Today we presented a very interesting case of anti-MPO vasculitis with renal biopsy confirming a pauci-immune necrotizing, crescenteric glomerulonephritis.

We first reviewed the common features of small-vessel ANCA associated vasculitides [AAV] -granulomatosis with polyangiitis; microscopic polyangiitis; eosinophilic granulomatosis with polyangiitis:

Common Systemic Signs and Symptoms– fevers, weight loss, arthralgias, malaise

• Common Organ-Specific Manifestations
  • Kidney
    • Hematuria, proteinuria, AKI caused by GN
  • Skin
    • Purpura caused by leukocytoclasic angiitis in dermal venues and atertioles
  • Abdominal Pain and Fecal Occult Blood
    • From mucosal and bowel wall infarcts
  • Mononeuritis Multiplex from arteritis in peripheral nerves
  • Necrotizing sinusitis from upper respiratory tract mucosal angiitis
  • Pulmonary hemorrhage from alveolar capillaritis
• Unique Organ-Specific Manifestations
  • GPA has necrotizing granulomatous inflammation seen most commonly in the respiratory tract
  • eGPA has blood eosinophilia and a history of asthma

Classification Systems

We reviewed that renal biopsy is not generally able to distinguish between the various AAVs, but rather will only be ‘pauci-immune’. The diagnosis, like all of rheumatology, truly is a beautiful integration of clinical, serological, and histological.

The 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitides clarified nomenclature for us and several important aspects of care has emerged from it.

Serologies in AAV

We know that vascular inflammation is cased by activated neutrophils and monocytes because of ANCAs. These ANCAs bind to a variety of antigens, most notably proteinase 3 (PR3-ANCA) and myeloperoxidase (MPO-ANCA). PR3 is tightly linked to C-ANCA and MPO to P-ANCA. In relation to our traditional clinicopathological (CPC) diagnoses of MPA, GPA and eGPA, we note the following:

Key takeaways are that not all “MPA, GPA and EGPA” is ANCA+, and when it is, the pattern of antigen-antibody complex is not specific! In other words, in a patient with PR3-ANCA, 75% of the time their CPC diagnosis is GPA but 40% of the time it is MPA. Putting aside the CPC diagnosis for a moment, we see that there are consistent, specific associations between PR3-ANCA/MPO-ANCA and certain clinical manifestations. For example, there is worse renal survival in MPO-ANCA patients and PR3-ANCA has consistently been shown to have a higher relapse rate and mortality rate compared to MPO-ANCA. For now, both systems of identification are useful (a serotype and CPC diagnosis) and in the future, I wonder if treatment will differ between the two. For now, regardless of the serotype of CPC diagnosis of MPA or GPA, the treatment is the same!

Treatment of MPA/GPA (eGPA tx is slightly different)

Induction

• High dose steroids and either cyclophosphamide OR Rituximab (decision is complex and based on side effect profile i.e Rituximab in patients with concerns fertility or alopecia or if previously been on cyclophosphamide)
• Indications for plasmapheresis include
  • Evidence of pulmonary hemorrhage (some say all, some say those who did not respond quickly to steroids)
  • Rapidly deteriorating kidney function or severe kidney dysfunction
  • Patients who have a concomitantly positive anti-GBM

Maintenance

• Approx 80% of patients enter remission with induction therapy, but relapses are common (especially with PR3-ANCA serotype and lung or URT disease
• Either azathioprine, mycophenolate or rituximab
• Optimal duration not well-established, some say 12 months after remission is attained, followed by a gradual reduction

Source: National Kidney Foundation’s Primer on Kidney Diseases 7th ed, Gilbert & Weiner, 2018

UpToDate- https://www.uptodate.com/contents/granulomatosis-with-polyangiitis-and-microscopic-polyangiitis-initial-immunosuppressive-therapy?