Small Vessel Vasculitis Research Articles

#6178 ANCA-ASSOCIATED VASCULITIS FOLLOWING PFIZER-BIONTECH COVID-19 VACCINE: TRUE ASSOCIATION OR CIRCUMSTANTIAL?

Abstract Background and Aims Antineutrophil cytoplasmatic antibody (ANCA)- associated vasculitis (AAV) is a small vessel vasculitis hallmarked by the presence of antibodies against antigens in cytoplasmic granules of neutrophils. Vaccines per se stimulate the immune system, including the innate and the adaptive immune response. Therefore, it is possible that an excess of autoimmunity is observed after vaccine administration. Vaccination (notably influenza) is a recognized trigger for the relapse of ANCA-associated vasculitis. ANCA associated vasculitis and autoimmune reactions have been reported with COVID-19 infection and following vaccination. Results We report the case of a Caucasian, 62 year-old-man, with a previous history of type 2 diabetes mellitus, hypertension and atrial fibrillation. Blood analysis one year before presentation showed preserved renal function and normal urinalysis. He received the first dose of Pfizer-BioNTech COVID-19 vaccine and two weeks later routine blood analysis showed acute kidney injury with serum Creatinine 1.75 mg/dL with de novo hematuria, a protein to creatinine ratio (RPC) 1.1 mg/g and candersartan (4 mg twice daily) was started. The patient received the second dose of COVID-19 vaccine 21 days after the first injection. Two weeks later he developed anorexia, nausea and de novo hematuria. He was admitted at the emergency department with deteriorating renal function with a sCr of 5.5 mg/dL, worsening hematuria with dysmorphic red blood cells and proteinuria (RPC 2.9 mg/g). Renal ultrasound was normal. Immunological studies revealed an elevated ANCA-MPO titer of 561. A kidney biopsy was performed and showed a crescentic necrotizing glomerulonephritis. Immunofluorescence confirmed pauciimmune glomerulonephritis. He was diagnosed with renal limited myeloperoxidase (MPO) ANCA AAV. He started 3 pulses of 500mg I.V methylprednisolone followed by prednisolone 1 mg/kg/day after that. He also started rituximab (4 doses of 500mg I.V once week apart). Despite the immunosuppression, the patient never recovered renal function and remained dialysis dependent. Conclusion Whether autoimmune diseases can be triggered after vaccination remains a matter of discussion among experts. ANCA associated vasculitis and autoimmune reactions have been reported with COVID-19 infection and following vaccination, which prompts the question whether this response could be a direct reaction to the RNA present in the vaccine. While an association with de novo ANCA vasculitis and COVID-19 vaccine may be possible, further investigation is necessary.

#6407 RENAL LIMITED VASCULITIS: DATA FROM A CROATION REFERRAL CENTER

Abstract Background and Aims Small vessel vasculitis and in particular ANCA associated vasculitis (AAV) are diseases with variable clinical presentation. Renal limited vasculitis (RLV) can vary in presentation and characteristics compared to systemic disease. There is a tendency to categorise RLV as a part of microscopic polyangiitis (MPA) spectrum though there seem to be differences in terms of both histology and serology between RLV and MPA. We present data on patients with renal limited vasculitis from our referral center. Method This study included 106 consecutive AAV patients with biopsy proven renal involvement in the period from 2007-2017. Category variables were analysed with Fisher Exact testom and continuous with Kruskal-Wallis testom. Statistical difference was then analysed posthoc with Chi-square test. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between clinical phenotypes and finding significant predictors regarding outcomes which were defined as combined outcome end-stage renal disease and death (ESRDD), ESRD alone, the death outcome alone and relapse rate. Results Out of 106 AAV patients with renal involvement in our database: 66 (61,1%) MPA, 20 (18,5%) GPA (granulomatosis with polyangiitis), 20 (18,5%) RLV. In RLV group 14 (70%) were female and average age was 55 (IQR 47-60). Average SCr in RLV group was 234 μmol/l (IQR 168-376,5) and median proteinuria was 3,3g/24h (IQR 0,9-3,8) and most of these patients presented with either nephrotic syndrome (30%) or RPGN (30%). Serologicaly 90% of RLV patients were ANCA negative and 10% were MPO-ANCA positive. Histologicaly (Berden classification) 60% had mixed class, 25% crescentic, 10% focal and 1% sclerotic. Average BVAS score was 14 (IQR 12-17). Compared to MPA and GPA, RLV patients were younger (p=0,058), had less expressed constitutional symptoms (p= 0,013) with lower average BVAS (p=0,0001) and lower CRP levels (p=0,001). Though there was no significant difference of average SCr level RLV patients presented more often with nephrotic syndrome (p=0,014), had histological predominantly mixed class (p=0,006) and higher interstitial fibrosis and tubular atrophy (IFTA) percentage (p=0,086). Interestingly, compared to MPA and GPA majority of RLV patients were ANCA negative (p=0,001). There were no statistically significant differences in treatment used both in induction (including need for dialysis and/or PLEX) or remission maintenance treatment between RLV, MPO and GPA group. In survival analysis there was no statistical differences for all of the outcomes between RLV group, MPA and GPA group. Conclusion RLV can be challenging disease considering it's clinical presentation but also characteristics of renal involvement in terms of more often nephrotic proteinuria and higher IFTA percentage. This might suggest that these patients could have slower disease course (so called slower progressors). Also interestingly in our cohort most of these patients were ANCA negative which also makes diagnosis predominantly a combination of clinical presentation and histology thus prompting a question of how should we classify RLV within a spectrum of small vessel vasculitis. More research is needed to better understand the RLV.

#6045 TWO-YEAR INPATIENT ACTIVITY OF A DEDICATED ONCONEPHROLOGY DEPARTMENT

Abstract Background and Aims Onconephrology is a rapidly evolving nephrology subspecialty that focuses on the interaction between cancer and the kidney. Our aim was to describe the clinical activity of a Nephrology Department in a cancer care center, in a 2-year period. Method We retrospectively analyzed the patients observed by the Nephrology Department at our center between 2021 and 2022. Demographic, clinical and laboratory data were collected. The statistical analysis was performed with SPSS software. Results During the 2-year period, there were 26,015 admissions, 636 of which required a Nephrology observation. Sixty-two per cent were female; the mean age was 68 years (SD ±12.4) with a median Charlson Comorbidity Index of 7. Most cancers were from gastrointestinal (24.1%, n = 153) or urologic origins (22.3%, n = 142), 37% had metastatic disease. Hematologic malignancies accounted for 12.1% of patients (n = 77). Nearly 44.5% of patients (n = 283) had chronic kidney disease (CKD), 20.8% (n = 59) of which were on hemodialysis (HD). Urinary tract obstruction (23.3%), cardiovascular risk factors (17.3%) and nephron loss (10.6%) were the most common causes of CKD. The main reasons for admission were renal dysfunction (23.7%; n = 151), infectious complications (23.3%, n = 148) and elective surgery (20.3%; n = 129). Of the patients observed, 40.7% (n = 259) had acute kidney injury (AKI), 23.3% (n = 148) acute-on-chronic kidney disease and 11.8% (n = 75) hydro-electrolytic disorders. Ten patients (1.6%) were evaluated for nephrotic syndrome (NS) or rapidly progressive renal failure (RPRF). Among AKI patients, intrinsic causes were the most prevalent (48.7% of all cases), with sepsis and ischemic and toxic acute tubular necrosis being the most frequent. Pre-renal and post-renal etiologies occurred in 29.7% and 21.6% of cases, respectively. Gynaecological and prostate tumours were the main neoplastic cause of post-renal AKI. There were 5 TMA cases in allogenic stem cell transplanted patients or treated with gemcitabine and six cases of acute interstitial nephritis, the majority immune check-point inhibitors-related. Over 54% (n = 142) of patients presented with AKI stage 3. About 13% (n = 34) needed renal replacement therapy (RRT), mainly continuous or hybrid techniques (58.8%; n = 20), and only 38% (n = 13) recovered renal function. The group of acute-on-chronic CKD patients included mostly stage 3b and 4 CKD. Most of them (54.1%; n = 80) had an intrinsic cause for kidney dysfunction. There was an equal distribution between stages of AKI severity. About 5% (n = 8) needed RRT and only two of those recovered. Hyponatremia was the most common electrolyte disturbance (56%; n = 42), followed by hypercalcemia (17.3%; n = 13). Over 40% of all cases of hyponatremia occurred in patients with metastatic lung cancer, probably related with the high prevalence of SIADH in this population. All but two patients with NS or RPRF underwent kidney biopsy. Among the patients with NS, its etiologies were: focal and segmental glomerulosclerosis secondary to pamidronate (n = 2), podocytopathy related to pazopanib (n = 1), paraneoplastic membranous nephropathy (n = 1), AL amyloidosis (n = 1) and TMA secondary to gemcitabine (n = 1). The causes of RPRF were ANCA-negative small vessel vasculitis, crescentic glomerulonephritis (GN) related to pembrolizumab and TMA. We also followed two patients with acute kidney disease, one with ATN secondary to bisphosphonates therapy and other with paraneoplastic fibrillary glomerulopathy. The median duration of hospitalization was 10 days (IQR 7.0 – 20.8), with median Nephrology follow-up time of 5.5 days (IQR 3.0 – 9.0). The overall mortality rate was 21.5%, and it was even higher on the subgroup with AKI (27.4%; p = 0.03). About 44% (n = 219) of patients were referred to outpatient Nephrology follow-up, at discharge. Conclusion Our data provides a picture of the rich inward activity developed at our cancer center by the nephrology team. The complexity of these patients highlights the importance of a multidisciplinary approach in their management. No surprisingly, there was a high mortality rate, which was even higher in the AKI-patients subset.

#3420 CLINICAL CHARACTERISTICS AND PRIMARY OUTCOMES OF PATIENTS WITH ANCA-ASSOCIATED VASCULITIS AND CENTRAL DIABETES INSIPIDUS

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by systemic small-vessel vasculitis and may rarely present as central diabetes insipidus (CDI). AAV-associated CDI should be recognized to avoid unnecessary biopsies of the pituitary gland and minimize the risk of irreversible loss of pituitary function. In this study, we aimed to determine the clinical characteristics and prognosis of patients with AAV-associated CDI. Method This was a nested case-control study where AAV patients with CDI at the Peking Union Medical College Hospital were followed from January 2012 to April 2022. Case-control matching with AAV patients without CDI was performed (1:2), and participants were matched by age, sex, and AAV classification. We collected clinical data every 3–6 months and conducted a literature review using PubMed to identify relevant articles published from 1983–2022. Results Among 1203 hospitalized AAV patients, 16 patients with CDI were included (1.3%). The average age was 49 years, and men accounted for 56.3%. Granulomatosis with polyangiitis (GPA) accounted for 87.5% of patients. AAV patients with CDI had more ear, nose, and throat (ENT) (81.3%) involvement and less renal impairment than those in the control group (P<0.05). After a mean follow-up of four years, 50% of patients were in remission, 37.5% relapsed, and 12.5% died. Our literature review suggested that patients in Asian countries tend to be older men and have higher MPO-ANCA positivity than those in European countries. Furthermore, PR3-ANCA positivity may predict disease recurrence. Conclusion AAV patients with CDI had more ENT involvement and a higher eGFR. MPO-ANCA positivity is more commonly observed in Asian countries than in European countries, and PR3-ANCA positivity may predict recurrence.

#2777 RISK FACTORS ASSOCIATED WITH OUTCOMES IN PATIENTS WITH HENOCH - SCHӧNLEIN PURPURA NEPHRITIS

Abstract Background and Aims Henoch - Schӧnlein purpura (HSP) is an immuno-mediated small-vessel vasculitis that manifests as non—thrombocytopenic purpura, arthritis or arthralgia, abdominal pain and/or kidney involvement. HSP nephritis can presented is micro- or macroscopic hematuria, proteinuria, nephrotic or nephritic syndrome, as well as acute renal failure. The aim of the study is to identify risk factors associated with unfavorable outcomes in patients with HSP nephritis. Method This retrospective study enrolled 68 patients with HSP nephritis. Renal and extra-renal symptoms were analyzed. A diagnosis of HSP nephritis was made when hematuria and/or proteinuria, and/or renal failure was associated with a palpable purpuric eruption or abdominal or joint pains (at least two of these three clinical signs) and predominant mesangial IgA immune deposits, confirmed by renal biopsy. The patients were subdivided into five classes according to the renal manifestation at onset of disease: 1) micro- or macroscopic hematuria; 2) mild proteinuria (<1 g/L) ± hematuria; 3) acute nephritic syndrome, defined as moderate proteinuria, hematuria, increased serum creatinine and/or hypertension; 4) nephrotic syndrome; 5) mixed nephritic-nephrotic syndrome. Results Of 68 patients with HSP nephritis, diagnosed by kidney biopsy, 41 (60,29%) were male and 27 (39,71%) - female. Age of onset was between 18 and 66 years (mean 37,28 ± 9,34). Duration of follow-up was between 2 and 28 years. 29 patients had histories of infection preceding presentation. At onset all patients had palpable purpura and urinary abnormalities (only hematuria - in 16,18%; mild proteinuria ± hematuria – in 44,12%; moderate or severe proteinuria and hematuria – in 39,70%). Arthralgias were present in 49 patients (72,06%), gastrointestinal involvement – in 32 patients (47,05%). Renal function was impaired in 26,47% of patients, and 51,47% were hypertensive. Mesangial hypercellularity lesions were found in most patients (97,06%), endocapillary proliferation – in 20,58%, segmental sclerosis – in 32,35%, tubular atrophy/interstitial fibrosis – in 38,23%. Corticosteroids and cyclophosphamide were prescribed in patients who presented with severe clinical and histological features and/or rapidly progressing renal disease. During follow-up classical extra-renal organ diseases were seen in 55,88% of patients, and hematuria and/or proteinuria – in 77,94%. At final review 26,47% had progression of renal failure. Risk factors for renal failure were moderate or severe proteinuria during follow-up (p<0,001), renal impairment at presentation (p<0,001), hypertension at presentation and during follow up (p<0,05), crescents, interstitial fibrosis and tubular atrophy (p<0,001). No significant difference in renal outcome was observed between patients who had relapses in extra-renal organs versus in those who did not. Conclusion Our results indicated that lower GFR, nephrotic syndrome, nephritic-nephrotic syndrome and crescentic nephritis were risk factors for unfavorable outcomes.

Lupus Enteritis: A Case Report

Lupus enteritis is a rare presentation of systemic lupus erythematous, clinically manifested by abdominal pain, vomiting, and diarrhoea. Proper diagnosis and treatment are essential to avoid complications, including death. Here, the authors report a case of a 52-year-old White female who presented with abdominal pain and chronic diarrhoea, with diagnostic tests compatible with lupus enteritis. Such a condition is an uncommon manifestation of systemic lupus erythematosus, an autoimmune disease that affects young females, resulting from gastrointestinal involvement by small vessel vasculitis. Early detection and proper management of lupus enteritis are essential to improve long-term survival. The present case addresses the clinical characteristics of lupus enteritis, emphasising its pathophysiology, diagnosis, and treatment.

Pulmonary-Renal Syndrome from Levamisole-Adulterated Cocaine-Induced Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: A Systematic Review.

Levamisole is an anti-helminthic drug with immunomodulatory properties that is added to cocaine to increase its potency and weight. Levamisole-adulterated cocaine (LAC) may cause an antineutrophil cytoplasmic antibody (ANCA)-associated systemic small vessel vasculitis (AAV). We aimed to characterize the phenotype of persons developing pulmonary-renal syndrome (PRS) in LAC-induced AAV and summarize its treatment and outcomes. Pubmed and Web of Science were searched (until September 2022). Reports that described co-existing diffuse alveolar hemorrhage and glomerulonephritis in an adult (age ≥ 18) with confirmed or suspected LAC exposure were included. Reports, demographics, clinical and serologic features, treatment and outcome characteristics were extracted. Of the 280 records identified, eight met the inclusion criteria, including eight unique cases. Persons were aged 22-58 years, and 50% were women. Cutaneous involvement occurred in only half of the cases. Other associated vasculitis findings and serologies were heterogeneous. All patients received immunosuppression with steroids, with cyclophosphamide and rituximab commonly added. We concluded that PRS could occur from LAC-induced AAV. Distinguishing LAC-induced AAV from primary AAV is challenging as clinical and serologic presentations overlap. Asking about cocaine use is requisite in persons presenting with PRS to guide diagnosis and appropriately counsel on cocaine cessation in conjunction with immunosuppression as treatment.

Anti-IL5 Monoclonal Antibodies Reduce Asthma Exacerbations and Corticosteroids Dose in Three Eosinophilic Granulomatosis with Polyangiitis Case Reports.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystem necrotizing small and medium-sized vessel vasculitis with eosinophilic adult-onset asthma as part of its spectrum. Therapeutic choices include corticosteroids, immunosuppressive agents, and novel immunomodulators. Mepolizumab and benralizumab are monoclonal antibodies targeting Interleukin-5 (IL-5), which plays a leading role in every stage of production and maturation of eosinophils and are recently undergoing evaluation and administered in steroid-dependent, relapsing and/or refractory EGPA. Herein we describe the cases of three patients with a prior EGPA diagnosis, experiencing frequent asthmatic exacerbations despite oral and inhaled corticosteroid treatment (two patients) and adverse effects of corticosteroids (one patient). Two patients are under treatment with mepolizumab and one patient with benralizumab as an add-on supplemental regimen. In our case series anti-IL5 monoclonal antibodies proved efficient asthma-controlling and corticosteroid-sparing agents.

ASSOCIATION DE GRANULOMATOSE EOSINOPHILIQUE AVEC POLYANGEITEAVEC RECTOCOLITE HEMORRAGIQUE: A PROPOS DUN CAS

Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis of small vessels, which is part of the anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides. It evolves through a prodromal phase characterized by allergic manifestations, followed by blood and tissue hypereosinophilia contributing to visceral infiltration. Finally, the necrotizing vasculitis phase explains the systemic manifestations occurring several years after the prodromal phase. Hemorrhagic rectocolitis (UC) belongs to the chronic inflammatory bowel diseases (IBD).the inflammation typically begins in the rectum and spreads proximally and continuously to affect a variable extent of the colon. It most often evolves in flare-ups interspersed with remissions.The coexistence of ANCA-associated vasculitis and IBD is a rare condition that is rarely described in the literature. We report a new case of association of IBD and GEPA.

Una “vistosa” vasculite con edema, che riguarda gli arti e il viso e risparmia il tronco

Acute haemorrhagic oedema of infancy (AHEI) is a small vessel vasculitis that affects boys between 4 months and 2 years. It presents with a characteristic purpuric skin rash but with marked bruising and “typical” localizations in auricles and is often accompanied by oedema of face and extremities. It is typically post-infectious, especially after infections of the upper respiratory tract and rarely can be associated with gastrointestinal, renal, articular or testicular complications. The paper reports the case of a 2-year-and-5-month-old boy who, 5 days after the resolution of a febrile infection of the upper airways (with subsequent detection of positive IgM and IgG serology for SARS-Cov-2), presented with a rash with ecchymotic/purpuric lesions in his lower limbs, face and auricles associated with intense arthralgia, arthritis of a knee and deterioration of general conditions. The diagnosis of acute infantile haemorrhagic oedema was clear but the clinical presentation required an “important” therapeutic approach with intravenous steroids and an infusion of immunoglobulins.

An Atypical Case of Anti GBM Disease

Anti GBM disease is a very rare type of small vessel vasculitis. The incidence is around less than 1 per million per year .This disease is also known as “Good Pasteur Disease”. Usually it presents with rapidly progressive glomerulonephritis with or without lung haemorrhage. The pathognomonic hallmark of the disease is strong linear IgG deposition along the GBM along with positive anti GBM antibody. But when the circulating antibody is absent in the blood, with mild renal impairment it is termed as atypical anti GBM disease. Recently we have found a 26 years old gentleman who presented with leg swelling for 1.5 months along with decreased urine output. He was non diabetic, normotensive, there was no history of joint pain, rash, no offending medication intake, or coughing out of blood. His urine R/E report showed Alb+++, RBC-plenty. After admission his serum creatinine was increasing rapidly. We have done renal biopsy and started treatment with I/V methylprednisolone followed by oral steroid. He had nephrotic range proteinuria. His auto antibody profile and HBsAg, Anti HCV was negative. We have done renal biopsy and it showed crescentic GN with strong linear deposition of IgG. His anti GBM Ab was negative. Thus we labelled the case as atypical anti GBM disease. Now patient is on RRT and we started therapeutic plasma exchange. J Medicine 2023; Vol. 34, No. 2(1) Supplement: 220

Dilated Cardiomyopathy in a Patient with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare pathology that belongs to a group of diseases characterized by necrotizing vasculitis of small and medium-sized systemic blood vessels. Symptomatic cardiovascular involvement occurs in 27%–47% of cases of EGPA and is one of the most severe manifestations. The diagnosis is usually confirmed by eosinophilic infiltration observed in tissue biopsy, but with the recent inclusion of cardiac magnetic resonance imaging (MRI), the former can be replaced. Early diagnosis is important because timely treatment is often associated with improvement.

Segmental cutaneous leukocytoclastic vasculitis associated with herpes zoster: a case report and literature review.

Varicella zoster virus (VZV) infection may cause large or medium vessel vasculitis, including granulomatous arteritis of the nervous system and central nervous system vasculitis. However, small vessel vasculitis, such as cutaneous leukocytoclastic vasculitis (LCV) associated with localized cutaneous VZV infection, herpes zoster, is uncommon. Herein, we present the case of a 75- year-old man with segmental leukocytoclastic vasculitis associated with herpes zoster on the leg. To the best of our knowledge, there are four cases of segmental leukocytoclastic vasculitis in herpes zoster reported in the English literature; we compared our case with these previous reports. Our review of five patients suggests that most patients were immunosuppressed. We also found that the leg is susceptible to LCV associated with herpes zoster. Anti-viral treatment was effective for LCV as well as herpes zoster. Prior reports have proposed etiologies inducing LCV; for example, immune complexes are mediated by vessel wall damage. In support of this, histopathology in our case showed a C3-positive reaction with the small vessel walls in the dermis in direct immunofluorescence. Although the mechanism of LCV associated with herpes zoster remains unclear, we should consider LCV while diagnosing and treating patients with herpes zoster, especially immunosuppressed patients.

Clinical characteristics and primary outcomes of patients with ANCA-associated vasculitis and central diabetes insipidus.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by systemic small-vessel vasculitis and may rarely present as central diabetes insipidus (CDI). In this study, we aimed to determine the clinical characteristics and prognosis of patients with AAV-associated CDI. This was a nested case-control study where AAV patients with CDI at the Peking Union Medical College Hospital were followed from January 2012 to April 2022. Case-control matching with AAV patients without CDI was performed (1:5), and participants were matched by age, sex, and AAV classification. We collected clinical data every 3-6 months and conducted a literature review using PubMed to identify relevant articles published from 1983-2022. Among 1203 hospitalized AAV patients, 16 patients with CDI were included (1.3%). The average age was 49 years, and men accounted for 56.3%. Granulomatosis with polyangiitis (GPA) accounted for 87.5% of patients. AAV patients with CDI had more ear, nose, and throat (ENT) (81.3%) involvement and less renal impairment than those in the control group (P<0.05). After a mean follow-up of four years, 50% of patients were in remission from AAV, 37.5% relapsed, and 12.5% died. Our literature review suggested that patients in Asian countries tend to be older men and have higher myeloperoxidase (MPO-ANCA) positivity than those in Western countries. Furthermore, proteinase 3 (PR3-ANCA) positivity may predict disease recurrence. AAV patients with CDI had more ENT involvement and a higher eGFR. MPO-ANCA positivity is more commonly observed in Asian countries than Western countries, and PR3-ANCA positivity may predict recurrence.

Histopathologic features predictive of perivascular deposition of IgA on direct immunofluorescence in cases of leukocytoclastic vasculitis: A retrospective study of 112 specimens.

IgA vasculitis is a small-vessel vasculitis subtype with increased risk of systemic involvement. We aimed to investigate if any light-microscopic features can predict the presence of perivascular granular IgA deposits on direct immunofluorescence (DIF) microscopy. We performed a retrospective search of cutaneous pathology reports from our internal and consultation practice (January 1, 2010-October 5, 2021) with a diagnosis of leukocytoclastic vasculitis and accompanying DIF. A blinded dermatopathologist reviewed standard microscopy slides for predetermined histopathological features. Fifty-six biopsies (48 patients) and 56 biopsies (42 patients) met inclusion criteria for IgA+ and IgA-, respectively. The presence of eosinophils and mid and deep dermal inflammation were statistically more associated with IgA- (41/56 [73.2%] and 31/56 [55.4%], respectively) than IgA+ cases (28/56 [50.0%] and 14/56 [25.0%]; p = 0.049 and 0.006, respectively, chi-squared test). Other microscopic criteria recorded were not significantly different between the two groups (p > 0.05, chi-squared and Fisher's exact tests). In this retrospective study of 112 cases, we found that while the absence of eosinophils and absence of mid- and deep inflammation were correlated with increased likelihood of IgA perivascular deposition on DIF, no other histopathological features on light microscopy tested could reliably predict the presence of IgA perivascular deposition on DIF. Therefore, DIF remains a necessary component for the accurate diagnosis of cutaneous IgA vasculitis.

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.

De Novo Vasculitis after COVID-19 Vaccination.

The coronavirus disease 2019 (COVID-19) pandemic continues to spread around the world. Vaccinations have been administered globally and have been proven to be safe and effective. However, vasculitis has been reported as an adverse event occurring after COVID-19 vaccination. In this review, we analyzed the literature to identify original articles that reported on patients who developed vasculitis following COVID-19 vaccination and summarized their clinical manifestations. PubMed and Web of Knowledge were searched to identify relevant studies. A total of 27 patients who developed vasculitis following COVID-19 vaccination were identified from 21 studies. The involved organs included the skin and kidney. The main clinical features of patients whose skin was affected were papules, maculopapular rashes, and plaques. Most of the patients exhibited small vessel vasculitis and single-organ vasculitis; these were resolved within one month. Patients whose kidneys were affected exhibited vasculitis, including anti-neutrophil cytoplasmic antibody glomerulonephritis and IgA nephritis. Most patients were treated with corticosteroid, rituximab, and cyclophosphamide, and one patient needed hemodialysis. The renal function of most patients was improved or recovered, but one patient needed maintenance dialysis. Vasculitis was rarely reported after COVID-19 vaccine administration. It often manifested as cutaneous small-vessel vasculitis or glomerulonephritis. Notably, when a patient demonstrates hematuria, proteinuria, and acute kidney injury after COVID-19 vaccination, there is a possibility that the patient could have developed vasculitis. Skin-related problems were quickly resolved, while kidney-related problems may progress to chronic kidney disease.

Change over time of lipid profile relates to steroid treatment but not to an inflammatory state in Granulomatosis with poliangioitis polyangiitis (GPA)

Aim: Granulomatosis with polyangiitis (GPA) is a small vessel vasculitis. Inflammation of the vessel wall may induce multiple vascular damages. Atherosclerosis is accelerated during vasa inflammation. Metabolic profile and cardiovascular risk are far to be determined in these patients. Thus, Cardiovascular atherosclerotic disease (ASCVD) may represent a risk for patients' outcomes. The purpose is to evaluate ASCVD risk in GPA over time during disease follow-up. Methods: We retrospectively evaluated 37 patients (22 Females, aged 51.45±17.15) who received a diagnosis of GPA (T0). Patients were evaluated at 1 (T1) and 2 (T2) year follow-up. All patients were treated with high steroid dose followed by a one-year tapering, associated to another immunosuppressant. Lipid profile included total cholesterol, HDL, LDL and Triacylglycerol. To evaluate inflammatory activity, we evaluate erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and neutrophil to lymphocyte ratio (NLR) at the same time points. ANOVA for repeated values was used to evaluate the trend over time and Tukey's multiple comparisons test was a second step evaluation. Results: At T1 there was an increase in total cholesterol compared to baseline (T1vsT0, p&lt;0.05) and T2 (T1vs T2, p&lt;0.05). Similarly, LDL (T1vsT0, p&lt;0.05) presents the same trend, while Triacylglycerol increased in T1 compared to baseline (T1vsT0, p&lt;0.05), but no difference there was in T2 compared to T1 or T0. No difference was found in HDL between the different time points. CRP was no different, despite a reduction being noticed. On the contrary, we found a reduction at T2 but not in T1 in ESR (T1vsT0, p&lt;0.05) and NLR (T1vsT0, p&lt;0.05). Conclusion: Our data suggest that a change in lipid profile may not relate to better control of inflammation. On the contrary, the increase in the first year of follow-up should be a consequence of steroid treatment needed to spread disease control. These data may be helpful in the evaluation of both cardiovascular disease and lipid metabolism due to the connection between the two parameters with vessel inflammation. Further studies are needed to better evaluate the cardiovascular effect of vasculitis and consequent treatment.

Small Vessel Vasculitis in Small Fiber Neuropathy with TS-HDS, FGFR-3, or Plexin D1 antibodies (P14-8.007)

Small Vessel Vasculitis in Small Fiber Neuropathy with TS-HDS, FGFR-3, or Plexin D1 antibodies (P14-8.007)

Cerebral Vasculitis in a patient receiving Risankizumab, an Inhibitor of Interleukin-23: First Case Report (P12-3.013)

<h3>Objective:</h3> NA <h3>Background:</h3> Iatrogenic neuroinflammation has been frequently reported in recent years owing to expanding biologic therapies for the treatment of a wide range of disorders including Psoriasis. Here we report a case of Central Nervous System (CNS) vasculitis after initiation of Risankizumab, a monoclonal antibody against Interleukin-23 (IL23) used to treat Psoriasis. <h3>Design/Methods:</h3> Case report. <h3>Results:</h3> A 29-year-old female with moderate psoriasis who was started on Risankizumab about one month prior, presented with encephalopathy and left temporal lobe focal seizures with refractory status epilepticus. Her MRI showed punctate infarcts and areas of enhancement in the left temporal lobe and leptomeninges overlying the left convexity. Extensive work up revealed increased Erythrocyte Sedimentation Rate (72 mm/hr) and positive Cardiolipin (IgM and IgG) and Beta-2 Glycoprotein (IgM and IgG) antibodies suggesting antiphospholipid syndrome (APS) for which she was started on anticoagulation. Lumbar puncture revealed normal opening pressure, glucose, protein and five nucleated cells. Oligoclonal bands, meningitis/encephalitis and autoimmune encephalitis panels were negative. Subsequent brain MRI showed new areas of ischemic lesions. Cerebral angiogram was unremarkable. Biopsy revealed focal perivascular lymphocytes (CD45 and CD3 immunohistochemical stained) infiltration in dural vessels consistent with small-vessel vasculitis. She was treated with high dose steroids with clinical improvement and subsequently planned to treat with Cyclophosphamide. Risankizumab was discontinued due to possible association. <h3>Conclusions:</h3> Iatrogenic neuroinflammation has been increasingly recognized during the new era of biological molecules and monoclonal antibodies for systemic inflammatory disorders and malignancies. Tumor necrosis factor inhibitors and immune checkpoint inhibitors are more commonly associated with neuroinflammation. To the best of our knowledge, this is the first reported case of APS and CNS vasculitis possibly associated with the initiation of IL23 inhibitor Risankizumab. Although causality cannot be established with a single case, it suggests a possible association. <b>Disclosure:</b> Dr. Cabrera Pulla has nothing to disclose. Dr. Amirjanyan has nothing to disclose. Qian Wu has nothing to disclose. Dr. Mui has nothing to disclose. Dr. Imitola has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis . The institution of Dr. Imitola has received research support from biogen. Dr. Imitola has a non-compensated relationship as a Board Member with National MS Society that is relevant to AAN interests or activities. Dr. Imitola has a non-compensated relationship as a Committee Member with International Society for Stem Cell Research that is relevant to AAN interests or activities. Dr. Coban has nothing to disclose.