Transcript ppt
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 • 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 Film on Admission 7/7/03 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 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 Film prior to discharge 7/16/03 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 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 Film on second admission Differential Diagnosis • Relapse of PCP? • New opportunistic infection? – CMV? – MAI? – Histo? • Drug Reaction? • Adrenal Insufficiency? • Immune Reconstitution Inflammatory Syndrome? Hospital Evaluation • • • • • • Fluid resuscitation successful Normal ACTH stimulation Negative marrow biopsy Negative gallium scan Tolerated rechallenge with HAART Bronchoscopy 8/5/03 Second Bronchoscopy 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 Pneumocystis Carini (PCP) Pneumocystis Pneumonia Usual/typical Pathology Untreated • Inconsistent findings - pneumocyte proliferation - mild interstitial edema - interstitial lymphocyte/plasma cell infiltrate PCP Pneumonia Atypical Pathology • Diffuse alveolar damage (DAD) • Granulomas • Multifocal giant cells • Desquamative interstitial pneumonitis-like • Interstitial fibrosis PCP Pneumonia Atypical Pathology • PCP induced • Treated PCP • Coincident injury - chemo/radiation therapy - infection - oxygen toxicity PCP Pneumonia Diagnosis • Optimal specimens -bronchial lavage -induced bronchial secretions -biopsy * NOT sputum • Special stains required to detect cyst -silver stains (i.e. GMS) -immunostain How do we interpret the bronchoscopy? • Relapse of PCP? • Expected response after successful therapy for PCP? • What about the granuloma? Natural History of Treated PCP O’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 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 IRIS: clinical features • Inflammatory process at site of previous infection, known or unknown • Lymphadenitis • Cutaneous • Vitreitis • Pneumonitis IRIS: pathogens • • • • • MAI, Mycobacterium tuberculosis Cryptococcus neoformans CMV, HSV, VZV PCP Hepatitis C and B IRIS: non infectious • • • • Kaposi’s Sarcoma (HHV 8) Castleman’s Disease (HHV 8) Sarcoid Graves Disease Features of IRIS PCP • Five cases reported in detail • Pathology – Few organisms – Granuloma around the cysts • Immune reconstitution demonstrated in all • Outcomes were good Treatment of IRIS • • • • None: self limited Adding steroids Stopping HAART Retreat the infection? 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 Management • Resume steroids • Start new therapy for PCP – Clindamycin and Primaquine for 21 days • Patient doing very well 8/21/03