Medium Vessel Vasculitis Research Articles

EP08 A case of granulomatosis with polyangiitis complicated by COVID-19: challenges in diagnosis and management

EP08 A case of granulomatosis with polyangiitis complicated by COVID-19: challenges in diagnosis and management

Zapalenie tętnic Takayasu — obraz kliniczny, diagnostyka i leczenie

Systemic vasculitis is a heterogeneous group of diseases of a not fully understood etiology. The common feature is the development of immune-mediated inflammation in the vessel walls, which can lead to the weakening of the wall and formation of aneurysms or occlusion of the lumen, resulting in tissue ischemia. Skin lesions may be present in many conditions of this group. In small and medium vessel vasculitis, the skin may be directly affected by the pathological process. On the other hand, in large vessel vasculitis dermatological symptoms develop secondarily to the involvement of larger vessels. Clinical manifestations, diagnosis and treatment of Takayasu arteritis (TA), classified according to the International Chapel Hill Consensus Conference from 2012 in the group of large vessel vasculitis, are discussed in this article. The aim of the paper is to draw attention to the cutaneous lesions that may raise suspicion of systemic vasculitis. In patients with TA, Raynaud’s phenomenon (especially unilateral), finger necrosis, digital clubbing, erythema nodosum-like lesions or pyoderma gangrenosum-like lesions, erythema induratum, purpuric or necrotic eruptions, livedo reticularis and superficial phlebitis may be observed.

Cellular Signaling Pathways in Medium and Large Vessel Vasculitis.

Autoimmune and autoinflammatory diseases of the medium and large arteries, including the aorta, cause life-threatening complications due to vessel wall destruction but also by wall remodeling, such as the formation of wall-penetrating microvessels and lumen-stenosing neointima. The two most frequent large vessel vasculitides, giant cell arteritis (GCA) and Takayasu arteritis (TAK), are HLA-associated diseases, strongly suggestive for a critical role of T cells and antigen recognition in disease pathogenesis. Recent studies have revealed a growing spectrum of effector functions through which T cells participate in the immunopathology of GCA and TAK; causing the disease-specific patterning of pathology and clinical outcome. Core pathogenic features of disease-relevant T cells rely on the interaction with endothelial cells, dendritic cells and macrophages and lead to vessel wall invasion, formation of tissue-damaging granulomatous infiltrates and induction of the name-giving multinucleated giant cells. Besides antigen, pathogenic T cells encounter danger signals in their immediate microenvironment that they translate into disease-relevant effector functions. Decisive signaling pathways, such as the AKT pathway, the NOTCH pathway, and the JAK/STAT pathway modify antigen-induced T cell activation and emerge as promising therapeutic targets to halt disease progression and, eventually, reset the immune system to reestablish the immune privilege of the arterial wall.

The Many Faces of a Monogenic Autoinflammatory Disease: Adenosine Deaminase 2 Deficiency.

Purpose of ReviewWe aim to describe the pathophysiology, clinical findings, diagnosis, and treatment of deficiency of adenosine deaminase 2 (DADA2).Recent FindingsDADA2 is a multi-organ disease of children and less often adults, which can present with wide-ranging manifestations including strokes, medium vessel vasculitis, hematologic disease, and immunodeficiency. Diagnosis is through detection of reduced activity level of the adenosine deaminase 2 (ADA2) enzyme and/or identification of bi-allelic mutations in the ADA2 gene. Outside of high-dose glucocorticoids, conventional immunosuppression has been largely ineffective in treating this relapsing and remitting disease. Vasculitic-predominant manifestations respond extremely well to tumor necrosis factor-α inhibition. Hematopoietic stem cell transplantation can lead to normalization of enzyme activity, as well as resolution of vasculitic, hematologic, and immunologic manifestations, although treatment-related adverse effects are not uncommon.SummaryEarly detection of this disease across multiple disciplines could prevent devastating clinical outcomes, especially in genetically pre-disposed populations.

Pregnancy Outcomes in Systemic Vasculitides.

Purpose of ReviewIn recent years, improvements in the recognition of primary vasculitides and increased treatment options have led to greater survival rates and a better quality of life for patients. Therefore, pregnancy in women with vasculitis has become a more frequent consideration or event. Literature on pregnancy outcomes in this population has grown and allowed us, in this article, to review the effects of pregnancy on disease activity, as well as maternal and fetal outcomes for each type of vasculitides.Recent FindingsSuccessful pregnancies in patients with vasculitides are possible, especially when conception is planned, and the disease is in remission. The risk of vasculitis flare is highly dependent on the type of vasculitis, but overall limited. The most frequent complication associated with large-vessel vasculitis (mainly Takayasu arteritis) is hypertension and preeclampsia. Preterm deliveries and intrauterine growth restriction occur more frequently with small- and medium-vessel vasculitis.SummaryPregnancies in patients with vasculitis should be considered high risk and followed by a multidisciplinary team with expertise in the field. Flares should be managed as in the non-pregnant population, while avoiding medications with unknown safety in pregnancy or known teratogens. Although commonly prescribed for the prevention of preeclampsia, there is limited evidence supporting the use of low-dose aspirin for pregnant women with vasculitis. Prospective registries or studies are needed, to better assess the value of aspirin, the place and long-term impact of new biologics and, to identify predictors of pregnancy outcomes other than disease status at conception.

Kawasaki disease in siblings in close temporal proximity to each other-what are the implications?

Kawasaki disease (KD) is the commonest medium vessel vasculitis in children. The etiology of KD remains an enigma despite extensive research. Infections are considered to be one of the triggers for KD, especially in genetically susceptible hosts. KD occurring within a short time interval among siblings is an important clinical observation supporting this hypothesis. In addition, siblings of children with KD are at a higher risk of developing the disease as compared with other children. Screening for KD in febrile siblings, therefore, seems prudent. This would help initiate timely therapy and prevent complications. We briefly review 16 English language reports of KD in siblings diagnosed within 1 month of each other to highlight its etiological and therapeutic implications.Key Points• KD should be suspected in febrile children who have a sibling recently diagnosed with KD.• Etiological studies should also focus on siblings who develop KD in close temporal proximity.

Neonatal Kawasaki disease with multiple arterial aneurysms: a case report

BackgroundKawasaki disease (KD) is a medium vessel vasculitis that typically occurs in children aged between 6 months and 5 years. It is extraordinarily rare in the neonatal period. KD-related systemic artery aneurysms (SAAs) have never been reported in neonates.Case presentationA male infant was transferred to our institution for persistent high-grade fever lasting 16 days. Symptoms started at day 14 of life, and he was admitted to a children’s hospital on the second day of fever. Physical examination at the time found no signs suggestive of KD. The only laboratory parameters which were of significance were values suggestive of systemic inflammation. However, his fever persisted and inflammatory markers continued to rise despite 2 weeks of antibiotic therapy. KD as a noninfectious cause of fever was considered when he came to our institution, and echocardiographic findings of left and right medium coronary artery aneurysms (CAAs) confirmed our suspicions. Full-body magnetic resonance angiography also revealed bilateral axillary artery aneurysms. Administration of intravenous gamma globulin resulted in rapid improvement. His fever resolved on the next day and CAAs and SAAs regressed to normal at 6 months and 3 months after diagnosis, respectively.ConclusionThis unique case of incomplete KD highlights the importance of considering KD in neonates with unexplained prolonged fever and reinforces the need to remain vigilant for SAAs in KD.

THU0325 REDUCED OF TREG CELLS ASSOCIATED WITH THE DISEASE ACTIVITY OF ANCA-ASSOCIATED VASCULITIS

Background:Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune disease that can cause systemic organ damage, characterized with the presence of abnormal antibodies (ANCAs) in the circulation and the small- and medium-vessel vasculitis[1].However,the etiology of AAV remained unclear. Several observations have showed that the breakdown of immune tolerance caused by many complex interactions was involved in the pathogenesis of AAV[2].It has been confirmed that the disorder of the CD4+T cell,especially the imbalance of Th17 and Treg cells can destroy the immune tolerance and cause many autoimmune disease[3]. But the relationship between the Th17/Treg and AAV is unknown.Objectives:We investigated the absolute numbers of CD4+T subsets cells in peripheral blood of patients with AAV and healthy adults,and then compared them in different disease activity of AAV to explore the role of CD4+T subsets cells in the pathogenesis and development of AAV.Methods:49 patients with AAV,hospitalized at the Second Hospital of Shanxi Medical University from the May 2016 to the November 2019 were enrolled, and 31 age and gender-matched healthy adults were anticipated as controls.According to BVAS, the patients were divided into disease-activity group (BVAS≥15, n=27) and non-disease-activity group (BVAS<15, n=22). The absolute numbers of CD4+T subsets cells including Th17 and Tregs in peripheral blood of these individuals were detected by flow cytometry.We analyzed whether there was difference of CD4+T subsets between the patients and healthy controls,and between disease-activity group and non-disease-activity group.Results:There was significant decreased level of Treg cells in the patients with AAV compared with healthy controls,especially in the disease-activity group. The absolute numbers of Treg cells was decreased in the patients with AAV compared with healthy controls (P<0.001) leading to a higher Th17/Treg ratio in the patients (P<0.01).Similarly,the absolute number of Treg cells was decreased in the disease- activity group (P<0.01) compared with the non-disease-activity group, and the absolute number of Treg cells was significant negative correlation with the disease activity indexes such as BVAS (r=-0.342,P=0.016), erythrocyte sedimentation rate(ESR) (r=-0.315,P=0.027) and C-reactive protein(CRP) (r=-0.305,P=0.033). But there was no statistically significant in the absolute number of Th17 cells between the patients and healthy controls, and between disease-activity group and non-disease-activity group.Conclusion:The results we investigated here suggested that the decreased number of Treg cells failed to control autoimmune inflammatory response and maintain immune tolerance, and the disease activity of AAV was associated with the reduced number of Treg cells.Figure 1.(A-C) Characteristics of the absolute number of Th17 cells and Treg cells in peripheral blood of healthy controls (n=31) and the patients with AAV (n=49). There was significant decreased level of Treg cells in the patients with AAV compared with healthy controls leading to a higher Th17/Treg ratio in the patients with AAV. (D-F) The absolute number of Treg cells was decreased in the disease- activity group (n=27) compared with the non-disease-activity group (n=21). The absolute number of Th17 cells and Treg cells was detected by flow cytometry. Statistical analyses were performed by the Mann-Whitney U test. *p<0.05,**p<0.01, ***p<0.001.

A detailed analysis of the distribution, morphology, and histopathology of complex purpura in hospitalized patients: A case series of 68 patients

Purpura in inpatients commonly leads to dermatologic consultation. The differential diagnosis is broad and algorithms are intricate. We evaluated inpatient consultations for complex purpura to document the most common diagnoses and to validate the true diagnostic utility of histopathology, clinical morphology, and distribution. We reviewed a case series of 68 inpatients during a 4-year period with a dermatologic consultation for purpura and biopsy findings of vasculitis or microvascular occlusion. Key features of complex purpura are nonbranching (round) versus branching (retiform) morphology, dependent versus acral or generalized distribution, and leukocytoclastic vasculitis versus microvascular occlusion (with emphasis on depth of involvement). Dependent nonbranching purpura with only superficial vessels involved by leukocytoclastic vasculitis was most often due to IgA vasculitis or cutaneous single-organ small-vessel vasculitis. In contrast, deeper involvement by leukocytoclastic vasculitis was suggestive of systemic disease (eg, antineutrophil cytoplasmic antibody-associated vasculitis). Branching purpura was concerning, with greater than 90% sensitivity and specificity for microvascular occlusion and associated high mortality (≈50%). The majority of patients who died had acral branching lesions. Small sample size, inpatients at a tertiary care center, and retrospective nature are some limitations. Nonbranching dependent purpura corresponded to leukocytoclastic vasculitis, with the most common diagnoses being IgA vasculitis or skin-limited small-vessel vasculitis; patients with deep involvement often had systemic diseases. In this series, branching purpura was due to microvascular occlusion rather than medium-vessel vasculitis, and had associated high mortality.

Protocol for a randomized multicenter study for isolated skin vasculitis (ARAMIS) comparing the efficacy of three drugs: azathioprine, colchicine, and dapsone

BackgroundSkin-limited forms of vasculitis, while lacking systemic manifestations, can persist or recur indefinitely, cause pain, itch, or ulceration, and be complicated by infection or scarring. High-quality evidence on how to treat these conditions is lacking. The aim of this comparative effectiveness study is to determine the optimal management of patients with chronic skin-limited vasculitis.MethodsARAMIS is a multicenter, sequential, multiple assignment randomized trial with an enrichment design (SMARTER) aimed at comparing the efficacy of three drugs—azathioprine, colchicine, and dapsone—commonly used to treat various forms of isolated skin vasculitis. ARAMIS will enroll patients with isolated cutaneous small or medium vessel vasculitis, including cutaneous small vessel vasculitis, immunoglobulin A (IgA) vasculitis (skin-limited Henoch-Schönlein purpura), and cutaneous polyarteritis nodosa. Patients not responding to the initial assigned therapy will be re-randomized to one of the remaining two study drugs (Stage 2). Those with intolerance or contraindication to a study drug can be randomized directly into Stage 2. Target enrollment is 90 participants, recruited from international centers affiliated with the Vasculitis Clinical Research Consortium. The number of patients enrolled directly into Stage 2 of the study will be capped at 10% of the total recruitment target. The primary study endpoint is the proportion of participants from the pooled study stages with a response to therapy at month 6, according to the study definition.DiscussionARAMIS will help identify effective agents for skin-limited forms of vasculitis, an understudied group of diseases. The SMARTER design may serve as an example for future trials in rare diseases.Trial registrationClinicalTrials.gov: NCT02939573. Registered on 18 October 2016.

The vascular armamentarium explored-the ultimate goal achieved

Peripheral arterial disease is one of the commonest causes for a limb being amputated most often, we present this case of medium vessel vasculitis with chronic threatening limb ischemia to make a note of our attempt to save her limb by multiple modalities which included medical management with steroids, immunosuppressants, pulsed cyclophosphamide, interventional radiological procedure of catheter directed thrombolysis with urokinase, surgical procedures like bypass, split skin grafting and minor amputations, implemented novel modalities like hyperbaric oxygen therapy. By exploring the armamentarium available, involving a multidisciplinary team which included vascular surgeon, rheumatologist, intervention radiologist, plastic surgeon, physiotherapist and aptly using the right modality at the right time we were able to ultimately achieve our goal of limb salvage.

O40 Trends in incidence of GCA in the UK

Abstract Background Giant cell arteritis (GCA) is the most common form of medium and large vessel vasculitis. Diagnosis remains difficult since there are a multitude of symptoms experienced by patients with GCA and if not promptly identified or treated, patients with GCA are at risk of irreversible visual loss. Therefore, a clear understanding of recent trends in incidence is important for clinicians, researchers and policy-holders to better understand and address future healthcare resource needs. Our objective was to estimate the annual UK incidence of GCA and assess whether this is changing over time. Methods We used the Clinical Practice Research Datalink (CPRD), a database of routinely recorded primary care records from across the UK. CPRD is representative of the UK population and contains patient information from approximately 15% of the UK population. For each year from 1992-2017, the number of patients with a first Read coded record of GCA in that year, and aged 40 years or older at the time of diagnosis, was determined. The annual denominator population included the registered practice population without a prior record of GCA, aged 40 years or older. Annual incidence per 10,000 person-years (P-Y) at risk was derived overall and stratified by age, gender and region of the UK. Trends over time were modelled using Joinpoint regression. To be confident of the primary care diagnosis of GCA, a sensitivity analysis was undertaken which included a prescription of corticosteroids alongside the GCA Read code. Results There was a decrease in annual incidence of GCA in the UK between 1992 and 2017. Incidence was highest in 1994 (2.29/10,000 P-Y; 95% CI: 1.96, 2.67). This decreased to 1.51/10,000 P-Y in 2006, after which the incidence rates stabilised. Incidence rates for women were higher than men, irrespective of year. Incidence peaked between 70 and 89 years of age, with females aged 70-79 having the highest overall incidence rate of 5.20/10,000 P-Y (95% CI: 5.00, 5.40). The region of the UK with the highest incidence rate of GCA from 2015-2017 was Yorkshire & the Humber with 2.63/10,000 P-Y. The regions with the lowest incidence of 1.13/10,000 P-Y were the North East and West Midlands. Sensitivity analysis gave similar patterns. Conclusion The incidence of GCA in the UK has decreased slightly in recent years, which may reflect developments in more definitive early GCA diagnosis through fast-track clinics and improvements in imaging. However, further research into the presenting features of GCA in primary care is required. A set of early clinical features and comorbidities that are positively associated and predictive of a subsequent diagnosis of GCA would improve diagnosis and avert significant complications associated with delayed treatment. Disclosures L.A. Barnett None. T. Helliwell None. K. Jordan None. J. Prior None.

Immunogenetics of Kawasaki disease.

Kawasaki disease (KD) is a medium vessel vasculitis that affects young children. Despite extensive research over the last 50years, the etiology of KD remains an enigma. Seasonal change in wind patterns was shown to have correlation with the epidemics of KD in Japan. Occurrence of disease in epidemiological clusters, seasonal variation, and a very low risk of recurrence suggest that KD is triggered by an infectious agent. The identification of oligoclonal IgA response in the affected tissues suggests an antigen-driven inflammation. The recent identification of a viral antigen in the cytoplasm of bronchial ciliated epithelium also favors infection as the main trigger for KD. Pointers that suggest a genetic basis of KD include a high disease prevalence in North-East Asian populations, a high risk among siblings, and familial occurrence of cases. Dysregulated innate and adaptive immune responses are evident in the acute stages of KD. In addition to the coronary wall inflammation, endothelial dysfunction and impaired vascular remodeling contribute to the development of coronary artery abnormalities (CAAs) and thrombosis. Genetic aberrations in certain intracellular signaling pathways involving immune effector functions are found to be associated with increased susceptibility to KD and development of coronary artery abnormalities (CAAs). Several susceptible genes have been identified through genome-wide association studies (GWAS) and linkage studies (GWLS). The genes that are studied in KD can be classified under 4 major groups-enhanced T cell activation (ITPKC, ORAI1, STIM1), dysregulated B cell signaling (CD40, BLK, FCGR2A), decreased apoptosis (CASP3), and altered transforming growth factor beta signaling (TGFB2, TGFBR2, MMP, SMAD). The review aims to highlight the role of several genetic risk factors that are linked with the increased susceptibility to KD.

Programmed cell death protein 1 inhibitor-induced recalcitrant mixed small and medium vessel vasculitis

Pembrolizumab, a programmed cell death protein 1 (PD1) inhibitor, has been known to be associated with several adverse reactions, including immune related adverse events. In less than one percent of patients, PD1 inhibitors have been linked to the development of connective tissue disease. Patients with previously known connective tissue disease are hypothesized to be at increased risk of flares in as many as 40% of cases. A 70-year-old man with a past medical history significant for rheumatoid arthritis in remission and stage IV lung adenocarcinoma presented to the dermatology clinic after one cycle of nivolumab and eight cycles of pembrolizumab exhibiting worsening, painful bilateral lower extremity ulcers for approximately one month. On the lower legs, three large black retiform eschars and bullous purpuric plaques were observed. Vasculitis is a rare complication of PD1 inhibitor therapy, with the majority of cases reported in literature either medium vessel or large vessel vasculitis. Only glucocorticoids have proven effective for PD1-induced vasculitis and these patients generally require multi-specialty management.

Common and rare forms of vasculitis associated with Sjögren's syndrome.

Although uncommon, systemic vasculitis is one of the most severe extraglandular manifestations of primary Sjögren's syndrome (pSS) accounting for the increased morbidity and mortality of the disease. This review aims to describe major previous and recent reports regarding the clinical presentation, prognosis and treatment of systemic vasculitis associated with pSS. Both older and recent pSS cohort studies performed over the past several and recent years, have clearly shown that cryoglobulinaemic vasculitis is the most frequent type of systemic vasculitis accompanying pSS. Antineutrophil cytoplasmic antibody-associated, large and medium vessel vasculitis are described only in sporadic cases. In addition to the overt clinical manifestations of cryoglobulinaemic vasculitis, type II cryoglobulinaemia, glomerulonephritis and purpura have been correlated with increased risk for B-cell non-Hodgkin lymphoma (NHL) in pSS. pSS is characterized by autoreactive B and T-cell infiltrates around the epithelial structures of the affected organs, as well as, B-cell hyperreactivity. The latter, is attested by the increased production of autoantibodies, directed against many different organ and nonorgan self-antigens. Vasculitis is a significant and potentially life-threatening complication of the disease depending on the size, localization, histologic type and the pathogenetic mechanisms of the inflammatory process. The potentially irreversible tissue damage, as well as the increased risk for NHL development, prompts the need for early diagnosis and treatment of cryoglobulinaemic vasculitis in pSS.

An Atypical Case of Vasculitis: When 'Occult' 18FDG-PET Scan Findings Create a Classification Dilemma.

We describe a 66-year old patient with a recurrent ulcer on her right ankle. Biopsy revealed medium-vessel vasculitis consistent with cutaneous polyarteritis nodosa. There were no signs or symptoms suggestive of systemic vasculitis, but a 18FDG-PET scan showed areas of increased uptake around the large arteries and the pelvic and shoulder girdles. These findings suggested polymyalgia rheumatica in the setting of large-vessel vasculitis. This case thus supports the statement from the Chapel-Hill consensus conference that classification of systemic vasculitis by vessel size is based on the vessels predominantly involved, but vessels of other sizes may also be affected.LEARNING POINTSThe classification of vasculitis needs further refinement as some patients may not easily fit into just one category.Conditions that include aspects of different vasculitis also exist and cannot be classified using the Chapel Hill nomenclature.The role of PET scan in the assessment of PAN needs further evaluation.

Giant Cell Arteritis (GCA): Pathogenesis, Clinical Aspects and Treatment Approaches.

Giant Cell Arteritis (GCA), or Horton's Arteritis, is a chronic form of vasculitis of the large and medium vessels, especially involving the extracranial branches of the carotid arteries, in particular, the temporal artery, with the involvement of the axillary, femoral and iliac arteries too. Arterial wall inflammation leads to luminal occlusion and tissue ischemia, which is responsible for the clinical manifestations of the disease. A substantial number of patients affected by GCA present head and neck symptoms, including ocular, neurological and otorhinolaryngological manifestations. The aim of this article is to present pathogenesis, clinical aspects and treatment approaches of GCA manifestations.

2658 Henoch-Schonlein Purpura Duodenitis

INTRODUCTION: Henoch-Schonlein Purpura (HSP) is an IgA mediated systemic, small and medium vessel vasculitis that typically presents with palpable purpura, arthralgias, abdominal pain and hematuria. Gastrointestinal manifestations occur in about 20% of patients prior to skin involvement. We report a case of a 51-year-old woman that presented with HSP duodenitis. CASE DESCRIPTION/METHODS: A 51-year-old female presented with a several week history of nausea, vomiting and epigastric abdominal pain. In addition, she had been experiencing dysphagia, arthralgias, fever and, later on, a palpable, petechial and purpuric rash on her face, ears and all extremities. She had no previous medical history. Physical exam showed an extensive palpable, ecchymotic and purpuric rash involving her arms, face, right ear and purpura on plantar surface of her feet (See Figure 1). Her wrist, elbow, knee and ankle joints were tender to palpation, warm and swollen. She had epigastric tenderness to palpation with no rebound or guarding. Laboratory workup was notable for a white blood cell count of 18.32 M/μL (4.20–5.60 M/μL). Computed tomography of the abdomen showed bowel wall thickening at the junction of duodenum and jejunum with fat stranding in the central mesentery. Biopsy of the skin showed features of leukocytoclastic vasculitis with associated perivascular necrotizing inflammation and hemorrhage (See Figure 2). EGD showed diffuse circumferential erythema with boggy mucosa as well as friability with touch bleeding consistent with ischemic type changes from distal bulb to the second portion of the duodenum (See Figure 3). Biopsies of the duodenum showed evidence of intramucosal hemorrhage, a mixed inflammatory infiltrate of neutrophils, lymphocytes and some plasma cells within the lamina propria. There were also fragments of advanced necrosis with evidence of small vessel thrombosis and vasculitis. Her abdominal pain and oral intake improved after treatment with 1 g methylprednisone for three days. The patient was discharged from the hospital with an oral steroid taper. DISCUSSION: HSP is rare in adults with roughly 20-fold fewer cases than in children. The range of endoscopic findings includes gastritis, ulceration, duodenitis, and submucosal hemorrhage with the second portion of the duodenum being involved more than the duodenal bulb. The end capillaries of small intestinal villi are particularly susceptible to ischemic injury. HSP is a self-limiting disease and majority of the patients improve spontaneously.

GRANULOMATOSIS WITH POLYANGIITIS PRESENTING AS BILATERAL DIFFUSE ALVEOLAR HEMORRHAGE

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Granulomatosis with Polyangiitis (GPA) most commonly occurs in older adults with multi-organ involvement including skin, kidneys and respiratory tract. Some of the pulmonary complications include dyspnea, small airway obstruction, pulmonary infiltrates, cavitary lesions and rarely, pulmonary hemorrhage. We present a case diffuse alveolar hemorrhage (DAH) as the initial presentation of GPA. CASE PRESENTATION: 57-year-old African American female with history of hypertension, diabetes mellitus, ductal carcinoma in situ, ischemic stroke, tobacco abuse and obesity presented with cough, progressive dyspnea and mild hemoptysis. On pulmonary examination, she had labored breathing and expiratory wheezes. Initial laboratory examinations were all within normal limits. A chest radiograph showed diffuse bilateral infiltrates. A high-resolution computed tomography of her chest revealed diffuse bilateral alveolar infiltrates with sparing of the lung peripheries and bases with confluent ground glass nodularity. She was empirically started on intravenous methylprednisolone and oral levofloxacin. Due to worsening respiratory symptoms and increased oxygen requirements, she was intubated. Bronchoscopy revealed bilateral alveolar hemorrhage across four dilutions. Bronchoalveolar lavage was negative for bacterial growth. Video-assisted thoracoscopic surgery (VATS) wedge biopsy showed diffuse neutrophilic inflammation, without evidence of granuloma or vasculitis. Plasmapheresis was initiated. She was successfully extubated after three sessions of plasmapheresis. Rheumatological workup returned positive for PR3 antibody. She was sarted on Rituximab for presumed GPA. She was discharged to a nursing facility. On a subsequent admission 10 days later, she was diagnosed with rapidly progressive glomerulonephritis, confirmed on renal biopsy. A skin lesion biopsy showed retiform purpura with ulcerations, consistent with medium and small vessel vasculitis. She was transitioned from rituximab to induction with cyclophosphamide and plasmapheresis was continued until she was stable and discharged back to nursing facility. DISCUSSION: This is an unfortunate but interesting initial presentation of GPA with mild hemoptysis and dyspnea resulting in alveolar hemorrhage, a rare complication of GPA. In addition, her renal involvement contributes to a worse prognosis with an estimated 10-year survival rate of 40%. CONCLUSIONS: GPA is a necrotizing systemic vasculitis that involves multiple organs, most commonly affecting skin, kidneys and lungs. However, these organs can have an array of symptoms that pose a difficulty in recognizing the disease, therefore, requiring a high clinical suspicion. DAH is a rare and life-threatening complication of GPA. Some clues to further explore DAH would include hemoptysis, dyspnea, anemia and hypoxia. Early diagnosis and initiation of treatment is important to preventing morbidity and mortality. Reference #1: Greco A, Marinelli C, Fusconi M, et al. Clinic manifestations in granulomatosis with polyangiitis. Int J Immunopathol Pharmacol. 2015;29(2):151-9. Reference #2: West S, Arulkumaran N, Ind PW, Pusey CD: Diffuse alveolar haemorrhage in ANCAassociated vasculitis. Intern Med 52: 5–13, 2013 DISCLOSURES: No relevant relationships by Kylee Dawson, source=Web Response No relevant relationships by Navneet Kaur, source=Web Response No relevant relationships by Sowjanya Yenigalla, source=Web Response

Pregnancy outcomes in women with primary systemic vasculitis: a retrospective study

Background/aims Pregnancies in women with systemic vasculitis constitute high-risk pregnancies, and outcomes vary based on the size of the affected blood vessels. Currently, there is limited data describing pregnancy outcomes in these women. The aim of this paper is to evaluate pregnancy outcomes in women with large, medium, or small vessel vasculitis to aid preconceptional counseling and inform antepartum and intrapartum care. Methods We included all women with large-, medium-, or small-vessel vasculitis and documented pregnancies attending high-risk pregnancy clinics at Mount Sinai Hospital, Toronto, Canada between 2001 and 2016. Pregnancy characteristics and outcomes were reported as proportions. Maternal, fetal/neonatal, and obstetric outcomes, stratified by type of vasculitis, were the main outcomes measured. Results We identified 60 pregnancies in 50 women with systemic vasculitis. These included large-vessel (n = 10), medium-vessel (n = 5), small-vessel [n = 30, of which 16 were AntiNeutrophil Cytoplasmic Autoantibody (ANCA)-associated and 14 were immune-complex mediated], central nervous system (n = 3), and retinal (n = 2). Although vasculitis flares occurred with large-vessel (3/12), small-vessel (13/36), and retinal (2/3) vasculitis, only one was severe and involved hemoptysis requiring blood transfusion in a woman with ANCA-associated vasculitis. Preeclampsia complicated two pregnancies each with large- (25%) and small- (6%) vessel vasculitis. Intrauterine growth restriction (IUGR) only occurred with small-vessel vasculitis (10, 29.4%). Although seven (26.4%) viable pregnancies resulted in preterm birth, the mean gestational age was over 35 weeks. Conclusion Although women with systemic vasculitis can have successful pregnancies, they are at increased risk for late preterm birth. In addition, those with small-vessel vasculitis are at increased risk for IUGR and vasculitis flares.