Clinical Pathology Conference 42 yo man with recurrent pneumonia

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Clinical Pathology Conference42 yo man with
recurrent pneumonia

• J. R. Hartig, MD
• November 28, 2006

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CPC Goals

• Its all about the discussion
• (If Im wrong!)
• Its all about being correct
• (If the discussion is bad)
• Its all about having the diagnosis in the
  differential
• (My DDx will include all of Harrisons)
• Its all about getting even with the CMRs
• (If this is something totally ridiculous)

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CPC Goals

• Discuss the approach that I used in this case
• Discuss some uncommon pulmonary conditions
• Make an educated guess after narrowing the
  differential

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Start from the start

• 42 yo white male with blood-tinged productive
  cough

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Differential Diagnosis

• Common things are common
• Bronchitis
• Viral URI
• Rhinosinusitis (Allergies)
• Pneumonia
• GERD

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Start from the start

• 42 yo white male with blood-tinged productive
  cough
• Recurrent pneumonias
• Several CAP during the past year

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Missouri State Motto
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Recurrent pneumonias

• Pulmonary
• Local
• Diffuse
• Immune
• Gastrointestinal Problems
• Neurological Conditions

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Recurrent pneumonias

• Pulmonary
• Local
• Anatomic abnormality
• Bronchial compression
• LAD
• Neoplasm
• Vascular anomaly
• Foreign body
• Bronchiectasis
• Bronchomalacia / stenosis
• Tracheo-esopahgeal or bronchial fistulas

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Recurrent pneumonias

• Pulmonary
• Diffuse recurrence
• Underlying pulmonary process
• Cystic fibrosis
• Immotile cilia syndromes
• Neurological dysfunctions
• Dysphagia
• Seizures
• Etoh/drugs

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Cystic Fibrosis

• Autosomal recessive disease
• 12000 to 3000
• CFTR protein abnormality
• Multi-organ disease
• mild mutations
• Productive cough
• No hint of disease earlier in life

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Recurrent pneumonias

• Pulmonary
• Diffuse recurrence
• Underlying pulmonary process
• Cystic fibrosis
• Immotile cilia syndromes
• Neurological dysfunctions
• Dysphagia
• Seizures
• Etoh/drugs

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Recurrent pneumonias

• Immune
• Quantitative or Qualitative granulocytic
• Chronic Granulomatous Disease
• Multiple Myeloma
• Common Variable Immune Deficiency
• Chronic lymphocytic leukemia
• HIV

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Recurrent pneumonias

• Gastrointestinal Problems
• Aspiration (primary or secondary)
• GERD
• Zenkers diverticula
• Achalasia
• Neurologic Conditions

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More History

• Chronic non-productive cough
• Progressive dyspnea over the coarse of a year
• No fevers, chills, night sweats
• Weight loss 20lbs
• Antibiotics give short term relief
• Steroids do not seem to help

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Some of the teasers

• Works as a hairstylist
• MSM
• 27 pk/yr tobacco use
• No drugs, No Etoh, No TB risks (? homeless)
• ROS no other signs of bleeding problems

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Exam

• Marked hypoxia on room air (80)
• Chronically hypoxic (clubbing)
• Pulmonary exam
• Mild tachypnea
• Bibasilar rales

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Clubbing
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Labs

• Marked A-a gradient
• Elevated bicarb
• Hct 49
• LDH 603
• WBC 19K
• But not really lymphopenic
• Numerous other negative labs

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Additional Testing

• Normal Transthoracic echocardiogram
• CXR and CT
• Patchy ground glass opacities diffusely with a
  hilar predominance. No lymphadenopathy.

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Lucy!!! You got some splaining to do

• Young W? chronic non-productive cough
• Recurrent Pneumonias
• Severe Dyspnea
• Weight Loss
• Antibiotics some help. Prednisone none.
• Chronic hypoxia
• Hilar predominant radiographic changes

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Where to now?

• Infections
• Vascular
• Malignancy
• Pulmonary
• Interstitial Lung Diseases (Diffuse Parenchymal
  Lung Diseases)
• Diffuse Alveolar Hemorrhage Syndromes

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Infections (Pneumonia)

• Previously healthy host
• Diagnosed with pneumonia
• Elevated WBC (left shift)
• Gets better with antibiotics

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Infections (Pneumonia)

• Viral
• Bacterial
• Nocardia
• Mycobacterial
• M. tuberculosis
• Non-tuberculous Mycobacterial infections
• Fungal
• Histoplasmosis
• Coccidioidomycosis
• Other/Parasitic
• Pneumocystis jiroveci

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Nocardia

• Aerobic gram bacteria
• 16 species causing human disease
• Immunocompromised hosts
• Pulmonary manifestations
• Non-improving pneumonia
• TB mimic on x-ray
• Diagnosis
• Treatment
• Sulfonamides

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Tuberculosis

• Common in Alabama
• Always in the differential on a CPC
• No risk factors
• ? Homeless
• PPD (-)
• No hilar adenopathy
• Too many other things are possible

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Nontuberculous Mycobacteria

• M. avium and M. intracellulare (MAC)
• Older individuals with COPD
• Bronchiectasis (cystic fibrosis)
• Clinically similar to TB
• M. kansasii
• Similar to TB cavitation common
• Diagnosis and Treatment

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Histoplasmosis

• First described in 1906
• Common among Ohio and Mississippi River valleys
• Most individuals have few symptoms
• Pulmonary disease
• Bronchopneumonia
• Hilar LAD
• Diagnosis
• Urine 75 pulmonary disease
• Serology 90 acute pulmonary disease

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Histoplasmosis
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Pneumocystis carinii (P. jiroveci) pneumonia

• HIV (-) individuals
• Malignancy
• Hematologic solid
• Steroids
• Mean dose 30mg/d and 12 weeks therapy
• Often seen after therapy is stopped
• Diagnosis and Therapy

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Differential Diagnosis

• Congenital
• Cystic fibrosis (better not be)
• Infections
• PCP

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Where to now?

• Infections
• Vascular
• Malignancy
• Pulmonary
• Interstitial Lung Diseases (Diffuse Parenchymal
  Lung Diseases)
• Diffuse Alveolar Hemorrhage Syndromes

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Vascular/Vasculitis

• No obvious bleeding abnormality
• No specific evidence to indicate PTE or pulmonary
  veno-occlusive disease
• Wegeners granulomatosis
• Churg-Strauss syndrome
• Microscopic polyangiitis

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Wegeners granulomatosis

• Lungs and kidneys
• 25 of cases have only respiratory involvement
• Primarily have sinus involvement
• 90 antineutrophil cytoplasmic antibodies
• X-ray usually demonstrate nodules or LAD

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Wegeners granulomatosis
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Vasculitis

• Churg-Strauss syndrome
• Usually starts with asthma (8-10 years)
• Skin and nasal disease is common
• No specific labs eosinophilia, anca, others
• Microscopic polyangiitis
• Also has predominance of anca ()

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Differential Diagnosis

• Congenital
• Cystic fibrosis (better not be)
• Infections
• PCP
• Vasculitis
• ?

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Malignancy

• Lymphoma
• Bronchogenic carcinoma

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Differential Diagnosis

• Congenital
• Cystic fibrosis (better not be)
• Infections
• PCP
• Vasculitis/Malignancy
• ?

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Where to now?

• Infections
• Vascular
• Malignancy
• Pulmonary
• Interstitial Lung Diseases (Diffuse Parenchymal
  Lung Diseases)
• Diffuse Alveolar Hemorrhage Syndromes
• Other

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Interstitial Lung Disease Diffuse Parenchymal
Lung Disease

• Idiopathic Pulmonary Fibrosis (UIP)
• Other Idiopathic Interstitial Pneumonia
• Desquamative IP
• Acute IP
• Nonspecific IP
• Respiratory bronchiolitis assoc -ILD
• Cryptogenic Organizing Pneumonia
• Known causes (Hypersensitivity, CTD)

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Idiopathic Pulmonary Fibrosis

• Present in 5th or 6th decade of life
• Progressive dyspnea and non-prod cough
• ?? of 21
• Elevated LDH
• Follows relentless coarse difficult to treat
• Radiographically
• Peripheral and bibasilar reticulonodular
  opacities with traction bronchiectasis

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Idiopathic Pulmonary Fibrosis
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Desquamative IP
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Desquamative IP
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Respiratory bronchiolitis assoc -ILD
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Cryptogenic Organizing Pneumonia

• Clinically presents in the 5th to 6th decade
• Idiopathic form of BOOP
• Persistent non-productive cough
• Dyspnea
• Weight loss (10lbs average)
• Steroids help antibiotics generally do not

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Cryptogenic Organizing Pneumonia
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Hypersensitivity Pneumonitis

• Certainly could explain the radiographic findings
• Lack of specific agent (work exposure?)
• Chronic recurrent exposure
• Generally improves with corticosteroids

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Differential Diagnosis

• Congenital
• Cystic fibrosis (better not be)
• Infections
• PCP
• Vasculitis/Malignancy ?
• DPLDs
• Idiopathic Pulmonary Fibrosis
• Desquamative Interstitial Pneumonia

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Diffuse Alveolar Hemorrhage Syndromes

• Anti-GBM disease (Goodpastures)
• Idiopathic Pulmonary Hemosiderosis
• Hct is normal
• UA is normal

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Other

• Sarcoidosis
• Pulmonary Langerhans cell histiocytosis
• Pulmonary Alveolar Proteinosis

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Sarcoidosis

• Worldwide disease young adults
• Multisystem granulomatous disorder
• Characteristics
• Bilateral hilar adenopathy
• Pulmonary infiltrates
• Skin/eye abnormalities
• Treatment
• Generally involves steroids

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Pulmonary Langerhans cell Histiocytosis

• Younger smoking patients (20-30s)
• Caucasian
• Fever, weight loss, other symptoms
• Spontaneous pneumothorax
• Variable clinical coarse
• PFTs
• Reticular nodular infiltrates and honeycombing in
  upper lung zones

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Pulmonary Alveolar Proteinosis

• Accumulation of lipoproteinaceous in the distal
  airways
• No inflammation or architectural changes
• Alveolar macrophage dysfunction
• Impaired response to GM-CSF
• Increased risk of superinfections

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Pulmonary Alveolar Proteinosis

• Clinical Presentation
• Typically age 30-50
• Male to female 21
• Insidious onset
• Symptoms
• Progressive dyspnea on exertion
• Fatigue
• Weight loss
• Non-productive cough is common

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Pulmonary Alveolar Proteinosis

• Radiographic findings
• Bat-wing distribution
• Air bronchograms are rare
• Crazy paving

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Pulmonary Alveolar Proteinosis
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Pulmonary Alveolar Proteinosis

• Laboratory findings
• Polycythemia
• Increased LDH
• Hypergammaglobulinemia
• Marked hypoxia
• serum anti-GM-CSF titer elevation

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Pulmonary Alveolar Proteinosis

• Diagnosis
• Bronchoalveolar lavage or biopsy
• Treatment
• Whole lung lavage
• Prognosis
• ??

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Differential Diagnosis

• Congenital
• Cystic fibrosis (better not be)
• Infections
• PCP
• Vasculitis/Malignancy ?
• DPLDs
• Idiopathic Pulmonary Fibrosis
• Desquamative Interstitial Pneumonia
• DAH
• Sarcoid
• PAP

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Final Answer

• Procedure
• Bronchoscopy with BAL and TBBx
• Diagnosis
• Pulmonary Alveolar Proteinosis