Necrotizing Vasculitides (necrotizing vasculitis)

name: Necrotizing Vasculitides
display_name: Necrotizing Vasculitides (necrotizing vasculitis)
creation_date: "2026-08-18T00:00:00Z"
description: >-
  The necrotizing vasculitides are the systemic and organ-limited vasculitides
  whose characteristic biopsy appearance is transmural fibrinoid necrosis of the
  vessel wall: leukocyte recruitment into and through the wall, destruction of
  the internal elastic lamina and smooth muscle, plasma-protein (fibrin)
  insudation into the necrotic wall, and — depending on calibre — aneurysm
  formation, thrombosis, haemorrhage, or downstream ischaemic infarction. The
  group cuts across the Chapel Hill vessel-size axis: it includes the
  pauci-immune ANCA-associated small-vessel vasculitides (granulomatosis with
  polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with
  polyangiitis), the medium-vessel necrotizing arteritis of polyarteritis
  nodosa, the immune-complex small-vessel vasculitides in which the biopsy
  hallmark is leukocytoclastic vasculitis with fibrinoid necrosis
  (IgA vasculitis, cryoglobulinaemic vasculitis, cutaneous
  leukocytoclastic/allergic vasculitis), and secondary forms complicating
  connective-tissue disease (rheumatoid vasculitis). What is shared is the
  pattern of tissue injury and the therapeutic consequence — necrotizing
  vasculitis is an organ- and life-threatening lesion that is treated with
  induction immunosuppression — not a shared aetiology, autoantibody, or
  vessel calibre.
grouping_basis:
- SHARED_PHENOTYPE
- SHARED_MECHANISM
grouping_rationale: >-
  Grouped on a shared histopathologic lesion and the shared effector mechanism
  that produces it: leukocyte-mediated destruction of the vessel wall with
  fibrinoid necrosis. This is a deliberately histopathology-anchored union
  rather than an aetiologic one, because the immunologic triggers of the members
  are mutually exclusive — ANCA-driven neutrophil activation in GPA/MPA/EGPA,
  immune-complex deposition and complement activation in IgA and
  cryoglobulinaemic vasculitis, hepatitis-B-associated and idiopathic
  medium-artery disease in polyarteritis nodosa, and long-standing seropositive
  rheumatoid arthritis in rheumatoid vasculitis. Each is kept as its own
  Disease entry because the trigger, the ANCA/immune-deposit status, the
  vessel calibre, the organ pattern, and the treatment algorithm all differ;
  the grouping exists so that the recurrent lesion — and the fact that a
  "necrotizing vasculitis" biopsy report does not by itself name a disease — is
  represented explicitly.

  The criteria are stated as NECESSARY, not NECESSARY_AND_SUFFICIENT. Membership
  entails the necrotizing pattern, but the converse does not hold: the pattern
  is seen in a minority of biopsies in vasculitides whose dominant histology is
  something else (primary CNS vasculitis is granulomatous or lymphocytic in most
  biopsy series, with a necrotizing pattern in a subset), and focal fibrinoid
  necrosis also occurs in malignant hypertension and in thrombotic
  microangiopathy, neither of which is a vasculitis. Presence of the lesion in
  some patients is therefore not sufficient to make a disease a member.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0800113
      label: necrotizing vasculitis
    mapping_predicate: skos:closeMatch
    mapping_source: MONDO
    mapping_justification: >-
      MONDO:0800113 is definitionally a class over other diseases ("A type of
      vasculitis that is comprised of vasculitides that present with necrosis"),
      which is exactly what this Grouping models, so the concepts correspond.
      It is recorded as closeMatch rather than exactMatch because the membership
      here is curated from the clinical/histopathologic definition rather than
      copied from MONDO's asserted is_a subtree, and the two sets differ in both
      directions (see the consistency note).
    consistency:
    - reference: MONDO
      consistent: INCONSISTENT
      notes: >-
        MONDO's asserted is_a descendants of MONDO:0800113 are granulomatosis
        with polyangiitis, ANCA-associated vasculitis, eosinophilic
        granulomatosis with polyangiitis, microscopic polyangiitis,
        immunoglobulin A vasculitis, and disseminated visceral giant cell
        angiitis. Four of the eight members listed here fall outside that
        subtree — primary polyarteritis nodosa (MONDO:0018593), rheumatoid
        vasculitis (MONDO:0043267), cryoglobulinaemic vasculitis
        (MONDO:0007407), and allergic cutaneous vasculitis (MONDO:0001290) —
        even though the standard definition of each names necrotizing or
        fibrinoid-necrotic vessel-wall injury. Polyarteritis nodosa is the most
        striking omission, since the 2012 Chapel Hill definition of PAN is
        "necrotizing arteritis of medium or small arteries". Conversely,
        MONDO:0015492 (ANCA-associated vasculitis) is an intermediate grouping
        term with no dismech Disease entry, and MONDO:0800125 (disseminated
        visceral giant cell angiitis) has no dismech entry at all, so neither is
        listed as a member. This is recorded as an upstream MONDO
        subtree-coverage gap, not as a scope difference.
membership_criteria:
- description: >-
    Every member is a vasculitis whose characteristic — not merely incidental —
    biopsy appearance is the necrotizing pattern: fibrinoid necrosis of the
    vessel wall accompanying the vascular inflammation (HP:6000253 Necrotizing
    vasculitis, a descendant of HP:0002633 Vasculitis).
  criteria_semantics: NECESSARY
  logic:
    criterion_predicate: HAS_PHENOTYPE
    description: >-
      Necrotizing vasculitis (fibrinoid necrosis of the inflamed vessel wall) is
      the characteristic histopathology.
    phenotype_term:
      preferred_term: Necrotizing vasculitis
      term:
        id: HP:6000253
        label: Necrotizing vasculitis
  evidence:
  - reference: PMID:27536680
    reference_title: "Overview of the Pathogenesis of ANCA-Associated Vasculitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Antineutrophil cytoplasmic autoantibodies (ANCA) are associated with a
      spectrum of necrotizing vasculitis including granulomatosis with
      polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with
      polyangiitis, and renal-limited necrotizing and crescentic
      glomerulonephritis.
    explanation: >-
      Establishes that "necrotizing vasculitis" names a spectrum spanning several
      distinct clinical diagnoses rather than one disease - the premise of this
      grouping - and enumerates three of its members.
  - reference: PMID:33713282
    reference_title: "Diagnosis and management of leukocytoclastic vasculitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Among systemic diseases, the most frequently associated with LCV are
      ANCA-associated vasculitides, connective tissue diseases, cryoglobulinemic
      vasculitis, IgA vasculitis (formerly known as Henoch-Schonlein purpura) and
      hypocomplementemic urticarial vasculitis (HUV).
    explanation: >-
      Covers the immune-complex arm of the grouping: the leukocytoclastic lesion,
      whose defining histology is neutrophilic infiltration with fibrinoid
      necrosis, is shared by cryoglobulinemic vasculitis, IgA vasculitis and the
      connective-tissue-disease-associated forms.
- description: >-
    Vessel-wall necrosis in every member is produced by recruited leukocytes
    degranulating within the wall — neutrophils in the ANCA-associated and
    leukocytoclastic forms, with eosinophils additionally in EGPA — rather than
    by a non-inflammatory mechanism (thrombotic microangiopathy, malignant
    hypertension, calciphylaxis, embolic occlusion), and the lesion is severe
    enough that untreated disease causes organ infarction. This criterion is
    stated in prose only: it is a claim about the effector mechanism of the
    lesion for which no single shared GO process is annotated across the
    members, and encoding it as a HAS_BIOLOGICAL_PROCESS leaf would assert a
    machine-checkable agreement that the member entries do not yet carry.
  criteria_semantics: NECESSARY
  evidence:
  - reference: PMID:27536680
    reference_title: "Overview of the Pathogenesis of ANCA-Associated Vasculitis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Activated neutrophils adhere to and penetrate vessel walls, and they release
      toxic oxygen radicals and destructive enzymes that cause apoptosis and
      necrosis of the neutrophils as well as of the adjacent vessel wall cells and
      matrix.
    explanation: >-
      Describes the effector step this criterion asserts is common to the members:
      leukocytes that have entered the wall degranulate there, and it is their
      oxidants and proteases - not a non-inflammatory process - that necrose the
      wall.
members:
- member: Granulomatosis with Polyangiitis
  member_type: DISEASE
  disease_term:
    preferred_term: granulomatosis with polyangiitis
    term:
      id: MONDO:0012105
      label: granulomatosis with polyangiitis
  differentiating_mechanisms:
  - description: >-
      PR3-ANCA-associated. Uniquely combines the necrotizing small-to-medium
      vessel vasculitis with necrotizing granulomatous inflammation of the upper
      and lower respiratory tract, giving the destructive sinonasal, orbital and
      cavitating pulmonary lesions that MPA lacks.
- member: Microscopic Polyangiitis
  member_type: DISEASE
  disease_term:
    preferred_term: microscopic polyangiitis
    term:
      id: MONDO:0019124
      label: microscopic polyangiitis
  differentiating_mechanisms:
  - description: >-
      MPO-ANCA-associated and defined by the ABSENCE of granulomatous
      inflammation: a pauci-immune necrotizing small-vessel vasculitis whose
      dominant expression is necrotizing crescentic glomerulonephritis and
      alveolar capillaritis. The pauci-immune (few or no immune deposits)
      character separates it from the immune-complex members.
- member: Eosinophilic granulomatosis with polyangiitis
  member_type: DISEASE
  disease_term:
    preferred_term: eosinophilic granulomatosis with polyangiitis
    term:
      id: MONDO:0015943
      label: eosinophilic granulomatosis with polyangiitis
  differentiating_mechanisms:
  - description: >-
      The eosinophilic member: severe asthma and blood/tissue eosinophilia
      precede an eosinophil-rich necrotizing granulomatous inflammation and
      vasculitis. ANCA is positive in only a minority, splitting the disease
      into an ANCA-positive vasculitic phenotype and an ANCA-negative
      eosinophilic-infiltrative phenotype (cardiomyopathy) — a heterogeneity
      the other ANCA-associated members do not show.
- member: Primary Polyarteritis Nodosa
  member_type: DISEASE
  disease_term:
    preferred_term: primary polyarteritis nodosa
    term:
      id: MONDO:0018593
      label: primary polyarteritis nodosa
  differentiating_mechanisms:
  - description: >-
      The medium-vessel member and the historical prototype of the group:
      segmental necrotizing arteritis of medium and small ARTERIES, sparing
      arterioles, capillaries and venules. That vessel-calibre restriction is
      the defining contrast with the ANCA-associated members — PAN is
      ANCA-negative, causes microaneurysms and infarction rather than
      glomerulonephritis or alveolar haemorrhage, and has a hepatitis-B-driven
      secondary form.
- member: Rheumatoid Vasculitis
  member_type: DISEASE
  disease_term:
    preferred_term: rheumatoid vasculitis
    term:
      id: MONDO:0043267
      label: rheumatoid vasculitis
  differentiating_mechanisms:
  - description: >-
      Secondary rather than primary: a necrotizing or leukocytoclastic
      vasculitis arising as an extra-articular complication of long-standing,
      seropositive (rheumatoid factor / anti-CCP) erosive rheumatoid arthritis,
      typically presenting as digital infarcts, cutaneous ulceration and
      mononeuritis multiplex. Requires the underlying RA for diagnosis, and its
      incidence has fallen with modern RA therapy.
- member: Cryoglobulinemic Vasculitis
  member_type: DISEASE
  disease_term:
    preferred_term: Cryoglobulinemic vasculitis
    term:
      id: MONDO:0007407
      label: Cryoglobulinemic vasculitis
  differentiating_mechanisms:
  - description: >-
      Immune-complex member driven by circulating cold-precipitable
      immunoglobulins, overwhelmingly secondary to chronic hepatitis C virus
      infection. Distinguished by cryoglobulin positivity with low C4,
      membranoproliferative glomerulonephritis, and a treatment algorithm that
      is antiviral first — eradicating the antigenic drive — rather than
      immunosuppression first.
- member: IgA Vasculitis
  member_type: DISEASE
  disease_term:
    preferred_term: immunoglobulin A vasculitis
    term:
      id: MONDO:0019167
      label: immunoglobulin A vasculitis
  differentiating_mechanisms:
  - description: >-
      Immune-complex member defined by vessel-wall deposition of
      galactose-deficient IgA1-containing complexes. The only predominantly
      paediatric, typically post-infectious and self-limiting member, with the
      characteristic tetrad of palpable purpura, arthralgia, abdominal pain and
      IgA nephropathy-like glomerulonephritis. Direct immunofluorescence showing
      IgA is what separates it from the other leukocytoclastic members.
- member: Allergic Cutaneous Vasculitis
  member_type: DISEASE
  disease_term:
    preferred_term: allergic cutaneous vasculitis
    term:
      id: MONDO:0001290
      label: allergic cutaneous vasculitis
  differentiating_mechanisms:
  - description: >-
      The single-organ member: cutaneous leukocytoclastic angiitis limited to
      dermal postcapillary venules, most often a hypersensitivity reaction to a
      drug or infection, without the systemic organ involvement of the other
      members. Fibrinoid necrosis with leukocytoclasia is the defining biopsy
      finding, but by Chapel Hill definition it must not be part of a systemic
      vasculitis — so it is the group's diagnosis of exclusion.
notes: >-
  Deliberately excluded, with reasons, because the grouping is
  histopathology-anchored:

  - CNS Vasculitis (primary CNS vasculitis, MONDO:0015374) — the dominant biopsy
    patterns are granulomatous and lymphocytic; the necrotizing pattern appears
    in a minority of cases (5/10 in the Mayo spinal-cord cohort curated on that
    entry). It is a candidate member only if a future curation shows the
    necrotizing pattern is characteristic rather than a subset finding.
  - Giant Cell Arteritis and Takayasu Arteritis — large-vessel granulomatous
    arteritides; the lesion is granulomatous panarteritis with giant cells, not
    fibrinoid necrosis.
  - Kawasaki Disease — necrotizing arteritis is described in the acute phase,
    but the Chapel Hill definition does not classify it as a necrotizing
    vasculitis and the dismech entry does not yet curate the histology; left as
    an open candidate.
  - Behcet Disease, Postinfectious Vasculitis, Livedoid Vasculopathy — variable
    or non-necrotizing vessel pathology (livedoid vasculopathy is a thrombotic
    vasculopathy, not a vasculitis at all).

  The advisory audit for this grouping is driven by the HP:6000253 leaf. All
  eight members were annotated with that term (with per-disease evidence) as part
  of creating this grouping, so `just check-groupings` currently reports
  SATISFIED for all eight rather than leaving the criteria aspirational.