CLINICAL PRESENTATION OF THE FAMILIAL CASES OF ANCA-ASSOCIATED VASCULITIS: A SYSTEMATIC REVIEW

Introduction:

Genetic factors are associated with the risk of ANCA-associated vasculitis (AAV) occurrence and disease phenotype. However familial cases of AAV are rarely reported. The aim of our systematic review was to analyze the published cases of AAV affecting first-, second- or third-degree relatives.

Methods:

We systematically searched EMBASE and MEDLINE databases for case reports and case series that reported the occurrence of AAV in two or more members of the same family. No restrictions on the language or study period were imposed. The study protocol was registered at the OSF Registries (https://osf.io/zjfkd). Title and abstract screening, full-text screening, and data extraction were performed by two independent reviewers. All conflicts were resolved by reaching a consensus with the help of the third reviewer. Screening and data extraction were managed in accordance with the PRISMA guidelines using the COVIDENCE tool. To assess the risk of bias we used the Critical Appraisal tools for case reports and case series by Joanna Briggs Institute.

Results:

The literature search was conducted on 15 August 2022 and repeated prior to final analysis in 2024. In total 3968 references were identified, 640 were removed as duplicates, 39 studies were selected for the full-text screening, and 28 were included for data extraction. In total 31 families with 65 affected family members from 15 countries were described. There were 32 (49%) males and 33 (51%) females, median age at AAV onset was 47 (33-60) years, the youngest patient being 2 weeks old, and the oldest 77 years old.

In 17 families the affected members were siblings, in 11 - parents and children, and in other cases: niece and two aunts, niece and uncle, two cousins and uncle.

Thirty-four patients were diagnosed with granulomatosis with polyangiitis (GPA), 11 with eosinophilic granulomatosis with polyangiitis (EGPA), 6 with microscopic polyangiitis (MPA), two with renal limited vasculitis, in 12 the type of AAV was not defined. In most cases members of the same family were diagnosed with the same type of AAV: in 14 families - with GPA, in 5 - with EGPA, in 2 - with MPA, in one with renal-limited vasculitis (RLV). In three families, different types of AAV were diagnosed: MPA and GPA - in 2, EGPA and GPA in one. No combinations of MPA and EGPA were reported.

ANCA status was reported in 47 patients, among them 38 (80%) were ANCA positive. In 13 families the affected relatives had the same ANCA status: negative - in one family (EGPA), MPO- or pANCA in 6 families, pr3- or cANCA in 6. In one family one relative had MPO-ANCA and another pr3-ANCA.

Among the reported manifestations, lung, kidney, ENT, and general manifestations were the most common, followed by skin, nervous system, GI tract, and cardiovascular involvement (Figure 1). AAV manifestations varied between the members of the same family, however in six families identical presentation with the involvement of the same organs and systems was reported.

Figure 1. Radial plot representing AAV manifestations. Each segment represents a single patient. Thick black lines are used to distinct different families.  

Conclusions:

Familial cases of AAV demonstrate clinical and serological heterogeneity among the affected relatives with a high prevalence of kidney and lung involvement.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.