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A Case of IRIS

A Case of IRIS. Edward L. Goodman, MD October 8, 2003. 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. Film in ER 7/03/03. First admission.

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A Case of IRIS

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  1. A Case of IRIS Edward L. Goodman, MD October 8, 2003

  2. 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

  3. Film in ER 7/03/03

  4. 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

  5. Film on Admission 7/7/03

  6. 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

  7. 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

  8. Film prior to discharge 7/16/03

  9. 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

  10. 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

  11. Film on second admission

  12. Differential Diagnosis • Relapse of PCP? • New opportunistic infection? • CMV? • MAI? • Histo? • Drug Reaction? • Adrenal Insufficiency? • Immune Reconstitution Inflammatory Syndrome?

  13. Hospital Evaluation • Fluid resuscitation successful • Normal ACTH stimulation • Negative marrow biopsy • Negative gallium scan • Tolerated rechallenge with HAART • Bronchoscopy 8/5/03

  14. Second Bronchoscopy

  15. 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

  16. Pneumocystis Carini (PCP)Pneumocystis PneumoniaUsual/typical Pathology Untreated • Inconsistent findings - pneumocyte proliferation - mild interstitial edema - interstitial lymphocyte/plasma cell infiltrate

  17. PCP Pneumonia • Atypical Pathology • Diffuse alveolar damage (DAD) • Granulomas • Multifocal giant cells • Desquamative interstitial pneumonitis-like • Interstitial fibrosis

  18. PCP PneumoniaAtypical Pathology • PCP induced • Treated PCP • Coincident injury • - chemo/radiation therapy • - infection • - oxygen toxicity

  19. PCP PneumoniaDiagnosis • Optimal specimens -bronchial lavage -induced bronchial secretions -biopsy * NOT sputum • Special stains required to detect cyst -silver stains (i.e. GMS) -immunostain

  20. How do we interpret the bronchoscopy? • Relapse of PCP? • Expected response after successful therapy for PCP? • What about the granuloma?

  21. 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

  22. 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

  23. IRIS: clinical features • Inflammatory process at site of previous infection, known or unknown • Lymphadenitis • Cutaneous • Vitreitis • Pneumonitis

  24. IRIS: pathogens • MAI, Mycobacterium tuberculosis • Cryptococcus neoformans • CMV, HSV, VZV • PCP • Hepatitis C and B

  25. IRIS: non infectious • Kaposi’s Sarcoma (HHV 8) • Castleman’s Disease (HHV 8) • Sarcoid • Graves Disease

  26. Features of IRIS PCP • Five cases reported in detail • Pathology • Few organisms • Granuloma around the cysts • Immune reconstitution demonstrated in all • Outcomes were good

  27. Treatment of IRIS • None: self limited • Adding steroids • Stopping HAART • Retreat the infection?

  28. Case Under Discussion: response to HAART

  29. 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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