5. • 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.
6. • Results of a physical examination are normal
other than multiple skin colored papules over
the central face and nose.
7. • Results of a chest radiograph demonstrated
right apical pleural thickening but were
otherwise normal. The C-T scan
8. The most likely diagnosis of this
condition is:
A. Langerhans cell histiocytosis.
B. Lymphangioleiomyomatosis (LAM).
C. Sarcoidosis.
D. Birt-Hogg-Dubé syndrome (BHDS).
9. • The CT scan reveals several cysts in the left
lung and scarring at the right apex related to
the previous surgery.
10. • 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).
11. • 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).
12. • 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).
13. • 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.
14. • 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.
15. • 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
30. 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
36. LIP = Lymphocytic Interstitial
Pneumonia
Rarely idiopathic
In association with:
Sjögren’s syndrome
Immune deficiency syndromes, AIDS
Primary biliary cirrhosis
Multicentric Castlemean’s disease
37. 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
41. 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
42. • 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.
48. 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
49. 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
50. 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
57. 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
63. • 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.
64. • 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.
65. • 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.
66. • 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.
69. • 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.
70. 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
71. • 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).
72. • 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.
73. • 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.
74. • 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.
75. • 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
76. • 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
77.
78. Antibiotic Strategy in CAP
Gamal Rabie Agmy, MD,FCCP
Professor of Chest Diseases, Assiut university
79. 79
Pneumonias – Classification
• Community AcquiredCAP
• Health Care AssociatedHCAP
• Hospital AcquiredHAP
• ICU AcquiredICUAP
• VentilatorAcquiredVAP
Nosocomial Pneumonias
80. *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
81. 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
82. 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
84. 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
85. 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
86. 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.
The Bacteriological Diagnosis of CAP
87. Blood Culture:
Recommended for all patients with
moderate and high severity CAP,
preferably before antibiotic therapy is
commenced.
Examination of sputum for
Mycobacterium TB
The Bacteriological Diagnosis of CAP
90. 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. 91
Classification of Severity - PORT
Predictors
Absent
Class
I
70
Class
II
71 – 90
Class
III
91 - 130
Class
IV
> 130
Class
V
92. 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. 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
94.
95. 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
97. 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. 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
118. Pneumonia
Posterior intercostal scan shows a hypoechoic
consolidated area that contains multiple
echogenic lines that represent an air
bronchogram.
119. Post-stenotic pneumonia
Posterior intercostal scan shows a hypoechoic
consolidated area that contains anechoic,
branched tubular structures in the bronchial tree
(fluid bronchogram).
120. 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.
123. 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
124. 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.
125. EFFECTS OF
COMBINATIONS OF DRUGS
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.
126. EFFECTS OF
COMBINATIONS OF DRUGS
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.
127. 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
128. 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
130. 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
131. Empirical Treatment is the
recommended strategy in
treatment of CAP and
shouldn’t be delayed.
132. 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
133. 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:
134. 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
Recommendations for the Empirical Treatment:
135. In-patient treatment: ICU:
No Monotherapy.
IV Respiratory fluoroquinolone + 3rd or
4th generation cephalosporin
OR IV Imipenem + IV New Macrolide
Recommendations for the Empirical Treatment:
136. In-patient treatment: ICU:
No Monotherapy.
IV Respiratory fluoroquinolone + 3rd or
4th generation cephalosporin
OR IV Imipenem + IV New Macrolide
Recommendations for the Empirical Treatment:
137. 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)
Recommendations for the Empirical Treatment:
138. 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. 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. 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. 141
Management of Poor Responders
Consider non-infectious illnesses
Consider less common pathogens
Consider serologic testing
Broaden antibiotic therapy
Consider bronchoscopy
142. 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. 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
146. • 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.
147. • 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.
148. • 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
150. A histologic specimen obtained via
bronchoscopy with transbronchial biopsy from
the right upper lobe is shown.
151. 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.
152. • 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%.
153. • 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.
154. • 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.
155. • 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.
156. • 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.
157. • 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.
158. • 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
159. • 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.
160. • 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)
161. 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.
162. MALIGNANT LYMPHOPROLIFRATIVE
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
163. MALIGNANT LYMPHOPROLIFRATIVE
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
164. MALIGNANT LYMPHOPROLIFRATIVE
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.
166. MALIGNANT LYMPHOPROLIFRATIVE
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
167. MALIGNANT LYMPHOPROLIFRATIVE
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
169. MALIGNANT LYMPHOPROLIFRATIVE
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
170. MALIGNANT LYMPHOPROLIFRATIVE
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
171. MALIGNANT LYMPHOPROLIFRATIVE
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
172. MALIGNANT LYMPHOPROLIFRATIVE
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.
175. • 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.
176. • 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.
177. • Laboratory findings:
WBC count of 14,300/L (14.3 × 109/L) with a
left shift
Hematocrit concentration of 42% (0.42).
181. • 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
182. 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.
183. • 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).
184. • 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.
185. • 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
186. • 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.
187. • 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).
188. • 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.
204. 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
211. • 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.”
212. • 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
213. • 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
214. • 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
217. 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
218. • 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).
219. • 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)
220. • 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
221. • 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
222. • 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.
223. • 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
224. • Treatment of LEMS includes treatment of the
underlying malignancy, if present. Additional
therapies, including plasmapheresis and
immunosuppression, are often required, as
well
226. • 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.
227. • 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
228. • 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.
231. 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.
232. • 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).
233. • 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.
234. • 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
235. • 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
236. • 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.
237. • 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).