Pulmonary vasculitis

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Pulmonary vasculitis

• Sanitra Sirithangkul M.D.
• Division of Pulmonary and Critical care
• Department of Pediatrics
• Phramongkutklao Hospital

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Systemic diseases and the lung

• relatively rare in pediatric practice
• CNT diseases SLE, dermatomyositis
• Pulmonary vasculitis
• Inherited CNT disorders Ehlers-Danlos
• Mucopolysaccharidoses, familial
• dysautonomia, sarcoidosis
• LCH, pulmonary lymphangiomatosis
• Pediatr Respir
  Rev 20056181-189

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Systemic diseases and the lung

• may cause significant respiratory
• complications
• treatment often requires corticosteroids
• immunosuppressants
• outcome variable
• when they affect the lung, carry a small but
• significant mortality
• 
  
• 
  Pediatr Respir Rev 20056181-189

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Systemic vasculitis

• true incidence in children is not known
• around 2-5 cases/million/year
• pathology of vasculitis cellular
• inflammation, vessel destruction,
• tissue necrosis
• clinical features site, size and type
• of vessel involved

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Classification ??????????????? Vasculitis

• Primary idiopathic vasculitis
• - Small vessel
• Wegeners granulomatosis
• Microscopic polyangitis
• Churg-Strauss syndrome
• Idiopatic pauci-immune rapidly
• progressive glomerulonephritis
• Isolated pauci-immune pulmonary
• capillaritis

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Primary idiopathic vasculitis - Medium
vessel Polyarteritis nodosa
Kawasaki disease - Large vessel Giant
cell arteritis Takayasu s arteritis
Primary immune complex-mediated vasculitis
Goodpastures syndrome
Henoch-Schonlein purpura Behcets disease

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Classification ??????????????? vasculitis
(cont.) Secondary vasculitis - Classic
autoimmune disease Systemic lupus
erythematosus Rheumatoid arthritis
Polymyositis / dermatomysitis Scleroderma
Antiphospholipid antibody syndrome
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Secondary vasculitis Essential
cryoglobulinemia Inflammatory bowel disease
Hypocomplementemic urticarial vasculitis
Drug-induced (e.g., propylthiouracil,
diphenylhydantoin) Paraneoplastic Infection
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Pulmonary vasculitis

• one component of systemic vasculitis
• pathology fibrin thrombi, fibrinoid
• necrosis
• the inflammation may lead to
• - a progressive destruction of pulmonary
• circulation
• - granuloma formation
• - end organ failure

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?????????? vasculitis ???????????????????????????

• Pulmonary involvement common
• - Wegeners granulomatosis
• - Goodpastures syndrome
• - Idiopathic pulmonary hemosiderosis
• - Kawasaki disease
• Positive serum anti-neutrophil cytoplasmic
  antibody (ANCA)

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?????????? vasculitis ???????? ???????????????????
(???)
B. Pulmonary involvement uncommon -
Henoch-Shonlein purpura - Churg-Strauss
vasculitis - Polyarteritis nodosa - Takayasu
arteritis - Temporal arteritis - Serum
sickness - Cryoglobulinemia Positive serum
anti-neutrophil cytoplasmic antibody (ANCA)
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Clinical scenarios suggestive of vasculitis

• 1. Diffuse alveolar hemorrhage (DAH)
• - hemoptysis
• - diffuse alveolar infiltration in
• CXR
• - a drop in hematocrit

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????????? Diffuse alveolar hemorrhage

• With pathologic capillaritis
• - Primary idiopathic small vessel
• vasculitis
• - Primary immune complex-mediated
• vasculitis
• - Secondary vasculitis

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Without pathologic capillaritis (bland
hemorrhage) - Idiopathic pulmonary
hemosiderosis - Coagulopathy - Mitral
stenosis - Inhalation injury - Goodpasture
syndrome - Systemic Lupus erythematosus - Bone
marrow transplantation (associated with diffuse
alveolar damage) - Drug associated disease
(e.g., chemotherapeutic agents)
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Clinical scenarios suggestive of vasculitis

• 2. Acute glomerulonephritis
• - rapidly progressive
• glomerulonephritis (RPGN)
• - to be considered
• SLE, post-infectious GN, IgA
• nephropathy, MPGN,
• ANCA-associated vasculitis

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Clinical scenarios suggestive of vasculitis

• 3. Pulmonary-renal syndrome
• - DAH / pulmonary capillaritis
• glomerulonephritis
• 4. Destructive upper airway lesions
• 5. Chest imaging findings
• 6. Palpable purpura
• 7. Mononeuritis multiplex
• 8. Multisystem disease

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Specific testing

• 1. Antineutrophil cytoplasmic
• antibodies (ANCA)
• - circulating autoantibodies against
• intracellular antigens found in neutrophils
• - cytoplasmic ANCA (c-ANCA),
• perinuclear ANCA (p-ANCA)

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?????????????????? c-ANCA ??? p-ANCA
p - ANCA c - ANCA
Antibodies to strong cations Target antigen is usually myeloperoxidase but nonspecific antigenic interactions may occur Most often positive in patients with microscopic polyangiitis or pauci immune, rapidly progressive glomerulonephritis Antibodies to neutral proteins or weak cations (e.g.,proteinase3) Target antigen is proteinase3 Highly specific for Wegeners granulomatosis
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?????????????????? c-ANCA ??? p-ANCA
p - ANCA c - ANCA
Positive in approximately 50 of patients with microscopic polyangiitis Positive in 5-30 of patients with Wegeners granulomatosis May be positive in patients with systemic lupus erythematosus, Goodpastures syndrome, inflammatory bowel disease, or rheumatoid arthritis Positive in 70-90 of patients with Wegeners granulomatosis Occasionaly positive in patients with microscopic polyangiitis or Churg-Strauss syndrome (15-25) Very rarely positive in patients with certain infectious diseases (e.g., amoebiasia)
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Specific testing

• 2. Radiographic imaging
• - CT chest cavity, nodule, diffuse
• ground glass opacification
• - CT sinus
• 3. Bronchoscopy
• - assess for infection / alveolar
• hemorrhage / endobronchial lesion

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Specific testing

• 4. Diagnostic biopsy
• - skin, sinus or upper airway lesions
• - renal biopsy
• - lung biopsy
• - collect tissue in saline for culture
• - frozen tissue for
• immunofluorescence
• - formaline-fixed tissue for HE

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Wegeners granulomatosis (WG)

• the most common of the ANCA-associated
• vasculitis
• triad upper airway disease, lower
• respiratory tract disease,
• glomerulonephritis
• abnormal CXR findings alveolar,
• interstitial, mixed infiltration
• nodule/cavity

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Wegeners granulomatosis (WG)

• c-ANCA / antiPR3 positive 85-95 of
• active, systemic WG
• poor outcomes advanced age, severe
• renal involvement, alveolar hemorrhage,
• anti PR3 positive

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Microscopic polyangiitis (MPA)

• long prodromal phase of constitutional
• symptoms ? development of RPGN
• pulmonary involvement seen in up to
• 30
• most common pulmonary involvement
• DAH with pulmonary capillaritis

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Microscopic polyangiitis (MPA)

• p-ANCA ve 50-70, anti MPO ve
• 35-65, c-ANCA ve 10-15
• pathology focal, segmental necrotizing
• vasculitis, mixed inflammatory infiltrate
• without granuloma

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Churg-Strauss syndrome (CSS)

• to be considered when other eosinophilic
• lung diseases are in the differential or
• difficult-to-control asthmatic patients
• develop significant cardiac, GI or
• neurologic disease
• triad asthma, hypereosinophilia,
• necrotizing vasculitis

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Churg-Strauss syndrome (CSS)

• pulmonary hemorrhage and
• glomerulonephritis less common
• p-ANCA /anti MPO ve 50-75,
• c- NCA ve 10
• mortality morbidity due to cardiac
• complications, GI, status asthmaticus
• respiratory failure

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Therapy

• induction of remission 12 months
• maintenance 12-18 months
• - cyclophosphamide ? azathioprine/
• methotrexate
• - additional agents mycophenolate
• mofetil (MMF), leflunomide, cyclosporine
• - Pneumocystis carinii prophylaxis with
• trimetroprim-sulfametoxazole

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EUVAS grading of disease severity
Clinical class Constitutional symptoms Renal function Threatened vital organ function Options for induction therapy
Limited No Creatinine lt 120 ?mol/l (1.4 mg/dl) No Corticosteroids OR methotrexate OR azathioprine
Early generalized Yes Creatinine lt 120 ?mol/l (1.4 mg/dl) No Cyclophosphamide OR methotrexate corticosteroids
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EUVAS grading of disease severity
Clinical class Constitutional symptoms Renal function Threatened vital organ function Options for induction therapy
Active generalized Yes Creatinine lt 500 ?mol/l (5.7 mg/dl) Yes Cyclophosphamide corticosteroids
Severe Yes Creatinine gt 500 ?mol/l (5.7 mg/dl) Yes Cyclophosphamide corticosteroids plasma exchange
Refractory Yes Any Yes Consider investigational agents
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Monitoring

• to minimize morbidity mortality of the
• vasculitides and their therapy
• differential diagnosis in pts with clinical
• deterioration
• - infection
• - drug toxicity
• - disease relapse
• - a new unrelated problem

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Take home message

• Pulmonary vasculitis is one
• component of a variety of systemic
• vasculitis
• Early diagnosis using common
• clinical scenarios and appropriate
• investigations

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Take home message

• Aggressive early treatment to
• minimize disease related mortality
• irreversible damage
• Regular monitoring for disease
• activity and medication toxicity