Eosinophilic Lung Disease Cases by rtu13707

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									        Eosinophilic
        Lung
        Disease
        Cases

William Kelly, MD
    Eosinophil – our friend and foe
•   Two-lobed, polymorphonuclear leukocyte
•   12 to 15 um diameter
•   Created by IL-3, Il-5 and GM-CSF
•   Three granule types, largest made up of
    MBP (major basic protein), kills
    – Parasites, tumor cells, respiratory epithelium
• Hypodense and normodense varieties
 Eosinophil – our friend and foe
• Circulates <18 hours
• Chemotaxis
  – complement, histamine, ECF-A, PAF,
    leukotrienes, lymphokines, tumor factos, IL-5
• 100-400x more in tissues than in blood
Eosinophil – competing theories
• Host defense
• Modulator of inflammation
• Tissue destroyer
   Eosinophils: What’s Normal
• Blood EOS (#) = 50-250 per microliter
• Bronchoscopy (BAL) EOS
  –   Percentage (%) rather than absolute number
  –   Normal volunteers = < 1%
  –   ARDS usually none
  –   Increased (= >5%) five percent of the time
       • Mostly PCP, drug-related, idiopathic
                Classification
• Reeder and Goodrich, 1952
  – Pulmonary Infiltrates & Eosinophilia (PIE)
• Croften et al, 1952
  –   Simple pulmonary eosinophilia (Loffler’s)
  –   Prolonged pulmonary eosinophilia
  –   Tropical eosinophilia
  –   Pulmonary eosinophilia with asthma
  –   Polyarteritis nodosa (PAN)
             Classification
• Liebow and Carrington, 1969
  – Added Chronic eosinophilic pneumonia (CEP)
• McCarthy and Pepys, 1973
  – Either ABPA or “cryptogenic”
• Schatz et al, 1981
  – Back to “PIE”
            Classification
• Airway
• Lung parenchyma – known systemic illness
• Lung parenchyma – idiopathic
          Airway disorders
• Asthma
• Allergic Bronchopulmonary Aspergillosis
• Bronchocentric granulomatosis
            Lung parenchyma
               known systemic illness
• Infections
   – Bacterial, mycobacterial, fungal, parasites,
     AIDS (PCP)
• Interstitial lung disease
   – IPF/UIP
   – Sarcoid
   – SLE
           Lung parenchyma
            known systemic illness
•   Hypereosinophilic syndrome
•   Vasculitis (Churg-Strauss)
•   Hodgkin’s disease
•   Drug reactions
•   Lung cancer
         Lung parenchyma
                idiopathic
• Simple eosinophilic pneumonia
     (SEP, Loffler’s pneumonia)
• Chronic eosinophilic pneumonia (CEP)
• Acute eosinophilic pneumonia (AEP)
                  Case 1
• 23 y.o. male nonsmoker with over a year of
  nonproductive cough, wheezing, exertional
  dyspnea
• Personal and family history of allergies
• WBC 9400 with 6% eosinophils
• Refers himself to “U-SCAN” at the mall
     Case 1 – you should next…
A)   Start oral steroids
B)   Order thick and thin smears of blood
C)   Obtain PFTs with bronchodilator
D)   Start diethyl-carbamazine
     Case 1 – you should next…
A)   Start oral steroids
B)   Order thick and thin smears of blood
C)   Obtain PFTs with bronchodilator
D)   Start diethyl-carbamazine
                   Asthma
•   Peripheral eosinophilia often noted
•   “intrinsic” and “extrinsic”
•   Proportional to airflow obstruction
•   Eosinophil MBP results in airway shedding,
    may contribute to “creola bodies”
                  Case 2
• 44 y.o. female with hard-to-treat asthma,
  just weaned off oral steroids (again),
  presents with increased shortness of breath
• Treated with antibiotics over the years for
  pneumonias with radiographic clearing
• Coughs up “brown plugs” of mucous
• Sputum culture does not show fungus
            Case 2 (cont’d)
• Peripheral eosinophils and IgE are increased
• Allergist gets “wheal and flare” when they
  prick the skin with aspergillus antigens
• Radiologist says CXR shows “tram-tracking”
• Chest CT is obtained…
     Case 2 – you should next…
A)   Oral steroid “burst” for 5 days then Advair
B)   Oral steroids for months
C)   Itraconazole
D)   A and C
E)   B and C
     Case 2 – you should next…
A)   Oral steroid “burst” for 5 days then Advair
B)   Oral steroids for months
C)   Itraconazole
D)   A and C
E)   B and C
                   ABPA
• Asthmatics (6%), Cystic fibrosis (10%)
• Aspergillus fumigatus
  – Others= Candida albicans, Heliminthosporium,
    Curvularia lunata
• Proximal obstruction and bronchiectasis
                          ABPA
• Difficult asthma          • Aspergillus in sputum
• Blood eosinophilia        • Brown mucous plugs
• Elevated IgE              • Arthus (Type III) skin
   – Total and specific       reaction
• Aspergillus skin prick    • Radiographic clues
• Aspergillus precipitins      – “gloved-finger”
• Radiographic                 – “ring shadows”
  infiltrates                  – “tram-tracking”
  ABPA Staging
I      Acute
II     Remission
III    Exacerbation
IV     Steroid-dependent
V      Fibrotic
           ABPA treatment
• Oral corticosteroids
  – Hi-dose for 1-4 weeks
  – Change to QOD over next three months
  – Slow taper over following three months
• Itraconazole*
• Surveillance
  – CXR Q4 x 6, Q6 x 2, Q12 months
  – IgE Q1 month

                              *Salez F. Chest 1999; 116(6): 1665-8
                 Case 3
• 54 y.o. male non-smoker presents with an
  abnormal CXR done for a physical exam
• On review he does complain of cough,
  malaise and occasional fevers
• PFTs show mild obstruction which
  normalize after bronchodilator
             Case 3 (cont’d)
• Blood eosonophils are increased
• Serum RF and C-ANCA are negative
• Biopsy is performed
  – No malignancy is found
  – Special stains for AFB and fungus are negative
  – You review the slides with the pathologist…
      Case 3 – your diagnosis…
A)   Eosinophilic granuloma
B)   Smear negative, culture negative TB
C)   Bronchocentric granulomatosis
D)   Sarcoidosis
      Case 3 – your diagnosis…
A)   Eosinophilic granuloma
B)   Smear negative, culture negative TB
C)   Bronchocentric granulomatosis
D)   Sarcoidosis
  Bronchocentric granulomatosis
• Liebow 1973
• Clinical and radiographic pattern variable
• Surgical biopsy required
   – Inflammation, esosinophilia, Charcot-Leyden crystals
   – NO extrabronchial granulomas
• Diagnosis of exclusion
   – TB, fungal infection
   – Wegener’s or Rheumatoid lung disease
   – Aspiration
 Bronchocentric granulomatosis
• 1/3 of patients
  – Asthma, eosinophilia, fungal hyphae on bx,
    aspergillus in sputum
  – “tissue-destructive” ABPA
• 2/3 of patients
  – Neutrophils without asthma or fungi evident
• Corticosteroids can be effective
                   Case 4
• 32 y.o. male with night sweats, weight loss,
  fever, pruritis presents with a cold, pulseless
  foot
• CXR shows interstitial infiltrates and a
  small effusion
• CBC: WBC 12000, 56% eosinophils
   Case 4 – which is FALSE…
A) Cardiac involvement is the leading cause
   of mortality
B) 50% will have a good response to steroids
C) 40% have pulmonary involvement
D) Venous thrombosis is more common than
   arterial
   Case 4 – which is FALSE…
A) Cardiac involvement is the leading cause
   of mortality
B) 50% will have a good response to steroids
C) 40% have pulmonary involvement
D) Venous thrombosis is more common than
   arterial
     Idiopathic Hypereosinophilic
           Syndrome (HES)
•   “eosinophilic leukemia”
•   Rare, often fatal
•   EOS >1500/microliter for six months
•   7:1 male predominance
•   Usually age 30s (oldest reported = 70)
•   Blood EOS 30-70%
•   Bronchoscopy (BAL) EOS up to 73%
                  Case 5
• 38 y.o. male with 8 year history of asthma,
  chronic rhinitis, presents with fever,
  malaise, weight loss
• Hypertension, mononeuritis multiplex noted
• Labs notable for anemia; increased EOS
  (9400), IGE and ESR; RF weakly positive;
  microscopic hematuria, Scr 0.8; P-ANCA is
  positive
            Case 5 (cont’d)
• PFTs show obstruction
• Bronchoscopy reveals 32% eosinophils but
  cultures are negative for bacteria, AFB or
  fungus
• Thoracentesis reveals an exudate with
  increased eosinophils
• Biopsy is performed …
Necrotizing giant cell vasculitis, small vessel, with granulomas and eosinophils
    Case 5 – which is FALSE…
A) 50% die in three months without treatment
B) With treatment, mean survival has been reported
   as 9 years
C) 50% of patients may be ANCA positive (usually
   perinuclear – P-ANCA)
D) Unlike Wegener’s, pulmonary nodules do NOT
   tend to cavitate
E) Treatment requires corticosteroids along with
   cytotoxic agents
    Case 5 – which is FALSE…
A) 50% die in three months without treatment
B) With treatment, mean survival has been reported
   as 9 years
C) 50% of patients may be ANCA positive (usually
   perinuclear – P-ANCA)
D) Unlike Wegener’s, pulmonary nodules do NOT
   tend to cavitate
E) Treatment requires corticosteroids along with
   cytotoxic agents
     Churg-Strauss Syndrome
• Churg and Strauss - 1951
• “Allergic angiitis and granulomatosis”
• Three phases
  – Prodromal allergic rhinitis, asthma (years)
  – Dramatic peripheral eosinophilia (months, yrs)
     • Tissue infiltration like Loffler’s or CEP
  – Systemic vasculitis
      Churg-Strauss Syndrome
• Upper airway             • Gastrointestinal
  – Rhinitis, polyps,         – Abd pain (59%)
    sinusitis                 – Diarrhea (33%)
• Skin (70%)                  – Bleeding (18%)
  – Nodules, purpura,      • Cardiac
    urticaria                 – CHF (47%)
                              – Pericarditis (32%)
• Neurologic
                              – HTN (29%)
  – Mono.Multiplex (66%)
                           • Renal (49%)
  – CNS (27%)
      Churg-Strauss Syndrome
• Pathologic diagnosis
  – Renal histology non-specific,
     often no granulomas
  – TBBX probably inadequate
  – Open lung biopsy = “gold standard”
• Treatment = steroids x 1 yr, relapse rare
  – Pulse steroids or cytotoxic agents for failure
      Churg-Strauss Syndrome
             differential diagnosis
• Wegener’s                • CEP
  – Nodules cavitate         – No granulomas
  – C-ANCA positive          – Not “extra-pulmonary”
  – Histology different    • Idiopathic hyper-
• PAN                        eosinophilia syndrome
  – Medium-sized vessels     – No granulomas
  – No lung involvement      – No vasculitis
  – No eosinophilia
      Churg-Strauss Syndrome
• Associated with leukotriene antagonists
  – Zafirlukast, montelukast
• Incidence = 1:20,000
• Probably coincidental with steroid tapering
  of primary eosinophilic infiltrative disorder
                    Case 6
• 22 y.o. female referred to you for management of
  refractory asthma since returning from the Peace
  Corps in India consisting of nocturnal cough with
  wheezing and malaise
• Moist crackles and wheezes are auscultated, No
  adenopathy or hepatosplenomegaly
• PFTs show a mixed defect
• Serum Eosinophilia is 3400
     Case 6 – which is FALSE…
A)   Mosquitoes spread this disease
B)   Bronchoscopy (BAL) may show 50% EOS
C)   Blood sampling is not helpful
D)   Tissue biopsy is required
E)   Treatment is diethyl-carbamazine
     Case 6 – which is FALSE…
A)   Mosquitoes spread this disease
B)   Bronchoscopy (BAL) may show 50% eos
C)   Blood sampling is not helpful
D)   Tissue biopsy is required
E)   Treatment is diethyl-carbamazine
Wuchereria bancrofti, filarial worm
Tropical Pulmonary Eosinophilia
•   Ancylostoma sp.*           • Paragonimus westermani
•   Ascaris sp.*               • Schistosoma sp.
•   Brugia Malayi              • Strongyloides
•   Clonorchis sinesis           steratocolis*
•   Dicrofilaria immitis       • Toxocara sp.*
•   Echinococcus sp.           • Trichinella spiralis
•   Opisthorchiasis sp.        • Wuchereria bancrofti


                           * Can cause infection in United States
Tropical Pulmonary Eosinophilia
• Ex: W. bancrofti
  –   GI symptoms predominate
  –   Lymphadenopathy common in children
  –   Blood EOS > 3000
  –   Bronchoscopy (BAL) high EOS, IgE, IgG
  –   PFTS – usually restriction, 30% mixed
                 Case 7
• 32 y.o. from southern Texas, 31 weeks
  pregnant, with dry cough and mild SOB
• Dysuria two months ago, nitrofurantoin QD
• Tolerated same with last pregnancy
• PFTs show restriction
• Blood eosinophils are mildly elevated
• Abnormal CXR prompts shielded CT…
     Case 7 – you recommend…
A) Induce delivery or C-section
B) Stop all medications
C) Add oral steroids
D) Start empiric anti-parasite medication,
   using one with best FDA pregnancy class
E) Open lung biopsy
     Case 7 – you recommend…
A) Induce delivery or C-section
B) Stop all medications
C) Add oral steroids
D) Start empiric anti-parasite medication,
   using one with best FDA pregnancy class
E) Open lung biopsy
             Drug reactions
• Common cause of pulmonary infiltrates and
  blood or BAL eosinophilia
• Multiple medications:
  – Nitrofurantoin, Sulfasalazine, Phenytoin,
    Bleomycin, Tetracycline
• Treatment with dicontinuation of drug and
  possibly corticosteroids
       Drug reactions (Ex. 1)
• Eosinophilic-myalgia syndrome (late 1980s)
  – Contaminated L-tryptophan
  – 50% of ingestions had myalgias, eosinophilia
  – 50% of these had pulmonary involvement =
    cough, dyspnea, cxr infiltrates, effusions,
    muscle weakness
• IgE, CK normal, PFTs with restriction
• Histology with vasculitis, eosinophils
          Drug reactions (Ex. 2)
• “Toxic oil syndrome” (1981-1982)
  –   20,000 cases – 300 deaths in Spain
  –   “olive oil” – rapeseed oil with oleoanilide
  –   Fever, respiratory/GI distress, rash, adenopathy
  –   CXR – interstitial/alveolar infiltrates, Kerley B’s
  –   Steroids helpful acutely, others progressed to
      pulmonary fibrosis of hypertension
                  Case 8
• 54 y.o. female with history of atopy, seven
  months of slowly progressive cough,
  dyspnea, fever, malaise and weight loss
• PFTS consistent with asthma
• Blood shows increased IgE and eos
• CXR and CT are obtained…
Diffuse, peripherally-based infiltrates (outer 2/3rds of lung)
       “photographic negative of pulmonary edema”
Interstitial and alveolar degranulated eosinophils, eosinophilic microabscesses,
                  Low-grade vasculitis, and interstitial fibrosis
     Case 8 – you can tell her…
A)   Most cases resolve spontaneously
B)   It is unusual for women to get this
C)   It is unusual to get this at her age
D)   Her asthma was likely diagnosed within
     the past few years
     Case 8 – you can tell her…
A)   Most cases resolve spontaneously
B)   It is unusual for women to get this
C)   It is unusual to get this at her age
D)   Her asthma was likely diagnosed within
     the past few years
Chronic Eosinophilic Pneumonia
•   Christoforodis and Molnar 1960 (n=2)
•   Carrington
•   Peak incidence age - 50s
•   Insidious onset – 7.7 months sxs pre dx
    – Cough (90%), fever (87%), SOB (57%), weight loss
      (57%), asthma (50% - less than 5 yr duration)
• Peripheral EOS (>6%) = 88%
• BAL EOS usually >25% and may be 44%
                   CEP
• IgE elevated (66%)
• ESR, RF, immune complexes,
  thrombocytosis may be found
• Hypoxemia, PFTs with mild restriction
• Peripheral CXR infiltrates (63%)
  – “photonegative of CHF” only 25%
                     CEP
• Unlike simple pulmonary eosinophilia
  (SPE, “Loffler’s pneumonia”) spontaneous
  resolution is rare (<10%)
• Steroids 40 mg/day – dramatic resolution
  – Symptoms within 1-2 days
  – CXR infiltrates within 10 days
• Relapse common in first 6 months
                   Case 9
• 39 y.o. male “crashes” in through the ER
  with Sao2 70s on room air and is intubated
• Per his wife he was in excellent health until
  the onset of the “flu” with fever to 104 and
  myalgias 3 days ago
• CXR shows only a mild interstitial
  infiltrate– in fact a CTPA gram is done to
  exclude PE- but infiltrates progress…
              Case 9 (cont’d)
•   CBC and blood eosinophils are normal
•   Sputum/urine/blood cultures/HIV negative
•   Thoracentesis- elevated pH and eosinophils
•   Bronchoscopy (BAL) is done to exclude
    infection- 42% eosinophilia is noted
 Case 9 – you know this differs
     from CEP because…
A)   Steroids are not effective
B)   Relapse is uncommon
C)   Bronchoscopy (BAL) shows EOS
D)   Peripheral blood EOS can be normal
E)   B and D
 Case 9 – you know this differs
     from CEP because…
A)   Steroids are not effective
B)   Relapse is uncommon
C)   Bronchoscopy (BAL) shows EOS
D)   Peripheral blood EOS can be normal
E)   B and D
 Acute Eosinophilic Pneumonia
• First described 1989
• Unknown cause
  – ? Inhaled antigen hypersensitivity
  – Similar to some cases in CML patients
  – Similar to some postoperative events
• Unlike other ARDS (BAL = neutrophils)
• Must exclude infection (esp. fungus)
    Acute Eosinophilic Pneumonia
•   Acute febrile illness < 5 days duration
•   Hypoxemic respiratory failure
•   Diffuse alveolar or mixed CXR infiltrates
•   BAL EOS > 25%
•   Absence of parasitic, fungal or other infxn
•   Prompt/complete response to steroids
•   Failure to relapse after steroids
      Miscellaneous thoughts (1)
• Pleural fluid eosinophilia (PFE)
  –   Pneumothorax = most common
  –   Hemothorax (may take 1-2 weeks)
  –   Benign asbestos effusion
  –   Pulmonary embolism
  –   Parasites/ Fungus/ TB (rare)
  –   Drug induced
  –   Lymphoma/ Carcinoma (5-8%)
      Miscellaneous thoughts (2)
• Eosinophilic Granuloma (EG)
  –   “Langerhans cell granulomatosis”
  –   2-5 cases/million, whites, smokers (90%)
  –   Pneumothorax (6-20%)
  –   “stellate” (star-shaped) fibrosis
       • 50% atypical lymphocytes, +OKT6, S100
  – NO eosinophilia
  – Treatment = smoking cessation, steroids
          Airway disorders
• Asthma
• Allergic Bronchopulmonary Aspergillosis
• Bronchocentric granulomatosis
            Lung parenchyma
               known systemic illness
• Infections
   – Bacterial, mycobacterial, fungal, parasites,
     AIDS (PCP)
• Interstitial lung disease
   – IPF/UIP
   – Sarcoid
   – SLE
           Lung parenchyma
            known systemic illness
•   Hypereosinophilic syndrome
•   Vasculitis (Churg-Strauss)
•   Hodgkin’s disease
•   Drug reactions
•   Lung cancer
         Lung parenchyma
                idiopathic
• Simple eosinophilic pneumonia
     (SEP, Loffler’s pneumonia)
• Chronic eosinophilic pneumonia (CEP)
• Acute eosinophilic pneumonia (AEP)
Questions ?

								
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