pulmonary vasculitis sanitra sirithangkul m.d. division of pulmonary and critical care department of...
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Pulmonary vasculitis
Sanitra Sirithangkul M.D.
Division of Pulmonary and Critical care
Department of Pediatrics
Phramongkutklao Hospital
Systemic diseases and the lung
• • relatively rare in pediatric practice
•• CNT diseases : SLE, dermatomyositis CNT diseases : SLE, dermatomyositis
•• Pulmonary vasculitisPulmonary vasculitis
•• Inherited CNT disorders : Ehlers-DanlosInherited CNT disorders : Ehlers-Danlos
•• Mucopolysaccharidoses, familial Mucopolysaccharidoses, familial
dysautonomia, sarcoidosisdysautonomia, sarcoidosis
•• LCH, pulmonary lymphangiomatosisLCH, pulmonary lymphangiomatosis
Pediatr Respir Rev 2005;6:181-189
Systemic diseases and the lung •• may may cause significant respiratory complications•• treatment : often requires corticosteroids & immunosuppressants•• outcome : variableoutcome : variable• when they affect the lung, carry a small but
significant mortality Pediatr Respir Rev 2005;6:181-189
Systemic vasculitis•• true incidence in children is not known
•• around 2-5 cases/million/year
•• pathology of vasculitis : cellular pathology of vasculitis : cellular
inflammation, vessel destruction, inflammation, vessel destruction,
tissue necrosistissue necrosis
•• clinical features : site, size and type clinical features : site, size and type
of vessel involved of vessel involved
Classification ของในโรคในกลุ่��ม Vasculitis
Primary idiopathic vasculitis - Small vessel
• Wegener’s granulomatosis
• Microscopic polyangitis
• Churg-Strauss syndrome
• Idiopatic pauci-immune rapidly
progressive glomerulonephritis
• Isolated pauci-immune pulmonary
capillaritis
Primary idiopathic vasculitis
- Medium vessel
• Polyarteritis nodosa
• Kawasaki disease
- Large vessel
• Giant cell arteritis
• Takayasu’ s arteritis
Primary immune complex-mediated
vasculitis • Goodpasture’s syndrome
• Henoch-Schonlein purpura
• Behcet’s disease
Classification ของในโรคในกลุ่��ม vasculitis (cont.) Secondary vasculitis - Classic autoimmune disease
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Polymyositis / dermatomysitis
• Scleroderma
• Antiphospholipid antibody syndrome
Secondary vasculitis • Essential cryoglobulinemia
• Inflammatory bowel disease
• Hypocomplementemic urticarial
vasculitis
• Drug-induced (e.g., propylthiouracil,
diphenylhydantoin)
• Paraneoplastic
• Infection
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
โรคในกลุ่��ม vasculitis ที่��ที่��ให้�เก�ดพย�ธิ�สภ�พที่��ปอด
A. Pulmonary involvement common
- Wegener’s granulomatosis*
- Goodpasture’s syndrome*
- Idiopathic pulmonary hemosiderosis
- Kawasaki disease
* Positive serum anti-neutrophil cytoplasmic antibody (ANCA)
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)
โรคในกลุ่��ม vasculitis ที่��ที่��ให้� เก�ดพย�ธิ�สภ�พที่��ปอด (ต่�อ)
Clinical scenarios suggestive of vasculitis
1. Diffuse alveolar hemorrhage (DAH)
- hemoptysis
- diffuse alveolar infiltration in
CXR
- a drop in hematocrit
ส�เห้ต่�ของ Diffuse alveolar hemorrhage
With pathologic capillaritis
- Primary idiopathic small vessel
vasculitis
- Primary immune complex-mediated
vasculitis
- Secondary vasculitis
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)
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
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
Specific testing
1. Antineutrophil cytoplasmic
antibodies (ANCA)
- circulating autoantibodies against
intracellular antigens found in neutrophils
- cytoplasmic ANCA (c-ANCA),
perinuclear ANCA (p-ANCA)
แสดงก�รเปร�ยบเที่�ยบ c-ANCA แลุ่ะ p-ANCA
p - ANCAp - ANCA c - ANCAc - ANCA
Antibodies to strong cationsAntibodies to strong cations
Target antigen is usually Target antigen is usually myeloperoxidase myeloperoxidase but but nonspecific antigenic nonspecific antigenic interactions may occurinteractions may occur
Most often positive in patients Most often positive in patients with microscopic polyangiitis or with microscopic polyangiitis or pauci immune, rapidly pauci immune, rapidly progressive glomerulonephritisprogressive glomerulonephritis
Antibodies to neutral proteins or Antibodies to neutral proteins or weak cations (e.g.,proteinase3)weak cations (e.g.,proteinase3)
Target antigen is Target antigen is proteinase3proteinase3
Highly specific for Wegener’s Highly specific for Wegener’s granulomatosisgranulomatosis
แสดงก�รเปร�ยบเที่�ยบ c-ANCA แลุ่ะ p-ANCA
p - ANCAp - ANCA c - ANCAc - ANCAPositive in approximately 50% Positive in approximately 50% of patients with microscopic of patients with microscopic polyangiitispolyangiitis
Positive in 5-30% of patients Positive in 5-30% of patients with Wegener’s granulomatosiswith Wegener’s granulomatosis
May be positive in patients with May be positive in patients with systemic lupus erythematosus, systemic lupus erythematosus, Goodpasture’s syndrome, Goodpasture’s syndrome, inflammatory bowel disease, or inflammatory bowel disease, or rheumatoid arthritisrheumatoid arthritis
Positive in 70-90% of patients Positive in 70-90% of patients with Wegener’s granulomatosiswith Wegener’s granulomatosis
Occasionaly positive in patients Occasionaly positive in patients with microscopic polyangiitis or with microscopic polyangiitis or Churg-Strauss syndrome (15- Churg-Strauss syndrome (15-25%)25%)
Very rarely positive in patients Very rarely positive in patients with certain infectious diseases with certain infectious diseases (e.g., amoebiasia)(e.g., amoebiasia)
Specific testing
2. Radiographic imaging - CT chest : cavity, nodule, diffuse
ground glass opacification
- CT sinus
3. Bronchoscopy - assess for infection / alveolar
hemorrhage / endobronchial lesion
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 H&E
Wegener’s 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
Wegener’s granulomatosis (WG)
• c-ANCA / antiPR3 positive 85-95% of
active, systemic WG
• poor outcomes : advanced age, severe
renal involvement, alveolar hemorrhage,
anti PR3 positive
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
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
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
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
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
EUVAS grading of disease severity
Clinical classClinical class
ConstitutionalConstitutional
symptomssymptoms
Renal functionRenal function Threatened Threatened vital organ vital organ
functionfunction
Options forOptions for
inductioninduction
therapytherapy
LimitedLimited NoNo Creatinine < Creatinine < 120 120 mol/lmol/l
(1.4 mg/dl)(1.4 mg/dl)
NoNo Corticosteroids ORCorticosteroids OR
methotrexate ORmethotrexate OR
azathioprineazathioprine
EarlyEarly
generalizedgeneralized
YesYes Creatinine < Creatinine < 120 120 mol/lmol/l
(1.4 mg/dl)(1.4 mg/dl)
NoNo CyclophosphamideCyclophosphamide
OR methotrexate+OR methotrexate+
corticosteroidscorticosteroids
EUVAS grading of disease severity
Clinical classClinical class
ConstitutionalConstitutional
symptomssymptoms
Renal Renal functionfunction
Threatened Threatened vital organ vital organ
functionfunction
Options forOptions for
inductioninduction
therapytherapy
ActiveActive
generalizedgeneralized
YesYes Creatinine < Creatinine < 500 500 mol/lmol/l
(5.7 mg/dl)(5.7 mg/dl)
YesYes Cyclophosphamide+Cyclophosphamide+
corticosteroidscorticosteroids
SevereSevere YesYes Creatinine > Creatinine > 500 500 mol/lmol/l
(5.7 mg/dl)(5.7 mg/dl)
YesYes Cyclophosphamide+Cyclophosphamide+
corticosteroids+corticosteroids+
plasma exchangeplasma exchange
RefractoryRefractory YesYes AnyAny YesYes Consider Consider investigational agentsinvestigational agents
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
Take home message
• Pulmonary vasculitis is one
component of a variety of systemic
vasculitis
• Early diagnosis using common
clinical scenarios and appropriate
investigations
Take home message
• Aggressive early treatment to
minimize disease related mortality &
irreversible damage
• Regular monitoring for disease
activity and medication toxicity
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