Blood Res.  2013 Dec;48(4):258-265. 10.5045/br.2013.48.4.258.

Posterior reversible encephalopathy syndrome in pediatric patients undergoing treatment for hemophagocytic lymphohistiocytosis: clinical outcomes and putative risk factors

• Lee G
• Lee SE
• Ryu KH
• Yoo ES

• KMID: 2172873
• DOI: http://doi.org/10.5045/br.2013.48.4.258

Abstract

BACKGROUND
Hemophagocytic lymphohistiocytosis (HLH) is a rare multiorgan disease of toxic immune activation caused by the interaction of cytotoxic T cells and innate immune cells and frequently involves the central nervous system (CNS). Posterior reversible encephalopathy syndrome (PRES) might develop during treatment with the HLH-2004 protocol from the Histiocyte Society. The aims of this study were to evaluate clinical outcomes and putative risk factors for prediction of PRES related to HLH.
METHODS
We reviewed the medical records of 28 patients with HLH who were treated between April 2005 and April 2012. We compared various clinical and laboratory parameters in patients without or with PRES to evaluate putative risk factors related to development of PRES.
RESULTS
Six (21.4%) of the patients experienced PRES during treatment with the HLH-2004 protocol. Clinical and laboratory manifestations were not different compared with other conditions causing PRES. The main mechanism of PRES may be related to the HLH-2004 protocol and a high pro-inflammatory state. Most patients recovered quickly from neurologic manifestations without significant long-term sequelae. Preceding hypertension, an increase in ferritin level >50% compared with 1 week before development of PRES and hyponatremia were statistically significant factors.
CONCLUSION
PRES is clinically reversible and has a favorable outcome in patients with HLH. Awareness of PRES and a differential diagnosis of other causes of neurologic complications, including CNS involvement of HLH, can help avoid unnecessary treatment or delayed management. Patients with preceding hypertension, hyponatremia, and rising ferritin levels during HLH treatment should be closely monitored for PRES.

Keyword

Hemophagocytic lymphohistiocytosis; Posterior reversible encephalopathy syndrome; HLH-2004; Risk factors; Reversible; Child

MeSH Terms

Central Nervous System
Child
Diagnosis, Differential
Ferritins
Histiocytes
Humans
Hypertension
Hyponatremia
Lymphohistiocytosis, Hemophagocytic*
Medical Records
Neurologic Manifestations
Risk Factors*
T-Lymphocytes
Ferritins

Figure

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  Fig. 1 Magnetic resonance images (MRI) in patients with posterior reversible encephalopathy during treatment with the HLH-2004 protocol. MRI showed decreased signal on T1-weighted images and hyperintense abnormalities on T2-weighted and fluid attenuated inversion recovery (FLAIR) images (A-F) typical for PRES, bilaterally in the subcortical white matter and cortical gray matter of the posterior parietal and occipital lobes. These initial increased signal lesions completely disappeared after 1 to 2 months of treatment (D2 and E2).

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