Perinuclear Antineutrophil Cytoplasmic Antibodies Research Articles

Perinuclear Antineutrophil Cytoplasmic Antibodies Vasculitis Presenting as Pulmonary-Renal Syndrome in a Patient With a History of Seropositive Rheumatoid Arthritis.

Perinuclear Antineutrophil Cytoplasmic Antibodies Vasculitis Presenting as Pulmonary-Renal Syndrome in a Patient With a History of Seropositive Rheumatoid Arthritis.

SADDLE NOSE DEFORMITY FROM EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS: THE VERY FIRST CASE

SESSION TITLE: Pulmonary Pathology SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/20/2019 01:00 pm - 02:00 pm INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystem vasculitic disorder that predominantly affects medium and small sized blood vessels. EGPA belongs to a group of vasculitides known as anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). Upper airway involvement is seen in all ANCA associated vasculitides, but destructive upper airway disease has never been reported in patients with EGPA. CASE PRESENTATION: A 50-year-old female with a history of difficult to control asthma for more than 15 years and chronic rhinitis presented to the hospital with severe jaw and ear pain. Vital signs on admission were unremarkable. Physical examination revealed bilateral mandibular tenderness and a normal appearing nasal mucosa. A CT scan of her neck with contrast demonstrated left maxillary sinus thickening and multiple nodules bilaterally at the lung apices. CT scan of the chest revealed bilateral nodules. A clinical diagnosis of EGPA was made and serologic work up was positive for perinuclear ANCA (P-ANCA) and Anti- myeloperoxidase (MPO-ANCA) antibody. Open lung biopsy was performed, and histopathology was consistent with necrotizing granulomatous vasculitis with extravascular eosinophilic infiltrate. She was treated with prednisone and azathioprine. Later on, she developed nonischemic cardiomyopathy. She was started on IV cyclophosphamide with good response. During an office visit, the patient was noted to have depressed nasal bridge with erythematous nasal mucosa. The patient underwent reconstruction of her nasal bridge and currently doing well. DISCUSSION: EGPA most commonly involves upper airway, peripheral nerves, skin and lungs. Destructive upper airway disease, such as saddle nose deformity (SND) is a well-known complication of other AAV, especially granulomatosis with polyangiitis (GPA) but has never been reported in EGPA patients. Other causes of SND include relapsing polychondritis, granulomatous infection, lymphomatoid granulomatosis, lymphoma, carcinoma and trauma. Ear, nose and throat (ENT) involvement is common with EGPA with a reported incidence of 48% on presentation. The most common symptoms include rhinitis, non-erosive sinusitis and nasal polyposis. According to five factors scoring (FFS) system presence of ENT symptoms is considered to convey a better prognosis. It is possible that the SND in our patient was a manifestation of severe systemic inflammation and developed slowly over a 2-year period. The severity of AAV have been proposed to be related to the type of autoantibody rather than the individual vasculitic syndrome. Presence of anti-proteinase 3 antibody (PR3-ANCA) is associated with worse disease severity and more chances of relapse. CONCLUSIONS: Erosive upper airway disease from EGPA has never been reported. We are reporting the first case of SND from EGPA with the hope to enrich the medical literature and encourage further research. Reference #1: Sinico RA, Bottero P. Churg-Strauss angiitis. Best practice & research Clinical rheumatology. 2009;23(3):355-66. DISCLOSURES: No relevant relationships by Scott Beegle, source=Web Response No relevant relationships by Biplab Kumar Saha, source=Web Response No relevant relationships by Aditi Saha, source=Web Response No relevant relationships by Boris Shkolnik, source=Web Response

Abstract 2663: Regulation of ER stress-mediated cell death by calcium mobilization: A potential mitochondrial pathway for 15-deoxy-Δ12,14prostamide J2cytotoxicity in melanoma

Abstract Melanoma is the most aggressive and deadly form of cutaneous cancer in the United States, representing a major clinical challenge. Our lab previously demonstrated that the endocannabinoid metabolite, 15-deoxy, Δ12,14 prostamide J2 (15d-PMJ2), was an effective and selective inducer of apoptotic cell death in B16F10 murine melanoma cells. Furthermore, we found that 15d-PMJ2 mediated apoptosis was regulated by endoplasmic reticulum (ER) stress. Numerous studies have determined that ER stress causes Ca+2 flux, and that this action initiates cellular apoptosis. As such, we investigated Ca+2 mobilization in the context of 15d-PMJ2-mediated ER stress. In B16F10 melanoma cells, 15d-PMJ2 significantly increased cytosolic Ca+2 levels. Blockade of Ca+2 channels using ruthenium red (a pan Ca+2 channel inhibitor) or 2-APB (an IP3 selective inhibitor) decreased the cytotoxicity of 15d-PMJ2. To investigate the role of ER stress in Ca+2 mobilization, cells were pretreated with the ER stress inhibitors, phenylbutyric acid (PBA) and GSK2602 (a PERK-selective inhibitor). Both inhibitors significantly lowered cytosolic Ca+2 levels suggesting Ca+2 flux is mediated by ER stress. Moreover, BAP31, an important regulator of endoplasmic Ca+2 release and ER stress was activated following exposure to 15d-PMJ2. To understand the impact of elevated Ca+2 levels, we investigated cysteine proteases (calpains) and mitochondrial Ca+2, both of which induce apoptosis in a Ca+2-dependent manner. Our results show that mitochondrial Ca+2 levels were significantly increased by 15d-PMJ2 and that this effect was prevented by blocking ER stress. In contrast, 15d-PMJ2 increased calpain-2 activity however, the inhibition of calpain had no effect on the cytotoxicity of 15d-PMJ2. These findings indicate that mitochondrial Ca2+ flux, but not calpains regulate ER stress apoptosis induced by 15d-PMJ2. It has been reported that the activity of J-series prostaglandins is conferred by an electrophilic double bond contained within its cyclopentenone ring. To evaluate the significance of this moiety in 15d-PMJ2, a neutral analog (neutral-15d-PMJ2) lacking the double bond was synthesized. We determined that that the accumulation of intracellular and mitochondrial Ca2+ was dependent on the electrophilic double bond, suggesting it is a critical structural component required for activity. Taken together, these data indicate that the mobilization of calcium to the cytoplasm and mitochondria may critically regulate ER stress apoptosis that is mediated by 15d-PMJ2. Citation Format: Daniel Alexander Ladin, Estefani Cota, Rukiyah Van Dross. Regulation of ER stress-mediated cell death by calcium mobilization: A potential mitochondrial pathway for 15-deoxy-Δ12,14prostamide J2cytotoxicity in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2663.

Abstract 4294: C6 Ceramide potentiates paclitaxel and gemcitabine mediated antitumor effects against pancreatic cancer via inhibition of prosurvival PI3k/AKT/mTOR and ERK pathways

Abstract The 5% survival of pancreatic cancer emphasizes need for new treatment strategies. Our studies suggest potential value of C6Ceramide (C6Cer) as a chemotherapeutic adjunct. The current study demonstrates that combination chemotherapy of Paclitaxel with adjunct C6Cer significantly increased cell death (apoptosis) in pancreatic cancer cell lines (L3.6,PANC-1, MIA (PaCa-2) in vitro as well as in vivo - enhancing tumor regression in SCID mice bearing L3.6 transplants. A similar synergistic effect was observed with addition of C6Cer to cetuximab which is not effective in KRAS mutant Pancreatic or Colorectal cancer and thus is not used clinically. At the molecular level combining C6Cer with Gemcitabine or Paclitaxel resulted in significant decreased p-AKT and p-GSK-a/b(PI3K/AKT (survival)pathway in L3.6 cells. Conclusion: C6Cer significantly inhibited key cancer survival pathways resulting in significant synergism with chemotherapeutics in therapy of Pan Ca and KRAS mutant CRC. Citation Format: Harold J. Wanebo. C6 Ceramide potentiates paclitaxel and gemcitabine mediated antitumor effects against pancreatic cancer via inhibition of prosurvival PI3k/AKT/mTOR and ERK pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4294.

Epidemiology and Clinical Outcomes of Inflammatory Bowel Disease: A Hospital-Based Study in Central Taiwan.

The incidence and prevalence of inflammatory bowel disease (IBD) are low but increasing in Taiwan. We aimed to investigate the epidemiology and clinical outcomes of IBD in central Taiwan. We retrospectively analyzed patients with IBD diagnosed at our hospital between January 2000 and September 2018. The diagnostic criteria were based on endoscopic and pathologic findings. Clinical characteristics, treatment regimens, and treatment outcomes were analyzed. A total of 190 patients with IBD were enrolled (80 with Crohn's disease (CD) and 110 with ulcerative colitis (UC)). The mean age at diagnosis was 38.4 years (CD: 36 years, UC: 40 years). Male patients accounted for the majority of patients (71.1%). The male-to-female ratio was 3 : 1 for CD and 2.1 : 1 for UC. Current and ever smokers accounted for 30.5% of all patients. Only 4.2% of patients had a family history of IBD. Extraintestinal manifestations (EIMs) were reported in 7.9%, and colorectal cancers (CRCs) were reported in 2.1% of all patients. In patients with CD, the ileal type was the most common disease phenotype (57.5%), and the stricturing type was the most common disease behavior (60.0%). In patients with UC, left-sided colitis was the predominant disease extent (42.7%). The seroprevalence of hepatitis B virus (HBV) was 13.3%. The incidence of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in patients with UC was 22%. 5-Aminosalicylic acids were the preferred treatment for UC, whereas corticosteroids, immunomodulators, and biologic agents were preferred for CD. In patients with CD, the bowel resection rate was 38.8%, and the incidence of hip avascular necrosis was 3.8%. In Taiwan, patients with IBD showed a male predominance, lack of familial clustering, a higher prevalence of HBV infection, and a lower prevalence of p-ANCA, EIMs, and CRC. Moreover, a higher incidence of the ileal type with poor outcomes of CD and left-sided predominance in UC were found.

Bilateral optic perineuritis associated with p-ANCA vasculitis

A 69-year-old Chinese woman with underlying perinuclear anti-neutrophil cytoplasmic antibody associated with vasculitis (p-ANCA vasculitis) with no previous history of ocular involvement experienced one week of blurred vision in both eyes associated with pain. Ophthalmological evaluation demonstrated severe visual loss in both eyes, with pale optic discs but without other signs of ocular vasculitis. Magnetic resonance imaging (MRI) of the brain and orbit revealed bilateral enhancement of the optic nerve sheath with classical tram-track and doughnut signs. Intravenous methylprednisolone was given for five days and marked improvement of vision was seen. In patients with p-ANCA vasculitis, bilateral optic perineuritis (OPN) is uncommon but can be one of the treatable causes to be considered, with good response to prompt steroid treatment.

Detection of Anti-Lactoferrin and Anti-Lysozyme in Ulcerative Colitis Patients

Background: Ulcerative colitis is an autoimmune inflammatory disease. Perinuclear anti-neutrophil cytoplasmic antibodies have been described in patients with inflammatory bowel disease, mainly ulcerative colitis, their role in pathogenesis and diagnostic value are still contentious. Objective: This study targeted at evaluating the incidence of auto antibodies against lactoferrin and lysozyme which belongs to perinuclear antineutrophil cytoplasmic antibodies and measurement the levels of C-reactive protein ,Study the relationship between anti-lactorferrin and anti-lysozyme antibodies , Study the association between anti-lactorferrin, anti-lysozyme antibodies and C-reactive protein concentration among ulcerative colitis patients. Patients and Methods: Fifty patients with ulcerative colitis be present at Al-Kadhimiya Teaching Hospital in Baghdad-Iraq and 25 healthy subjects were selected as the control group. Enzyme linked immune sorbent assay technique was used to detect the anti-lactoferrin and lysozyme antibody in sera of patients and healthy control groups and C- reactive protein was measured by qualitative and semi quantitative agglutination methods. Results: The results of study have showed the male were more affected with UC than female with ratio (1.2:1). The study showed statistically important variances for anti-lactoferrin and lysozyme antibodies between patients and control groups. The present study shown that the (30%) and (38%) of ulcerative colitis patients were seropositive for anti-lactoferrin and lysozyme antibodies, respectively. Conclusion: The prevalence of anti-lactoferrin and anti-lysozyme antibodies were similar to that reported in previous studies and their presence was associated with severity of ulcerative colitis .

Early vedolizumab trough levels at induction in inflammatory bowel disease patients with treatment failure during maintenance

Vedolizumab (VDZ) is effective as an induction and maintenance treatment for Crohn's disease and ulcerative colitis, but, as observed with antitumour necrosis factor-α (anti-TNFα) agents, some patients are nonetheless experiencing loss of response. The aim of this study was to investigate the impact of the pharmacokinetics of VDZ during induction on long-term treatment response. This study focused on a single cohort of 103 inflammatory bowel disease patients treated with VDZ. VDZ trough levels (TLs) were measured by enzyme-linked immunosorbent assay (n=536 samples), and thereafter correlated to clinical, biological, endoscopic and serological data. For patients exposed previously to infliximab, antibodies to infliximab were measured at baseline. On the basis of the outcome at the end of follow-up, patients were then categorized into long-term response, optimized and treatment failure groups. During VDZ induction, at week 6, inflammatory bowel disease patients with long-term response had higher TLs compared with patients in the treatment failure group (33 vs. 24 µg/ml, P=0.02). A cut-off TL of 28 µg/ml predicted a sustained response in the follow-up with an area under curve of 0.723 (95% confidence interval=0.567-0.878, P=0.02). Patients with mucosal healing in maintenance had higher TLs at week 6 (41.65 µg/ml) compared with patients with mild (26 µg/ml) or severe endoscopic activity (20.8 µg/ml), P=0.009. Positive perinuclear antineutrophil cytoplasmic antibody serology was associated with lower TLs. Patients previously exposed to anti-TNFα had lower TLs than naive patients (22.5 vs. 36 µg/ml, P=0.03) without any impact of detectable antibodies to infliximab. Finally, the presence of an immunomodulator at induction did not impact on VDZ TLs at induction. We confirmed that a drug exposure-efficacy association was found early on at induction. This study emphasizes that previous exposure to anti-TNFα and positive perinuclear antineutrophil cytoplasmic antibody serology are important factors influencing VDZ TLs at induction.

Significance of anti-neutrophil cytoplasmic antibodies in systemic sclerosis

BackgroundUp to 12% of patients with systemic sclerosis (SSc) have anti-neutrophil cytoplasmic antibodies (ANCA). However, the majority of these patients do not manifest ANCA-associated vasculitis (AAV) and the significance of ANCA in these patients is unclear. The aim of this study is to determine the prevalence of ANCA in a well-characterised SSc cohort and to examine the association between ANCA and SSc clinical characteristics, other autoantibodies, treatments and mortality.MethodsClinical data were obtained from 5 centres in the Australian Scleroderma Cohort Study (ASCS). ANCA positive was defined as the presence of any one or combination of cytoplasmic ANCA (c-ANCA), perinuclear ANCA (p-ANCA), atypical ANCA, anti-myeloperoxidase (anti-MPO) or anti-proteinase-3 (anti-PR3). Associations of demographic and clinical features with ANCA were investigated by logistic or linear regression. Survival analysis was performed using Kaplan-Meyer curves and Cox regression models.ResultsOf 1303 patients, 116 (8.9%) were ANCA positive. Anti-PR3 was more common than anti-MPO (13.8% and 11.2% of ANCA-positive patients, respectively). Only 3 ANCA-positive patients had AAV. Anti-Scl-70 was more common in ANCA positive vs ANCA negative (25% vs 12.8%, p < 0.001), anti-MPO positive vs anti-MPO negative (38.5% vs 13.6%, p = 0.006) and anti-PR3 positive vs anti-PR3 negative patients (44.4% vs 13.4%, p < 0.001). A higher prevalence of interstitial lung disease (ILD) was found in the ANCA positive (44.8% vs 21.8%, p < 0.001) and the anti-PR3 positive groups (50.0% vs 23.4%, p = 0.009). In multivariable analysis, ANCA-positive status remained associated with ILD after adjusting for anti-Scl-70 antibodies. Pulmonary embolism (PE) was more common in ANCA-positive patients (8.6% vs 3.0%, p = 0.002) and anti-PR3-positive patients (16.7% vs 3.3%, p = 0.022). ANCA-positive status remained associated with PE in a multivariable analysis adjusting for anti-phospholipid antibodies. Kaplan-Meier analysis revealed increased mortality in ANCA-positive patients (p = 0.006). In Cox regression analysis, ANCA was associated with increased mortality, after adjusting for age and sex.ConclusionsANCA is associated with increased prevalence of ILD and PE in SSc. ANCA should be tested in SSc, as it identifies individuals with worse prognosis who require close monitoring for adverse outcomes.

Alendronate Associated Minimal Change Disease: A Case Report and Literature Review

1. Abstract Kidney injury associated with bisphosphonates is well known in literature, though its more common with intravenous bisphosphonates. Case reports about focal segmental glomerulosclerosis are reported with oral and intravenous bisphosphonates. We present a case of 87-year-old female with acute renal failure and volume overload found to have minimal change disease on biopsy while on Alendronate for a period of four months. She has failed oral prednisone treatment and is now dependent on hemodialysis. This is probably the first case report of minimal change disease with oral bisphosphonates. 2. Keywords: <span style=font-size:10.0pt;mso-bidi-font-size:11.0pt;font-family: times= new= roman,serif;color:black;mso-themecolor:text1=>Alendronate; Acute renal failure; Hemodialysis; Minimal change disease 3. Abbreviations: <span style=font-size:10.0pt;mso-bidi-font-size:11.0pt;font-family: times= new= roman,serif;color:black;mso-themecolor:text1=> mm:Millimeters; Hg:Mercury; g/dl:Grams per deciliter;LPF: Low Power Field;WBC:White Blood Cells;HPF:High Power Field;RBC:Red Blood Cells; HIV:Human Immunodeficiency Virus; ANA: Antinuclear Antibody; pANCA: perinuclear Antineutrophil Cytoplasmic Antibody; GBM: Glomerular Basement Membrane; Ab:Antibody; PO:Per Oral

STUDY OF THE PROTEOMIC PROFILE IN PATIENTS WITH ULCERATIVE COLITIS, ITS CORRELATION WITH DIAGNOSIS AND DISEASE ACTIVITY

Background: Inflammatory bowel disease (IBD) comprises primarily 2 disorders: ulcerative colitis (UC) and Crohn's disease (CD). The hallmark of IBD is chronic, uncontrolled inflammation of the intestinal mucosa. The diagnosis is based on a combination of disease history, colonscopy, inflammatory biomarkers, radiological and histological evaluation. Most biomarkers used are not reliable and not disease specific, but reflect generalized inflammation. Aim: The aim of the work is to identify plasma proteomic profiles of UC cases and correlating this profile with the other diagnostic markers and activity of the disease. Methods: We performed a study with 70 plasma samples collected from patients classified in two groups (37 UC, 33 healthy controls) according to accredited criteria. They were subjected to: complete history taking, thorough clinical examination, laboratory investigations (erythrocyte sedimentation rate (ESR), C- reactive protein (CRP), fecal calprotectin, perinuclear antineutrophil cytoplasmic antibodies (P-ANCA), ileocolonscopy, histopathology, imaging. Plasma proteomic pattern of UC patients and control subjects was determined using Matrix-Assisted Laser Desorption/Ionization (MALDI) Time of Flight (TOF) Mass Spectrometer (MS) analysis. All plasma samples were subjected to solid-phase extraction (SPE). We analyzed the spectra obtained from all the samples using ClinProTool software. Results: There was a statistically significant difference of the plasma proteome profiles of UC group in comparison to health volunteers. 64 signals were identified by the ClinProTool software and of these 16 peptide peaks were highly significant (sensitivity was 100%, specificity was 84.4%, positive predictive value was 100, and negative predictive value was 82). There was a statistically significant difference between active versus inactive UC group, 5 integration regions used for classification between active and inactive UC patients using Genetic Algorithm model (GA) which gave 88.5% cross validation and 100% recognition capability. Markers as ESR, CRP, fecal calprotectin, P-ANCA are statistically correlated to the plasma proteomics found in UC patients. Conclusion: Proteomic profile has the potential to improve diagnosis and evaluate UC activity, reducing the need for more invasive techniques. The pattern of these peptides holds the promise of distinguishing disease states and providing clinically important information such as prognosis, response to therapy or perhaps targets of therapy.

Anti-neutrophil cytoplasmic antibody associated central nervous system vasculitis with brain and spinal cord subarachnoid hemorrhage: A rare case report and review of the literature

This case report describes a 48-year old female who presented with altered mental status, lower extremity weakness, low back pain and a recent history of subjective fevers and night sweats found to have posterior parieto-occipital and spinal subarachnoid hemorrhage on imaging. Further work-up revealed vasculitic changes in the intracranial vasculature and the external carotid artery on angiography. She also demonstrated positivity for perinuclear anti-neutrophil cytoplasmic (p-ANCA) antibodies overall consistent with ANCA associated central nervous system vasculitis (AAV). The present case describes a rare and new presentation of AAV that caused both a cerebral and spinal subarachnoid hemorrhage. There has been no documentation of spinal subarachnoid hemorrhage associated with primary or secondary vasculitis in the literature. Ultimately, this case demonstrates the important finding that AAV can have spinal cord manifestations and cervical vasculature involvement along with the more classic intra-cranial vasculitis findings.

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.

MICROSCOPIC POLYANGIITIS PRESENTING AS TRANSFUSION-RELATED ACUTE LUNG INJURY IN PATIENT WITH SOLITARY KIDNEY

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease 1 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Microscopic polyangiitis (MPA) is a type of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) characterized by small to medium sized vessel inflammation. We present a rare case of MPA which manifested following blood transfusion for symptomatic anemia. CASE PRESENTATION: A 60 year old female with type 2 diabetes mellitus and hypothyroidism presented with diabetic ketoacidosis (DKA), atrial fibrillation and normocytic anemia. She was managed with IV fluids, insulin drip, and amiodarone with good response. She received 2 units of packed RBCs resulting in respiratory distress and intubation. Chest X-ray showed bilateral fluffy infiltrates with no cardiomegaly. She was transferred to our facility for possible transfusion related acute lung injury (TRALI). She was found to be in acute hypoxic respiratory failure, septic shock and acute kidney injury. She was treated with broad spectrum antibiotics, vasopressors, and inotropes. Suspected TRALI was managed with supportive measures. Renal function continued to deteriorate necessitating dialysis. Patient was difficult to wean from ventilator and required tracheostomy for long term ventilation. Because of lack of improvement and concern for pulmonary renal syndrome, ANCA studies were ordered. Anti-myeloperoxidase (MPO) antibodies were 19.8 (normal <9) and perinuclear antineutrophil cytoplasmic antibody (p-ANCA) titers were elevated at 1:160. Anti-nuclear antibodies were negative. Discussion with multiple specialists concluded that renal biopsy would be risky due to solitary kidney and the patient would not tolerate thoracotomy for open lung biopsy; however, the clinical picture was consistent with microscopic polyangiitis. Under guidance of rheumatology, patient was started on high-dose prednisone and cyclophosphamide. Following this, she showed marked improvement in pulmonary and renal function. Dialysis was stopped and creatinine trended to acceptable levels. She was able to be discharged to rehab facility for physical therapy and subsequently sent home. She did not require dialysis on an outpatient basis. DISCUSSION: This case illustrates the difficulty in diagnosing MPA in the setting of other diseases such as DKA and anemia requiring transfusion. In addition, this case highlights the importance of prompt detection of MPA and AAV as these conditions are quick to respond to immunosuppressive therapies1. Although we were not able to obtain confirmatory tissue biopsy, our patient’s lingering disease was rapidly improved following initiation of immunosuppressive therapy. CONCLUSIONS: This is an interesting case of MPA masking as TRALI with concomitant AKI. While MPA is an uncommon entity2, our case teaches that AAV should be considered in all patients with unexplainable renal dysfunction and pulmonary infiltrates, even without confirmatory biopsy. Reference #1: 1. P H Nachman, S L Hogan, J C Jennette and R J Falk. Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. JASN. January 1, 1996 vol. 7 no. 1 33-39 Reference #2: 2. Watts RA, Mooney J, Skinner J, Scott DG, Macgregor AJ. The contrasting epidemiology of granulomatosis with polyangiitis (Wegener's) and microscopic polyangiitis. Rheumatology. 2012 May;51(5):926-31. https://doi.org/10.1093/rheumatology/ker454. Epub 2012 Jan 17. DISCLOSURES: No relevant relationships by Alexander Goldstein, source=Web Response No relevant relationships by Muhammad Habib, source=Web Response No relevant relationships by Muhammad Malik, source=Web Response No relevant relationships by Lusine Nahapetyan, source=Web Response No relevant relationships by Manish Patel, source=Web Response No relevant relationships by Thien Vo, source=Web Response

Atypical Perinuclear Anti-Neutrophil Cytoplasmic Antibodies in Ocular Inflammatory Diseases

ABSTRACTPurpose: To characterize the clinical features of patients with ocular inflammatory diseases (OID) who tested positive for atypical perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA).Methods: Retrospective case series of patients with OID seen at the Massachusetts Eye Research and Surgery Institute (MERSI) from April 2014 to April 2016.Results: 813 patients were tested for ANCA with 34 patients (4%) being positive for atypical P-ANCA. Among those with positive atypical P-ANCA, the most frequent diagnoses were anterior uveitis in 62% (n = 21) followed by scleritis in 20% (n = 7). Only one patient had an episode of recurrent disease flare-up. All but one patient, who had concomitant C-ANCA seropositivity and granulomatosis with polyangiitis, had a favorable disease course with controlled inflammation using topical and/or systemic immunomodulatory therapy.Conclusion: In contrast to typical C-ANCA and P-ANCA, atypical P-ANCA seropositivity was not associated with severe vasculitis or poor prognosis in patients with the OID.

Serologic Reactivity Reflects Clinical Expression of Ulcerative Colitis in Children.

In contrast to pediatric Crohn's disease (CD), little is known in pediatric ulcerative colitis (UC) about the relationship between disease phenotype and serologic reactivity to microbial and other antigens. The aim of this study was to examine disease phenotype and serology in a well-characterized inception cohort of children newly diagnosed with UC during the PROTECT Study (Predicting Response to Standardized Pediatric Colitis Therapy). Patients were recruited from 29 participating centers. Demographic, clinical, laboratory, and serologic (pANCA, ASCA IgA/IgG, Anti-CBir1, and Anti-OmpC) data were obtained from children 4-17 years old with UC. Sixty-five percent of the patients had positive serology for pANCA, with 62% less than 12 years old and 66% 12 years old or older. Perinuclear anti-neutrophil cytoplasmic antibodies did not correspond to a specific phenotype though pANCA ≥100, found in 19%, was strongly associated with pancolitis (P = 0.003). Anti-CBir1 was positive in 19% and more common in younger children with 32% less than 12 years old as compared with 14% 12 years old or older (P < 0.001). No association was found in any age group between pANCA and Anti-CBir1. Relative rectal sparing was more common in +CBir1, 16% versus 7% (P = 0.02). Calprotectin was lower in Anti-CBir1+ (Median [IQR] 1495 mcg/g [973-3333] vs 2648 mcg/g [1343-4038]; P = 0.04). Vitamin D 25-OH sufficiency was associated with Anti-CBir1+ (P = 0.0009). The frequency of pANCA in children was consistent with adult observations. High titer pANCA was associated with more extensive disease, supporting the idea that the magnitude of immune reactivity may reflect disease severity. Anti-CBir1+ was more common in younger ages, suggesting host-microbial interactions may differ by patient age.

Immunology-Rheumatology Approach to Sudden Sensorineural Hearing Loss.

Sensorineural hearing loss (SNHL) and vestibular dysfunction have been described in various autoimmune disorders and systemic vasculitides. A high prevalence of SNHL is reported to occur in established rheumatologic diseases; however, immunologic and rheumatologic disorders make up a small proportion of patients with sudden sensorineural hearing loss (SSNHL). This prospective study was carried out in order to determine the prevalence of rheumatologic and immunologic disorders in patients with SSNHL in Northeast Iran. Patients with a diagnosis of SSNHL referred to our University Hospital were enrolled in this prospective study conducted over a period of 3 years. Immunology-rheumatology evaluations were performed in all patients, including detailed history, physical exams and laboratory tests such as erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), rheumatoid factor (RF), anti neutrophil cytoplasmic antibody (PR3, c-ANCA), perinuclear anti neutrophil cytoplasmic antibody (p-ANCA), antiphospholipid antibody, anti-cyclic citrullinated peptide (ACCP), and complement proteins C3 and C4. Eighty-three patients with a mean age of 42.04±16.94 years were admitted into the study. The female-to-male ratio was 47% to 53%. ANA was positive in one patient, RF in six, p-ANCA in two, ACCP in one, and antiphospholipid antibody was positive in three patients with low titers. No diagnosis of rheumatologic diseases was detected, except for one patient who was diagnosed with primary Sjögren's syndrome. Fewer than 5% all cases had specific positive immunologic tests. The low frequency of immunology-rheumatology positive tests and disorders in our patients with SSNHL indicates that it is not reasonable to routinely perform all related tests for every patient. Instead, clinical evaluations should be used to decide whether or not to conduct these tests.

Serologic and fecal markers to predict response to induction therapy in dogs with idiopathic inflammatory bowel disease.

BackgroundLittle information is available of markers that assess the disease course in dogs with idiopathic inflammatory bowel disease (IBD).ObjectivesEvaluate relationship between disease severity and serum and fecal biomarkers in dogs with idiopathic IBD before and after treatment.AnimalsSixteen dogs with idioptahic IBD and 13 healthy dogs.MethodsProspective case control study. Canine IBD activity index (CIBDAI) clinical score, serum concentrations of C‐reactive protein (CRP), perinuclear antineutrophil cytoplasmic antibodies (pANCA), and serum and fecal canine calprotectin (cCP) were measured before and after 21 days of treatment.ResultsSerum CRP (median 3.5 mg/L; range: 0.1‐52.4 mg/L), fecal cCP (median 92.3 μg/g; range: 0.03‐637.5 μg/g), and CIBDAI scores significantly increased in dogs with IBD before treatment compared with serum CRP (median 0.2 mg/L; range: 0.1‐11.8 mg/L; P < .001), fecal cCP (median 0.67 μg/g; range: 0.03‐27.9 μg/g; P < .001) and CIBDAI (P < .001) after treatment. No significant associations between CIBDAI scores and before or after treatment serum biomarkers. There was a significant association between fecal cCP and CIBDAI scores before treatment (rho = 0.60, P = .01). CRP and fecal cCP significantly decreased after treatment (median 3.5 mg/L v. 0.2 mg/L; P < .001 and 92.3 μg/g v. 0.67 μg/g; P = .001, respectively).Conclusions and Clinical ImportanceOur data indicate that measurement of fecal cCP concentration is a useful biomarker for noninvasive evaluation of intestinal inflammation. Dogs with severe signs of GI disease more often have abnormal markers than dogs having less severe disease.

Mesenteric vasculitis and ischaemia: every second counts

A 65-year-old woman with past medical history significant for Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (p-ANCA) vasculitis, peripheral arterial disease requiring left femoral-popliteal bypass, chronic anaemia, hypertension, hyperlipidaemia and hyponatraemia secondary to...

Intestinal inflammation markers in inflammatory bowel disease

During the past few decades, extensive researches were conducted to identify serological markers in patients with inflammatory bowel disease (IBD) that can reliably diagnose and monitor disease activity and help in predicting relapses. To date, several serological markers have been identified. This review will address the different serological markers and their clinical significance and applicability in medical practice. Serological markers include antibodies against microbial antigens, peptide antigens, autoantibodies, and basic inflammatory markers. Some serological markers such as anti-Saccharomyces cerevisiae antibodies (ASCA) and antibodies against exocrine pancreas (PAB) help the confirmation of the diagnosis of IBD to differentiate it from other non-IBD. Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and ASCA can distinguish Chron’s disease and ulcerative colitis. Certain markers can aid stratification of Chron’s disease including antibodies to Pseudomonas fluorescens associated sequence I2 (Anti-I2), antibodies to bacterial flagellin (Anti-CBir1), ASCA, and antibodies to outer membrane porin C (Anti-OmpC). ASCA and pANCA can predict disease response to therapeutic agents (e.g. Infliximab). ASCA can also unaffected family members at risk of developing Chron’s disease.