Eosinophilic Pneumonia

Eosinophilic Pneumonia

Or

Churg-Strauss Syndrome?

Case Report- J.N., 40 WF• Admitted 9/19/03 – 9/24/03 for fever, congestion,

dyspnea, chest tightness, abdominal cramps, and diarrhea

• Extensive PMHAsthma since age 17ImmunotherapyPrednisone use since age 20Hx nasal polyp surgeryHx IVIG for HypogammaglobulinemiaOsteoporosis

Initial Laboratory Eval

• CXR, later CT scan – Dr. Hamilton

• Hgb 14.9

• Hct 44.5

• Platelets 412K

• WBC 19.5 Neutrophils 62% Eosinophils 31%

• ESR 50

Additional Laboratory Data

• BNP 309• TSH 1.16• INR 1.2• IgA 243 (69-309)• IgE 711 (0-180)• IgG 1450 (613-1295)• IgM 207 (53-334)

• IgG sub 1 597 (240-1118)• IgG sub 2 537 (124-549)• IgG sub 3 32 (21-134)• IgG sub 4 609 (7-89)• ANA <1:40• RA negative• Crypto Ag negative• Histoplasma Ag negative

More Laboratory Data

• Neutrophil Cytoplasmic

AB <1:16

Blood cultures neg

Legionella Neg(urine)

Strept. Pneumo neg(urine)

Stool parasites neg

Fungal Serology neg

• Bronchoscopy Data

AFB neg

Routine cult neg

Fungus-yeast, - crypto

Biopsy – Dr. O’Dell

Hospital Course

• Rx – O2, albuterol, ipratropium,Cefepime,

Azithromycin, Bactrim, SoluMedrol

Bronchoscopy 9/22 – bronchitis, mucous

Home on Prednisone 20 mg. BID

Later Outpatient Data

• WBC (on 10/2) 10.4 with 1% Eos

• P-ANCA neg

• C_ANCA neg

• Anti-myeloperoxidase neg

• Anti-proteinase neg

• Atypical ANCA neg

Pulmonary Eosinophilia - Causes

• Drug and Toxin Induced

• Helminthic and Fungal Infection

• Acute Eosinophilic Pneumonia

• Chronic Eosinophilic Pneumonia

• Churg – Strauss Syndrome

• Others

Drug and Toxin Induced Eosinophilic Lung Disease

• Nitrofurantoin, Ampicillin, NSAIDs, Pentamidine.

• Phenytoin, L-Tryptophan, Ranitidine, Trazadone

• Metals, Scorpion stings, Heroin, Cocaine, Dust, Smoke, Scotchguard, Sulfite exposure, Organic chemicals

Helminthic/Fungal Infection related

• Transpulmonary larvae migration-Loffler’s

Ascaris lumbricoides

Hookworm

Strongyloides stercoralis• Pulmonary Parenchymal Invasion

Helminths, e.g. Paragonimiasis• Heavy hematogenous seeding-Trichinosis,

Strongyloidiasis, Schistosomiasis, Cutaneous and visceral larva migrans

Helminthic/Fungal Infection related

• Tropical Pulmonary Eosinophilia

Wuchereria bancrofti

Brugia malayi

Allergic Broncho-Pulmonary Aspergillosis

Acute Eosinophilic Pneumonia

• Acute, febrile, hypoxic, RF often, mechanical ventilation

• Bx - DAD, hyaline membranes

• Blood eosinophilia absent

• HIV often

Chronic Eosinophilic Pneumonia

• Subacute, cough, fever,dyspnea, wheeze, sweats

• Asthma precedes/accompanies in 50%

• CXR –”photographic negative” of CHF in less than 1/3. Occasional pleural effusion, cavitations

• Bx - Giant cells, BOOP often

Churg – Strauss SyndromeAllergic granulomatosis and

angiitis

• Vasculitis

• Sinusitis, asthma, blood eosinophilia

• Lung, skin, cardiovascular, GI, nervous

• Patchy opacities

• Bx-eosinophilic infiltrates, eosinophilic vasculitis, necrotizing granulomas, and necrosis

Allergic Broncho-Pulmonary Aspergillosis

Come back January 14, 2004

Other Causes of Pulmonary Eosinophilia

• Idiopathic Hypereosinophilic Syndrome

• Idiopathic Lung Diseases

• Neoplasms

• Nonhelminthic Infections – Cocci and rarely Tuberculosis

9/19/03

9/19/03

9/24/03

Differential diagnosis for peripheral, bilateral airspace disease

• Eosinophilic pneumonia

• BOOP

• BAC

• Sarcoid

Eosinophilic Pneumonia

• Eosinophils in alveolar spaces and/or interstitium

• Variable:organizing pneumonia

alveolar macrophages

granulomas

mild vascular inflammation

Etiology

Idiopathic– Chronic eosinophilic pneumonia– Acute eosinophilic pneumonia– Simple eosinophilic pneumonia (Loeffler’s)– Incidental eosinophilic pneumonia

Etiology

Secondary Eosinophilic Pneumonia– Infection: parasites, fungi– Drugs– Immunologic: asthma, allergic

bronchopulmonary fungal disease, collagen vascular disease, Churg-Strauss syndrome

– Systemic: HIV, malignancy, idiopathic hypereosinophilia syndrome

Significant Histologic Findings

• Vasculitis: Churg-Strauss syndrome

drug toxicity• Asthmatic bronchitis:

asthmachronic eosinophilic

pneumoniaallergic bronchopulmonary fungal disease

• Infectious agents:fungusparasites

Dr. Brodsky’s Presentation

CHURG-STRAUSS SYNDROME(ALLERGIC GRANULOMATOSIS AND ANGITIS)

MULTI SYSTEM DISORDER Allergic Rhinitis Asthma Peripheral Blood Eosinophilia Lung involvement most common followed by skin Cardiovascular, GI, CNS

CHURG-STRAUSS SYNDROME

Approximately 10% of systemic vasculitis patients. No gender predominance Median age –50, but may appear in late 30’s Uncommon after 65

CHURG-STRAUSS SYNDROMEETIOLOGY

Autoimmune Disorder Allergic Features Heightened T Cell Immunity

(Pulmonary angiocentric granulomatosis) Altered humoral immunity (Hyperglobulinemia,

IgE, RF) Immune Complexes (vasculitis, IC’s, P ANCA) Rare complication with leukotriene receptor

antogonists Rare complication with free based cocaine

CHURG-STRAUSS SYNDOMECLINICAL FEATURES

Prodromal Phase-Second and Third decades-atopic disease, allergic rhinitis, asthma

Eosinopilic Phase-Eosinophilia, infiltration of multiple organs-lung, GI tract.

Vasculitic Phase-Third and Fourth Decades-life threatening systemic vasculitis medium and small vessels. Constitutional complaints

CHURG-STRAUSS SYNDROMECLINICAL FEATURES

Asthma-precedes vasculitis by 8-10 years: Usually chronic, severe, steroid dependent.

Nasal and Sinus Disease: nasal obstruction, recurrent sinusitis, nasal polyposis, chronic otitis

Skin disease-sub Q nodules extensor surfaces, hands, legs. Palpable purpura, nodules (67%)

Cardiovascular Disease-pericarditis, CHF, MI’s (50% of deaths)

CHURG-STRAUSS SYNDROMECLINICAL FEATURES

Neurologic Disease-peripheral neuropathy mononeuritis multiplex, strokes (75%)

Renal Disease-focal segmental GN with crescents, necrosis, P ANCA (80%)

GI Disease-Abdominal pain, diarrhea, GI Bleeding, Colitis (59%)

Muscoloskeletol disease-Myalgias, migiatory polyarthralgias, arthritis (uncommon)

CHURG-STRAUSS SYNDROME LABORATORY FEATURES

Eosinophilia –5,000-9,000 NC/NC Anemia ESR IgE Circulating Immune Complexes Hyperglobulinemia +RF P ANCA IL2R BAL – 33% Eos

CHURG-STRAUSS SYNDROMERADIOGRAPHIC FEATURES

Transient patchy opcacities (75%) without lobar or segmental distribution

Axillary, peripheral distribution Diffuse Interstitial/Miliary pattern Pulmonary Hemorrhage Nodular Disease Pleural effusions (exudative, Eos) (30%) Pulmonary arteries enlarged, vasculitis sign

CHURG-STRAUSS SYNDROMEPATHOLOGY

Eosinophilic Infiltrates Extensive Necrosis Eosinophilic Giant Cell Vasculitis, small arteries

and veins Interstitial and perivascular granulomas Eosinophilic Lymphadenopathy

CHURG-STRAUSS SYNDROMETREATMENT

Corticosteroids: 0.5 to 1.5 mg/kg for 6-12 wks Monitor ESR, EOS, CXR Late relapses uncommon; 70% 5 yr survival Inhaled Steroids CTX, AZA, IVIG Poorer Prognosis: Cardiac Failure or MI, Cerebral

hemorrhage, Renal Failure, GI bleed

CHURG-STRAUSS SYNDROMEACR CLASSIFICATION CRITERIA

Asthma Eosinophilia – 10% or greater Mononeuritis multiplex or polyneuropathy Migratory or transient pulmonary opacities Paranasal sinus abnormalities Bx evidence of eosinophilic vasculitis/tissue

eosinophils

ACUTE EOSINOPHILIC PNEUMONIA

Acute febrile illness of short duration Hypoxemic Respiratory Failure Diffuse pulmonary opacities on CXR BAL Eosinophilia >25% Lung Bx – eosinophilic infiltrates (Acute and/or

organizing DAD/eosinophils) Dx of exclusion (Drugs, Infections, Asthma, Atopic

Disease)

AEP C-S S

HX Asthma, Sinusitis,Diarrhea, Neuropathy

PE Mild to Moderate SOB

CXR Diffuse Infiltrates

LAB IGE- P ANCA

BX Tissue Eos Tissue Eos

RX + Steroids + SteroidsResponse