IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME

Presented by:HAMISI MKINDI,MD4

SFUCHAS

INTRODUCTION

Is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.

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Risk factors

• Risk factors at base line:– Lower CD4 count prior to start of ART

– Initiating ART in close proximity to starting therapy for an OI

• Response to therapy & the development of IRIS:– Rapid fall in HIV RNA level during the first 3

months of therapy

PATHOGENESIS

There are 2 presentations• Paradoxical IRIS: worsening of symptoms of a

known disease during ART• Unmasking IRIS: present of an occult

opportunistic infection , in which disease that was not clinically apparent prior to ART, manifests during ART

DiagnosisMajor criteria

• Atypical presentation of ‘opportunistic infections or tumours’ in patients responding to antiretroviral therapy

• Decrease in plasma HIV RNA level by 1log10 copies/mL

DiagnosisMinor criteria

• Increased blood CD4 T-cell count after HAART• Increase in an immune response specific to

the relevant pathogen.• Spontaneous resolution of disease without

specific antimicrobial therapy or tumour chemotherapy with continuation of anti-retroviral therapy anti-retroviral therapy

Paradoxical iris

Unmasking IRIS

DISEASE SPECIFIC IRIS

Disease Specific IRISTB IRIS• The paradoxical reaction that follows the

commencement of anti-TB therapy for pulmonary TB is usually characterized by fever, malaise, weight loss, and worsening respiratory symptoms

• Patients with extrapulmonary TB infection may develop worsening lymphadenitis, new pleural effusions, or expansion of preexisting intracranial tuberculomas, as well as a variety of other neurological symptoms after anti-tuberculosis therapy is begun

• Most occur within 2 months of ART initiation

Disease Specific IRISMAC IRIS• In the majority of cases, IRIS due to MAC manifests

as fever and painful lymphadenitis that occurs one to eight weeks after HAART is commenced

• Individual case reports or small case series also exist describing IRIS syndrome manifesting as necrotic subcutaneous nodules, osteomyelitis, bursitis, granulomatous hepatitis, paravertebral abscesses, brain abscess, worsening lung infiltrates, or diffuse intestinal involvement presenting with abdominal pain

Disease Specific IRISCryptococcus IRIS• IRIS associated with preexisting cryptococcal infection & HIV-

infected patients previously infected with Cryptococcus spp. may develop symptoms of IRIS localized to the central nervous system (CNS) or the lungs

• Symptoms often occur within two months after commencement of therapy, but may be delayed for more than six months

• Despite the use of concurrent antifungal therapy, patients with preexisting cryptococcal meningoencephalitis may develop fever, increased headache, nausea, eye pain, photophobia, and nuchal rigidity following the initiation of HAART

Disease Specific IRIS

Cryptococcus IRIS• Repeat lumbar puncture in patients with IRIS associated with

cryptococcal meningitis often reveals more inflammatory cells than were found prior to the initiation of antifungal therapy and HAART

• Cultures usually remain sterile• Patients with IRIS-related cryptococcal meningitis had significantly

higher opening pressures, CD4 cell counts, and lower HIV viral loads• HIV-infected patients with preexisting cryptococcal pulmonary

infection may develop cavitary lung lesions, hypoxia, respiratory failure, and ARDS following the initiation of HAART

• Rarely, patients with disseminated cryptococcal infections may develop mediastinal lymphadenitis, hypercalcemia, and cutaneous abscesses as part of the IRIS syndrome

Management• Proper history: Time course of symptoms

-History of Ois, recently diagnosed Ois

-Treatment of Ois: date of initiation, adherence, duration and clinical response

-ART initiation date, specific antiretroviral regimen, medication adherence, and previous history of ART

-CD4 cell count and HIV viral load before ART initiation

-Current CD4 cell count and HIV viral load, if knownOther medications

ManagementDiagnostic evaluation:Important to r/o other cond’s before concluding IRIS• Complete blood count (CBC) with differential, electrolytes and

creatinine, liver function tests• CD4 cell count and HIV viral load• Blood cultures for bacteria, acid-fast bacteria (MAC), fungi• Chest X ray; other radiographic studies• Sputum stain and culture• Biopsy or culture of skin or other lesions• Lumbar puncture and cerebrospinal fluid studies• Drug resistance testing for the OI being treated, if indicated

Management

TreatementBest treatment????Depend on severityTreatment options• Observation• Corticosteroids• Temporary cessation of ART

Prevention

• Patient Education• Patients starting ART who have CD4 counts of <100

cells/µL or known concomitant OIs should be counseled about the possibility of IRIS.

• All patients starting ART should be advised to contact the clinic promptly if they experience new or worsening symptoms.

• Advise patients to take their medications for HIV and for the treatment or prevention of OIs exactly as prescribed.

References

• Centers for Disease Control and Prevention. Guidelines for Prevention and Treatment of Opportunistic Infections among HIV-Exposed and HIV-Infected Children.

• http://en.wikipedia.org/wiki/Progressive_multifocal_leukoencephalopathy.

• HIV Medicine book 2006 www.HIVMedicine.com• 0E_Baylor HIV curriculum 2005complete.• Journal of Antimicrobial Chemotherapy (2006) 57, 167-

170;Samuel A. Shelburne, Martin Montes and Richard J.Hamill

COMMENTS/QUESTIONS/ADDITIONS