a case of iris edward l. goodman, md october 8, 2003
TRANSCRIPT
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A Case of IRIS
Edward L. Goodman, MD
October 8, 2003
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First Admission
• 36 year old gay man with two weeks fatigue, dyspnea, mild cough and fever.
• He was first seen in ER 7/3/03 four days prior to admission where a CXR was interpreted as normal
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Film in ER 7/03/03
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First admission
• He returned 7/7/03 with worsening symptoms and was admitted
• Therapy for CAP was started with Levaquin and TMP/SMX plus prednisone.
• ID consult 7/10/03
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Film on Admission 7/7/03
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First Admission
• Exam revealed harsh breath sounds with possible consolidation in LLL.
• Lab revealed mildly elevated LDH and transaminases.
• HIV EIA was positive• Bronchoscopy was performed: PCP was
identified• CD 48, viral load 220,000
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Course in Hospital
• 7/16/03 a florid rash developed– Bactrim was stopped– Dapsone and Trimethoprim were substituted
• Hypoxemia persisted. CXR slowly improved
• Discharged 7/21 to complete final week of anti PCP therapy with Dap/TMP and tapering prednisone
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Film prior to discharge 7/16/03
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First Office Visit 7/28/2003
• Feeling well
• Completed “induction therapy” for PCP
• Exam normal except for resolving rash
• PCP prophylaxis: Dapsone daily
• MAI prophylaxis: Azithromycin weekly
• HAART : once daily Tenofovir, Lamivudine and Efavirenz
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Second Admission 8/04/03
• Within four days of starting HAART, he had headache, followed by chills, fever and orthostatic dizziness
• No respiratory or GI symptoms
• On exam: BP 84/56, HR 128 rising to 156 on sitting
• Otherwise negative exam
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Film on second admission
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Differential Diagnosis
• Relapse of PCP? • New opportunistic infection?
– CMV?– MAI?– Histo?
• Drug Reaction?• Adrenal Insufficiency?• Immune Reconstitution Inflammatory
Syndrome?
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Hospital Evaluation
• Fluid resuscitation successful
• Normal ACTH stimulation
• Negative marrow biopsy
• Negative gallium scan
• Tolerated rechallenge with HAART
• Bronchoscopy 8/5/03
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Second Bronchoscopy
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Pneumocystis Carini (PCP)Pneumocystis Pneumonia
Usual/typical Pathology
Untreated• Changes confined to alveoli/terminal airways• Alveoli filled with “foamy” pink material
- proliferating organisms (trophozoites, cysts)- cellular debris- +/- fibrin, red cells
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Pneumocystis Carini (PCP)Pneumocystis Pneumonia
Usual/typical Pathology
Untreated• Inconsistent findings
- pneumocyte proliferation
- mild interstitial edema
- interstitial lymphocyte/plasma cell infiltrate
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PCP PneumoniaAtypical Pathology
• Diffuse alveolar damage (DAD)
• Granulomas
• Multifocal giant cells
• Desquamative interstitial pneumonitis-like
• Interstitial fibrosis
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PCP PneumoniaAtypical Pathology
• PCP induced
• Treated PCP
• Coincident injury- chemo/radiation therapy- infection- oxygen toxicity
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PCP PneumoniaDiagnosis
• Optimal specimens
-bronchial lavage
-induced bronchial secretions
-biopsy
* NOT sputum• Special stains required to detect cyst
-silver stains (i.e. GMS)
-immunostain
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How do we interpret the bronchoscopy?
• Relapse of PCP?
• Expected response after successful therapy for PCP?
• What about the granuloma?
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Natural History of Treated PCPO’Donnell et al, Chest 114; Nov 1998, 1264
• Induced sputum at 2,3,4,6 weeks and year
• At two weeks: 88% +
• Three weeks: 76%+
• Four weeks: 29%+
• Six weeks: 24%+
• Persisting cysts did not predict relapse.
• THUS, THIS IS NOT A FAILURE OF RX
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Immune Reconstitution Inflammatory Syndrome (IRIS)
Shelburne et al. Medicine 2002; 81:213
• Define: a paradoxical deterioration in clinical status attributable to the recovery of the immune system during HAART
• Pathophysiology– Rapid fall in viral load– Increase in immune effector cells– Functional T cell immunity return
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IRIS: clinical features
• Inflammatory process at site of previous infection, known or unknown
• Lymphadenitis
• Cutaneous
• Vitreitis
• Pneumonitis
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IRIS: pathogens
• MAI, Mycobacterium tuberculosis
• Cryptococcus neoformans
• CMV, HSV, VZV
• PCP
• Hepatitis C and B
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IRIS: non infectious
• Kaposi’s Sarcoma (HHV 8)
• Castleman’s Disease (HHV 8)
• Sarcoid
• Graves Disease
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Features of IRIS PCP
• Five cases reported in detail
• Pathology– Few organisms– Granuloma around the cysts
• Immune reconstitution demonstrated in all
• Outcomes were good
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Treatment of IRIS
• None: self limited
• Adding steroids
• Stopping HAART
• Retreat the infection?
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Case Under Discussion: response to HAART
CD 4 Viral Load
7/9/03 48 220,000
7/28/03 44 661,000
8/13/03 120 921
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Management
• Resume steroids
• Start new therapy for PCP– Clindamycin and Primaquine for 21 days
• Patient doing very well 8/21/03
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