OP0145 MALIGNANCY IN ANCA-ASSOCIATED VASCULITIS AND POLYARTERITIS NODOSA: AN AUSTRALIAN POPULATION-BASED STUDY

Background:The increased risk of malignancy in patients with ANCA-associated vasculitis (AAV) and polyarteritis nodosa (PAN) has been attributed to late treatment related effects, with non-melanoma skin and genitourinary cancers most frequently reported in European studies1,2,3. Malignancy has not been examined in patients with AAV/PAN in Australia, where environmental factors may influence risk.Objectives:To determine the risk and timing of incident cancer in Western Australian (WA) AAV/PAN patients compared to controls.Methods:Patients and controls were ascertained through the WA Hospital Morbidity Data collection System (HMDS). Administrative hospitalisation data were linked with the WA cancer and death registries. Data was available between 1980-2015. Patients were classified into two sub-groups using International Classification of Disease (ICD) -9 and/or -10 codes: (1) GPA/MPA- granulomatosis with polyangiitis (GPA)/microscopic polyangiitis (MPA), and (2) other-AAV/PAN- eosinophilic granulomatosis with polyangiitis (EGPA), PAN, and other patients with any AAV or PAN where more specific ICD-10 coding was not available. Controls were age, sex and temporally matched (at patient diagnosis date) and had no rheumatological diagnosis. Patients and controls with prior cancer were excluded from the analysis.Spline-based estimation of time-varying hazard ratios (HR) for incident cancer in patientsvscontrols was performed using the Stata library stpm2cr4. Results for cause-specific models, which treated deaths in patients without cancer as censored, were confirmed using models treating death as a competing risk. The risk of specific cancers was analysed by Cox regression.Results:The analysis included 391 patients (165 GPA/MPA, 217 other-AAV/PAN) and 4913 controls, with 86 incident cancers (over 3556.7 person-years) observed in patients and 1119 (over 64997.0 person-years) in controls. Patients and controls were well matched for age (mean ± standard deviation GPA/MPA: 55 ± 18 years, other AAV/PAN: 59 ± 17 years, controls 57 ± 16 years), and sex (female: GPA/MPA 48%, other AAV/PAN 46%, controls 46%).Incident cancer risk and timing differed between the two patient subgroups (Figure 1). The risk of incident cancer in GPA/MPA patients, compared to controls, increased with disease duration, whilst other-AAV/PAN patients had a greater risk within the first two years of diagnosis, but a similar risk to controls in the longer term.By specific cancers, GPA/MPA patients had an increased risk of skin cancers (excluding squamous and basal cell carcinomas): hazard radio (HR) 2.71 95% confidence interval (CI) 1.55 – 4.74, and genitourinary cancers: HR 3.64, 95% CI 1.58, 8.39, which was not observed in other-AAV/PAN patients. While there was trend for an overall increase in haematological cancers, this was inconclusive.Conclusion:Incident cancer risk, driven by skin and genitourinary cancers, increased with disease duration in GPA/MPA patients, consistent with previous studies, suggestive of a treatment related effect. In contrast, cancer was more frequently observed early after diagnosis in other-AAV/PAN patients. Our findings suggest that vigilance for incident cancers is required for all patients with AAV and PAN after diagnosis and in long term management, considering distinct periods of greater risk by disease subgroup.References:[1]Heijl C et al. Ann Rheum Dis 2011;70:1415-1421[2]Lafarge A et al. Ann Rheum Dis 2019;0:1-2[3]Farschou M et al. Rheumatology 2015;54:1345-1350[4]Mozumder S et al. Stata J. 2017;17(2):462-489Disclosure of Interests:Joanna Tieu: None declared, Susan Lester: None declared, Warren Raymond: None declared, Helen Keen Speakers bureau: Pfizer Austrlaia, Abbvie Australia, Catherine Hill: None declared, Johannes (“Hans”) Nossent Speakers bureau: Janssen

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POS0830 FACTORS INFLUENCING PATIENT-REPORTED OUTCOMES IN ANCA-ASSOCIATED VASCULITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2367 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 668.2-669

Author(s):

S. Monti ◽

P. Delvino ◽

C. Klersy ◽

G. Coppa ◽

A. Milanesi ◽

...

Keyword(s):

Disease Activity ◽

Global Assessment ◽

Patient Reported Outcomes ◽

Granulomatosis With Polyangiitis ◽

Disease Duration ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

Anca Associated Vasculitis ◽

Organ Systems ◽

Damage Accrual ◽

Patient Reported

Background:Patient-reported outcomes (PROs) are currently poorly integrated in the clinical evaluation of disease activity in patients with ANCA-associated vasculitis (AAV).Objectives:To assess the distribution of the Patient Global Assessment (PtGA) in patients with AAV in stable remission, and to identify correlates of PtGA; to assess the discordance between PtGA score and PhGA.Methods:Patients with a diagnosis of AAV [eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, microscopic polyangiitis] in stable, complete remission (defined by a BVAS=0) and with a Physician Global Assessment (PhGA)=0 were included. A questionnaire including several aspects of disease captured by PROs was collected. PtGA on a 0-100 mm visual analogue scale (VAS) was assessed, with higher scores representing higher/worse levels of disease activity. Similarly, VAS for pain, chronic damage according to the patient’s opinion, general health (GH), fatigue, and sleep quality were collected. The worst symptom in the patient’s opinion affecting the overall assessment of disease activity was recorded. The Cragg Hurdle model was used to assess the predictors of PtGA.Results:65 patients were included, female 57%, mean age 61±12 years. Mean disease duration at enrollment was 8±6 years. Mean vasculitis damage index (VDI) was 4.4 ±2.3, with 45% of patients having a VDI ≥ 5. Despite having been classified as being in remission, PtGA was elevated in 37% of patients. We explored several correlates of PtGA. Higher degree of damage accrual (VDI) did not influence the patient’s evaluation of current disease activity. Similarly, we did not identify a correlation between older age, educational level, number of organ-systems involved, number of comorbidities, the number of previous major or minor relapses, higher disease duration, nor the type of AAV diagnosis (figure 1, panel A). Only sex significantly correlated with PtGA scores: 19 (51%) of female patients reported an elevated PtGA compared to only 5 (18%) of male (p=0.009). PtGA resulted to be significantly correlated with other (mostly modifiable) PROs including VAS pain, perception of the level of chronic damage accrual, GH, and fatigue (figure 1, panel B). The agreement between patients’ and physicians’ assessments of disease activity was 63%. Patients reported pain, followed by chronic respiratory symptoms to be the worst-experienced ongoing manifestations affecting their evaluation of disease activity.Conclusion:A significant proportion of patients with AAV considered to be in remission by the physician still declares to have persistent aspects of uncontrolled disease. PtGA is significantly influenced by persistent pain and fatigue, which warrant better assessment in the future.Disclosure of Interests:None declared

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Cancer Risk in Patients with Autoimmune Hepatitis: A Nationwide Population-Based Cohort Study with Histopathology

American Journal of Epidemiology ◽

10.1093/aje/kwab119 ◽

2021 ◽

Author(s):

Rajani Sharma ◽

Elizabeth C Verna ◽

Tracey G Simon ◽

Jonas Söderling ◽

Hannes Hagström ◽

...

Keyword(s):

Cohort Study ◽

General Population ◽

Cancer Risk ◽

Autoimmune Hepatitis ◽

Cox Regression ◽

Population Based ◽

Swedish Population ◽

Non Melanoma Skin Cancer ◽

Incident Cancer ◽

Increased Risk

Abstract We aimed to determine the risk of incident cancer in autoimmune hepatitis (AIH) compared to the general population and siblings. AIH was defined by the presence of a medical diagnosis of AIH and a liver biopsy in a nationwide Swedish population-based cohort study. We identified 5,268 adults with AIH diagnosed 1969-2016 and 22,996 matched general population reference individuals and 4,170 sibling comparators. Using Cox regression, hazard ratios (HRs) were determined for any incident cancer and sub-types determined from the Swedish Cancer Register. During follow-up, a cancer diagnosis was made in 1,119 individuals with AIH (17.2/1000 person-years) and 4,450 reference individuals (12.0/1000 person-years). This corresponded to an HR of 1.53 (95%CI: 1.42,1.66). Cancer risk was highest in those with cirrhosis. There was a 29.18-fold increased risk of hepatocellular carcinoma (HCC) (95%CI, 17.52,48.61). The annual incidence risk of HCC in individuals with AIH who had cirrhosis was 1.1% per year. AIH was also linked to non-melanoma skin cancer (HR=2.69) and lymphoma (HR=1.89). Sibling analyses yielded similar risk estimates for any cancer (HR=1.84) and HCC (HR=23.10). AIH is associated with an increased risk of any cancer, in particular, HCC and extra-hepatic malignancies. The highest risk for cancer, especially HCC, is in patients with cirrhosis.

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Associations of self-reported obstructive sleep apnea with total and site-specific cancer risk in older women: a prospective study

SLEEP ◽

10.1093/sleep/zsaa198 ◽

2020 ◽

Cited By ~ 1

Author(s):

Tianyi Huang ◽

Brian M Lin ◽

Meir J Stampfer ◽

Eva S Schernhammer ◽

Richa Saxena ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Cancer Risk ◽

Older Women ◽

Cox Regression ◽

Site Specific ◽

Incident Cancer ◽

Obstructive Sleep ◽

Increased Risk ◽

Specific Cancer

Abstract Background and Objectives Chronic intermittent hypoxia resulting from obstructive sleep apnea (OSA) may activate multiple carcinogenic pathways and lead to cancer development. Methods We prospectively examined the association between OSA and cancer risk among 65,330 women in the Nurses’ Health Study who were free of cancer in 2008 (mean age: 73.3 years). Incident cancer diagnoses were collected until 2016 and confirmed by pathology reports. Clinically diagnosed OSA was self-reported in 2008 and updated in 2012. We used time-dependent Cox regression to estimate hazard ratios (HR) for the associations of OSA with total and site-specific cancer risk. Results We documented 5,257 incident cancer diagnoses during follow-up. In the age-adjusted model, OSA was associated with a 15% (95% CI: 1.03, 1.29) increase in total cancer risk. The association became nonsignificant after adjustment for multiple cancer risk factors (HR: 1.08; 95% CI: 0.96, 1.21). When examining cancer risk by site, OSA was associated with significantly increased risk for lung (fully adjusted HR: 1.52; 95% CI: 1.07, 2.17), bladder (fully adjusted HR: 1.94; 95% CI: 1.12, 3.35), and thyroid cancer (fully adjusted HR: 2.06; 95% CI: 1.01, 4.22) and possibly increased risk for kidney cancer (fully adjusted HR: 1.59; 95% CI: 0.84, 3.01). When grouping cancer sites by risk factor profiles, OSA was positively associated with smoking-related cancers (fully adjusted HR: 1.37; 95% CI: 1.11, 1.67), and this association was stronger in never smokers than ever smokers. Conclusion While OSA was not independently associated with overall cancer risk in older women, significant associations were observed for smoking-related cancers, especially in nonsmokers.

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Risk of acute arterial and venous thromboembolic events in Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss syndrome)

10.1101/2020.11.09.20228197 ◽

2020 ◽

Author(s):

Alessandra Bettiol ◽

Renato Alberto Sinico ◽

Franco Schiavon ◽

Sara Monti ◽

Enrica Paola Bozzolo ◽

...

Keyword(s):

Granulomatosis With Polyangiitis ◽

Cox Regression ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

Thromboembolic Events ◽

Multicenter Cohort Study ◽

Increased Risk ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Eosinophilic Granulomatosis ◽

Reference Cohort

ABSTRACTBackground and objectiveSystemic small vessel vasculitides carry an increased risk of acute arterial and venous thromboembolic events (AVTE); however, this risk has not been systematically explored in Eosinophilic Granulomatosis with Polyangiitis (EGPA). This study assessed the occurrence and main risk factors of AVTE among EGPA patients as compared to the general community from the population-based Bruneck cohort.MethodsWe conducted a retrospective multicenter cohort study on 573 EGPA patients. Clinical and serological data were collected at diagnosis. Occurrence of AVTE and time to the first AVTE after EGPA diagnosis were recorded. Age-standardized event rate (SER) of AVTE as compared to the reference cohort was assessed. Cox regression was applied to identify AVTE predictors.Results129 EGPA patients (22.5%) had AVTE, considered as potentially life-threatening in 55.8%. Seventy patients experienced an AVTE prior to diagnosis (of whom 58.6% in the two years before diagnosis) and 75 following EGPA diagnosis, of whom 56% in the two subsequent years. The SER of AVTE as compared to the reference cohort was 2.10 (95% CI 1.67-2.63). This risk was particularly increased in patients with history of AVTE and with a Birmingham Vasculitis Activity Score ≥20 at diagnosis. Patients receiving immunosuppression within 2 months of diagnosis were at lower risk, while antiplatelet or anticoagulant treatment did not confer measurable benefit.ConclusionEGPA is associated with AVTE in approximately one quarter of patients, particularly around diagnosis. Immunosuppressants seemed to exert a protective effect, while anticoagulant and antiplatelet agents did not.

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P182 Prevalence and mortality of ANCA-associated vasculitis in England

Rheumatology ◽

10.1093/rheumatology/keaa111.177 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Fiona A Pearce ◽

Bridget Griffiths ◽

Chetan Mukhtyar ◽

Reem Al-Jayoussi ◽

Richard A Watts ◽

...

Keyword(s):

Granulomatosis With Polyangiitis ◽

Adult Population ◽

Population Based ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

Standardised Mortality Ratio ◽

Anca Associated Vasculitis ◽

Background Population ◽

Routine Identification ◽

The Usa ◽

Mortality Ratio

Abstract Background The contemporary prevalence of ANCA-associated vasculitis (AAV) in England is unknown. Hospital Episode Statistics (HES) contain data on every hospital and day case NHS admission in England since 1997. In collaboration with the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) we validated the diagnosis of AAV using ICD codes in HES. The positive predictive value of these codes was 86%, which compares favourably to a median coding accuracy of 80% in a recent systematic review of NHS coding studies. This justifies using this novel dataset for population-based epidemiology with coverage of the whole population of England. Methods We worked within NCARDRS enabled by their Section 251 legal permissions (CAG 10-02(d)/2015). We extracted all cases of AAV from HES 2011/12 to 2016/17 using ICD-10 codes M313 Granulomatosis with polyangiitis (GPA), M317 Microscopic polyangiitis (MPA), and M301 Eosinophilic granulomatosis with polyangiitis (EGPA). We used the Summary Care Record to check vital status and record date of death where appropriate. We estimated point prevalence on 1 July 2016 using ONS mid-year population estimates for England in 2016 as the denominator. Standardised mortality ratio (SMR) was calculated using the Office for National Statistics death summary tables 2016 to provide expected number of deaths for each 5-year age-band and sex. Results We identified 9,890 patients who were coded as having AAV during a hospital admission 2011-2017. This included 6,856 (69.3%) with GPA, 964 (9.8%) with MPA and 2,070 (20.9%) with EGPA. On 1 July 2016, our dataset found 8,040 people in England were living with ANCA associated vasculitis. We estimate the prevalence was 14.55 (95% CI: 14.23-14.87)/100,000 adult population. The median age of these patients was 65.3 years (interquartile range 52.3-74.2). 47% were female. The prevalence of GPA was 9.97/100.000 (95% CI: 9.71-10.24), MPA was 1.40/100,000 (95% CI: 1.30-1.50), and EGPA was 3.18/100,000 (95% CI: 3.03-3.33). People with AAV were 4.6 times more likely to die than the background population of the same age and sex (Standardised Mortality Ratio = 4.58). Conclusion There are no recent UK prevalence estimates for all types of ANCA-associated vasculitis. Studies in Australia, Germany, Southern Sweden and the USA have found estimated prevalence to be between 4.6-18.4 cases per 100,000 individuals. Our estimate of 14.6/100,000 in England is consistent with this, and towards the higher end of the range. However, our estimates underestimate the prevalence of MPA compared to other studies, and further work is needed to increase the routine identification of cases of MPA. Further work within NCARDRS using their unique data linkages will enable more specific AAV case ascertainment as well as nationwide population-based studies on cause of death and studies using the database of English prescriptions dispensed in the community. Disclosures F.A. Pearce None. B. Griffiths None. C. Mukhtyar None. R. Al-Jayoussi None. R.A. Watts None. J. Aston None. M. Bythell None. S. Stevens None. P.C. Lanyon None.

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Methylation-Based Biological Age and Breast Cancer Risk

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djz020 ◽

2019 ◽

Vol 111 (10) ◽

pp. 1051-1058 ◽

Cited By ~ 34

Author(s):

Jacob K Kresovich ◽

Zongli Xu ◽

Katie M O’Brien ◽

Clarice R Weinberg ◽

Dale P Sandler ◽

...

Keyword(s):

Breast Cancer ◽

Dna Methylation ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cox Regression ◽

Disease Risk ◽

Statistical Tests ◽

Biological Age ◽

Cancer Case ◽

Increased Risk

Abstract Background Age is one of the strongest predictors of cancer, chronic disease, and mortality, but biological responses to aging differ among people. Epigenetic DNA modifications have been used to estimate “biological age,” which may be a useful predictor of disease risk. We tested this hypothesis for breast cancer. Methods Using a case-cohort approach, we measured baseline blood DNA methylation of 2764 women enrolled in the Sister Study, 1566 of whom subsequently developed breast cancer after an average of 6 years. Using three previously established methylation-based “clocks” (Hannum, Horvath, and Levine), we defined biological age acceleration for each woman by comparing her estimated biological age with her chronological age. Hazard ratios and 95% confidence intervals for breast cancer risk were estimated using Cox regression models. All statistical tests were two-sided. Results Each of the three clocks showed that biological age acceleration was statistically significantly associated with increased risk of developing breast cancer (5-year age acceleration, Hannum’s clock: hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.00 to 1.21, P = .04; Horvath’s clock: HR = 1.08, 95% CI = 1.00 to 1.17, P = .04; Levine’s clock: HR = 1.15, 95% CI = 1.07 to 1.23, P < .001). For Levine’s clock, each 5-year acceleration in biological age corresponded with a 15% increase in breast cancer risk. Although biological age may accelerate with menopausal transition, age acceleration in premenopausal women independently predicted breast cancer. Case-only analysis suggested that, among women who develop breast cancer, increased age acceleration is associated with invasive cancer (odds ratio for invasive = 1.09, 95% CI = 0.98 to 1.22, P = .10). Conclusions DNA methylation-based measures of biological age may be important predictors of breast cancer risk.

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Rotating Nightshift Work and Hematopoietic Cancer Risk in US Female Nurses

JNCI Cancer Spectrum ◽

10.1093/jncics/pkz106 ◽

2020 ◽

Vol 4 (2) ◽

Author(s):

Yin Zhang ◽

Brenda M Birmann ◽

Kyriaki Papantoniou ◽

Eric S Zhou ◽

Astrid C Erber ◽

...

Keyword(s):

Cancer Risk ◽

Hodgkin Lymphoma ◽

Cox Regression ◽

Statistical Tests ◽

B Cell Lymphoma ◽

Health Study ◽

Increased Risk ◽

Work Duration ◽

History Of ◽

Hematopoietic Cancer

Abstract Background Nightshift work is a plausible risk factor for hematologic cancer, but epidemiological evidence remains sparse, especially for individual subtypes. We prospectively examined the association of rotating nightshift work with hematopoietic cancer risk. Methods This cohort study included US women from the Nurses’ Health Study (NHS: n = 76 846, 1988–2012) and Nurses’ Health Study II (NHSII: n = 113 087, 1989–2013). Rotating nightshift work duration was assessed at baseline (both cohorts) and cumulatively updated (NHSII). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall hematopoietic cancer and specific histologic subtypes. All statistical tests were two-sided. Results We documented 1405 (NHS) and 505 (NHSII) incident hematopoietic cancer cases during follow-up. In NHS, compared with women who never worked rotating nightshifts, longer rotating nightshift work duration was associated with an increased risk of overall hematopoietic cancer (HR1–14y = 0.93, 95% CI = 0.83 to 1.04; HR≥15y = 1.28, 95% CI = 1.06 to 1.55; Ptrend = .009). In NHSII, results were similar though not statistically significant (HR1–14y = 0.99, 95% CI = 0.82 to 1.21; HR≥15y = 1.41, 95% CI = 0.88 to 2.26; Ptrend = .47). In the subtype analyses in the NHS, the association of history of rotating nightshift work with risk of diffuse large B-cell lymphoma varied by duration (HR1–14y = 0.71, 95% CI = 0.51 to 0.98; HR≥15y = 1.69, 95% CI = 1.07 to 2.67; Ptrend = .01) compared with those who never worked rotating nightshifts. Women reporting a longer history of rotating nightshifts also had suggestive (statistically nonsignificant) increased risks of overall non-Hodgkin lymphoma (HR≥15y = 1.19, 95% CI = 0.95 to 1.49), Hodgkin lymphoma (HR≥15y = 1.32, 95% CI = 0.43 to 4.06), and multiple myeloma (HR≥15y = 1.42, 95% CI = 0.85 to 2.39). Conclusions Longer duration (≥15 years) of rotating nightshift work was associated with increased risks of overall and several subtypes of hematopoietic cancer.

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Immunopathogenesis of ANCA-Associated Vasculitis

International Journal of Molecular Sciences ◽

10.3390/ijms21197319 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7319

Author(s):

Andreas Kronbichler ◽

Keum Hwa Lee ◽

Sara Denicolo ◽

Daeun Choi ◽

Hyojeong Lee ◽

...

Keyword(s):

Granulomatosis With Polyangiitis ◽

Microscopic Polyangiitis ◽

Autoimmune Disorder ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

Proteinase 3 ◽

Disease Biomarkers ◽

Disease Phenotypes ◽

Anca Associated Vasculitis ◽

Clinical Presentations ◽

Eosinophilic Granulomatosis

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disorder which affects small- and, to a lesser degree, medium-sized vessels. ANCA-associated vasculitis encompasses three disease phenotypes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). This classification is largely based on clinical presentations and has several limitations. Recent research provided evidence that genetic background, risk of relapse, prognosis, and co-morbidities are more closely related to the ANCA serotype, proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, compared to the disease phenotypes GPA or MPA. This finding has been extended to the investigation of biomarkers predicting disease activity, which again more closely relate to the ANCA serotype. Discoveries related to the immunopathogenesis translated into clinical practice as targeted therapies are on the rise. This review will summarize the current understanding of the immunopathogenesis of ANCA-associated vasculitis and the interplay between ANCA serotype and proposed disease biomarkers and illustrate how the extending knowledge of the immunopathogenesis will likely translate into development of a personalized medicine approach in the management of ANCA-associated vasculitis.

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ANCA-associated vasculitis in a 14 years-old patient: a clinical case

Kuban Scientific Medical Bulletin ◽

10.25207/1608-6228-2020-27-5-184-194 ◽

2020 ◽

Vol 27 (5) ◽

pp. 184-194

Author(s):

A. V. Burlutskaya ◽

N. V. Savelyeva ◽

N. S. Тaran

Keyword(s):

Respiratory Failure ◽

Immunosuppressive Therapy ◽

Clinical Case ◽

Granulomatosis With Polyangiitis ◽

Systemic Vasculitis ◽

Pulse Therapy ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

Anca Associated Vasculitis ◽

Nasal Bleeding ◽

Diagnostic Research

Background. ANCA-associated systemic vasculitis is a rare childhood disease. Antineutrophil cytoplasmic autoantibodies (ANCA)-related vasculitises include microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis. Their rarity often leads to a late diagnosis, rapid disability and high mortality in patients due to aggressive respiratory, pulmonary lesion and renal failure.Clinical Case Description. The patient suffered from a recurrent bronchoobstructive syndrome with signs of respiratory failure, obscure origin fever and chronic rhinitis with nasal bleeding for 6 months. The patient was diagnosed with obstructive bronchitis (putative bronchial asthma debut), received antibacterial therapy and inhalation bronchodilators without stable improvement during the entire period. Skin haemorrhages and arthralgia stimulated diagnostic research to establish ANCA-associated systemic vasculitis (presence of proteinase 3-specifi c ANCAs in titre 1/80). CT lung scanning revealed frosted glass foci of reduced pulmonary pneumatisation and signs of bilateral bronchoobstruction. Immunosuppressive therapy with glucocorticosteroids (methylprednisolone pulse therapy No. 3, 1000 mg intravenously on alternate days, subsequent per os administration of 1 mg/kg/day) and cyclophosphamide (500 mg intravenously once per 28 days) was prescribed. This led to the positive dynamics with eliminated fever and skin haemorrhages, as well as essentially reduced signs of respiratory failure.Conclusion. Diagnosis of systemic vasculitis is often complicated and long-term due to commonly non-specifi c debut symptoms of autoimmune disorders. In the described case, the fi rst 6 months of illness displayed intoxication and bronchoobstruction with signs of respiratory failure. Haemorrhagic rashes, arthralgias and the presence of ANCAs are proxy to vasculitis. Standard immunosuppressive therapy for ANCA-associated vasculitis improved the patient’s condition.

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ANCA-Associated Vasculitis with Cardiac Valve Vegetations in Two Teenage Males: A Case Report and Literature Review

10.21203/rs.3.rs-1178656/v1 ◽

2022 ◽

Author(s):

Alexandra Theisen ◽

Martha Rodriguez

Keyword(s):

Cardiac Involvement ◽

Granulomatosis With Polyangiitis ◽

Pediatric Population ◽

Adult Population ◽

High Dose ◽

Eosinophilic Granulomatosis With Polyangiitis ◽

Newly Diagnosed ◽

Cardiac Morbidity ◽

Anca Associated Vasculitis ◽

Cardiac Manifestations

Abstract Background: Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis is a term used to describe systemic vasculitides that affect small and medium-sized blood vessels. The three types of ANCA-associated vasculitis (AAV) are Granulomatosis with Polyangiitis (GPA), formerly Wegener’s granulomatosis , Microscopic Polyangiitis (MPA), and Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly Churg-Strauss, with clinical presentation most frequently involving the respiratory tract, the kidney, the skin and the joints. ANCA-associated vasculitis is rare in children, with estimated prevalence of 3-4 per million, and even more rare is the manifestation of cardiac abnormalities secondary to ANCA-associated vasculitis in the pediatric population. Case Presentation: We present the cases of two teenage males who presented with cardiac valvular lesions secondary to Granulomatosis with Polyangiitis in addition to sinus, pulmonary, renal, and cutaneous involvement. These findings of cardiac valvular abnormalities in GPA have rarely been described in the literature in pediatrics. Both patients were treated with rituximab, high-dose methylprednisolone, and plasma exchange (PLEX) and showed improvement in their disease manifestations. Conclusions: A review of the literature revealed only five pediatric cases of ANCA-associated vasculitis with cardiac manifestations, and interestingly, three of the five had valvular involvement. Subsequent valvular involvement makes obtaining the diagnosis of ANCA-Associated Vasculitis very difficult due to concern for underlying infectious endocarditis and can lead to misdiagnosis given the rarity of cardiac involvement in ANCA-associated vasculitis. Routine echocardiogram is not always completed in newly diagnosed GPA, yet cardiac involvement can lead to severe consequences as was seen with our first patient in the form of thromboembolic stroke. We discuss the importance of keeping AAV on the differential when cardiac lesions are present as well as the importance of regular cardiac screening in newly diagnosed patients with AAV, as it is a major factor of cardiac morbidity and mortality in the adult population and can contribute substantially to management decisions.

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