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Miscellanea
Images in paediatrics
Haemophagocytic lymphohistiocytosis restricted to the central nervous system
  1. Senthil Velan Bhoopalan,
  2. Patrick K Campbell,
  3. Asim K Bag,
  4. Mihaela Onciu,
  5. Ashok Srinivasan
  1. St. Jude Children's Research Hospital, Memphis, TN, USA
  1. Correspondence to Dr Senthil Velan Bhoopalan, Oncology, Saint Jude Children's Research Hospital, Memphis, TN 38018, USA; senthil.bhoopalan{at}stjude.org

https://doi.org/10.1136/archdischild-2020-319088

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    An 8-year-old boy presented with fatigue, weakness and altered mental status necessitating intubation. Contrast-enhanced magnetic resonance imaging (MRI) of the brain revealed multifocal perivascular enhancement at the supratentorial juxtacortical white matter (figure 1A) and diffuse cerebellar leptomeningeal enhancement (figure 1B), suggestive of central nervous system (CNS) vasculitis versus infection versus acute disseminated encephalomyelitis (ADEM). Workup for infectious and autoimmune encephalitis was unremarkable. Methylprednisolone (20 mg/kg/day) was initiated for presumed ADEM. Brain biopsy, obtained due to continued deterioration in mental status, revealed extensive meningoencephalitis (figure 2A) and small vessel wall inflammation (figure 2B). Treatment with methylprednisolone (30 mg/kg/day for 5 days followed by prednisone 2 mg/kg/day) and cyclophosphamide (500 mg/m2 monthly) was initiated for small vessel CNS vasculitis. Lack of mental status improvement despite immunosuppression prompted further review of pathology, which identified CD68-positive histiocytes (figure 2C) suggestive of haemophagocytic lymphohistiocytosis (HLH). Genetic testing revealed compound heterozygous mutation in the PRF1 gene (c.50delT (p.L17fs) and c.527G>A (p.C176Y)). The patient was diagnosed with CNS-restricted HLH as he did not meet criteria for systemic HLH, and he underwent bone marrow transplantation from a matched sibling donor after reduced intensity conditioning with alemtuzumab, fludarabine and melphalan.1 Four years after transplantation, he is asymptomatic and well.

    Figure 1
    Figure 1

    Postcontrast T1-weighted MRI of the brain at the level of lateral ventricles (A) and at the level of the inferior fourth ventricle (B) shows multifocal white matter perivascular enhancement (arrows) and diffuse cerebellar leptomeningeal enhancement (arrowheads).

    Figure 2
    Figure 2

    Pathological findings in the brain biopsy sample. (A) Increased numbers of mononuclear chronic inflammatory cells in the white matter (H&E stain, ×10 magnification). (B) Prominent cuffing of a small blood vessel by small lymphocytes, which also infiltrate the vessel wall (arrowheads) (H&E stain, ×20 magnification). (C) An immunohistochemical stain for CD68 highlights a marked increase in CD68-positive histiocytic cells and microglia (all CD68-positive cells are brown; negative cells are blue on the haematoxylin counterstain, ×10 magnification).

    Familial HLH is an uncommon condition characterised by intense inflammation resulting in fever, cytopaenias, multiorgan dysfunction and cytokine storm.2 Lack of characteristic radiological features makes diagnosis challenging.3 Brain biopsy and genetic testing can help with diagnosis in patients with persistent or worsening symptoms. Bone marrow transplantation is the only definitive treatment for these patients.4

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    Footnotes

    • Contributors SVB wrote the manuscript, with critical inputs from PKC, AKB and MO. AS supervised the work.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.