An Unusual form Lung Injury

Meir Krupsky MD

Tel –Aviv Sourasky Medical CTR

Case description

•

a 88 y.o. male•

No smoking history

•

Dancing instructor!!•

Past medical history:–

HTN

–

No TB contacts

1st admission

•

SOB -

Inspiratory, productive (whithish) cough, NO fever -

3 months duration

•

Weight loss 10Kg/ year•

Physical examination –rales

bilateral bases (more Rt)

•

FEV1=88% FEV1/FCV=76% O2 Sat=98%•

Labs:

101Glucose1.1Creat415KPlt12.3Hb

176LDH46Urea3.1Globulin13700WBC

Diagnosis

•

RLL pneumonia•

Treated with ofloxacine

•

No initial response•

Sputum & blood cultures neg.

•

Follow up CXR > CT recommended

2nd admission –

•

Fever, cough, Rt. Chest pain –

few days

•

Physical exam. –

bilateral Decreased respiratory

sounds and diffuse rales•

Continued infiltrate RLL

•

Labs:

113Glucose1.1Creat277KPlt12.3Hb

33Urea3.9Globulin13900WBC

Imaging : CXR

Imaging : CT

Imaging : CT

•

Rt. Lung base consolidation-homogeous, GGO, mix alveolar & interstitial opacities

•

Interlobular septal

thickening•

Crazy-

Paving Pattern

Additional testing

•

Bronchoscopy

–

Rt. thickened bronchial congested & hyperemic mucosa, easy bleed, No obsrtruction

No Mass/Infiltrative tumor

•

Biopsies -

RLL & RUL •

BAL-

RLL

Case description

•

a 77 y.o. male•

Past medical history:–

D.M. –

Insulin Rx.

–

CRF-

diabetic nephropathy–

HTN

–

Permanent pacemaker d/t

C-AVB–

CVA –

10 months ago

Medications

•

Insulin•

Furosamide

•

PPI’s•

???

1st admission

•

Fever without localizing complaints, 3 days duration•

Recent dental treatment

•

Physical examination –

rales

Rt. Lung base

•

Labs:

256Glucose1.8Creat415KPlt12.3Hb

176LDH56Urea3.5Globulin17800WBC

Imaging : CXR

Diagnosis

•

RLL pneumonia•

Treated with amoxycillin/clavulanate

&

ofloxacine•

No initial response, blood cultures neg.

•

TTE, oral surgeon consultation –

no abnormality

•

Slow decrease in temp. –

discharged•

Follow up CXR > CT recommended

•

CXR -

Continued infiltrate RLL•

ESR-

88

•

No further evaluation done

2nd admission

•

Fever, cough, Rt. Chest pain –

few days

•

Physical exam. –

bilateral Decreased

respiratory sounds and rales

•

Labs:

163Glucose2.1Creat277KPlt12.3Hb

63Urea4.1Globulin14200WBC

Imaging : CXR

Imaging : CT

Additional testing

•

Pulmonary Function tests –

low DLCO, mild combined restriction & obstruction

•

Sputum for culture and Sudan Black staining –

negative•

Gallium scan –

a Ga. avid pulmonary lesion –

bilateral (most

active -

RML)•

Bronchoscopy

–

thickened bronchial mucosa,

No obstruction No tumor•

Biopsies and BAL

Imaging : CT

Histology

•

Fragments of lung parenchyma showing:–

Numerous clear droplets

–

Intra-alveolar and intersitial

macrophages with vacuolated cytoplasm

–

Reactive hyperplasia and septal

thickening

–

No granulomata

–

No malignancy

Diagnosis: Lipoid pneumonia

Lipoid Pneumonia: an Unusual form of Drug Induced Lung Injury

Lipoid pneumonia (LP)

•

the result of foreign body type reaction to the presence of lipid material within the lung parenchyma.

•

LP can be caused by the deposition of:

–

Endogenous lipid material

–

aspiration or inhalation of Exogenous lipids

Many types of lipids•

East African countries -

a pediatric condition,

force feeding of infants with animal fat.

•

Far Eastern countries -

Squalene

(shark liver)

•

Animal fat more reactive than vegetable

or

mineral oils

LP in developed nations•

Oily foods (ketogenic

diet associated LP)

•

Vaporized lipids inhaled during metal processing.

•

The most frequent cause for LP : the medicinal use

of mineral oil (paraffin) –

usually as a laxative

agent.

Paraffin oil•

A mixture of liquid saturated hydrocarbons obtained from petroleum.

•

When administered orally it is only negligibly absorbed

•

Common side effects :–

rectal seepage

–

anal irritation.

•

Aspiration > > > LP

Usage associated with LP

•

Laxative•

Nasal drops

•

Fire Eaters

15-אסון ג שר המכ ביי ה ה

Incidence of LP

•

unknown. •

autopsy series : an incidence of about 1% .

•

clinically diagnosed LP appears to be rare.

•

The only national survey of LP

•

Based on a survey of medical departments.

•

1981 to 1993

•

only 44 cases of LP

•

This would represent a prevalence of less that 1:107

inhabitants.

•

¾

-

associated with paraffin oil

Common findings•

Mean age 61

•

M=F•

Long exposure (mean 9.5 years)

•

Only 60% symptomatic•

Fever, cough, weight loss

•

Occasional -

chest pain, hemoptysis•

Labs: ESR, leucocytosis

(20%)

•

PFT –

mostly DLCO, Restriction•

Imaging –

hypodense, peripheral sparing

Radiological - CT - finding in Exogenous Lipoid Pneumonia

J Thorac Imaging. 2003; 18(4): 217-24 BaronSE, Haramati LB, Rivera VT

Albert Einstein College of Medicine, NY, USA

•

Consolidation•

Ground glass opacities

•

Linear/nodular opacities•

Masses

•

Fat attenuation•

Pleural effusion

•

Lower lobes involvement•

“Crazy-paving” pattern ***

Radiological - CT - finding in Exogenous Lipoid Pneumonia

J Thorac Imaging. 2003; 18(4): 217-24 BaronSE, Haramati LB, Rivera VT

Albert Einstein College of Medicine, NY, USA

•

Consolidation and lower lobe involvement in acute and chronic LP

•

Pleural effusion and improvement on follow- up CT in acute LP

•

Pulmonary masses and progression on follow- up CT in chronic LP

““CrazyCrazy--PavingPaving”” pattern at pattern at thinthin--section CT of the lungssection CT of the lungs

Radiographics. 2003; 23(6): 1509-19 Rossi SE et al

•

Scattered or diffuse ground - glass attenuation with superimposed interlobular thickning and intralobular lines.

•

Pneumocystis carinii pneumonia•

Mucinous bronchioloalveolar carcinoma

•

Pulmonary alveolar proteinosis•

Nonspecific interstitial pneumonia

•

Exogenous lipoid pneumonia•

Pulmonary hemorrhagic syndromes

Radiological finding in chronic exogenous lipoid pneumonia

Treatment of LP

•

???–

Severe anecdotal cases:

•

Whole lung lavage•

Corticosteroids

–

Milder cases:•

Corticosteroids

•

Avoidance of further exposure without specific therapy

Natural history of LP - ????

•

two deaths unrelated to the lipid pneumonia.

•

In the 32 cases in which the oil was discontinued:

–

5 patients deteriorated (despite corticosteroid therapy in

one case)

–

27 patients remained stable/ improved regardless of

concomitant treatment

Imaging follow-up

•

3 complete cures (14%)•

6 improvements (29%)

•

10 stable courses (48%)•

2 deteriorations(10%)

Main lessons

•

Paraffin should not be administered to patients at risk:–

G-E reflux

–

Neurological abnormality

•

Not all febrile infiltrates are pneumonia

•

Search for atypical features

•

The importance of radiological evaluation and follow up

ExLP-

Exogenous Lipoid Pneumonia•

Most Elderly –late 7-8th decade

•

Infants and mentally retarded

•

Impaired swallowing mechanism: neurological and esophageal disorders.

•

Consistent use of Oils :mineral, animal, vegetable oils in laxatives, nasal drops, mout spray, oral lubricants, insecticides or traditional folk remedies, occupational fire hazar of fire eaters (maccabia

1997)

•

The irritation causing agent enters the lung: Aspiration, inhalation or ionized vegetable -

radiopaque medium for lymphangiography, bronchography

etc.

•

Vegetable oils, mostly expectorated, residual oils leads to ExLP

•

Mineral oil -

Liquid petroleum or paraffin, mixture of long chain saturated hydrocarbons.

ExLP- Exogenous Lipoid Pneumonia•

Lung irritation -

Diffuse parenchymal

reaction

-

localized masses / parafinnomas

•

Animal fat is the most harmful to lung tissue –

hydrolized

by (pulmonary) lipase into FFA > > severe inflammatory reaction & tissue necrosis. Observed in infants with ExLP, cultural practice of forced feedings of animal fat (Ghee).

•

ExLP

3 stages: 1. Toxic agitation of capillary endothelium -

alveolar exudative

damage

2. Macrophages (alveolar & interstitial) activation -

oil phagocytosis

& degradation

3. Fibrointerstitial

and granulomatous

reactions

•

High lipid content (animal) repress phagocytosis leaving the lymphocytes as the main cells responsible for fat removal.

•

Histology -

Fat-laden macrophages and prominant

pleural lymphocytes, easily mistaken as lymphocytic

carcinomatosis.

Questions? (and maybe some answers…)Paraffin: Yes or No?

EnLP-

Endogenous Lipoid Pneumonia (Golden pneumonitis / Cholesterol pneumonitis)

•

Collection of intrinsic lipids in the lungs

•

Chronic bronchial obstruction/Obstructive pneumonitis: foreign bodies, tumorsBronchiolitis

obliterans

( chemotherapy/ radiotherapy -

release of

lipids in alveoli )

•

Pulmonary alveolar proteinosis, repetitive fungal pneumonia, Fat embolism, Lipid storage diseases: Gaucher’s, Niemann-Pick and Disseminated lipogranulomatosis

•

Normal lung chemically analyzed-

fat content 8.63/100g of dry tissue 19% is cholesterol ( percentage marked increase in smokers)

EnLP-

Endogenous Lipoid Pneumonia (Golden pneumonitis

/ Cholesterol pneumonitis

)

•

EnLP-

Link to Lung Cancer (in resected

lungs of 33/147 patients with lung cancer) 18% in Adeno-ca, 31% in Squamous

cell ca.

•

Lung parenchyma distal

to obstructive tumor.Transbronchial

dissemination of breakdown products of

NSCLC cells, including mucin, could contribute to the spread of non-

obstructive component of EnLP.

•

Histology of coexisting NSCLC & EnLP (lipids) similar to coexisting Pulmonary alveolar proteinosis (surfactant=lipids & protein) & NSCLC (Squamous

cell ca

& Large cell ca)

EnLP - NSCLC

EnLP- Lung Cancer

Type I - obstructive LP

Type II & III – Non- obstructive LP

Transbronchial dissemination of:* Cancer cells breakdown products ( mucin)* Retained epithelial secretions* Vessels leakage in prolonged hypoxia

LP & PET

Take Home message Lipoid pneumonia (LP)

•

Old man & Lung infiltrate & Fever & ESR & WBC is not Sine qua non – Infective Pneumonia

•

ExLP

and EnLP

–

two different entities.

•

In contradistinction to ExLP-

External Oils :mineral, animal, vegetable oils , EnLP-

Obstructive pneumonitis

•

Unlike ExLP, the accumulation of lipid-rich cellular debris in EnLP does not manifest radiologically as lipid- containing opacities

•

Gallium scan – ExLP avid pulmonary lesion

•

Several entities (Infections, lipid storage, PAP) are considered

within the spectrum of EnLP.

•

EnLP

confirmed diagnosis is histopathologic -

imaging vary

•

EnLP Link to NSCLC (Type I , II & III)

•

PET-FDG scan - ExLP avid pulmonary lesion