Transcript Long Term Follow up of Tracheomalacia Following Surgical

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
• Pulmonary vasculitis
• Inherited CNT disorders : Ehlers-Danlos
• Mucopolysaccharidoses, familial
dysautonomia, sarcoidosis
• LCH, pulmonary lymphangiomatosis
Pediatr Respir Rev 2005;6:181-189
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 2005;6:181-189
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
Classification ของในโรคในกลุ่ม 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 ของในโรคในกลุม
่
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
โรคในกลุ่ม vasculitis ที่ทำให้ เกิดพยำธิสภำพที่ปอด
A. Pulmonary involvement common
- Wegener’s granulomatosis*
- Goodpasture’s syndrome*
- Idiopathic pulmonary hemosiderosis
- Kawasaki disease
* Positive serum anti-neutrophil cytoplasmic antibody (ANCA)
โรคในกลุม
่ vasculitis ทีท
่ ำให้ เกิดพยำธิ
สภำพทีป
่ อด (ต่อ)
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)
Clinical scenarios suggestive of
vasculitis
1. Diffuse alveolar hemorrhage (DAH)
- hemoptysis
- diffuse alveolar infiltration in
CXR
- a drop in hematocrit
สำเหตุของ 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)
แสดงกำรเปรียบเทียบ c-ANCA และ p-ANCA
p - ANCA
c - ANCA
Antibodies to strong cations
Antibodies to neutral proteins or
weak cations (e.g.,proteinase3)
Target antigen is usually
myeloperoxidase but
nonspecific antigenic
interactions may occur
Target antigen is proteinase3
Most often positive in patients
Highly specific for Wegener’s
with microscopic polyangiitis or granulomatosis
pauci immune, rapidly
progressive glomerulonephritis
แสดงกำรเปรียบเทียบ c-ANCA และ p-ANCA
p - ANCA
Positive in approximately 50%
of patients with microscopic
polyangiitis
Positive in 5-30% of patients
with Wegener’s granulomatosis
c - ANCA
Positive in 70-90% of patients
with Wegener’s granulomatosis
Occasionaly positive in patients
with microscopic polyangiitis or
Churg-Strauss syndrome (1525%)
May be positive in patients with Very rarely positive in patients
systemic lupus erythematosus,
with certain infectious diseases
(e.g., amoebiasia)
Goodpasture’s syndrome,
inflammatory bowel disease, or
rheumatoid arthritis
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
Constitutional
symptoms
Renal function
Threatened
vital organ
function
Options for
induction
therapy
Limited
No
Creatinine <
120 mol/l
(1.4 mg/dl)
No
Corticosteroids OR
methotrexate OR
azathioprine
Early
generalized
Yes
Creatinine <
120 mol/l
(1.4 mg/dl)
No
Cyclophosphamide
OR methotrexate+
corticosteroids
Clinical class
EUVAS grading of disease severity
Constitutional
symptoms
Renal
function
Threatened
vital organ
function
Options for
induction
therapy
Active
generalized
Yes
Creatinine <
500 mol/l
(5.7 mg/dl)
Yes
Cyclophosphamide+
corticosteroids
Severe
Yes
Creatinine >
500 mol/l
(5.7 mg/dl)
Yes
Cyclophosphamide+
corticosteroids+
plasma exchange
Refractory
Yes
Any
Yes
Consider
investigational agents
Clinical class
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