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

Goni Lee; Seung Eun Lee; Kyung-Ha Ryu; Eun Sun Yoo

doi:10.5045/br.2013.48.4.258

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Original Article

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Blood Res 2013; 48(4): 258-265

Published online December 31, 2013

https://doi.org/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

Goni Lee, Seung Eun Lee, Kyung-Ha Ryu, and Eun Sun Yoo^*

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Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.

Correspondence to : Correspondence to Eun Sun Yoo, M.D., Ph.D. Department of Pediatrics, Ewha Womans University Mokdong Hospital, 1071, Anyangcheon-ro, Yangcheon-gu, Seoul 158-710, Korea. Tel: +82-2-2650-5586, Fax: +82-2-2653-3718, eunsyoo@ewha.ac.kr

Received: September 15, 2013; Revised: October 21, 2013; Accepted: November 14, 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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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.

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

Article

Original Article

Blood Res 2013; 48(4): 258-265

Published online December 31, 2013 https://doi.org/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

Goni Lee, Seung Eun Lee, Kyung-Ha Ryu, and Eun Sun Yoo^*

Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea.

Correspondence to:Correspondence to Eun Sun Yoo, M.D., Ph.D. Department of Pediatrics, Ewha Womans University Mokdong Hospital, 1071, Anyangcheon-ro, Yangcheon-gu, Seoul 158-710, Korea. Tel: +82-2-2650-5586, Fax: +82-2-2653-3718, eunsyoo@ewha.ac.kr

Received: September 15, 2013; Revised: October 21, 2013; Accepted: November 14, 2013

Abstract

Background

Methods

Results

Conclusion

Keywords: Hemophagocytic lymphohistiocytosis, Posterior reversible encephalopathy syndrome, HLH-2004, Risk factors, Reversible, Child

Abstract

Fig 1.

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Figure 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).

Blood Research 2013; 48: 258-265https://doi.org/10.5045/br.2013.48.4.258

Table 1 . Clinical and laboratory findings of patients with HLH and PRES..

^a)Onset time of PRES from the start of treatment. ^b)Hypertension was defined as blood pressure that was the same as or higher than that of 95% of children who are the same gender, age, and height. ^c)First episode. ^d)Second episode..

Abbreviations: HLH, hemophagocytic lymphohistiocytosis; PRES, posterior reversible encephalopathy syndrome; CSA, cyclosporin A; CSF, cerebrospinal fluid; EEG, electroencephalogram; MRI, magnetic resonance imaging; M, male; HT, hypertension; F, female..

Table 2 . Concurrent treatment and clinical outcomes of 6 patients with HLH and PRES..

^a)First episode. ^b)Second episode..

Abbreviations: HLH, hemophagocytic lymphohistiocytosis; PRES, posterior reversible encephalopathy syndrome; CSA, cyclosporin A; HT, hypertension; EEG, electroencephalogram; MRI, magnetic resonance imaging; D, day; NED, no evidence of disease..

Table 3 . Comparison of clinical and laboratory findings at diagnosis of HLH without or with PRES..

All values are expressed as mean±SD unless otherwise noted..

Abbreviations: HLH, hemophagocytic lymphohistiocytosis; PRES, posterior reversible encephalopathy syndrome; AST, aspartate aminotransferase; ALT, alanine aminotransferase..

Table 4 . Putative risk factors for PRES at the development of PRES by univariate analysis..

All values are expressed as number or mean±SD unless otherwise noted..

^a)Preceding rise of ferritin level >50% compared with 1 week before development of PRES..

Abbreviations: PRES, posterior reversible encephalopathy syndrome; CNS, central nervous system; CSA, cyclosporin A; AST, aspartate aminotransferase; ALT, alanine aminotransferase..