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 PneumoniaAtypical Pathology

• Diffuse alveolar damage (DAD)

• Granulomas

• Multifocal giant cells

• Desquamative interstitial pneumonitis-like

• Interstitial fibrosis

PCP PneumoniaAtypical Pathology

• PCP induced

• Treated PCP

• Coincident injury- chemo/radiation therapy- infection- oxygen toxicity

PCP PneumoniaDiagnosis

• 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 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

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