Imaging characteristics of hemophagocytic lymphohistiocytosis

Abstract

Background: Hemophagocytic lymphohistiocytosis (HLH) is a nonmalignant disorder of immune regulation, with overproduction of cytokines and diminished immune surveillance. Symptoms are nonspecific and may affect multiple organs, including the central nervous system. Neuroimaging findings have been described in case reports and small series; body imaging findings have not been described extensively. OBJECTIVE. To summarize findings of the most frequently performed imaging studies of the brain, chest and abdomen in patients with HLH.

Materials and methods: Retrospective review of chest radiographs and CT, abdominal ultrasound and CT, brain CT and MRI, skeletal surveys, and autopsy data.

Results: Twenty-five patients were diagnosed and treated for HLH at our institution over an 11-year period; 15 patients (60%) died. Common chest radiograph findings included alveolar-interstitial opacities with pleural effusions, often with rapid evolution and resolution. Hepatosplenomegaly, gallbladder wall thickening, hyperechoic kidneys and ascites were common abdominal findings, which resolved after therapy in some cases. Brain-imaging studies revealed nonspecific periventricular white-matter abnormalities, brain-volume loss and enlargement of extra-axial fluid spaces. Three infant cases, one with intracranial hemorrhage, one with multiple pathologic rib fractures and one with diaphyseal periosteal reaction involving multiple long bones on skeletal survey, raised suspicion of child abuse at presentation. Abuse was not substantiated in any case.

Conclusions: Clinicians and radiologists should be aware of the radiographic manifestations of HLH, which are nonspecific and overlap with infectious, inflammatory and neoplastic disorders. Findings in the chest (similar to acute respiratory distress syndrome) and abdomen may progress rapidly and then regress with institution of appropriate anti-HLH therapy. CNS findings may be progressive. In some infants, initial imaging findings may mimic nonaccidental trauma.

Fig. 1a, b.

Chest radiographs at time of admission (a) and 9.5 h later (b) in a 6-year-old girl admitted with rash, fever, and hip pain. Nonspecific perihilar interstitial opacities are present initially, with thickening of the minor fissure. Image (b) following a decline in respiratory status shows increasing interstitial opacities, with development of right upper and middle-lobe airspace disease and small right pleural effusion (patient 18 in Table 2)

Fig. 2a, b.

Abdominal ultrasound images in a 10-year-old girl with HLH secondary to Kawasaki disease demonstrate marked gallbladder wall thickening (a) and an echogenic band in the porta hepatis region (b). Splenomegaly, large kidneys with increased cortical echogenicity, ascites, and a left pleural effusion were also present. Following chemotherapy, all findings resolved (patient 21 in Table 2)

Fig. 3a, b.

Unenhanced CT (a, b) with marked brain volume loss and abnormal periventricular white-matter lucencies in a 6-year-old boy with familial HLH, seizures, and developmental delay (patient 6 in Table 2)

Fig. 4a–c.

Axial (a) and sagittal (b) contrast-enhanced T1, axial T2 (c) brain MR images show multiple enhancing lesions of both cerebral hemispheres, the cerebellum and left pons with associated edema, and obstructive hydrocephalus in an 11-month-old girl. No infectious findings were seen at autopsy (patient 13 in Table 2)

Fig. 5.

Unenhanced CT of the brain in a 12-day-old boy with altered consciousness and retinal hemorrhages. Edema, left hemispheric parenchymal, and extra-axial hemorrhage were later determined to be caused by left transverse sinus thrombosis (patient 19 in Table 2)

Fig. 6.

Chest radiograph in a 3-month-old girl in respiratory distress. Multiple healing rib fractures (6–8 on the left, 6–9 on the right) initially raised concern for nonaccidental trauma. Osteopenia and lucent metaphyses were evident on skeletal survey (patient 16 in Table 2)