal Inflammation in Myeloperoxidase–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Epipharyngeal Inflammation in Myeloperoxidase–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Differential Diagnosis of Churg-Strauss Syndrome with Tingling Sensation and Weakness of the Lower Extremities

IntroductionChurg-Strauss syndrome (CSS; or eosinophilic granulomatosis with polyangiitis) is an extremely rare autoimmune condition characterized by hypereosinophilia and vasculitis of small or medium-sized blood vessels, occurring in patients with asthma and allergic rhinitis.Case PresentationA 47-year-old man (height, 175.8 cm and weight, 74.8 kg) complained of a tingling sensation in his leg. He had a history of hypertension and asthma in the previous two years, and history of sinus surgery for sinusitis in the previous one year. He showed weight loss of 6 kg during the last month, and the signal intensity of the bone marrow on magnetic resonance imaging was diffusively reduced to be less than or equal to the disc. These findings indicated a hematologic disease and the possibility of malignancy. However, a nerve conduction study suggested multiple mononeuropathies. In addition, his laboratory findings showed peripheral eosinophilia and positivity for myeloperoxidase anti-neutrophil cytoplasmic autoantibody. Therefore, CSS was strongly suspected.ConclusionsChurg-Strauss syndrome is considered to be a condition with variable presentation and is difficult to diagnose because it has various clinical symptoms and disease progression. This study reports on a case with CSS, who underwent nerve biopsy and cholecystectomy for pathological confirmation because of various symptoms, and early diagnosis was difficult.

Microscopic polyangiitis secondary to Mycobacterium abscessus in a patient with bronchiectasis: a case report

BackgroundNon-Tuberculous Mycobacterial–pulmonary disease (NTM-PD) is increasing in incidence and prevalence. Mycobacterium abscessus (M.abscessus) is a rapid growing multi-resistant NTM associated with severe NTM-PD requiring prolonged antibiotic therapy. Complications of therapy are common but reports on direct complications of active NTM-PD are rare. Vasculitis has been described as a rare complication of NTM-PD, most often in individuals with inherited immune defects. This case is the first to describe an ANCA positive vasculitide (Microscopic Polyangiitis) secondary to M.abscessus pulmonary disease.Case presentationA 70 year old female with bronchiectasis underwent a clinical decline associated with the growth of M.abscessus and was diagnosed with NTM-PD. Before treatment could be initiated she developed small joint arthralgia and a glove and stocking axonal loss sensorimotor neuropathy. Positive Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (P-ANCA) and Myeloperoxidase-ANCA (MPO-ANCA) titres led to a diagnosis of microscopic polyangiitis. Further investigation revealed reduced interferon-gamma production but no other significant immune dysfunction.Dual treatment with immunosuppressive therapy (Corticosteroids/Cyclophosphamide) for vasculitis and antimicrobial therapy for M.abscessus NTM-PD was initiated. Clinical stability was difficult to achieve with reductions in immunosuppression triggering vasculitic flares. One flare led to retinal vein occlusion with impending visual loss requiring escalation in immunosuppression to Rituximab infusions. An increase in immunosuppression led to a deterioration in NTM-PD necessitating alterations to antibiotic regimes. Adverse effects including alopecia and Achilles tendonitis have further limited antibiotic choices resulting in a strategy of pulsed intra-venous therapy to stabilise NTM-PD.ConclusionsThis is the first reported case of an ANCA positive vasculitis secondary to M.abscessus pulmonary disease. This rare but important complication had a significant impact on the patient adding to the complexity of an already significant disease and treatment burden. The potential role of reduced interferon-gamma production in this case highlights the importance of investigating immune function in those with mycobacterial infection and the intricate relationship between mycobacterial infection and immune dysfunction. Immune dysfunction caused by genetic defects or immunosuppressive therapy is a known risk factor for NTM-PD. Balancing immunosuppressive therapy with prolonged antimicrobial treatment is challenging and likely to become more common as the number of individuals being treated with biologics and immunosuppressive agents increases.

Is granulomatosis with polyangiitis in Asia different from the West?

The incidence and clinical features of antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) have been shown to vary according to geographical areas, with granulomatosis with polyangiitis (GPA) being more common in northern Europe and microscopic polyangiitis (MPA) being more common in Asian countries. The annual incidence of GPA among Asians varies between 0.37/million to 2.1/million population. The prevalence of GPA has been estimated to be 1.94/100000 in a Chinese population. Polymorphisms in class II major histocompatibility genes and ETS1 proto-oncogene has been shown in Asian patients with GPA. There is a difference in mean age at onset and proteinase 3 (PR3) or myeloperoxidase (MPO) positivity in GPA patients from different Asian countries. Those from India had mean age of 40years and those from Japan had mean age of 65years. Sixty percent of GPA patients from China and Japan were MPO ANCA positive while the majority of patients from India and Korea were PR3 positive. Geographical variation with lower frequency of renal involvement in Indian studies and higher frequency in Chinese patients has also been noted. Treatment outcomes have been similar to those reported from other parts of the world. Remission was achieved in about two-thirds of patients while relapses were noted in one-third to half of the patients. Apart from minor differences in the organ systems involved, MPO-ANCA GPA and PR3-ANCA GPA had similar rates of remission and relapses.

Prognostic Factors for Survival and Relapse in ANCA-Associated Vasculitis with Renal Involvement: A Clinical Long-Term Follow-Up Study.

Aim We describe the clinical pattern of ANCA-associated vasculitis (AAV) and assess long-term prognostic factors of patients and renal survival and relapse. Methods Data from 85 patients with renal biopsy-proven AAV at a single center with up to 20-year [median 16.2 years (95% CI 14.9-17.7)] follow-up were retrospectively collected. Results Overall, 55% of the patients had microscopic polyangiitis (MPA) and 45% had granulomatosis with polyangiitis (GPA). The histopathological classes were focal in 35%, crescentic in 26%, mixed in 20%, and sclerotic glomerulonephritis in 19% of the patients. As induction treatment, a combination of cyclophosphamide and corticosteroids was given to 82%, while a combination of azathioprine and corticosteroids was maintenance therapy in 79%. The twenty-year patient survival was 45%. In a multivariable analysis, age ≥58 years [hazard ratio (HR) 7.64, 95% CI 3.44-16.95] and myeloperoxidase (MPO) ANCA (HR 2.12, 95% CI 1.08-4.17) were associated with shorter patient survival time. Renal survival was 68% overall: 88% in focal, 71% in crescentic, 56% in mixed, and 37% in sclerotic class (p=0.01). Female sex (HR 0.26, 95% CI 0.10-0.73) was a predictor of improved renal survival, whereas GFR <30 ml/min and MPO-ANCA were associated with worse renal survival (HR 4.10, 95% CI 1.35-12.49 and HR 3.10, 95% CI 1.21-7.95, respectively). Relapse-free survival at 20 years was 10%. MPA was associated with a lower risk for relapse (HR 0.48, 95% CI 0.28–0.82). Conclusion We confirmed the improved patient and renal survival in AAV patients with glomerulonephritis, while relapse remained the primary challenge. Histopathological classification may be relevant for survival.

Clinical significance of myeloperoxidase-anti-neutrophil cytoplasmic antibody in idiopathic interstitial pneumonias

ObjectiveAlthough a possible association among myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA), microscopic polyangiitis (MPA), and idiopathic pulmonary fibrosis (IPF) has been suggested, the clinical significance of MPO-ANCA in idiopathic interstitial pneumonias (IIPs), including IPF and non-IPF, remains unclear. We aimed to investigate the frequency of MPO-ANCA positivity, as well as MPA incidence and risk factors for development in patients initially diagnosed with IIP.MethodsWe retrospectively analysed 305 consecutive patients who were initially diagnosed as IIP and had MPO-ANCA results available.ResultsOf the 305 patients, 26 (8.5%) were MPO-ANCA-positive. Baseline characteristics were similar between the MPO-ANCA-positive and -negative patients. The cumulative 5-year MPA incidence was 24.3% in the MPO-ANCA-positive patients and 0% in the -negative patients (P < 0.0001). MPO-ANCA was positive in 15 of 133 (11.3%) patients initially diagnosed with IPF and in 11 of 172 (6.3%) patients initially diagnosed with non-IPF (P = 0.56), with cumulative 5-year MPA incidence of 6.2% and 1.0%, respectively (P = 0.10). Multivariate analysis revealed that UIP pattern on HRCT (HR = 3.20, P < 0.01) and no treatment for IIP (HR = 3.52, P < 0.01) were independently associated with MPA development in MPO-ANCA-positive patients.ConclusionMPO-ANCA positivity was uncommon, but was associated with subsequent MPA development in patients initially diagnosed with IIP, including both IPF and non-IPF cases. The study suggested that attention should be paid to MPA development in MPO-ANCA-positive IIP patients with UIP pattern on HRCT and those without treatment for IIP.

Microscopic polyangiitis presented with biopsy-confirmed pleuritis.

We describe a case of microscopic polyangiitis manifested as pleuritis confirmed by thoracoscopic biopsy. An 80-year-old man presented with a three-day history of shortness of breath and cough. Chest radiography revealed patchy opacities in the lower fields of the bilateral lung and right-sided pleural effusion. Thoracentesis revealed lymphocytic pleural exudates. Thoracoscopic biopsy specimens were compatible with fibrotic pleuritis. He developed rapidly progressive glomerulonephritis with elevated myeloperoxidase anti-neutrophil cytoplasmic antibody titer in blood and pleural effusion. Although the patient was resistant to two weekly courses of pulse steroid therapy, he was successfully treated with a five-day course of intravenous immunoglobulin.

Brief Report: Circulating Cytokine Profiles and Antineutrophil Cytoplasmic Antibody Specificity in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

To evaluate circulating cytokine profiles in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), classified by antineutrophil cytoplasmic antibody (ANCA) specificity (proteinase 3 ANCA [PR3-ANCA] versus myeloperoxidase ANCA [MPO-ANCA]) or by clinical diagnosis (granulomatosis with polyangiitis [GPA] versus microscopic polyangiitis [MPA]). A panel of 29 cytokines was tested in 186 patients with active AAV at inclusion into the Rituximab in AAV trial. Cytokine concentrations were compared between groups within each classification system. Multivariable analyses adjusted for age, sex, and renal insufficiency were performed, with each biomarker as a dependent variable and ANCA specificity and clinical diagnosis as explanatory variables of interest. Levels of 9 circulating cytokines (interleukin-6 [IL-6], granulocyte-macrophage colony-stimulating factor [GM-CSF], IL-15, IL-18, CXCL8/IL-8, CCL-17/thymus and activation-regulated chemokine [TARC], IL-18 binding protein [IL-18 BP], soluble IL-2 receptor α [sIL-2Rα], and nerve growth factor β [NGFβ]) were significantly higher in PR3-AAV than MPO-AAV, 4 cytokines (sIL6R, soluble tumor necrosis factor receptor type II [sTNFRII], neutrophil gelatinase-associated lipocalin [NGAL], and soluble intercellular adhesion molecule 1 [sICAM-1]) were higher in MPO-AAV than in PR3-AAV, 6 cytokines (IL-6, GM-CSF, IL-15, IL-18, sIL-2Rα, and NGFβ) were higher in GPA than in MPA, and 3 cytokines (osteopontin, sTNFRII, and NGAL) were higher in MPA than in GPA (all P < 0.05). For nearly all cytokines, the difference between PR3-AAV and MPO-AAV was larger than that between GPA and MPA. The multivariate analysis showed that 8 cytokines (IL-15, IL-8, IL-18 BP, NGF-β, sICAM-1, TARC, osteopontin, andkidney injury molecule 1 (P < 0.05) distinguished patients with AAV better (lower P values and larger effect sizes) when grouped by ANCA specificity than by clinical diagnosis. Distinct cytokine profiles were identified for PR3-AAV versus MPO-AAV and for GPA versus MPA. Differences in these circulating immune mediators are more strongly associated with ANCA specificity than with clinical diagnosis, suggesting that heterogeneity in the AAV subtypes extends beyond clinical phenotypes.

56 Atypical Myeloperoxidase Anti-Neutrophil Cytoplasmic Antibody (MPO-ANCA ) Associated Cresentic Glomerulonephritis ( GN ) with Immune Deposits Overlap with Crest

56 Atypical Myeloperoxidase Anti-Neutrophil Cytoplasmic Antibody (MPO-ANCA ) Associated Cresentic Glomerulonephritis ( GN ) with Immune Deposits Overlap with Crest

Acantholytic squamous cell carcinoma of the lung with marked lymphogenous metastases and high titers of myeloperoxidase-antineutrophil cytoplasmic antibodies: a case report

BackgroundAcantholytic squamous cell carcinoma (ASQCC), histologically characterized by intercellular bridge loosening, is recognized as a rare variant of squamous cell carcinoma (SQCC). ASQCC may demonstrate a worse prognosis than conventional SQCC. Pulmonary ASQCC is particularly rare; its biological behavior and prognostic data have not been reported.Case presentationWe report the clinical and autopsy findings of a 71-year-old Japanese man with pulmonary ASQCC. Pulmonary lesions, suggestive of idiopathic interstitial pneumonia, were radiologically observed 3 and 6 years prior to the patient’s most recent hospitalization; however, the patient did not undergo further medical examinations. Upon being discovered unconscious, the patient was admitted to our hospital. Dehydration and lower limb muscle weakness were noted, as were laboratory findings of coagulation abnormalities and renal dysfunction. Computed tomography helped confirm a 21-mm peripheral nodule in the upper left lobe of the lung, with associated swollen lymph nodes in the bilateral hilar, mediastinal, and para-aortic regions. Brain and spinal lesions, suggestive of neurological disturbances, were not found. Small cell lung carcinoma was suspected, upon admission, but high serum levels of squamous cell carcinoma antigen and cytokeratin-19 fragments were present. Therefore, advanced lung cancer, possibly SQCC, was diagnosed. The patient was treated with best supportive therapy, and died one month after admission. Hypercalcemia and high serum levels of parathyroid hormone-related protein (PTHrP) and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titers were observed. Progressive renal insufficiency was absent due to improved renal function subsequent to hydration. An autopsy helped confirm the left lung tumor as an ASQCC associated with pulmonary lymphangitic carcinomatosis and multiple metastases in the lungs and lymph nodes. Skin lesions suggesting malignant tumors were absent. The metastatic lesions consisted largely of acantholytic tumor cells, and the lungs showed usual interstitial pneumonia pattern; vasculitis was absent.ConclusionsThis is the first reported case of pulmonary ASQCC resulting in an aggressive clinical course, with marked lymphogenous metastases and PTHrP-associated hypercalcemia. The high serum MPO-ANCA titers were clinicopathologically insignificant, but may have been related to the pulmonary interstitial lesion. Pulmonary ASQCC represents a highly malignant subset of lung cancer.

Clinical significance of Anti-neutrophil Cytoplasmic Antibodies to Proteinase-3 (PR3-ANCA) in Patients With Ulcerative Colitis

BACKGROUND: Recently, many reports have been made on diagnostic value of anti-neutrophil cytoplasmic antibodies (ANCA) in patients with ulcerative colitis (UC). However, clinical significance of PR3-ANCA for UC is not well understood yet. We aim to analyze the clinical significance of PR3-ANCA in patients with UC. METHODS: 74 patients with UC evaluated to proteinase-3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) from July 2013 to July 2017 in our hospital were analyzed. Clinical remission was defined as less than 5 points of Lichtiger index, and endoscopic mucosal healing (MH) was defined as Mayo endoscopic score 0 or 1, respectively. We evaluated the ratio of positive for PR3- and MPO-ANCA in UC patients, and also evaluated the differences of clinical features between ANCA-positive and ANCA-negative groups. RESULTS: Out of 74 UC-patients, 46 (62.1%) and 8 (10.8%) were positive for PR3-ANCA and MPO-ANCA, respectively. All cases positive for MPO-ANCA were also positive for PR3-ANCA. The ratio of patients with extensive colitis in the PR3-ANCA-positive group was significantly higher than that in the PR3-ANCA-negative group (71.7% and 46.6%, respectively; P=0.03). Moreover, the disease activity and MH rate of PR3-ANCA positive group was significantly higher and lower than those of PR3-ANCA negative group, respectively (disease activity: P=0.015, and MH rate: P<0.01). On the other hand, there was no significant difference in clinical characteristics, such as gender, age, serum level of C-reactive protein (CRP) and albumin levels, between the PR3-ANCA-positive and PR3-ANCA-negative group. However, regression analysis demonstrated that the titer of PR3-ANCA was significantly related with the serum level of albumin (r=0.396, P<0.01) and C-reactive protein (r=0.156, P<0.01), although there was no relationship between the titer of PR3-ANCA and Lichtiger index. In the sequent clinical course, the ratio of UC-patients requiring infliximab in the PR3-ANCA-positive group was also higher than that in the PR3-ANCA-negative group (17.4% and 0%, respectively; P=0.013). On the other hand, there was no significant difference in the ratio of UC-patients requiring surgery between the PR3-ANCA-positive and the PR3-ANCA-negative group (12.2% vs 0%, respectively; P>0.05). CONCLUSION(S): PR3-ANCA may be the prognostic factor for refractory UC requiring intensive therapies, because there is less rate of MH in the group of PR3-ANCA positive, apparently.

Diffuse Alveolar Hemorrhage Developing Immediately after Immunosuppressive Treatments in a Patient with Granulomatosis with Polyangiitis Who Had Pulmonary Nodules

A 65-year-old man was diagnosed with granulomatosis with polyangiitis (GPA) based on the detection of high myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), vasculitis and granulomas in a lung biopsy specimen and crescentic glomerulonephritis in a kidney biopsy specimen. Soon after the initiation of intravenous methylprednisolone pulse therapy (mPSL pulse) and intravenous cyclophosphamide pulse therapy (IVCY), the patient experienced cough and hemoptysis. Based on emerging anemia and bilateral diffuse lung consolidation on computed tomography, we judged that diffuse alveolar hemorrhage (DAH) was complicated by GPA. The patient's DAH improved following additional mPSL pulse and IVCY. Physicians should be aware of the possible occurrence of DAH, even when a patient's symptoms improve after mPSL pulse and IVCY.

Do you know otitis media with ANCA‐Associated Vasculitis (OMAAV)?

Hearing loss is often the only symptom of OMAAV at initial presentation, thus making early diagnosis difficult. We present OMAAV in a 70‐year‐old woman with hearing loss and dry cough. Otoscopy showed otitis media with effusion. Audiometry showed mixed hearing loss, especially in the right ear. Serum myeloperoxidase antineutrophil cytoplasmic antibody was positive. Image analyses showed lung lesion and interstitial pneumonia, while bronchoscopy showed possible microscopic polyangiitis. After starting and tapering prednisolone, respiratory and otologic symptoms improved. When examining patients with acute otologic symptoms and suspected lung and/or renal disease, OMAAV should be included in differential diagnosis.

A multicentre study to improve clinical interpretation of proteinase-3 and myeloperoxidase anti-neutrophil cytoplasmic antibodies.

Objective The objective of this multicentre study was to improve the clinical interpretation of PR3- and MPO-ANCAs as an adjunct for the diagnosis of ANCA-associated vasculitis (AAV) by defining thresholds and test result intervals based on predefined specificities and by calculating test result interval-specific likelihood ratios (LRs). Methods Eight different PR3- and MPO-ANCA immunoassays from seven companies were evaluated using 251 diagnostic samples from AAV patients and 924 diseased controls. Results Thresholds for antibody levels were determined based on predefined specificities (95, 97.5, 99 and 100%) and used to delimit test result intervals. Test result interval-specific LRs were determined. For all assays, the LR for AAV increased with increasing antibody level. For all but one immunoassay, high antibodies levels (associated with LR >55) were found in a substantial fraction (>65%) of patients. The area under the curve (AUC) of receiver operating characteristics analysis of a diagnostic approach in which positive results were confirmed by IIF or another immunoassay was not substantially higher than the AUC of performing immunoassay only. The highest AUC was found when immunoassay was combined with another immunoassay or with IIF. Conclusion To diagnose AAV based on PR3- and MPO-ANCA, it is useful to define thresholds for antibody levels and to assign test result interval-specific LRs. Higher antibody levels are associated with a higher likelihood for disease. Such information improves clinical interpretation.

Year in review 2016: Interstitial lung disease, pulmonary vascular disease, pulmonary function, paediatric lung disease, cystic fibrosis and sleep.

Year in review 2016: Interstitial lung disease, pulmonary vascular disease, pulmonary function, paediatric lung disease, cystic fibrosis and sleep.

Pre-existing chronic interstitial pneumonia is a poor prognostic factor of Goodpasture\u2019s syndrome: a case report and review of the literature

BackgroundGoodpasture’s syndrome is a rare disease that is characterized by rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage.Case presentationA 71-year-old Japanese man who had chronic interstitial pneumonia was diagnosed as having Goodpasture’s syndrome. Both anti-glomerular basement membrane antibody and myeloperoxidase anti-neutrophil cytoplasmic antibody were increased. Despite intensive treatments, including mechanical ventilation, he died from respiratory failure. Pathological findings at autopsy showed rapidly progressive glomerulonephritis in his kidneys, diffuse alveolar hemorrhage, hyaline membranes, and fibroblastic foci in his lungs. The cause of death was diagnosed as respiratory failure as a result of diffuse alveolar damage induced by a combination of diffuse alveolar hemorrhage and exacerbation of interstitial pneumonia.ConclusionsWe report a case of Goodpasture’s syndrome complicated with pre-existing chronic interstitial pneumonia and positive myeloperoxidase anti-neutrophil cytoplasmic antibody. We reviewed six similar cases reported in the literature and concluded that Goodpasture’s syndrome with pre-existing interstitial pneumonia and myeloperoxidase anti-neutrophil cytoplasmic antibody is related to a poor prognosis.

Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis.

Background The subclinical pathophysiology of proliferative lupus nephritis (PLN) has not been fully elucidated. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is associated with PLN, but prediagnostic levels have not been reported. Methods We performed a retrospective case-control Department of Defense Serum Repository (DoDSR) study comparing MPO-ANCA levels in longitudinal prediagnostic serum samples for 23 biopsy confirmed proliferative lupus nephritis (PLN) patients to DoDSR identified age, sex, race, and age of serum matched healthy and SLE without LN disease controls. We also compared the temporal relationship of MPO-ANCA to anti-double stranded DNA antibodies (dsDNAab). Results A greater proportion of PLN patients had prediagnostic MPO-ANCA levels above ≥3 U/mL and ≥6 U/mL compared to SLE without LN (91% versus 43%, p < 0.001; 57% versus 5%, p < 0.001, resp.). In subgroup analysis, the MPO-ANCA threshold of ≥3 U/mL was significant at <1 year (88% versus 39%, p = 0.007) and 1–4 years (87% versus 38%, p = 0.009) prior to diagnosis. Statistically significant subclinical MPO-ANCA levels (≥3 U/mL) occurred prior to statistically significant dsDNAab ≥ 3 IU/ml (89% versus 11%, p = 0.003). Conclusions Subclinical MPO-ANCA levels could distinguish future PLN from SLE without LN. MPO-ANCA manifests prior to clinical disease and subclinical dsDNAab to suggest that it may contribute directly to PLN pathogenicity.

Myeloperoxidase-Antineutrophil Cytoplasmic Antibody (ANCA)-Positive and ANCA-Negative Patients With Granulomatosis With Polyangiitis (Wegener's): Distinct Patient Subsets.

To examine the relationship of antineutrophil cytoplasmic antibody (ANCA) type and ANCA-associated vasculitis (AAV) diagnosis with demographic features, disease manifestations, and clinical outcomes. We focused on patients who account for the differences between ANCA type and disease type classifications: anti-myeloperoxidase (MPO)-ANCA-positive and ANCA-negative patients with granulomatosis with polyangiitis (Wegener's) (GPA). We performed a pooled analysis of the Wegener's Granulomatosis Etanercept Trial and the Rituximab in ANCA-Associated Vasculitis trial comparing patients with MPO-ANCA-positive GPA and patients with ANCA-negative GPA to patients with proteinase 3 (PR3)-ANCA-positive GPA and patients with MPO-ANCA-positive microscopic polyangiitis (MPA). Of the 365 patients analyzed, 273 (75%) had PR3-ANCA-positive GPA, 33 (9%) had MPO-ANCA-positive GPA, 15 (4%) had ANCA-negative GPA, and 44 (12%) had MPO-ANCA-positive MPA. MPO-ANCA-positive GPA patients were younger at diagnosis compared to MPO-ANCA-positive MPA patients (53 versus 61 years; P = 0.02). Their disease manifestations and rates of relapse were similar to those of PR3-ANCA-positive GPA patients. Relapse was more frequent in MPO-ANCA-positive GPA patients than in patients with MPO-ANCA-positive MPA at trial entry as well as at 12 and 18 months. ANCA-negative patients with GPA had lower Birmingham Vasculitis Activity Score for Wegener's Granulomatosis scores at trial entry than PR3-ANCA-positive patients with GPA (4.5 versus 7.7; P < 0.01), primarily because of a lower prevalence of renal involvement. We were unable to demonstrate important clinical differences between MPO-ANCA-positive and PR3-ANCA-positive patients with GPA. The risk of relapse was associated more closely with disease type than with ANCA type in this patient cohort. These findings deserve consideration in the assessment of relapse risk in patients with AAV.