Immune Reconstitution Inflammatory Syndrome in children

Abstract

Immune Reconstitution Inflammatory Syndrome (IRIS) refers to a collection of inflammatory disorders, predominantly related to infectious processes that manifest after the initiation of antiretroviral therapy (ART) and can be classified as unmasking or paradoxical. The prevalence of IRIS in children in sub-Saharan Africa is low. Approximately half of all cases are associated with Mycobacterium tuberculosis. It may be difficult to distinguish IRIS from tuberculosis and other opportunistic infections radiologically; therefore, radiological findings must be interpreted with clinical and laboratory findings. In this review article, we describe the clinical and radiological manifestations of IRIS in children and provide illustrative radiological examples.

FIGURE 1

An 11-year-old HIV-infected boy, CD4 count 9 cells/mm³ (4%), was initiated on ART. He developed progressive symptoms consistent with disseminated TB and responded well to continuation of ART and standard four-drug TB treatment. Frontal chest radiograph taken at the time of ART initiation (a) demonstrates a normal chest radiograph. Frontal chest radiograph (b) taken 3 weeks after ART initiation demonstrates a diffuse reticular nodular infiltrate with bilateral hilar lymphadenopathy (open arrows) and small pleural effusions (closed arrows). A diagnosis of unmasking TB-IRIS was made.

FIGURE 2

A 3-year-old HIV-infected girl initiated on ART 2 weeks after starting TB treatment. CD4 count was not available. Frontal chest radiograph taken at the time of ART initiation: (a) demonstrates bilateral hilar lymphadenopathy (open arrows). Chest radiograph taken 2 weeks after ART initiation; (b) demonstrates right middle lobe consolidation and collapse (closed arrow), with worsening hilar lymphadenopathy (open arrows). In combination with the clinical, radiological and laboratory findings, a diagnosis of paradoxical TB-IRIS was made.

FIGURE 3

A 4-year-old HIV-infected boy living with an adult diagnosed with pulmonary TB was initiated on ART. Three months later, he developed symptoms of pulmonary TB, which was microbiologically confirmed (Unmasking IRIS). He was initiated on appropriate TB treatment and initially improved; 3 weeks later he presented with fever and worsening respiratory symptoms and signs (Paradoxical IRIS). Computed tomography of the chest, axial, soft tissue window (a and b) demonstrates mediastinal and hilar lymph nodes (arrows) encasing the bronchi bilaterally. There is also posterior mediastinal involvement with anterior displacement of the left atrium and a small right pleural effusion; (c) axial lung window demonstrates dense right middle lobe and apical segment of right lower lobe consolidation with lingular consolidation. A diagnosis of paradoxical and unmasking TB-IRIS was made. ART and TB treatment were continued and corticosteroids were administered; he demonstrated a good clinical response and is currently well; (d) axial CT chest axial lung window performed 6 months later demonstrates resolution of the consolidation, with residual lymphadenopathy (open arrows).

FIGURE 4

A 9-month-old HIV-infected girl, with CD4 count 9 cells/mm³ (1.53%), was admitted with severe malnutrition, right axillary and left thigh abscesses, generalised lymphadenopathy, hepatosplenomegaly and clinical evidence of HIV encephalopathy. ART was initiated with subsequent worsening of the thigh abscess. An aspiration was performed on the left thigh abscess which cultured Mycobacterium bovis BCG, confirmed using molecular testing. Appropriate antimycobacterial treatment was provided: (a) (lateral) and (b) (AP), radiograph of the lower limbs demonstrate an air containing abscess in the upper left lateral thigh soft tissues (open arrow) and generalised left lower limb soft tissue swelling. No periosteal reaction was demonstrated in visualised bones. She was readmitted a year later, still on antimycobacterial treatment with soft tissue abscesses in the right thigh, forehead, abdominal wall and left forearm; (c) (left lateral knee) demonstrates osteomyelitis, with lytic lesions within the proximal tibial metaphysis and a cortical break along the anterosuperior tibial margin (open arrow). There is periosteal reaction along the tibia and distal femur (closed arrow) with generalised soft tissue oedema; (d) (left AP forearm) demonstrates another focus of osteomyelitis with lytic lesions in the proximal metadiaphysis of the ulna (open arrows), associated periosteal reaction and osteopenia of the left ulna and radius. Bone aspiration again confirmed M. bovis BCG, now resistant to first-line antimycobacterial agents, necessitating surgical drainage; however, the patient did not survive. A diagnosis of BCG-IRIS was made.