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