摘要
Colony stimulating factor-1 receptor (CSF1R) plays important roles in the differentiation and proliferation of macrophage and microglia in systemic organs and the brain. A genetic defect in CSF1R causes hereditary diffuse leukoencephalopathy with spheroids (HDLS). HDLS mainly affects the cerebral white matter and shows pre-senile cognitive decline, motor disturbance, and epilepsy. However, systemic manifestations outside the brain have not yet been described in patients with HDLS. Here, we report the case of a 41-year-old man with HDLS carrying the p. K793T mutation in CSF1R, who unexpectedly died of sepsis and hemophagocytic syndrome shortly after the onset of HDLS. The fetal sequence of sepsis and hemophagocytic syndrome was triggered by enterocolitis. An autopsy revealed that focal inflammation in the intestine had almost resolved. Most strikingly, massive infiltration of cluster of differentiation (CD) 68- and CD163-immunopositive macrophages with hemophagocytosis was observed in the bone marrow, spleen, and liver. Less abundant infiltration of CD68- and CD204-immunopositive macrophages without hemophagocytosis was also seen in the lung and intestine. At present, the pathogenetic link between CSF1R mutation and hemophagocytic syndrome in this patient is unclear. Our case, however, clearly shows that even in patients with HDLS, aberrant activation of functional macrophages can be induced under certain conditions in visceral organs.
Colony stimulating factor-1 receptor (CSF1R) plays important roles in the differentiation and proliferation of macrophage and microglia in systemic organs and the brain. A genetic defect in CSF1R causes hereditary diffuse leukoencephalopathy with spheroids (HDLS). HDLS mainly affects the cerebral white matter and shows pre-senile cognitive decline, motor disturbance, and epilepsy. However, systemic manifestations outside the brain have not yet been described in patients with HDLS. Here, we report the case of a 41-year-old man with HDLS carrying the p. K793T mutation in CSF1R, who unexpectedly died of sepsis and hemophagocytic syndrome shortly after the onset of HDLS. The fetal sequence of sepsis and hemophagocytic syndrome was triggered by enterocolitis. An autopsy revealed that focal inflammation in the intestine had almost resolved. Most strikingly, massive infiltration of cluster of differentiation (CD) 68- and CD163-immunopositive macrophages with hemophagocytosis was observed in the bone marrow, spleen, and liver. Less abundant infiltration of CD68- and CD204-immunopositive macrophages without hemophagocytosis was also seen in the lung and intestine. At present, the pathogenetic link between CSF1R mutation and hemophagocytic syndrome in this patient is unclear. Our case, however, clearly shows that even in patients with HDLS, aberrant activation of functional macrophages can be induced under certain conditions in visceral organs.
作者
Yasufumi Kondo
Michiaki Kinoshita
Takuhiro Yoshida
Hisanori Matoba
Takeshi Uehara
Meguru Ikeyama
Jun Nakayama
Kunihiro Yoshida
Shu-Ichi Ikeda
Yasufumi Kondo;Michiaki Kinoshita;Takuhiro Yoshida;Hisanori Matoba;Takeshi Uehara;Meguru Ikeyama;Jun Nakayama;Kunihiro Yoshida;Shu-Ichi Ikeda(Department of Medicine (Neurology & Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan;Department of Neurology, Komoro Kosei General Hospital, Komoro, Japan;Department of Neurology, Suwa Red Cross Hospital, Suwa, Japan;Department of Neurology, Ina Central Hospital, Ina, Japan;Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan;Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Japan;Department of Brain Disease Research, Shinshu University School of Medicine, Matsumoto, Japan)
