Microscopic Polyangitis

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Microscopic Polyangiitis MPA Jennifer O’Brien Morning Report

Transcript of Microscopic Polyangitis

Microscopic PolyangiitisMPA

Jennifer O’BrienMorning Report

MPA

• MPA is characterized by pauci-immune, small-vessel vasculitis without evidence of necrotizing granulomatous inflammation

• Leads to glomerulonephritis and renal failure

History of MPA

• First described as form of polyarteritis nodosa by Wohlwill in 1923 who preformed an autopsy which showed focal, segmental, necrotizing glomerulonephritis without the macroscopic vascular changes of PAN

• Today we think of it as small vessel ANCA vasculitis that leads to glomerulonephritis

Vasculitis

• Idiopathic or primary vasculitides include a group of diseases characterized by inflammation of blood vessels.

• Classification is based on size of vessels, histopathologic findings, clinical symptoms

Classification of vasculitis by vessel size

• Large vessel– Giant cell (temporal) and Takayasu arteritis

• Medium vessel– Polyarteritis nodosa* and Kawasaki disease

• Small vessel– Wegener’s granulomatosis*, Churg-Strass syndrome,

Micrscopic polyangiitis, HSP, Essential cryoglobulinemicvasculitis, cutaneous leukocytoclastic

Pauci-immune necrotizing vaculitis (Wegener’s and MPA)

• Presence of autoantibodies against neutrophil cytoplasmic constituents

• ANCA: antineutrophil cytoplasmic autoantibodies

• Neutrophils are the main effector cells in the lesions of pt with Wegener’s and MPA

ANCA• Anti-neutrophil cytoplamic

antibodies directed again neutrophils and monocytes

• Most common P-ANCA target (perinuclear staining) is MPO myeloperoxidase (MPA)

• Most common C-ANCA target (cytoplasmic staining) is PR3 proteinase 3 (Wegener’s)

• Binding of ANCA may induce activation of neutrophils with resultant endothelial cell damage.

ANCA

• MPA– 60% are positive for MPO-ANCA– 30% are positive for PR3-ANCA

• Wegener’s– 70-80% are positive PR3-ANCA– 10% are positive for MPO-ANCA

• A few people are ANCA negative

Rapidly progressing Glomerulonephritis

• Anti-glomerular basement membrane disease– Linear staining

• ANCA Vasculitis: Wegener’s, MPA, Polyarteritis– Pauci immune or minimal staining

• Lupus, HSP, Goodpasture syndrome, IgA nephropathy, post infectious GM– Granular staining

• Membranoproliferative GN• Glomerulonephritis if untreated will lead to rapid renal

failure

• Figure Rapidly Progressing Glomerulonephritis: The majority of glomeruli present "crescents". Formation of crescents is initiated by passage of fibrin into the Bowman space as a result of increased permeability of glomerular basement membrane. Fibrin stimulates the proliferation of parietal cells of Bowman capsule, and an influx of monocytes. Rapid growing and fibrosis of crescents compresses the capillary loops and decreases the Bowman space which leads to renal failure within weeks or months.

• http://www.pathologyatlas.ro/Crescentic%20Glomerulonephritis.html

Renal Biopsy

Kuttikat A et al. (2006) A case of polymyalgia rheumatica, microscopic polyangiitis, and B-cell lymphoma Nat Clin Pract Rheumatol 2: 686–690

doi:10.1038/ncprheum0352

(A) Crescents of proliferating epithelial cells (blue arrow) within the glomeruli, consistent with crescentic glomerulonephritis. (B) Red cell casts (blue arrow) consistent with vasculitis.

Figure 2 Photographs of renal biopsy

Diagnostic Criteria

• Symptoms• ANCA +• Histology

– Necrotizing crescentic glomerulonephritis on renal biopsy or necrotizing vasculitis of microscopic vessels (small arteries, arterioles, capillaries, venules)

Who is at risk?

• Average age 50 years• Males slightly more than females• More frequent among Caucasians as

opposed to African Americans• Prevalence is 1-2 cases per 100,000

population

Clinical signs MPA• Prodromal phase of several months of

constitutional symptoms, including polymyalgia• Macroscopic hematuria, edema, decreased urine

output (symptoms of glomerular nephritis)• Kidney involvement >80%• Weight Loss >70%• Skin lesions >60%

– Palpable purpura 41% and livedo reticularis 12%• Nerve Damage 60%• Fevers 55%• Myalgia 50%• Hemoptysis only 11%

MPA vs Wegener’s

• Organ involvement• Often indistinguishable clinically

Treatment• Induction

– Corticosteroids– Immunosupressive drugs: Cyclophosphamide– 75-90% patients will be in remission by 6 months– Methotrexate has also been used, but higher relapse rates– Plasmapheresis: reserved for patient with bleeding in the lungs or kidney failure

leading to dialysis • Maintenance therapy: 1/3 patients will relapse in 5 years

– Low dose steroids, Azathioprine, Methotrexate combo (short term studies only)– Leflunomide (Arava, disease-modifying antirheumatic drug) and

Mycophenolate mofetil also proposed, no randomized data• ? Long term therapy• Other drugs currently being studied IVIG, TNFα inhibitors, Rituximab• Antibiotic prophylaxis

Prognosis

• Untreated: poor prognosis• Studies with Wegener’s included state 90%

mortality if untreated

Thanks…

References

• A case of polymyalgia rheumatica, microscopic polyangiitis, and B-cell lymphoma. Anoop Kuttikat, Andrew Keat, Rod Hughes, Alan Hakim and Kuntal Chakravarty. Nature Clinical Practice Rheumatology (2006) 2, 686-690.

• UpToDate• Challenges in the management of microscopic

polyangiitis: past , present and future. Jayne. Current Opinion in Rheumatology 2008, 20:3-9.

• www.vasculitis.org/microscopicpolyangitis

• * Corticosteroids: prednisone, methyl prednisone, or Medrol) A type of steroid that can be given by IV or in pill form and help reduce swelling and slow down the autoimmune response in vasculitis.

• * Immunosuppressive Drugs: (cyclophosphamide, cyclosporine, azathioprine, mycophenolate mofetil, or Rituximab) Drugs that reduce the immune system's tendency to attack itself.

• * Antibiotics: (trimethoprim/sulfamethoxazole) Drugs that kill foreign infections that can flourish in the nose, or in patients with a weak immune system from immunosuppressive treatment.

• * Plasmapheresis: A treatment that removes the ANCA from the blood. This treatment is usually reserved for patients with bleeding in the lungs or kidney failure.