World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Case Report

Volume 3, Number 4, August 2012, pages 194-198

Early Recognition of Immune Reconstitution Inflammatory Syndrome Leads to Avoidance of Endotracheal Intubation

**Table 1.** Pathogenesis of Immune Reconstitution Inflammatory Syndrome and Potential Therapeutic Approaches
Category	Mechanism	Therapy
Abbreviations: NK: natural killer cells; Th: helper T cells; IRIS: immune reconstitution inflammatory syndrome; TNF-α: tumor necrosis factor alpha; GMI: galactomannan index; KIRs: killer immunoglobulin like receptors; N/A: non-applicable.
Proliferation of Th1 and Th17 cells	Proinflammatory. Activate macrophages. Promote NK cell cytotoxicity. Cause IRIS. Involved in solid organ transplant rejection.	Corticosteroids (decrease Th1). Statins (decrease Th1 and Th17). Infliximab for steroid refractory cases (TNF-α antagonist which inhibits macrophages).
Suppression of Th2 and regulatory T cells	Usually are anti-inflammatory and leads to tolerance but reduction in levels in IRIS potentiates inflammation.	Corticosteroids (increase Th2 and regulatory T cells). Statins (increase Th2 and regulatory T cell responses).
Leukotrienes	Produced by mast cells. Proinflammatory.	Monteleukast
Genetic predisposition	Ancestral haplotype HLA A2, B44, DR4. Regulatory cytokine gene polymorphisms of IL-6 and TNF-α	N/A
Unmasking IRIS	Immune response to covert infection (viable pathogen antigens) such as chronic disseminated candidiasis in neutropenic hematological malignancy patients after neutrophil recovery.	Antifungals. Corticosteroids.
Paradoxical IRIS	Immune response to nonviable dead pathogen debris, tumor antigens or host antigens. For example pulmonary IRIS after neutrophil recovery in effectively treated invasive pulmonary aspergillosis with decrease in serum GMI.	Corticosteroids
Natural killer cells	Activating KIRs encoded by KIR genes 3DS1 and 2DS5 more common in patients with IRIS.	N/A

Table 1. Pathogenesis of Immune Reconstitution Inflammatory Syndrome and Potential Therapeutic Approaches

Category

Mechanism

Therapy

Abbreviations: NK: natural killer cells; Th: helper T cells; IRIS: immune reconstitution inflammatory syndrome; TNF-α: tumor necrosis factor alpha; GMI: galactomannan index; KIRs: killer immunoglobulin like receptors; N/A: non-applicable.

Proliferation of Th1 and Th17 cells

Proinflammatory.
Activate macrophages.
Promote NK cell cytotoxicity.
Cause IRIS.
Involved in solid organ transplant rejection.

Corticosteroids (decrease Th1).
Statins (decrease Th1 and Th17).
Infliximab for steroid refractory cases (TNF-α antagonist which inhibits macrophages).

Suppression of Th2 and regulatory T cells

Usually are anti-inflammatory and leads to tolerance but reduction in levels in IRIS potentiates inflammation.

Corticosteroids (increase Th2 and regulatory T cells).
Statins (increase Th2 and regulatory T cell responses).

Leukotrienes

Produced by mast cells.
Proinflammatory.

Monteleukast

Genetic predisposition

Ancestral haplotype HLA A2, B44, DR4.
Regulatory cytokine gene polymorphisms of IL-6 and TNF-α

N/A

Unmasking IRIS

Immune response to covert infection (viable pathogen antigens) such as chronic disseminated candidiasis in neutropenic hematological malignancy patients after neutrophil recovery.

Antifungals.
Corticosteroids.

Paradoxical IRIS

Immune response to nonviable dead pathogen debris, tumor antigens or host antigens. For example pulmonary IRIS after neutrophil recovery in effectively treated invasive pulmonary aspergillosis with decrease in serum GMI.

Corticosteroids

Natural killer cells

Activating KIRs encoded by KIR genes 3DS1 and 2DS5 more common in patients with IRIS.

N/A

**Table 2.** When to Suspect Immune Reconstitution Syndrome in Hematologic Malignancy Patients Undergoing Cytotoxic Chemotherapy
Clinical Criteria	Laboratory Values
Temporal association with rapid onset of neutrophil recovery	absolute neutrophil count recovery < 100/microliter to > 4500/microliter within 5 days
Paradoxical onset of clinical and radiologic deterioration despite effective antimicrobial therapy	Exclusion of other causes. All cultures negative (blood, urine, sputum, bronchoalveolar lavage) and/or > 50% decrease in sequential serum galactomannan titers
Unmasking of covert infection (fever, abdominal pain)	New hepatosplenic lesions seen after neutrophil recovery, culture negative with liver biopsy showing granulomas with T cell infiltration (chronic disseminated candidiasis)
Granuloma formation in affected organ	Relies on Th 1 cytokines and 1 alpha-hydroxylase of activated macrophages increases synthesis of 1, 25 (OH)₂ vitamin D₃ causing hypercalcemia

Table 2. When to Suspect Immune Reconstitution Syndrome in Hematologic Malignancy Patients Undergoing Cytotoxic Chemotherapy

Clinical Criteria

Laboratory Values

Temporal association with rapid onset of neutrophil recovery

absolute neutrophil count recovery < 100/microliter to > 4500/microliter within 5 days

Paradoxical onset of clinical and radiologic deterioration despite effective antimicrobial therapy

Exclusion of other causes.
All cultures negative (blood, urine, sputum, bronchoalveolar lavage) and/or > 50% decrease in sequential serum galactomannan titers

Unmasking of covert infection (fever, abdominal pain)

New hepatosplenic lesions seen after neutrophil recovery, culture negative with liver biopsy showing granulomas with T cell infiltration
(chronic disseminated candidiasis)

Granuloma formation in affected organ

Relies on Th 1 cytokines and 1 alpha-hydroxylase of activated macrophages increases synthesis of 1, 25 (OH)₂ vitamin D₃ causing hypercalcemia