Positive p-ANCA Research Articles

S3843 A Rare Case of Non-Specific Interstitial Pneumonitis (NSIP) Secondary to Infliximab in a Patient With Ulcerative Pancolitis and PANCA Positivity

S3843 A Rare Case of Non-Specific Interstitial Pneumonitis (NSIP) Secondary to Infliximab in a Patient With Ulcerative Pancolitis and PANCA Positivity

Microscopic polyangiitis, an onset with diffuse alveolar hemorrhage

Introduction: antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a group of complex chronic diseases that cause morbidity, systemic organ damage, therapeutic overload, and risk of relapse. Microscopic polyangiitis (MPA) primarily affects small vessels in the lungs and kidneys, characterized by inflammation that can lead to necrosis of blood vessels, presence of ANCA in the bloodstream, and absence of necrotizing inflammation of the parenchyma in histopathology. Methods: we present the case of a 58-year-old female patient with hemoptysis, fever, and dyspnea. Results: laboratory tests show anemia, leukocytosis, positive p-ANCA, hematuria, and proteinuria. The CT scan reveals areas of increased attenuation with a ground-glass pattern and centrilobular nodular opacities occupying the middle lobe and both lower lobes. The patient also tested positive for MPO-ANCA, leading to the diagnosis of ANCA-positive vasculitis, specifically microscopic polyangiitis with pulmonary and renal involvement, pneumonia, and renal insufficiency. She received appropriate medical treatment, resulting in adequate resolution. Conclusions: microscopic polyangiitis requires interdisciplinary management, which, along with radiological findings, contributes to the early diagnosis and timely treatment of the pathology

A case of granulomatosis with polyangiitis presenting as cerebritis

Background: Isolated Central Nervous System (CNS) involvement in Granulomatosis with Polyangiitis (GPA) is rare. There are limited accounts of such a presentation in the literature. Case presentation: A 61-year-old gentleman presented with right upper limb and lower limb weakness, slurred speech and confusion following two instances of mechanical falls while at home. A cerebrovascular event was suspected. He underwent Computed Tomography (CT) brain and Magnetic Resonance Imaging (MRI) brain which demonstrated leptomeningeal thickening of left frontal region with vasogenic oedema. The differential diagnosis included malignancy, infection and contusion. He initially commenced on Dexamethasone 8 mg, Keppra 250 mg and a combination of Ceftriaxone, Linezolid, Metronidazole to treat vasogenic edema and possible infectious cerebritis, respectively. His vasculitis screen demonstrated a positive p-ANCA, positive for high titer PR3-ANCA. He was diagnosed with cerebral vasculitis secondary to GPA and commenced on immunosuppressant treatment.

Abstract 3209: Antibody mediated targeted drug delivery approach for pancreatic cancer

Abstract Pancreatic ductal adenocarcinomas, originating from the epithelial cell lining of ducts, account for approximately 95% of tumors in this category, showcasing a survival rate of less than 5-7%. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). The therapies are unable to penetrate to the fibrotic tumors leading to insufficient availability of the therapeutic drugs at the tumor site. We and others have shown that MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas, which makes MUC13 as an excellent protein for specifically targeting pancreatic tumors. Herein, we demonstrate a unique ability of our in-house generated mouse and humanized monoclonal antibody of MUC13 to penetrate and target pancreatic cancer. These antibodies have been conjugated with our recently developed novel patented superparamagnetic iron oxide nanoparticles (SPIONS) to deliver therapeutics specifically to pancreatic tumors. In this study, we are using curcumin that depletes tumor microenvironment and gemcitabine to investigate the efficacy of the MUC13 conjugated SPION in delivery of therapeutic drugs. Our results demonstrate that enhanced uptake of MUC13-SPION formulation in MUC13 positive (MUC13+) PanCa cells, compared with MUC13 null (MUC13-) cells as demonstrated by immunofluorescence, Prussian blue staining and flow cytometry experiments. Interestingly, the formulation resulted in sustained delivery of curcumin (CUR), enhanced inhibition of cell proliferation, migration and invasion in MUC13+ cells as compared with MUC13- cells, which suggests the targeting efficacy of the formulation. In PanCa orthotopic mice model, MUC13-SPION efficiently targeted pancreatic tumors resulting in significant tumor accumulation. We observed inhibition of tumor volume, metastasis, gem resistance and improved survival in mice treated with the formulation. Additionally, the tumor tissues from treated mice showed extensive downregulation of PCNA and expression of key proteins in SHH pathway, such as SHH, Gli-1, Gli-2, Patched 1, SMO, which has been associated with cancer progression and drug resistance. In conclusion, the results indicate high therapeutic significance of MUC13-SPIONS for achieving pancreatic tumor specific delivery of drugs. Citation Format: Nirnoy Dan, Saini Setua, Poornima Shaji, Sonam Kumari, Murali Mohan Yallapu, Sheema S. Khan, Subhash Chauhan. Antibody mediated targeted drug delivery approach for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3209.

Granulomatosis with Polyangiitis (Wegener’s Granulomatosis) Manifesting with Cranial Nerve Palsies and Pachymeningitis: A Case Report.

We present a case of a 78-year-old male patient diagnosed with pachymeningitis secondary to Wegener's granulomatosis (WG), also known as granulomatosis with polyangiitis (GPA), associated with p-ANCA positivity. This case report aims to highlight the clinical presentation and diagnosis, of pachymeningitis in WG and provide a review of the literature on this manifestation.

Effect of antinuclear antibody positivity on antineutrophil cytoplasmic antibody results by indirect immunofluorescence assay.

The indirect immunofluorescence assay (IIFA) utilizing antineutrophil cytoplasmic antibodies (ANCA) is widely used as a diagnostic test for autoimmune vasculitis. The presence of antinuclear antibodies (ANA) might lead to a misleading interpretation of ANCA. This study aims to explore the impact of the presence of ANA on the interpretation of ANCA. This retrospective research examined samples negative for antiMPO and antiPR3 ANCA by IIFA and explored correlations between the ANA-IIFA results and the ANCA interpretation frequencies. Our analysis involved the use of suitable statistical methods, including Chi-square and kappa statistics. Up to 75.2% of the ANCA-IIFA-positive samples exhibited a positive p-ANCA pattern when using the ethanol-fixed substrate, with c-ANCA positivity at 24.8%. In the ANA-IIFA-positive samples, ~77.3% displayed p-ANCA patterns on ethanol-fixed substrates. A comparison between the ANA-IIFA titers and the p-ANCA results revealed that p-ANCA positivity was notably more common in samples with higher titers, and this correlation was found to be statistically significant. Positive ANA results by IIFA tests are linked to a higher incidence of p-ANCA interpretation, particularly in cases with higher titer patterns. This insight aids laboratories in establishing effective workflows to investigate potential p-ANCA interference.

P264 The utility of ANCA in Ulcerative Colitis and Crohn’s Disease: A Retrospective Cohort Study in Taiwan

Abstract Background Inflammatory bowel disease (IBD) includes two chronic idiopathic inflammatory diseases: ulcerative colitis (UC) and Crohn disease (CD). The diagnosis of IBD depends on clinical, endoscopic, histological, radiological and biochemical criteria, which may be invasive, time consuming and usually not accepted by patients with IBD. Antineutrophil cytoplasmic antibodies (ANCAs) is believed to be related to IBD. The aim of this study was to investigate these serological markers and the evidence for their use in the diagnosis and management of IBD in Taiwan. Methods We conducted a retrospective cohort study in adult IBD patients who had received the serum examinations using the medical records of China Medical University Hospital between 1 January 1980 and 31 October. 2023. Results A total of 301 IBD patients (194 with UC, 107 with CD) were included in this current study. A high proportion were male (IBD 70.41%; UC 65.63%, and CD 76.71%). The mean diagnostic age of these enrolled patients was 42.9 years. In our patients, the prevalence of positive anti-HCV Ab is 0.0% in UC patients and 0.96% in CD patients. However, the prevalence of positive HBsAg was 14.5% in UC patients and 9.4% in CD patients. The prevalence of pANCA was 21.2% in UC patients and 1.4% in CD patients, respectively. The prevalence of cANCA was 3.1% in UC patients and 0.0% in CD patients. This pattern of low sensitivity and high specificity for pANCA is also seen in UC patients in various cohort studies. The serum positivity of p-ANCA was significantly higher in UC patients (Figure 1). UC patients with positive p-ANCA were older than CD patients with positive p-ANCA (44.9 vs. 37.3 years). Furthermore, we found that the incidence of positive p-ANCA in UC patients with E1, E2, and E3 at diagnosis was 3.5%, 39.2%, and 57.1%, respectively (Table 1). The serum levels of ANCA-IgG were indeed higher in patients in the severe group than those in the moderate and mild groups. Conclusion Serological biomarkers have been demonstrated to be a series of rapid, non-invasive approaches for assessments of early diagnosis, disease activity and prognosis for IBD. ANCA may be helpful in the early diagnosis of UC and in differentiating it from CD. UC patients with positive ANCA have a higher rate of intestinal mucosal vasculitis than UC patients with negative ANCA. Furthermore, ANCA may also contributes to the pathogenesis of HBV-related systemic vasculitis. Therefore, the management of HBV-related vasculitis includes control the immune complex formation and reaction as well as antiviral agents to reduce the antigenic load resulting in reduction of inflammation. Moreover, effective biomarkers with high sensitivity and specificity need to be investigated in the future.

Eosinophilic Granulomatosis with Polyangiitis (EGPA): A Case Report Presenting with Peripheral Polyneuropathy

Background: Eosinophilic granulomatosis with polyangiitis is a rare clinical condition with multiple organ involvement. We report a case of a 64-year-old male patient who presented with symptoms of chronic rhinosinusitis, numbness, and pain in both lower limbs, weight loss of 6 kg/3 months, and subcutaneous vasculitis lesions along the forearms and legs on both sides. The patient had peripheral eosinophilia with an eosinophil count of 11.6%, eosinophil count of 1.56G/l, positive pANCA test, and electromyography results showing damage to the left calf nerve, bilateral superficial peroneal nerve, and left deep peroneal nerve with axonal loss. Biopsy results of calf muscle showed chronic granulomatous vasculitis. The patient was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) according to the ACR/EULAR 2022 criteria. The patient was given intravenous Methylprednisolone, followed by maintenance treatment with reduced doses of Corticosteroids and Methotrexate. The patient’s leg pain was significantly reduced, numbness in both lower limbs was reduced, and the patient’s quality of life was improved. Methods: clinical case report. Results: The patient’s peripheral polyneuropathy and subcutaneous vasculitis were significantly reduced after treatment with Corticosteroids and Methotrexate. Conclusion: Eosinophilic granulomatosis with polyangiitis is a rare clinical condition with manifestations of multiple organ damage. Timely detection and diagnosis help increase treatment effectiveness and improve clinical symptoms for patients.

Ocular and orbital manifestations of granulomatosis with polyangiitis: a systematic review of published cases.

Objective: Granulomatosis with polyangiitis (GPA) is an autoimmune disorder characterized by necrotizing granulomatous inflammation of small and medium-sized vessels. This systematic review aimed to highlight the most common ophthalmic manifestations and to uncover their associations with antineutrophil cytoplasmic antibody (ANCA) positivity and the presence of granulomas. Methods: A literature search of PubMed, Web of Science, and Scopus electronic databases was performed from journal inception to March 21, 2021, for case reports and a series of ophthalmic GPAs. Cytoplasmic-ANCA (c-ANCA), perinuclear-ANCA (p-ANCA), and granulomas were analyzed against many ophthalmic signs and symptoms. 306 patients with GPA were retrospectively studied. Results: Granulomas were present in 47.7% of our sample, c-ANCA in 59.2%, and p-ANCA in 10.8%. Scleritis was significantly associated with higher odds for c-ANCA positivity. Eye discharge, episcleritis, proptosis, and central nervous system (CNS) involvement were each significantly associated with lower odds for c-ANCA positivity. Orbital mass was significantly associated with lower odds for p-ANCA positivity. CNS involvement was significantly associated with higher odds for p-ANCA positivity (OR:3.08, 95% CI:1.02, 9.36, p=0.047) and orbital mass was significantly associated with lower odds for p-ANCA positivity. Conclusions: We recommend that clinicians should consider ocular or orbital GPA in patients presenting with non-specific eye complaints, such as vision impairment, orbital mass, or proptosis, and obtain further assessments to determine the possible presence of granuloma, c-ANCA, or p-ANCA. Abbreviations: GPA = Granulomatosis with Polyangiitis, ANCA = antineutrophil cytoplasmic antibody, c-ANCA = cytoplasmic-ANCA, p-ANCA = perinuclear-ANCA, CNS = central nervous system, AAVs = ANCA-associated vasculitides, SD = standard deviation, GU = genitourinary, ENT = ear nose and throat, OR = odds ratio, CI = confidence interval.

FRI339 Hypophysitis Secondary To Small Vessel Anca Vasculitistreated With Rituximab

Abstract Disclosure: A. Rivadeneira: None. N. Kumar: None. S. Banerjee: None. M. Gubbiotti: None. D. Yoshor: None. J. Kharlip: None. C.A. White: None. Introduction: Granulomatosis with polyangiitis (GPA) is an autoimmune small-vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCAs) that rarely involves the pituitary. Conventional treatment of GPA includes high dose glucocorticoids with cyclophosphamide. Rituximab has been used in refractory cases with high rates of remission. We present a case of pituitary GPA treated with and excellent response to rituximab. Case: 51-year-old woman with hypothyroidism, post I-131 treatment for Graves’ disease. Patient presented with 1 year of worsening fatigue, myalgias, frontal headaches, sinus congestion and epistaxis. CT sinus showed pituitary enlargement and chronic mucosal disease. MRI pituitary showed diffusely enlarged pituitary with non-visualized posterior pituitary bright spot and thickened stalk. CT chest showed 18x11 mm nodular opacity and peribronchial fibrosis. Laboratory evaluation showed ACTH 26.7 pg/mL, cortisol 13.4 mcg/dL, TSH 1.1, T4 9.7, prolactin 53 ng/dL, estradiol <20, LH 4, FSH 23. Sodium 140 and urine osm 488. There was positive p-ANCA staining and elevated serum anti-proteinase 3 antibody (PR3), 74 units (0-20). Myeloperoxidase antibody was not elevated. ESR 73 mm/h (0 - 30) and CRP 7.9 (<7.4). Due to atypical ANCA pattern (p ANCA typically is associated with MPO not PR3), pituitary biopsy was performed and showed adenohypophysis with dense lymphoplasmacytic infiltration with nodularity of the inflammatory infiltrates, some arranged peri vascularly, compatible with involvement of the pituitary gland by GPA. She began rituximab 375 mg/m2 weekly for four weeks with plan to continue every 6 months. After treatment, the patient experienced resolution of daily frontal headaches, congestion, cough and epistaxis. CT chest showed improvement of prior lung findings, and ESR/CRP normalized. Repeat pituitary MRI is pending. Discussion: Pituitary involvement is uncommon in GPA, occurring in only 3.9% of cases. It may lead to partial or complete pituitary dysfunction, particularly central diabetes insipidus (87.5%) and hypogonadism (75%). Typical MRI abnormalities include diffusely enlarged pituitary gland, thickened pituitary stalk and absence of posterior bright spot. Treatment of GPA includes a combination of corticosteroids, Cyclophosphamide, Azathioprine and Rituximab. Remission is achieved in up to two thirds of patients. Treatment of lymphocytic hypophysitis, another common cause of diffuse pituitary enlargement, relies on high dose glucocorticoids, leading to many side effects and taper is limited by worsening symptoms. This case highlights the critical role in serologic evaluation and targeted pituitary biopsy to identify the specific etiology of pituitary infiltration to help guide alternate treatment options, and the emerging role of Rituximab as a steroid sparing agent for treatment of pituitary inflammation. Presentation: Friday, June 16, 2023

#2950 IGA NEPHROPATHY: PUTTING THE A IN THE UNACQUAINTED

Abstract Background and Aims IgA nephropathy (IgAN) is a common glomerulonephritis. Rarely it can be associated with other diseases and screening for these associations can be missed. We present 2 cases diagnosed as IgAN which were associated with rare underlying conditions. The first (patient X) is a 51-year-old female, who presented with new onset haematoproteinuria on a background of inflammatory arthritis, interstitial lung disease (ILD) and a recurrent maculopapular rash. The second case (patient Y) is a 34-year-old male, who presented with unexplained rapidly progressive chronic kidney disease and proteinuria. He had a background of hidradenitis suppurativa, acne rosacea, Crohn's disease and recurrent infections. Method X's immunology was negative aside from a weakly positive ANA and p-ANCA but negative ELISA. Her myositis panel was positive for PM/ScL antibody. Imaging showed multifocal ground glass opacification, consistent with ILD. Her renal function was normal, but renal histology demonstrated IgAN, without evidence of vasculitis. With these findings in mind, a diagnosis of anti-synthetase syndrome (AS) with IgAN was proposed. Y, conversely, had abnormal renal function, with significant proteinuria. Immunology screen was unremarkable other than a raised serum IgA, weakly positive MPO and equivocal PR3. Renal biopsy showed IgAN with severe interstitial fibrosis and tubular atrophy, and over 50% sclerosed glomeruli. Y later developed haemolytic anaemia; his neutrophil oxidase activity was absent, raising the possible diagnosis of chronic granulomatous disease (CGD). This was subsequently confirmed with genetic testing demonstrating an autosomal recessive gene for CGD. Results Both X's proteinuria and symptomatic burden significantly improved with methotrexate. Y was commenced on antibiotics and antifungals in light of the heightened risk of infection which CGD carries. He is now on maintenance haemodialysis. The only curative treatment for CGD is allogenic hematopoietic stem cell transplantation from a matched donor, for which he is being considered. Conclusion AS is a poorly defined, rare syndrome characterised clinically by ILD, arthritis and myositis. It is immunologically characterised by autoantibodies against aminoacyl tRNA synthetases; whilst X did not test positive, this does not preclude AS, as autoantibody titres fluctuate depending on disease activity [1]. Renal involvement in AS is extremely rare, or so the data would suggest. Couvrat-Desvergnes et al. examined 14 biopsies of patients with inflammatory myopathies plus renal involvement. Only 3 had AS; of these, 2 had IgAN. Other cases of IgA are described only in case reports. In all cases, immunosuppressive treatments were effective in achieving remission. Some cases describe other renal implications in AS, namely TMA and amyloidosis (Table 1). CGD is a rare primary immunodeficiency caused by genetic defects in the NADPH oxidase complex, which is critical in the destruction of phagocytes. Consequently, patients have recurrent infections and abnormal inflammatory responses result in granuloma formation. The incidence of renal disease in CGD has been suggested by some papers as being as low as 2.7% [2]. From review of the other cases of CGD with associated IgAN, it seems the patient we present is the oldest (Table 2). Interestingly, only 1 other case reports glomerulonephritis as the presenting complaint for CGD [3]. These cases highlight that, while IgAN is a disease in its own right, its diagnosis may shine light on other associated pathologies. It is crucial for nephrologists to be aware of rare associations as often it has impact on further management.

Clinical and Prognostic Significance of p-ANCA Positivity in Idiopathic Pulmonary Fibrosis: A Retrospective Observational Study.

Perinuclear Anti Neutrophil Cytoplasmic Antibody (p-ANCA) is a serological marker of Microscopic Polyangiitis (MPA), a vasculitis associated with lung involvement potentially mimicking Idiopathic Pulmonary Fibrosis (IPF). In this study, we evaluated the role of p-ANCA in predicting clinical evolution and prognosis in a cohort of IPF patients. In this observational, retrospective, case-control study, we compared 18 patients with an IPF diagnosis and p-ANCA positivity with 36 patients with seronegative IPF, matched for age and sex. IPF patients with and without p-ANCA showed similar lung function decline during the follow-up, but IPF p-ANCA+ showed better survival. Half of IPF p-ANCA+ patients were classified as MPA for the development of renal involvement (55%) or skin signs (45%). The progression towards MPA was associated with high levels of Rheumatoid Factor (RF) at baseline. In conclusion, p-ANCA, mainly when associated with RF, could predict the evolution of Usual Interstitial Pneumonia (UIP) towards a definite vasculitis in patients, with a better prognosis compared with IPF. In this view, ANCA testing should be included in the diagnostic workup of UIP patients.

Adult Henoch-Schönlein Purpura: Comprehensive Assessment of Demographic, Clinical, and Histopathological Features as Predictors for Systemic Involvement

Background: Henoch-Schönlein purpura (HSP) is a small-vessel IgA-predominant vasculitis. A major challenge in managing adult HSP is the difficulty assessing the risk of systemic involvement. There is currently a paucity of data in this area. Objective: The objective of this study was to determine demographic, clinical, and histopathological features associated with systemic involvement in adult HSP. Methods: In this retrospective study, we reviewed demographical features and clinical and pathology data of 112 adult HSP patients seen at Emek Medical Center between January 2008 and December 2020. Results: Of these patients, 41 (36.6%) had renal involvement, 24 (21.4%) had gastrointestinal tract involvement, and 31 (27.7%) had joint involvement. Age >30 years (p = 0.006) at diagnosis was an independent predictor of renal involvement. Platelet count (<150 K/µL) (p = 0.020) and apoptosis of keratinocytes on skin biopsy (p = 0.031) were also associated with renal involvement. History of autoimmune disease (p = 0.001), positive c-antineutrophil cytoplasmic antibody (p = 0.018), positive rheumatoid factor (p = 0.029), and elevated erythrocyte sedimentation rate (p = 0.04) were associated with joint involvement. Female sex (p = 0.003), Arab race (p = 0.036), and positive pANCA (p = 0.011) were associated with gastrointestinal tract involvement. Limitations: This study is retrospective. Conclusion: These findings may serve as a guide to stratify risk in adult HSP patients so that those at higher risk can be monitored more closely.

Antieosinophil Antibodies Alone or in Combination with Antineutrophil Cytoplasmic Antibodies (ANCA) Detected in Different Autoimmune Conditions.

Circulating antieosinophil antibodies (AEOSA) have been associated with various autoimmune conditions affecting the liver, kidneys, lungs, and joints but are not part of routine clinical diagnostics. While analyzing human sera for antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IIF) on granulocytes, 0.8% of analyzed samples were found to be reactive with eosinophils. Our aim was to determine the diagnostic relevance and antigenic specificity of AEOSA. AEOSA were seen either in combination with an myeloperoxidase (MPO)-positive p-ANCA (44%; AEOSA+/ANCA+) or on their own (56%; AEOSA+/ANCA-). AEOSA/ANCA positivity was seen in patients with thyroid disease (44%) or vasculitis (31%), while AEOSA+/ANCA- pattern was more common in patients with autoimmune disorders of the gastrointestinal tract and/or liver. Eosinophil peroxidase (EPX) was the main target recognized in 66% of the AEOSA+ sera by enzyme-linked immunosorbent assay (ELISA). Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) were also identified as target antigens but less frequently and only in combination with EPX. In conclusion, we confirmed that EPX is a major target of AEOSA, illustrating the high antigenic potential of EPX. Our results also demonstrate the presence of concomitant AEOSA/ANCA positivity in a defined patient group. Further research should aim to elucidate the association of AEOSA with autoimmunity.

Reduced circulating Tregs and positive pANCA were robustly associated with the occurrence of antiphospholipid syndrome in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a typical chronic immune disorder with clinical heterogeneity. The systemic abnormal immune response not only challenges the diagnosis and treatment of the disease itself but also the secondary antiphospholipid syndrome (APS), characterized by recurrent arterial or venous thrombosis, recurrent spontaneous abortion, or stillbirth. Clinical interest has primarily focused on primary APS's pathological and clinical features. However, differences in clinical features and laboratory indicators between SLE with or without APS are still lacking, especially differences between circulating lymphocytes, which are critical in the pathogenesis of SLE and its complications. In this retrospective study, we collected and analyzed clinical characteristics, general laboratory indicators, immunological indicators, and circulating lymphocyte subsets of SLE with or without APS. Systemic lupus erythematosus with APS (SLE-APS) had elevated SLEDAI scores, hospitalization costs and time, and frequencies of central nervous system symptoms and spontaneous abortion compared with those without APS. SLE-APS had higher positive anti-Cardiolipin antibodies, anti-β2 Glycoprotein 1 antibodies, and perinuclear antineutrophil cytoplasmic antibody (pANCA) than none-APS patients. Compared with healthy controls (HCs), the circulating lymphocyte subsets were altered to some extent in all patients, especially in patients with SLE-APS. Reduced Tregs and positive pANCA were independent risk factors for SLE secondary APS. The present study revealed a robust association between APS secondary to SLE and reduced Tregs and positive pANCA, which provides essential information regarding the diagnosis and therapeutic possibilities of APS secondary to SLE.

An insidious onset of Eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare small-vessel vasculitis, often associated with MPO p-ANCA (myeloperoxidase–perinuclear–anti-neutrophil cytoplasmic antibody) positivity. It is often difficult to diagnose.

REFRACTORY CHRONIC SPONTANEOUS URTICARIA AFTER TREATED GRAVES' DISEASE

<h3>Introduction</h3> Chronic spontaneous urticaria (CSU) has been well described in autoimmune thyroid disorders, but less associated with Graves' Disease (GD), and the mechanism of their relationship is still unknown. Thyroid-associated CSU has been shown to be more difficult to manage. <h3>Case Description</h3> We present a 10-year-old female with difficult to control CSU with associated facial angioedema that started six months after diagnosis of Graves' disease that was being treated with methimazole. Her symptoms presented multiple times each week as bodily hives, angioedema of her cheeks, tongue, and throat with difficulty breathing, which caused her to be treated multiple times with epinephrine for concern of anaphylaxis. Therapy was rapidly escalated with H1 and H2 antihistamines, leukotriene receptor antagonist, chronic steroids and omalizumab without resolution. She was positive for thyroid stimulating immunoglobulins and p-ANCA antibodies; and negative for anti-TPO and anti-FcεRI antibodies. Due to the concern of vasculitic conversion, methimazole was stopped and she underwent radioiodine ablation for her GD to eventually become euthyroid. She was subsequently started on cyclosporine, but symptoms continue intermittently. <h3>Discussion</h3> Thyroid-associated CSU remains difficult to control from standard therapies, even when the patient becomes euthyroid. Several reports show that controlling the thyroid levels would resolve the CSU and a few only after thyroidectomy. Most studies note that anti-TPO antibodies have been associated with CSU, but only a few report an association with GD. Methimazole can cause p-ANCA positivity for concern of vasculitic conversion. Further studies are needed to evaluate the mechanism of GD with CSU to better manage these complicated patients.

SMALL VESSELS, BIG PROBLEMS: MICROSCOPIC POLYANGIITIS PRESENTING AS DIFFUSE ALVEOLAR HEMORRHAGE

SMALL VESSELS, BIG PROBLEMS: MICROSCOPIC POLYANGIITIS PRESENTING AS DIFFUSE ALVEOLAR HEMORRHAGE

ATYPICAL VARIANT OF GRANULOMATOSIS WITH POLYANGIITIS WITH EOSINOPHILIA

ATYPICAL VARIANT OF GRANULOMATOSIS WITH POLYANGIITIS WITH EOSINOPHILIA

S3211 Weight Loss, Ascites, and Diarrhea as the Presenting Symptoms for Pseudo-Pseudo Meigs Syndrome

Introduction: Pseudo-pseudo Meigs syndrome (PPMS) is a rare presentation of systemic lupus erythematous (SLE) characterized by ascites, pleural effusion, and elevated CA-125 level. Case Description/Methods: A 30-year-old woman with SLE and history of small bowel obstruction presented with diarrhea, weight loss, anasarca, and alopecia. She was initially tachycardic and hypertensive. Her exam revealed profound anasarca with ascites and bilateral pleural effusions. Labs were notable for Cr=5.65 mg/dL (baseline 0.7 mg/dL), spot protein/creatinine=3.9, ferritin=554.6 ng/ml, ESR=145 mm/Hr, CRP=6 mm/Hr, C3=49 mg/dL, C4=19 mg/dL, unremarkable FSH and LH, +ANA, dsDNA 356 U/ml, and +pANCA/MPO. Outpatient workup showed elevated CA-125 to 260.8 U/mL but ovarian malignancy was ruled out by MRI and CT abdomen/pelvis. Transvaginal ultrasound was normal. Inflammatory bowel disease was ruled out by EGD and colonoscopy during a previous hospitalization. Renal ultrasound showed bilateral hydronephrosis. The patient underwent a paracentesis (SAAG 1.3), and thoracentesis that showed total serum protein 4.2 g/dl, pleural fluid LDH 67 U/L, no serum LDH or pleural protein available. Kidney biopsy demonstrated class IV / V lupus nephritis. She was treated with a three-day course of pulse dose methylprednisolone followed by prednisone, hydroxychloroquine, and furosemide infusion. Her symptoms mostly resolved and CA-125 trended down to 27 U/mL. Discussion: PPMS is a rare condition with few cases reported in the literature. This case illustrates the challenges of evaluating abdominal symptoms and ascites in patients with SLE, and the importance of a kidney biopsy in the evaluation of nephrotic range proteinuria. Due to infrequency and concern for malignancy due to elevated CA-125 level, patients with this syndrome undergo extensive workup. CA-125 has been shown to be elevated due to inflammatory markers enhancing its expression in peritoneal mesothelial cells. Prior publications have shown the correlation of CA-125 with extent of serositis in PPMS. Additionally, our patient has many other clinical features reported in PPMS patients including elevated ferritin, alopecia, and positive pANCA. CT scan of abdomen and pelvis is essential in the workup of this syndrome to rule out ovarian malignancy. Moreover, imaging may exclude mesenteric vasculitis, an uncommon feature of SLE which can be seen as targetoid lesions of the bowel on CT scan. Steroids are the treatment for PPMS.