Small Vessel Vasculitis

These diseases can be broken down into ANCA-associated vasculitis (AAV) and non-ANCA-associated vasculitis (ANCA: Anti-Neutrophil Cytoplasmic Antibodies)

cANCA = diffuse cytoplasmic staining of ANCA, most commonly associated with anti-PR3 (or anti-proteinase 3) ANCA

pANCA = perinuclear staining of ANCA, most commonly associated with anti-MPO (or anti-myeloperoxidase) ANCA

ANCA-associated vasculitis (AAV)

cANCA-associated

  • Granulomatosis with polyangiitis (GPA, formerly Wegener’s Granulomatosis)
    • ENT: Hearing loss, nasal inflammation/ulceration/discharge, sinusitis (1)
    • Lungs: Cough +/- hemoptysis, shortness of breath, nodules/cavities on chest x-ray (2)
    • Kidneys: Glomerulonephritis (3)
    • Diagnosis
      • p-ANCA sensitivity: ~66%, specificity: ~98% (4)
      • Clinical disease in ≥2/3 systems (upper airways, lungs, or kidneys), as well as positive biopsy results (granulomatous inflammation) in at least one of these organ systems (5)
    • Treatment (6)
      • Non-severe disease: Methotrexate + glucocorticoids
      • Severe disease
        • Induction: Glucocorticoids + either cyclophosphamide or rituximab
        • Maintenance: Azathioprine, methotrexate, or rituximab
        • Relapse: Rituximab > Cyclophosphamide (RAVE Trial) (23)

pANCA-associated

  • Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss)
    • Generally, patients have a history of asthma or nasal polyps, as well as peripheral eosinophilia (7)
    • Skin: Purpura
    • Lungs: Cough +/- hemoptysis, shortness of breath (8)
    • Kidneys: Glomerulonephritis
    • Diagnosis
      • ANCA sensitivity: 30-60%, of which 70-75% are p-ANCA positive (9)
      • ANCA specificity not well-reported
      • American College of Rheumatology diagnostic criteria (10)
        • ≥4/6 of the following: asthma, eosinophilia (>10%), neuropathy, pulmonary opacities, paranasal sinus abnormality, or blood vessel biopsy showing accumulation of eosinophils in extravascular areas
        • PLUS biopsy of tissue showing, classically, eosinophilic infiltration, extensive necrosis, and granulomas
    • Treatment (11)
      • Mild disease: Glucocorticoids
      • Severe disease:
        • Induction: Cyclophosphamide
        • Maintenance: Azathioprine, methotrexate, or leflunomide
  • Microscopic polyangiitis (MPA)
    • Upper airway not as frequently as involved as in GPA
    • Lungs: Cough +/- hemoptysis, shortness of breath
    • Kidneys: Necrotizing glomerulonephritis (12)
    • Diagnosis
      • pANCA sensitivity: ~58% (and ~23% of patients will have cANCA) (13)
      • Relies on biopsy, which will show necrotizing glomerulonephritis in the kidney (similar to GPA and EGPA) as well as non-granulomatous (different from GPA and EGPA) inflammation on lung biopsy (14)
    • Treatment (15)
      • Induction
        • Non-severe: Glucocorticoids + methotrexate, or monotherapy with rituximab
        • Severe: Glucocorticoids + cyclophosphamide or rituximab
      • Maintenance: Azathioprine, methotrexate, or rituximab

non-ANCA-associated vasculitis

  • IgA Vasculitis (formerly Henöch-Schonlein Purpura)
    • Most common in children ages 4-7, classically following a URI (16)
    • Skin: Palpable purpura
    • GI: Abdominal pain +/- GI bleed
    • MSK: Arthritis
    • Kidneys: Glomerulonephritis (This is different from IgA nephritis, however, the histopathologic findings are similar)
    • Diagnosis
      • Biopsy of skin or kidneys showing IgA deposition (17)
    • Treatment
      • Generally a self-resolving illness, so supportive treatment is the mainstay. However, moderate-severe abdominal pain can be managed with corticosteroids (18)
      • ACE Inhibitors or ARBs x 3–6 month course if proteinuria >0.5 g/day (including those with nephrotic syndrome). Glucocorticoids may be given if proteinuria is refractory to this treatment (19)
  • Cryoglobulinemia: Disease that arises from antibodies that precipitate at cold temperatures (“Cryo” = cold) and has potential to cause a vasculitis
    • 3 classifications (Type I, II, and III – see below) (20)
    • Vasculitis manifestations include purpura (typically of lower extremities), neuropathy, and glomerulonephritis
    • Diagnosis: serum cryoglobulins and biopsy
    • Treatment: tailored toward underlying disease. Type I is associated with clonal hematologic diseases such as Multiple Myeloma. Type II and III (“mixed” cryoglobulinemias) are strongly associated with Hepatitis C and hematologic malignancies (21)
      • Methotrexate or glucocorticoids + cyclophosphamide depending on severity. Rituximab given in refractory cases. Plasmapheresis may be performed in life-threatening situations (22)

 

References:

  1. Greco, A., Marinelli, C., Fusconi, M., Macri, G., Gallo, A., De Virgilio, A., . . . De Vincentiis, M. (2016, June). Clinic manifestations in granulomatosis with polyangiitis. Retrieved January 21, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806708/
  2. Li, J., Li, C., & Li, J. (2018, July). Thoracic manifestation of Wegener’s granulomatosis: Computed tomography findings and analysis of misdiagnosis. Retrieved January 21, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995034/
  3. Carazo, E. R., Benitez, A. M., Milena, G. L., Espigares, J. R., León, L., & Marquez, B. (2001). Multiple Renal Masses as Initial Manifestation of Wegener’s Granulomatosis. American Journal of Roentgenology, 176(1), 116-118. doi:10.2214/ajr.176.1.1760116
  4. Rao JK;Weinberger M;Oddone EZ;Allen NB;Landsman P;Feussner JR;. (n.d.). The role of antineutrophil cytoplasmic antibody (c-ANCA) testing in the diagnosis of Wegener granulomatosis. A literature review and meta-analysis. Retrieved January 21, 2021, from https://pubmed.ncbi.nlm.nih.gov/7486487/
  5. Kubaisi, B., Abu Samra, K., & Foster, C. (2016, May). Granulomatosis with polyangiitis (Wegener’s disease): An updated review of ocular disease manifestations. Retrieved January 21, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869584/
  6. CA;, L. (n.d.). Update on the treatment of granulomatosis with polyangiitis (Wegener’s). Retrieved January 21, 2021, from https://pubmed.ncbi.nlm.nih.gov/22270373/
  7. Eosinophilic Granulomatosis with Polyangiitis, formerly Churg-Strauss Syndrome (EGPA). (2014, August 01). Retrieved January 21, 2021, from https://www.hopkinsvasculitis.org/types-vasculitis/churgstrauss-syndrome-css/
  8. Churg Strauss Syndrome: AAAAI. (n.d.). Retrieved January 21, 2021, from https://www.aaaai.org/conditions-and-treatments/related-conditions/churg-strauss-syndrome
  9. King Jr, T. E., MD, Flaherty, K. A., MD, MS, Glassock, R. J., MD, MACP, Bochner, B. S., MD, & Hollingsworth, H., MD. (n.d.). Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Retrieved January 21, 2021, from https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-eosinophilic-granulomatosis-with-polyangiitis-churg-strauss?search=egpa+diagnosis§ionRank=1&usage_type=default&anchor=H15&source=machineLearning&selectedTitle=1~144&display_rank=1#H15
  10. Ghosh, S., Bhattacharya, M., & Dhar, S. (2011, November). Churg-strauss syndrome. Retrieved January 21, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276904/
  11. J;, M. (n.d.). [Current treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)]. Retrieved January 21, 2021, from https://pubmed.ncbi.nlm.nih.gov/30627842/
  12. Jennette, J., Falk, R., Bacon, P., Basu, N., Cid, M., Ferrario, F., . . . Watts, R. (2012, December 27). 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Retrieved January 21, 2021, from https://onlinelibrary.wiley.com/doi/full/10.1002/art.37715
  13. Hagen EC;Daha MR;Hermans J;Andrassy K;Csernok E;Gaskin G;Lesavre P;Lüdemann J;Rasmussen N;Sinico RA;Wiik A;van der Woude FJ;. (n.d.). Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. EC/BCR Project for ANCA Assay Standardization. Retrieved January 21, 2021, from https://pubmed.ncbi.nlm.nih.gov/9507222/
  14. Chung, S., & Seo, P. (2010, August). Microscopic polyangiitis. Retrieved January 21, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917831/
  15. Jain, V. (2020, December 14). Microscopic Polyangiitis. Retrieved January 21, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK531484/
  16. IgA Vasculitis. (2020, April 01). Retrieved January 22, 2021, from https://www.niddk.nih.gov/health-information/kidney-disease/iga-vasculitis
  17. Henoch-Schönlein Purpura. (2014, August 01). Retrieved January 22, 2021, from https://www.hopkinsvasculitis.org/types-vasculitis/henochschnlein-purpura/
  18. Kurnia, B. (2019, June 15). Henoch-Schonlein Purpura in Children: The Role of Corticosteroids. Retrieved January 22, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614272/
  19. Namgoong, M., & Namgoong, M. (2020, April 30). Management of IgA vasculitis nephritis (Henoch-Schonlein purpura nephritis) in Children. Retrieved January 22, 2021, from http://chikd.org/journal/view.php?number=717
  20. Cryoglobulinemia. (2014, August 01). Retrieved January 22, 2021, from https://www.hopkinsvasculitis.org/types-vasculitis/cryoglobulinemia/
  21. Cryoglobulinemia. (2019, April 01). Retrieved January 22, 2021, from https://www.vasculitisfoundation.org/education/forms/cryoglobulinemia/#1545061445202-657df321-5002
  22. MA;, M. (n.d.). How I treat cryoglobulinemia. Retrieved January 22, 2021, from https://pubmed.ncbi.nlm.nih.gov/27799164/
  23. Stone, J. H., Al., E., Group*, for the R. A. V. E. I. T. N. R., Author AffiliationsFrom Massachusetts General Hospital (J.H.S.) and Boston University Medical Center (P.A. Merkel, Jennette, R. J. F. and J. C., T. T. Shimabukuro and Others, P. O. Guimarães and Others, & F. P. Polack and Others. (2010, July 15). Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis: NEJM. New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/nejmoa0909905.

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