Pulmonary Vasculitis And Alveolar Hemorrhage

Front 1

Should be considered as a cause of thoracic aortic aneurysms in the elderly

Back 1

Giant Cell Arteritis

Front 2

Cough, hoarseness, or throat pain without other identifiable cause in an elderly patient

Back 2

Obtain ESR, respiratory complaints may be the presenting complaint in GCA (although very rare)

Front 3

Epidemiology of Takayasu's Arteritis

Back 3

Young women (classically Asian heritage)

Front 4

Pathophysiology of takayasu's arteritis

Back 4

Pulmonary complications are the result of a unique arteriopathy, predominantly of the large and medium sized pulmonary vessels.

Progresive defects int he outer media of the arteris and ingrowth of granulation tissue-like capillaries associated with thickened intima and subendothelial smooth muscle proliferation lead to pulmonary artery stenoses and occlusion.

The inflammatory infiltrate of the vessel wall is predominantly lymphoplasmacytic with variable amounts of giant cells.

Histopathologically difficult to tell from GCA.

Front 5

What more commonly affects the respiratory tract: ANCA-associated (pauciimmune) vasculitis vs. immune complex vascultides

Back 5

ANCA-associated (pauci-immune) --> most likely to cause respiratory symptoms (GPA, MPA

Exception of anti-GBM disease in the immune complex category

Front 6

Distinguishing histopathologic features of GPA (Wegener's) vs. MPA?

Back 6

Discrete necrotizing granulomatous inflammation with vasculitis.

Giant Cells are the hallmark of necrotizing granulomatous inflammation of GPA

Rare histopath features: boop, bronchocentric inflammation, or eosinophils in the inflammatory infiltrates.

Tracheobronchial disease involvement is also feature of GPA not shared with MPA

Nodules or mass lesions (which may or may not cavitate) can also distinguish

Front 7

Is relapse in GPA more likely to present in nonsevere disease or severe disease?

Back 7

Nonsevere GPA have a more protracted course, a greater likelihood of experiencing a disease relapse following a period of remission, and a higher prevalence of destructive upper respiratory tract disorders (e.g. saddle-nose deformity).

Front 8

Associations with GPA

Back 8

Staphylococcus aureus infections (linked to the onset of GPA as well as to relapses)

Week associations with silica containing compounds, grain dust, and heavy metal exposures.

Front 9

ANCA seems to play a pathogenic role int he development of vasculitis by...

Back 9

Directly inducing activation of neutrophils and injury to endothelial cells.

Front 10

How does the median age of GPA differ from MPA?

Back 10

GPA patients are usually in mid-30s (10 years younger than MPA who present with a median age of 45).

Front 11

Racial predilection for GPA

Back 11

>90% are white

Front 12

Ulcerated lesions of the larynx and trachea are present in what % of patients with GPA who go untreated?

Back 12

30%

Front 13

Alveolar hemorrhage occurs in about what % of all patients who have GPA or MPA?

Back 13

25%

Front 14

ANCA associations with GPA vs. MPA?

Back 14

GPA: C-ANCA, Anti-proteinase-3

MPA: P-ANCA, Anti-MPO

Only PR3-ANCA with C-ANCA combination and MPO-ANCA with P-ANCA combinations are sensitive and specific for ANCA associated vasculitis.

Front 15

Anti-GBM ANCA association

Back 15

Rare, but usually MPO-ANCA --> double-positive results may portend worse prognosis

Front 16

Formes Frustes

Back 16

Term to describe patients with Churg-Strauss (EGPA) who's full-blown picture of systemic eosinophilic vasculitis and/or granulmatosis was masked by glucocorticoid tx for asthma

Front 17

Auto-antibodies targe what specific tissue type in Anti-GBM disease

Back 17

Autoantibodies directed against theNC1 domains of the alpha-3 and alpha-5 chains of basement membrane collage type IV.

Front 18

Why is there always kidney involvement in Anti-GBM disease?

Back 18

The target epitope for anti-GBM antibodies is only accessible in the basement membranes of kidneys b/c of the unique fenestrations of the kidney endothelial layer.

Lung involvement is contingent upon additional, usually inhalations, injury such as smoking or volatile hydrocarbon exposure or an infection leading to exposure of the antigen to the anti-GBM antibodies

GOODPASTURE SYNDROME SHOULD BE RESERVED FOR ANTI-GBM DISEASE AFFECTING BOTH LUNG AND KIDNEY.

Front 19

Histopath of anti-GBM

Back 19

"Bland"

Linear IgG deposits on basement membranes confirms diagnosis

Front 20

BAL in DAH

Back 20

Progressively more bloody return indicates alveolar origin of blood

The presence of>20% hemosiderin-laden macrophages among the total number of alveolar macrophages recovered by BAL is reported to indicate alveolar hemorrhage even in the abscence of ongoing active bleeding.

Front 21

The most common cause of capillaritis and pulmonary renal syndrome, defined as DAH with glomerulopnephritis

Back 21

GPA or MPA

Front 22

Heart condition associated with DAH

Back 22

Mitral stenosis

Front 23

Idiopathic Pulmonary Hemosiderosis is associated with what disease?

Back 23

Celiac Disease -- check for anti-TTG/antigliadin antibodies.

Front 24

Lane-Hamilton Syndrome

Back 24

DAH + Celiac Sprue

Front 25

DAH + Celiac Sprue

Back 25

Lane-Hamilton Syndrome

Front 26

Inhalational exposure associated with DAH

Back 26

Trimellitic anhydride (a component of certain plastics, pains, and epoxy resins)

Caues acute rhinitis and asthma when exposure is minor --> DAH in severe exposure (Trimellitic Anhydridie Hemoptysis Anemia Syndrome - TAHAS)

Front 27

Illicit drug associated with DAH

Back 27

Crack-Cocaine inhalation

Front 28

Drugs associated wtih DAH

Back 28

Abciximab
D-pencillamine
Sirolumus
ATRA
Propylthiouracil (can also cause an ANCA-associated vasculitis with DAH)
Continued IV infusion of epoprostenol

Front 29

When does DAH usually occur after a bone marrow transplant?

Back 29

<30 days (typically day 12)

Front 30

RFs for BMT associated DAH

Back 30

Autologous BMT
Intensive conditioning chemotherapy
Older age (>40)`

Front 31

What % of patients with a bone marrow transplant present with DAH?

Back 31

5-7% (but 24% found on autopsy)

Front 32

What happens to DLCO in DAH?

Back 32

It rises

Front 33

A rare syndrome consisting of a combination of granulomatous involvement of the lung parenchyma but w/o significant hilar adenopathy, a vasculitis of the pulmonary arteries and veins and a benign clinical course. Thrombosis and aneurysms do not occur. Steroids tx of choice.

Back 33

Necrotizing sarcoid granulomatosis

Front 34

Association of bronchogenic granulomatosis

Back 34

Aspergillus

Front 35

Mononeuritis multiplex is associated with which vasculitides?

Back 35

Churg-Strauss Syndrome

Front 36

What are distinguishing features of PVOD

Back 36

Pulmonary Edema (w/o pulmonary artery pruning that may be seen in PPH); V/Q abnormal but not CTEPH.

Normal wedge pressure

Bx diagnosis shows pulmonary vein thrombosis only

Front 37

Large vessels (aorta and branches) usually involved. Pulmonary artery involvement --> pulmonarhy HTN reported as high as 50% of patietns.

Age <40; Female Predominance

Claudication, mesenteric ischemia, renal artery stenosis

Granulomatous transmural inflammation (similar to GPA) on pathology

Detected by V/Q scan or MR Angio

Back 37

Takayasu's Arteritis

Front 38

30 y/o female C-anca/PR3-ANCA positive patient with arthralgias, nasal crusting, and septal perforation, pulmonary nodules, normal ESR, CRP, UA. This patient should be treated with...

Back 38

Prednisone + Methotrexate + TMP/SMX + Folic Acid

Patient has GPA but it is nonaggressive - NORAM trial showed MTX just as good as Cyclophosphamide

Front 39

25 y/o M cANCA-pr3 positive with acute onset of malaise, arthralgias, pulmonary mass lesion, RBC casts on urine microscopy, Cr of 2.8, ESR of 78 should be treated with...

Back 39

Prednisone + Rituximab + TMP/SMX --> more modern tx (better tx to preserve fertility)*** Preferred per RAVE trial (NEJM 2010)

Rituximab vs. Cyclophosphamide - Rituximab is not inferior to Cyclophosphamide and there is some superiority for patients with severe disease.

Preferred for severe relapses or who want to preserve fertility.

Front 40

73 y/o M cANCA/Pr3-ANCA positive patient with 8 yr h/o relapsing GPA, on maintenance tx with Azathioprine, has history of bladder cancer, now flaring with Sx of arthralgias, nasal crusting, new cavitary pulmonary mass lesion, ESR of 52, WBC 3, should be tx with...

Back 40

Prednisone + Rituximab + TMP/SMX

This is a relapsing patient, but biologically the relapse is limited and there is nothing showing cappilaritis. But this is breakthrough disease on maintenance requiring an upgrade tx. The patient has 2 contraindications to Cyclophosphamide (bladder cancer and low WBC).

RAVE trial data [NEJM 2010]

Front 41

25 y/o M c-ANCA/PR3-ANCA positive pt with acute onset of malaise, arthralgias, pulmonary infiltrates, Hgb of 8, RBC casts on urine micro, Cr of 2.8 1 week ago is now 5.1, ESR 78, should be tx with...

Back 41

IV methyl-prednisolone + TMP/SMX + Plasma Exchange + Cyclophosphamide

...or can give rituximab after plasma exchange (note; can't give Rituximab concurrently b/c it will be exchanged off]

Patient has rapidly progressive disease with alveolar hemorrhage requiring aggressive tx.

MEPEX trial [JASN 2007; 18;2180-8]

Front 42

Which is NOT correct about EGPA

a) Asthma usually precedes eosinophilia and vasculitis
b) ANCA are common and of the pANCA type
c) Alveolar hemorrhage is frequent (>20%)
d) Cyclophosphamide should be added to glucocorticoids when heart involvement is present
e) Drugs reported with onset of EGPA include Leukotriene receptor antagonists, inhaled glucocorticoids, chromolyn sodium, and omalizumab
f) Glucocorticoids are the mainstay of tx

Back 42

C - alveolar hemorrhage is rare in EGPA

Front 43

Leukotriene receptor antagonists and EGPA

Back 43

seems to unmask not cause EGPA

Front 44

DAH will have >___% hemosiderin-laden macrophages

Back 44

20%

Front 45

Capillaritis is the cause of diffuse alveolar hemorrhage in all of the following EXCEPT:

a) Microscopic polyangiitis
b) Idiopathic pulmonary hemosiderosis
c) SLE
d) GPA (Wegener's)
e) EGPA (Churg-strauss)

Back 45

B - Idiopathic Pulmonary Hemiderosis is NOT a vasculitis

Front 46

Recurrent hemoptysis and ground glass infiltrates

Limited to the lung

Iron Deficiency Anemia

Bland histopath

Associated wtih gluten-sensitive disease

Mostly children; 20% adults

Diagnosis of exclusion

Back 46

Idiopathic pulmonary hemosiderosis

Rx - immunosuppression, plasmapharesis, gluten-free diet

Key to dx is IDA!