Interesting Case presentations

Case Studies

Gamal Rabie Agmy, MD, FCCP

Professor of chest Diseases, Assiut university

Second Session

SIX CASES

Case No. 1

• A 45-year-old nonsmoking woman was referred for an opinion regarding management of recurrent pneumothorax.

• She was well until age 27 when she had a right-sided spontaneous pneumothorax.

• Two years later, she had another right-sided pneumothorax and underwent thoracotomy and stapling of the right lung apex. She has had no further episodes since that time.

• She is seeing a dermatologist for multiple facial papules, but otherwise, her general health is excellent. She denies any respiratory symptoms.

• Results of a physical examination are normal other than multiple skin colored papules over the central face and nose.

• Results of a chest radiograph demonstrated right apical pleural thickening but were otherwise normal. The C-T scan

The most likely diagnosis of this condition is:

A. Langerhans cell histiocytosis.

B. Lymphangioleiomyomatosis (LAM).

C. Sarcoidosis.

D. Birt-Hogg-Dubé syndrome (BHDS).

• The CT scan reveals several cysts in the left lung and scarring at the right apex related to the previous surgery.

• A history of recurrent pneumothorax, lung cysts, and skin lesions (fibrofolliculomas) with normal lung function is consistent with the diagnosis of Birt-Hogg-Dubé syndrome (BHDS) (choice D is correct).

• Langerhans cell histiocytosis is characterized by diffuse cystic disease of the lung, spontaneous pneumothorax, and airway obstruction related to cigarette smoking. These findings are not present in this patient (choice A is incorrect).

• Similarly, airflow obstruction, recurrent pleural effusions, and diffuse pulmonary disease are characteristic of LAM, features that also are not found in this patient (choice B is incorrect).

• Sarcoidosis is a granulomatous inflammatory lung disease characterized by diff use parenchymal opacities, airflow obstruction, and possibly, skin lesions.

• Lupus pernio, one of the skin manifestations of sarcoidosis, appears as purple nodules on the nose, cheeks, and ears, and none of these features is present in this patient (choice C is incorrect).

• BHDS is an autosomal dominantly inherited genodermatosis that predisposes a person to the development of cutaneous hamartomas (fi brofolliculomas), kidney neoplasms, lung cysts, and spontaneous pneumothorax.

• The BHD locus has been mapped to the short arm of chromosome 17(17p11.2). BHD is composed of 14 exons, and more than 40 unique mutations in BHD have been reported.

• Most BHD germline mutations are frameshift or nonsense mutations that are predicted to truncate the BHD protein, folliculin.

• Patients exhibit multiple 1- to 5-mm white-colored or skin-coloured papules distributed over the face, neck, and/or upper trunk, which histologically, are fibrofolliculomas.

• BHDS is associated with a unique histologic spectrum of bilateral and multifocal kidney tumors ranging from hybrid oncocytic (67%) to chromophobe renal carcinoma (23%) to oncocytic renal carcinoma (3%).

• Clear cell renal cell carcinoma (3%) has also been reported in a few patients with BHDS. Pulmonary manifestations are a major feature of BHDS.

• Most patients who are affected (89%) have multiple pulmonary cysts. The number of lung cysts is clearly related to the risk of pneumothorax.

• Approximately one-quarter of patients with BHDS have a history of one or more pneumothoraces. Smoking does not appear to be a risk factor for pneumothorax in this population

Lung Cysts

By

Gamal Rabie Agmy , MD , FCCP

Professor of Chest Diseases ,Assiut University

Lung Cysts

Differential Diagnosis

Pulmonary fibrosis (Honeycombing)

Lymphangliomyomatosis

Langerhans cell histiocytosis

Lymphocytic Interstitial Pneumonia (LIP)

Birt-Hogg-Dubé syndrome (BHDS)

Rough Reticular Fine Reticular

Traction

Bronchiectasis

and

Interface

sign

Honey

combing

UIP UIP or NSIP

Usual Interstitial Pneumonia

UIP

HRCT Findings

Reticular opacities, thickened intra- and

interlobular septa

Irregular interfaces

Honey combing and parenchymal distorsion

Ground glass opacities (never prominent)

Basal and subpleural predominance

Basal and subpleural

distribution

UIP

The Many ‘HRCT Faces’ of NSIP

Honeycombing not a

prominent feature

!!!!

Lymphangioleiomyomatosis

(LAM)

HRCT Morphology

Thin-walled cysts (2mm - 5cm)

Uniform in size / rarely confluent

Homogeneous distribution

Chylous pleural effusion

Lymphadenopathy

in young women

Lymphangioleiomyomatosis

(LAM)

Tuberous Sclerosis (young man)

Langerhans Cell Histiocytosis

HRCT Findings

Small peribronchiolar nodules (1-5mm)

Thin-walled cysts (< 1cm),

Bizarre and confluent

Ground glass opacities

Late signs: irreversible / parenchymal fibrosis Honey comb lung, septal thickening,

bronchiectasis

1 year later

Peribronchiolar Nodules Cavitating nodules and cysts


Langerhans Cell Histiozytosis

Key Features

Upper lobe predominance

Combination of cysts and noduli

Characteristic stages

Increased Lung volume

Sparing of costophrenic angle

S

M

O

K

I

N

G


Differential Diagnosis

Only small nodules Sarcoidosis, Silicosis

Only cysts idiopathic Fibrosis

LAM

Destructive emphysema

.......after cessation of smoking

Benign lymphoproliferative

disorder Diffuse interstitial infiltration of

mononuclear cells

Not limited to the air ways as

in follicular Bronchiolitis

LIP = Lymphocytic Interstitial

Pneumonia

Sjögren: LIP

LIP = Lymphocytic Interstitial

Pneumonia

Rarely idiopathic

In association with: Sjögren’s syndrome

Immune deficiency syndromes, AIDS

Primary biliary cirrhosis

Multicentric Castlemean’s disease

Sjoegren disease

Dry eye and dry mouth

Fibrosis, bronchitis and bronchiolitis

LIP

Overlap

Sarcoid, DM/PM, MXCT

SLE, RA (pleural effusion)

Up to 40 x increased risk for lymphoma (mediastinal

adenopathy) and

2 x times increased risk for neoplasma

Young woman Dry mouth Smoker

LAM LIP Histiocytosis

Wegener‘s disease

Rheumatoid Arthritis

History of recurrent pneumothorax, lung cysts, and skin

lesions (fibrofolliculomas) with normal lung function is

consistent with the diagnosis of Birt-Hogg-Dubé

syndrome

Birt-Hogg-Dubé syndrome

• BHDS is an autosomal dominantly inherited genodermatosis that predisposes a person to the development of cutaneous hamartomas (fi brofolliculomas), kidney neoplasms, lung cysts, and spontaneous pneumothorax.

• The BHD locus has been mapped to the short arm of chromosome 17(17p11.2). BHD is composed of 14 exons, and more than 40 unique mutations in BHD have been reported.

• Most BHD germline mutations are frameshift or nonsense mutations that are predicted to truncate

the BHD protein, folliculin.

Centrilobular Emphysema

Panlobular Emphysema

Mosaic pattern and its

differential

Where is the pathology ???????

in the areas with increased density meaning there is ground glass

in the areas with decreased density meaning there is air trapping

Pathology in black areas

Airtrapping: Airway

Disease

Bronchiolitis obliterans (constrictive bronchiolitis) idiopathic, connective tissue diseases, drug reaction,

after transplantation, after infection

Hypersensitivity pneumonitis granulomatous inflammation of bronchiolar wall

Sarcoidosis granulomatous inflammation of bronchiolar wall

Asthma / Bronchiectasis / Airway diseases

Airway Disease

what you see……

In inspiration sharply demarcated areas of seemingly increased

density (normal) and decreased density

demarcation by interlobular septa

In expiration ‘black’ areas remain in volume and density

‘white’ areas decrease in volume and increase in

density

INCREASE IN CONTRAST

DIFFERENCES

AIRTRAPPING

Bronchiolitis

obliterans

Early Sarcoidosis

Chronic EAA

Hypersensitivity pneumonitis

Extr. Allerg. Alveolitis (EAA) HRCT

Morphology

chronic: fibrosis

Intra- / interlobular septal thickening

Irregular interfaces

Traction bronchiectasis

acute - subacute

acinar (centrilobular) unsharp densities

ground glass (patchy - diffuse)

Pathology in white Areas

Alveolitis / Pneumonitis

Ground glass desquamative intertitial pneumoinia (DIP)

nonspecific interstitial pneumonia (NSIP)

organizing pneumonia

In expiration both areas (white and black) decrease in

volume and increase in density

DECREASE IN CONTRAST

DIFFERENCES

Cellular

NSIP

Mosaic Perfusion

Chronic pulmonary embolism

LOOK FOR

Pulmonary hypertension

idiopathic, cardiac disease, pulmonary

disease

CTEPH =

Chronic thrombembolic

pulmonary hypertension

Case No. 2

• A 34-year-old woman is admitted with cough, fever, shortness of breath, and malaise.

• She has no past medical history and was well until 5 days prior to admission when she developed a sore throat, low-grade fever, and non-productive cough.

• After 3 days, she used acetaminophen and pseudoephedrine for increasing sputum and develops some anterior chest wall pain and increased cough.

• On the day of admission, she begins to have increasing shortness of breath, fatigue, and malaise.

• She denies contact with sick individuals or travel, and she works as an administrative assistant in a law office

• Her temperature is 39.2C, BP is 90/55 mm Hg, heart rate is 132/min, and respiratory rate is 34/min.

• Her oxygen saturations are 84% on room air.

• She is using accessory muscles of respiration and is in moderate respiratory distress.

• Fine inspiratory crackles are heard in all lung fields, with decreased breath sounds at the left lung base.

• Her WBC count is 15,400/L (15.4 × 109/L), hematocrit concentration is 41% (0.41), and platelet count is 185 × 103/L (185 × 109/L).

• Her BUN level is 11 mg/dL (3.93 mmol/L).

• Creatinine level is 0.9 mg/dL (79.6 mol/L)

• Arterial blood gas analysis reveals a pH of 7.55, Pco2 of 20 mm Hg, and a Po2 of 48 mm Hg.

• Chest radiograph are shown

• CT scan image

• Due to increasing respiratory fatigue and hypoxemia, she is intubated.

• Her sputum Gram stain shows 2 WBCs, 5 to 10 squamous epithelial cells, 2 gram-positive cocci, 1 gram-positive rods, and 1 gram-negative bacilli.

• A multiplex diagnostic polymerase chain reaction (PCR) of her nasal lavage fluid performed in the ED shows a positive result for rhinovirus.

Which is the next best step?

A. Start ceftriaxone and azithromycin therapy.

B. Start methylprednisolone therapy.

C. Start amantadine therapy.

D. Start trimethoprim/sulfamethoxazole therapy

• This patient has a fever, leukocytosis, diffuse alveolar opacities, and respiratory failure, along with multiple organisms seen on Gram stain of the sputum and rhinovirus detected on nasal lavage results.

• Thus, community-acquired pneumonia (CAP) is of high causative probability, and appropriate antibiotic administration must be rapid in order to improve survival.

• Therefore, ceftriaxone and azithromycin should be administered immediately (choice A is correct).

• The use of rapid viral testing is becoming more common, especially with multiplex PCR. In these instances, a virus respiratory panel can be applied to a nasal or bronchial lavage.

• The most common panel includes rhinovirus, coronavirus, infl uenza, parainfl uenza, respiratory syncytial virus (RSV), adenovirus, and metapneumovirus.

• Thus, the rapid detection of these viruses in cases of suspected CAP is becoming more common. However, a sole viral cause for CAP occurs in 10% to 30% of cases, depending on method of testing.

• In a prospective study of 105 adults with suspected CAP evaluated by conventional microbiologic techniques and multiplex real-time PCR, respiratory viral infections were detected in 15 patients (14%) and 59 patients (56%) by conventional methods and PCR, respectively.

• Rhinovirus occurred in 31% of patients, coronavirus and infl uenza in 23%, and band parainfl uenza in 13%. In the patients in whom rhinovirus or coronavirus were implicated, another pathogen was identified 93% of the time, most often bacterial.

• Thus, rhinovirus or coronavirus are likely not the cause of pneumonia but, rather, impair upper airway defenses, leading to lower airway disease from a bacterial agent.

• In patients with RSV and influenza, a second organism was found in a minority of patients, and thus, treatment focused on these viruses is warranted.

• Another study detected at least one virus by PCR in 32% of patients with CAP (lobar pneumonia), 5% of control subjects, and a surprising 55% of patients with diff use lower respiratory opacities.

• Adenovirus, rhinovirus, and RSV were most commonly associated with CAP, while influenza was the most common agent seen in diff use lower respiratory opacities.

• Therefore, in many patients with CAP, viral isolation does not preclude the use of antibiotics until other causes have been eliminated. It should also not delay the early administration of antibiotics in patients with CAP

• The use of methylprednisolone may be indicated, but in the absence of an etiology of this patient’s opacities, it is not warranted and could be harmful (choice B is incorrect).

• Although influenza can cause a similar picture, amantadine is not the treatment of choice for severe influenza due to resistance (oseltamivir is preferred) (choice C is incorrect).

• Trimethoprim/sulfamethoxazole is not an appropriate antibiotic for severe CAP (choice D is incorrect). This patient’s sputum culture grew Streptococcus pneumoniae, and she recovered after antibiotic administration

Antibiotic Strategy in CAP

Gamal Rabie Agmy, MD,FCCP Professor of Chest Diseases, Assiut university

79

Pneumonias – Classification

• Community Acquired CAP

• Health Care Associated HCAP

• Hospital Acquired HAP

• ICU Acquired ICUAP

• Ventilator Acquired VAP

Nosocomial Pneumonias

*HCAP: diagnosis made < 48h after

admission with any of the following risk

factors:

(1)hospitalized in an acute care hospital for >

48h within 90d of the diagnosis;

(2) resided in a nursing home or long-term

care facility;

(3) received recent IV antibiotic therapy,

chemotherapy, or wound care within the 30d

preceding the current diagnosis; and

(4) attended a hospital or hemodialysis

clinic

HCAP

Infection of the lung parenchyma in a

person who is not hospitalized or living

in a long-term care facility for ≥ 2

weeks. This pneumonia develops in

the outpatient setting or within 48

hours of admission to a hospital.

Definition of CAP

Symptoms:

• Respiratory: Cough dry or productive,

mucopurulent sputum , sometimes

rusty, dyspnea, sometimes pleuritic

chest pain

• Non-respiratory: Fever, body aches,

altered mental state, vomiting or

diarrhea.

The clinical diagnosis of CAP

Signs:

Generally: Fever, sometimes

hypothermia, tachycardia, tachypnea.

Local: signs of consolidation

The clinical diagnosis of CAP

84

CAP – The Two Types of Presentations

Classical

• Sudden onset of CAP

• High fever, shaking chills

• Pleuritic chest pain, SOB

• Productive cough

• Rusty sputum, blood tinge

• Poor general condition

• High mortality up to 20% in

patients with bacteremia

• S.pneumoniae causative

• Gradual & insidious onset

• Low grade fever

• Dry cough, No blood tinge

• Good GC – Walking CAP

• Low mortality 1-2%; except

in cases of Legionellosis

• Mycoplasma, Chlamydiae,

Legionella, Ricketessiae,

Viruses are causative

Atypical

Sputum Gram stain:

is a rapid and inexpensive test that can

help a lot:

• Differentiate Gm –ve from Gm +ve

bacteria.

• Excess pus cells without organism

suspect atypical infection.

The Bacteriological Diagnosis of CAP

Cultures to identify the causative

organism:

Sputum cultures are not recommended in

cases of CAP except in certain occasions:

• Patients admitted in hospital or ICU.

• Patients who do not respond to

empirical antibiotic therapy.

• Suspection of resistant strains of

S.pneumoniae.


Blood Culture:

Recommended for all patients with

moderate and high severity CAP,

preferably before antibiotic therapy is

commenced.

Examination of sputum for

Mycobacterium TB


88

CAP – Pathogenesis

Inhalation

Aspiration

Hematogenous

90

PORT Scoring – PSI

Clinical Parameter Scoring

Age in years Example

For Men (Age in yrs) 50

For Women (Age -10) (50-10)

NH Resident 10 points

Co-morbid Illnesses

Neoplasia 30 points

Liver Disease 20 points

CHF 10 points

CVD 10 points

Renal Disease (CKD) 10 points

Clinical Parameter Scoring

Clinical Findings

Altered Sensorium 20 points

Respiratory Rate > 30 20 points

SBP < 90 mm 20 points

Temp < 350 C or > 400 C 15 points

Pulse > 125 per min 10 points

Investigation Findings

Arterial pH < 7.35 30 points

BUN > 30 20 points

Serum Na < 130 20 points

Hematocrit < 30% 10 points

Blood Glucose > 250 10 points

Pa O2 10 points

X Ray e/o Pleural Effusion 10 points

Pneumonia Patient Outcomes

Research Team (PORT)

91

Classification of Severity - PORT

Predictors Absent

Class I

70

Class II

71 – 90

Class III

91 - 130

Class IV

> 130

Class V

92

CAP – Management based on PSI Score

PORT Class PSI Score Mortality % Treatment Strategy

Class I No RF 0.1 – 0.4 Out patient

Class II 70 0.6 – 0.7 Out patient

Class III 71 - 90 0.9 – 2.8 Brief hospitalization

Class IV 91 - 130 8.5 – 9.3 Inpatient

Class V > 130 27 – 31.1 IP - ICU

93

CURB 65 Rule – Management of CAP

CURB 65

Confusion

BUN > 30

RR > 30

BP SBP <90

DBP <60

Age > 65

CURB 0 or 1 Home Rx

CURB 2 Short Hosp

CURB 3 Medical Ward

CURB 4 or 5 ICU care

95

CAP – Criteria for ICU Admission

Major criteria

Invasive mechanical ventilation required

Septic shock with the need of vasopressors

Minor criteria (least 3)

Confusion/disorientation

Blood urea nitrogen ≥ 20 mg%

Respiratory rate ≥ 30 / min;

Core temperature < 36ºC

Severe hypotension;

PaO2/FiO2 ratio ≤ 250

Multi-lobar infiltrates

WBC < 4000 cells;

Platelets <100,000

The Radiological Diagnosis

of CAP

97

CAP – Value of Chest Radiograph

• Usually needed to establish diagnosis

• It is a prognostic indicator

• To rule out other disorders

• May help in etiological diagnosis

J Chr Dis 1984;37:215-25

98

Infiltrate Patterns and Pathogens

CXR Pattern Possible Pathogens

Lobar S.pneumo, Kleb, H. influ, Gram Neg

Patchy Atypicals, Viral, Legionella

Interstitial Viral, PCP, Legionella

Cavitatory Anerobes, Kleb, TB, S.aureus, Fungi

Large effusion Staph, Anaerobes, Klebsiella

99

Normal CXR & Pneumonic Consolidation

100

Lobar Pneumonia – S.pneumoniae

101

CXR – PA and Lateral Views

102

Lobar versus Segmental - Right Side

103

Lobar Pneumonia

104

Special forms of Consolidation

105

Round Pneumonic Consolidation

106

Special Forms of Pneumonia

107

Special Forms of Pneumonia

108

Complications of Pneumonia

109

Empyema

110

Mycoplasma Pneumonia

111

Mycoplasma Pneumonia

112

Chlamydia Trachomatis

113

Rare Types of Pneumonia

http://radiographics.rsnajnls.org/cgi/content/full/20/3/653/F6A

http://radiographics.rsnajnls.org/cgi/content/full/20/3/653/F6B

http://radiographics.rsnajnls.org/cgi/content/full/20/3/653/F6C

http://radiographics.rsnajnls.org/cgi/content/full/22/1/e1/F8A

http://radiographics.rsnajnls.org/cgi/content/full/22/1/e1/F8B

http://radiographics.rsnajnls.org/cgi/content/full/22/1/e1/F8C

http://intl-radiographics.rsnajnls.org/cgi/content/full/20/3/653/F2



Pneumonia Posterior intercostal scan shows a hypoechoic

consolidated area that contains multiple

echogenic lines that represent an air

bronchogram.

Post-stenotic pneumonia Posterior intercostal scan shows a hypoechoic

consolidated area that contains anechoic,

branched tubular structures in the bronchial tree

(fluid bronchogram).

Contrast-enhanced ultrasonography

of pneumonia

A: Baseline scan shows

a hypoechoic

consolidated area

B: Seven seconds after

iv bolus of contrast

agent, the lesion shows

marked and

homogeneous

enhancement

C: The lesion remains

substantially unmodified

after 90 s.

The Treatment of CAP

ANTIMICROBIAL DRUGS

MECHANISMS OF ACTION OF

ANTIBACTERIAL DRUGS

Mechanism of action include: Inhibition of cell wall

synthesis

Inhibition of protein synthesis

Inhibition of nucleic acid synthesis

Inhibition of metabolic pathways

Interference with cell membrane integrity

EFFECTS OF

COMBINATIONS OF DRUGS

Sometimes the chemotherapeutic effects of two drugs given simultaneously is greater than the effect of either given alone.

This is called synergism. For example, penicillin and streptomycin in the treatment of bacterial endocarditis. Damage to bacterial cell walls by penicillin makes it easier for streptomycin to enter.

EFFECTS OF


Other combinations of drugs can be antagonistic.

For example, the simultaneous use of penicillin and tetracycline is often less effective than when wither drugs is used alone. By stopping the growth of the bacteria, the bacteriostatic drug tetracycline interferes with the action of penicillin, which requires bacterial growth.

EFFECTS OF


Combinations of antimicrobial drugs should be used only for:

1. To prevent or minimize the emergence of resistant strains.

2. To take advantage of the synergistic effect.

3. To lessen the toxicity of individual drugs.

Patterns of Microbial Killing

Concentration dependent

– Higher concentration greater killing Aminoglycosides, Flouroquinolones, Ketolides, metronidazole, Ampho B.

Time-dependent killing

– Minimal concentration-dependent killing (4x MIC)

– More exposure more killing Beta lactams, glycopeptides, clindamycin, macrolides, tetracyclines, bactrim

The Ideal Drug* 1. Selective toxicity: against target pathogen but

not against host

LD50 (high) vs. MIC and/or MBC (low)

2. Bactericidal vs. bacteriostatic

3. Favorable pharmacokinetics: reach target site

in body with effective concentration

4. Spectrum of activity: broad vs. narrow

5. Lack of “side effects”

Therapeutic index: effective to toxic dose ratio

6. Little resistance development

Resistance

Physiological Mechanisms

1. Lack of entry – tet, fosfomycin

2. Greater exit

efflux pumps

tet (R factors)

3. Enzymatic inactivation

bla (penase) – hydrolysis

CAT – chloramphenicol acetyl transferase

Aminogylcosides transferases REVIEW

Resistance

Physiological Mechanisms

4. Altered target

RIF – altered RNA polymerase (mutants)

NAL – altered DNA gyrase

STR – altered ribosomal proteins

ERY – methylation of 23S rRNA

5. Synthesis of resistant pathway

TMPr plasmid has gene for DHF reductase; insensitive to TMP

(cont’d)

REVIEW

Empirical Treatment is the

recommended strategy in

treatment of CAP and

shouldn’t be delayed.

132

CAP – Special Features – Pathogen wise

Typical – S.pneumoniae, H.influenza, M.catarrhalis

Blood tinged sputum - Pneumococcal, Klebsiella, Legionella

H.influenzae

CAP has associated of pleural effusion:S.Pneumoniae – commonest – penicillin resistance problem

S.aureus, K.pneumoniae, P.aeruginosa

S.aureus causes CAP in post-viral influenza; Serious CAP

K.pneumoniae primarily in patients of chronic alcoholism

P.Aeruginosa causes CAP in pts with CSLD or CF, Nosocom

Aspiration CAP only is caused by multiple pathogens

Extra pulmonary manifestations only in Atypical CAP

Outpatient treatment:

Oral Respiratory Fluroquinolones

OR Oral B-Lactam/ B-Lactamase + Oral

New Macrolide

OR IM 3rd Generation Cefalosporines +

New Macrolide

Recommendations for the Empirical Treatment:

In-patient treatment: Non-ICU:

Intravenous ( IV )Respiratory fluoro-

quinolone

OR IV B-Lactam/ B-Lactamase + IV New

Macrolide

OR IV 3rd Generation Cephalosporin + IV

New Macrolide


In-patient treatment: ICU:

No Monotherapy.

IV Respiratory fluoroquinolone + 3rd or

4th generation cephalosporin

OR IV Imipenem + IV New Macrolide


Special entities in ICU: Aspiration: As Before + i.v. Clindamycin OR Metronidazole

Risk of Pseudomonas Infection:

Antipseudomonal beta-lactam (3rd or 4th generation

cephalosporin OR Piperacillin-tazobactam OR

carbapenem) Plus (aminoglycoside OR

antipseudomonal fluoroquinolone)

For community-acquired methicillin-resistant

Staphylococcus aureus infection (MRSA):

Add Teicoplanin OR linezolid Alternative: Vancomycin

(considering its renal side effects)


138

Duration of Therapy

• Minimum of 5 days

• Afebrile for at least 48 to 72 h

• No > 1 CAP-associated sign of clinical instability

• Longer duration of therapy

If initial therapy was not active against the identified

pathogen or complicated by extra pulmonary infection

139

Strategies for Prevention of CAP

• Cessation smoking

• Influenza Vaccine It offers 90% protection and reduces mortality by 80%

• Pneumococcal Vaccine (Pneumonia shot)

It protects against 23 types of Pneumococci

70% of us have Pneumococci in our RT

It is not 100% protective but reduces mortality

Age 19-64 with co morbidity of high for pneumonia

Above 65 all must get it even without high risk

• Starting first dose of antibiotic within 4 h & O2 status

140

Switch to Oral Therapy

Four criteria

Improvement in cough, dyspnea & clinical signs

Afebrile on two occasions 8 h apart

WBC decreasing towards normal

Functioning GI tract with adequate oral intake

If overall clinical picture is otherwise favorable,

hemodynamically stable; can switch to oral

therapy while still febrile.

141

Management of Poor Responders

Consider non-infectious illnesses

Consider less common pathogens

Consider serologic testing

Broaden antibiotic therapy

Consider bronchoscopy

142

CAP – Complications

Hypotension and septic shock

3-5% Pleural effusion; Clear fluid + pus cells

1% Empyema thoracis pus in the pleural space

Lung abscess – destruction of lung - CSLD

Single (aspiration) anaerobes, Pseudomonas

Multiple (metastatic) Staphylococcus aureus

Septicemia – Brain abscess, Liver Abscess

Multiple Pyemic Abscesses

143

CAP – So How Best to Win the War?

Early antibiotic administration within 4-6 hours

Empiric antibiotic Rx. as per guidelines (IDSA / ATS)

PORT – PSI scoring and Classification of cases

Early hospitalization in Class IV and V

Change Abx. as per pathogen & sensitivity pattern

Decrease smoking cessation - advice / counseling

Arterial oxygenation assessment in the first 24 h

Blood culture collection in the first 24 h prior to Abx.

Pneumococcal & Influenza vaccination; Smoking cessation

Case No. 3

• A 63-year-old man who is 15 months postoperative from a right single-lung transplant for idiopathic pulmonary fibrosis is seen in follow-up.

• His initial postoperative course was unremarkable.

• He was cytomegalovirus (CMV)-positive prior to transplant and received a graft from a CMV-positive donor.

• The patient reports that he has noted some mild dyspnea on exertion with an occasional dry cough and intermittent wheezing.

• He has had subjective fevers but denies chills or weight loss.

• His medications include tacrolimus, mycophenolate mofetil, and prednisone. Valganciclovir and trimethoprim-sulfamethoxazole were discontinued at 12 months.

• His last polymerase chain reaction test results were negative for CMV.

• On physical examination, he is afebrile.

• The right lung examination reveals scattered expiratory wheezes, and the left native lung reveals crackles.

• The remainder of the examination results are unremarkable. Laboratory studies are within normal limits.

• His tacrolimus level is 8 ng/mL.

• His FEV1 has decreased by 5% since his last visit 2 months ago

His chest CT revealed

A histologic specimen obtained via bronchoscopy with transbronchial biopsy from the right upper lobe is shown.

The next best step in this patient’s management is which of the following?

A. Administer a corticosteroid bolus and increase the tacrolimus dose.

B. Begin evaluation for retransplantation.

C. Continue current immunosuppression and begin IV ganciclovir.

D. Decrease current immunosuppression and begin rituximab.

• This patient has developed a posttransplant lymphoproliferative disorder (PTLD) as seen in the pathology specimen showing numerous small lymphocytes and a reduction in immunosuppression and initiation of rituximab are indicated (choice D is correct).

• PTLDs are reported more frequently following lung transplantation than following other types of solid-organ transplantation, with an incidence reported to range between 1.8% and 9.4%.

• The PTLDs are composed of a heterogeneous group of lymphoid proliferations of variable clonality.

• B-cell non-Hodgkin lymphoma is the most frequent form of PTLD and have been associated with Epstein-Barr virus (EBV) activity, either serologically or by identification of viral DNA in tissue.

• Most PTLDs in solid organ transplant recipients are of recipient origin. There is no clear correlation between episodes of rejection, specific immunosuppressive drugs, and the development of PTLD.

• Those patients who have negative serologic findings for EBV prior to transplantation and receive an organ from a donor who is EBV-positive, resulting in seroconversion, are at a significantly higher risk for developing PTLD.

• Children are at higher risk due to their frequent EBV-negative status.

• The clinical features of PTLD in lung transplant recipients include development in the first or second posttransplant year, involvement of the allograft, and radiographic findings of solitary or multiple pulmonary nodules, mediastinal adenopathy, and/or nodular opacities, with multiple nodules in the right transplanted lung and fibrosis in the left native lung.

• Extrapulmonary involvement of the skin, CNS, and GI tract has been described.

• Treatment for PTLD includes the anti-CD20 monoclonal antibody rituximab and a reduction in immunosuppression.

• Case series using rituximab report complete remissions in the majority of patients, with minimal side effects.

• In a series of B-cell patients with PTLD treated with rituximab and a decrease in immunosuppression, median relapse-free survival was 34 months as assessed by conventional imaging and PET scans.

• The most common reported side effect with rituximab is a transient infusion reaction. Pulmonary toxicity including interstitial pneumonitis, organizing pneumonia, pulmonary edema, and diffuse alveolar hemorrhage has been described. Adjunctive treatment of PTLD with antiviral therapy can be considered. Radiation, chemotherapy, and/or surgery are second-line treatment choices if the patient does not respond to rituximab.

• Throughout treatment, there must be a careful attempt to balance treatment of the PTLD and rejection.

• With high-grade PTLD, as staged by standard lymphoma staging systems, mortality may be significant. An increased incidence of other nonlymphomatous malignancies, most commonly skin cancers, has been reported in the lung transplant population, and careful screening is recommended

• An increase in immunosuppression, not indicated for PTLD (choice A is incorrect) would be indicated for acute rejection, which usually occurs in the first year following lung transplantation and is characterized histologically by a lymphocytic vasculitis.

• An increase would also be indicated for chronic rejection, characterized by a decline in pulmonary function, with pathologic findings showing obliterative bronchiolitis or a nondiagnostic bronchoscopy in the setting of a reduction in pulmonary function tests, the bronchiolitis obliterans syndrome.

• Retransplantation might be considered for refractory chronic rejection but would never be considered for PTLD (choice B is incorrect).

• Ganciclovir and a reduction in immunosuppression might be indicated for the treatment of cytomegalovirus infection, also not present in this patient (choice C is incorrect)

MALIGNANT LYMPHOPROLIFRATIVE

DISORDERS

What is the difference between a leukemia and a lymphoma? In leukemias the neoplastic cell originates

in the bone marrow and the neoplastic cells are found predominantly in the bone marrow and peripheral blood.

In lymphomas, the neoplastic cell originates in the lymph nodes or spleen and causes the development of a solid tumor.

Some lymphomas have a “leukemic phase” where the neoplastic cells are found in the peripheral blood.

They may be difficult to differentiate from a leukemia.


DISORDERS

Lymphomas

Lymphomas are divided into 2 major categories: Hodgkins lymphoma and non-Hodgkins lymphoma Hodgkins lymphoma:

Can occur at any age with peak incidences at 20-30 and over 50.

Patients present to the doctor with symptoms of lymphadenopathy and may have fever, night sweats, weight loss and malaise

Diagnosis depends upon finding the Reed-Sternberg (RS) cell (something a pathologist must identify)

Are divided into 2 basic types based on the histopathology of the involved lymph nodes


DISORDERS Nodular lymphocyte predominance – occasional

or rare RS cell seen; rare, but has a good prognosis

Classic Hodgkins lymphoma which is further subdivided into:

Nodular sclerosis - bands of collagen are seen in the lymph nodes. There are mature appearing lymphocytes (T helper cells) associated with varying numbers of granulocytes, macrophages and eosinophils. Numerous RS cells are seen. This is the most common form of the disease.

Mixed cellularity – the lymph nodes contain proliferating lymphocytes, histiocytes, plasma cells, and eosinophils. There are a moderate number of RS cells

Lymphocyte depleted – there are few lymphocytes and a predominance of RS cells

Lymphocyte rich – there are numerous small T lymphocytes and occasional RS cells


DISORDERS

Extranodal Hodgkins lymphoma – involves tumors in bone marrow, liver, or spleen

Lab features – normochromic, normocytic anemia with transitory increase in lymphocytes, monocytes, eosinophils, and sometimes platlets

Prognosis depends upon

The clinical stage of the disease (see next slide)

The histiologic type of the disease – in general, the prognosis is better the higher the number of lymphocytes and the lower the number of RS cells

Treatment

Combination chemotherapy

Radiation

A combination of chemotherapy and radiation

Cure rates are 80% or more, particularly if diagnosis occurs in an early stage of the disease.

CLINICAL STAGING OF LYMPHOMAS


DISORDERS

Non-Hodgkins lymphoma (malignant lymphoma)

Many are associated with specific chromosomal translocations

Can be grouped morphologically by cell size into Small

Intermediate

Large

Can be grouped functionally into B cell

T cell

Null cell


DISORDERS

Can be grouped based on cell

maturity into

Well differentiated

Poorly differentiated

Can be grouped based on how

aggressive the disease is into

Low grade

Intermediate grade

High grade

LYMPHOMAS - CLASSIFICATION


DISORDERS

Prognosis –

Prognosis worsens generally with

increased cell size

Prognosis worsens with decreased

differentiation of the malignant cell

Low grade lymphomas have a better

prognosis than high grade lymphomas


DISORDERS

Multiple myeloma (plasma cell myeloma)

This is usually seen in older adults

When the patient is first diagnosed the following are usually seen: Multiple bone lesions with bone marrow

infiltration of malignant cells

Monoclonal gamopathy (usually IgG or IgA)

Generalized hypogammaglobulinemia

Bence Jones proteinuria

What does this all mean? A single immunoglobulin(antibody) is

produced in excess = monoclonal gamopathy


DISORDERS

Synthesis of normal immunoglobulins is suppressed = generalized hypogammaglobulinemia

There is an overproduction of light chains resulting in light chains being found in the urine = Bence Jones proteinuria

A common complication is renal impairment

On a peripheral smear, rouleaux is the hallmark of the disease and occasional circulating plasma cells may be seen


DISORDERS

Waldenstrom’s macroglobulinemia

This is a plasma cell dyscrasia (abnormality) in which a monoclonal IgM is secreted.

Soft tissue involvement rather than bone marrow involvement is seen

Patients have problems with hyperviscosity of the blood.


DISORDERS

Heavy chain disease

This results from an overproduction of abnormal heavy chains.

Clinically the patients present with symptoms typical of malignant lymphoma.

Case No. 4

• A 66-year-old man complains of increasing shortness of breath at rest and with exertion accompanied by cough productive of purulent sputum for the last 5 days.

• He notes he had upper respiratory symptoms 1 week ago consisting of a dry cough, nasal congestion, and an intermittent fever up to 38.3C, and his fever still persists.

• His past medical history is significant for coronary artery disease.

• Physical examination:

Moderately short of breath

Temperature of 38.3C,

Respiratory rate of 24/min

Decreased breath sounds in the left mid chest laterally

Cardiac examination without a murmur or S3.

• Laboratory findings:

WBC count of 14,300/L (14.3 × 109/L) with a left shift

Hematocrit concentration of 42% (0.42).

Chest radiograph

CT scan of the chest

Ultrasound of the left chest are obtained

• Thoracentesis is performed, showing:

Cloudy pleural fluid

Protein level of 3.9 g/dL (39 g/L),

Lactate dehydrogenase level of 1,213 U/L (20.3 kat/L) (serum: 214 U/L, 3.6 kat/L),

Glucose level of 32 mg/dL (1.8 mmol/L), and

pH of 7.15.

Gram stain is positive for Gram-positive diplococci

Which is the most appropriate next therapeutic step for this patient in addition to starting antibiotics?

A. Image-guided large-bore chest tube (32F) placement, streptokinase.

B. Image-guided small-bore chest tube (14F) placement.

C. Continue antibiotics with no additional intervention.

D. Decortication.

• This patient has a complicated parapneumonic effusion evidenced by a loculated pleural effusion seen on chest radiograph (moving up the lateral chest wall and not obeying the law of gravity), chest CT scan (with similarly gravity defying fluid), and ultrasound showing multiple septations (loculations).

• The low pleural fluid pH and low pleural fluid glucose indicate the need for small-bore chest tube drainage, ideally placed under image guidance, in addition to antibiotic therapy (choice B is correct).

• At a minimum, antibiotic therapy is required, but drainage must also occur (choice C is incorrect), with a pH 7.20 being the most powerful predictor of the need for chest tube drainage.

• Purulent, turbid, cloudy, or loculated fluid, in addition to organisms on fluid Gram stain, are also all indications for tube placement in a parapneumonic effusion. Complicated parapneumonic effusions and empyema occupy a continuum of disease, with the distinction often blurred, as many confine the term empyema to the presence of frank pus.

• The failure of the C-reactive protein level to fall by 50% in a patient with community-acquired pneumonia is associated with increased incidence of empyema and an adverse outcome. Antibiotics must be selected, recognizing a distinct difference in the organisms causing community-acquired vs hospital-acquired pleural space infections.

• Community-acquired pleural space infections have a greater proportion of Streptococcus species and anaerobes.

• Hospital-acquired empyemas have a greater predominance of Staphylococci, including methicillin-resistant Staphylococcus aureus and Enterobacteriaceae

• A small-bore chest tube (10-14 F) is adequate for most pleural infections and is the recommendation of the 2010 British Thoracic Society pleural diseases guidelines. Regular flushing of these small-bore catheters to prevent blockage is recommended. Ideally, chest tube insertion should be performed under image guidance.

• However, successful drainage of infected pleural fluid is central to management, regardless of the chest tube size chosen.

• Most importantly, the addition of streptokinase does not improve survival or reduce hospital time, regardless of the chest tube size chosen (choice A is incorrect).

• Currently, there is no indication for the routine use of intrapleural fibrinolytics in pleural infection. Only patients with persistent pleural-related sepsis and/or a residual pleural fluid collection should be referred for evaluation for surgical intervention (choice D is incorrect).

• This patient has not had an attempt at pleural drainage and antibiotic therapy. The exact timing and indications for surgical intervention in complicated parapneumonic effusions and empyema remain controversial.

Pleural Ultrasound

By

Gamal Rabie Agmy , MD , FCCP Professor of Chest Diseases ,Assiut University

http://intl-radiographics.rsnajnls.org/cgi/content/full/20/3/653/F10A

http://intl-radiographics.rsnajnls.org/cgi/content/full/20/3/653/F10B


http://intl-radiographics.rsnajnls.org/cgi/content/full/20/3/653/F12A

http://intl-radiographics.rsnajnls.org/cgi/content/full/20/3/653/F12B

http://radiographics.rsnajnls.org/cgi/content/full/22/1/e1/F3C

the "seashore sign" (Fig.3).

Absent lung sliding

Exaggerated horizontal artifacts

Loss of comet-tail artifacts

Broadening of the pleural line to a band

Lung point

Loss of lung impulse

The key sonographic signs of

Pneumothorax


http://radiographics.rsnajnls.org/cgi/content/full/22/1/e1/F5B

Case No. 5

• A 57-year-old man was in good health until 2 months ago when he noted some difficulty walking. At first, he felt some fatigue when walking from the parking lot to his office at work.

• However, he then noted his feet catching on the edge of stairs, and he had to use his arms to rise up from a chair.

• Over the subsequent weeks, he began to notice difficulty lifting objects over his head, and at this time, his wife noted his eyes were “droopy.”

• He was referred by his primary care physician to a neurologist who documented a neurologic examination with normal cognitive function and memory.

• He was slightly dysarthric.

• His pupils were round and reactive to light, and extraocular movements were normal, but there was bilateral ptosis

• Muscle bulk and tone were normal and there were no fasciculations. Muscle strength was 3-4/5 in the proximal lower extremities but normal elsewhere. His deep tendon reflexes were diminished at all sites. There was no ataxia of the upper limbs.

• His gait was slow, and he had difficulty lifting his legs, as well as difficulty getting from a sitting to a standing position

• The patient has been treated for hypertension and type 2 diabetes for a number of years. He works as a lab technician in a steel mill. He has smoked 1 pack of cigarettes a day for 25 years.

• A neurologic evaluation is initiated, and as part of his routine testing,

• The patient is referred to your clinic for evaluation of his thoracic abnormalities

Chest X-ray

C-T scan chest

Which of the following findings gathered with additional testing would be consistent with this patient’s presentation and underlying problem?

A. Aortography demonstrating an aortic dissection involving the spinal arteries at a thoracic level.

B. CT-guided biopsy of the thoracic abnormalities revealing squamous cell carcinoma.

C. Serum antibodies directed against the acetylcholine receptor.

D. Increased tendon reflexes and strength after maximal isometric contraction of a muscle group

• This patient has Lambert-Eaton myasthenic syndrome (LEMS), a neuromuscular disorder similar in some respects to myasthenia gravis and strongly associated with lung cancer.

• This patient’s chest imaging reveals a large mass in the aortopulmonary window and a peripheral lung nodule on the left.

• CT-guided biopsy of the peripheral nodule revealed small cell lung cancer (SCLC).

• One clinical feature of LEMS that is distinct and different from myasthenia is postexercise or postactivation facilitation, which can sometimes lead to improved deep tendon reflexes or improvement in weakness by examining the patient before and after maximal isometric contraction (choice D is correct).

• This phenomenon can also be demonstrated at the time of electromyography, when repetitive nerve stimulation leads to an increase in the compound muscle action potential amplitude, a means of distinguishing LEMS from myasthenia gravis electrophysiologically.

• The radiologic abnormalities do not suggest an aortic dissection, and aortic dissection with spinal cord involvement would not explain the full range of this patient’s neurologic symptoms and findings (choice A is incorrect)

• LEMS has been shown to result from a disordered release of acetylcholine from the motor neuron, not an abnormality of the acetylcholine receptor and not from blocking antibodies against the receptor, as have been described in myasthenia gravis (choice C is incorrect).

• Instead, antibodies directed against the voltage-gated calcium channel (VGCC) have been shown to play a central role in LEMS, creating a mechanism by which acetylcholine release may be impaired. Antibodies to VGCC were identified in this patient

• LEMS is rare and likely much less common than myasthenia gravis. Approximately one-half of LEMS cases are associated with malignancy, primarily SCLC (choice B is incorrect).

• The incidence of LEMS in patients with SCLC is estimated to be approximately 3%.

• Other tumors that have been associated with LEMS include atypical carcinoid, malignant thymoma, and Hodgkin lymphoma

• Initial symmetric limb weakness is a presenting symptom in the vast majority of patients with LEMS and is somewhat unusual as the predominant early symptom for myasthenia gravis, a disorder with very prominent early ocular symptoms.

• However, ptosis is common in LEMS. Muscle weakness can be profound in LEMS, and this disorder should be included in the differential diagnosis of patients who have undiagnosed neuromuscular respiratory failure.

• Signs of autonomic dysfunction are also common in LEMS, with sluggish pupillary light reflexes and reduced salivation being most common. The diagnosis of LEMS rests on the clinical presentation, with confirmation by detection of VGCC antibodies and a typical electrodiagnostic study

• Treatment of LEMS includes treatment of the underlying malignancy, if present. Additional therapies, including plasmapheresis and immunosuppression, are often required, as well

Case No. 6

• You are asked to evaluate a 62-year-old man for an abnormal chest CT.

• The patient reports that he was in his usual state of health until 2 months ago when he began to notice the onset of dyspnea when performing his usual activities. He reports a dry cough without hemoptysis.

• Review of systems is notable for a 20-lb (9-kg) unintentional weight loss and some blurry and double vision.

• For the past 2 weeks he has had several episodes of dizziness, a sensation of the “room spinning,” and an unsteady feeling when he walks.

• He has recently lost his balance on two occasions. A friend said he has been slurring his speech.

• He is a 100 pack-year smoker. On physical examination, the patient is in no distress.

• Lung examination is clear

• Neurologic examination reveals:

Diplopia

Ataxic gait

difficulty with finger-to-nose testing.

He has a mild tremor.

There is nystagmus.

There are no focal motor or sensory abnormalities.

• The remainder of the physical examination results are unremarkable.

His chest CT scan is shown.

A contrasted head CT scan is unremarkable.

Which of the following is true about the likely disease process?

A. Squamous cell carcinoma is the likely cell type.

B. A common pathogenic mechanism is production of anti-Hu antibodies.

C. Nerve conduction studies show augmentation of the action potential with repeated stimulation.

D. Th e syndrome is likely to resolve with treatment of the underlying cause.

• This patient with a history of tobacco use has a chest CT that reveals a right hilar lung mass, mediastinal adenopathy, and postobstructive pneumonia. This patient also has a clinical picture of a paraneoplastic neurologic syndrome; in this case, paraneoplastic cerebellar degeneration (PCD).

• The pathophysiology in PCD, and in most paraneoplastic neurologic syndromes, is an autoimmune process.

• In PCD, it is most commonly (44% of cases) due to tumor production of Hu antigen, which stimulates production of type 1 antineuronal nuclear antibodies (ANNA-1), also known as anti-Hu-antibodies, directed against like cellular proteins in the cerebellum (choice B is correct).

• The Hu antigen is found in neurons, but in the normal host, these antigens are protected from exposure to the circulation due to the blood-brain barrier.

• Small cell cancers express Hu antigen and stimulate self anti-Hu antibody formation. Up to 20% of patients with small cell lung cancer can have detectable levels of circulating anti-Hu antibody.

• The anti-Hu antibody reacts with 35- to 42-kD proteins present in nuclei and cytoplasm of virtually all neurons. Autopsy specimens may reveal lymphocytic opacities in the corresponding aff ected areas of the nervous system.

• Anti-Hu (ANNA-1) antibodies are also associated with other paraneoplastic neurologic syndromes associated with small-cell carcinoma of the lung, such as encephalomyelitis and paraneoplastic sensory neuropathy

• Patients with PCD usually have the subacute acute onset of nausea and vomiting, dizziness, vertigo, ataxia, blurry vision, double vision, dysarthria, and tremor. Physical examination reveals fi ndings seen in patients with cerebellar disease

• Up to 80% of patients with PCD have associated lung cancer, and this is nearly always small cell carcinoma, which was the diagnosis in this patient (choice A is incorrect).

• PCD can occur in up to 1% of patients with a small cell lung cancer. The remainder of cases is associated with other malignancies, including several types of sarcoma and prostate carcinoma and neuroblastomas, also via an anti-Hu mechanism.

• The neurologic findings may precede the lung cancer on plain chest radiograph, in some patients, by as long as 2 years. Unlike other paraneoplastic neurologic symptoms, such as Lambert-Eaton myasthenic syndrome (LEMS), cerebellar dysfunction typically does not respond to treatment of the tumor (choice D is incorrect).

• The nerve conduction findings described in choice C are characteristic of LEMS, not PCD (choice C is incorrect).

THANK YOU

Interesting Case presentations

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