Here, the authors present the first documented case of a patient developing central nervous system (CNS) vasculitis secondary to Langerhans cell histiocytosis (LCH) ultimately leading to stroke. LCH is a rare histiocytic disorder affecting males and females equally and typically presents in pediatric patients with a median age of 30 months. Presentation of the disease can be single-site or multisystem; and, classification of treatment is further demarcated by high risk and low risk depending on the organ systems involved. Treatment of LCH typically involves vinblastine and prednisone, as well as salvage treatment as needed.
Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder of unknown etiology affecting 2-10 per one million children younger than age 15 years, with a median age of presentation of 30 months and a roughly equal male: female ratio [1-2]. LCH typically presents with a skin rash and/or bone lesion and can affect single or multiple organ systems including marrow, liver, and lungs. Common presentations of a lytic bone lesion secondary to LCH include cervical lymphadenopathy (40.9%) and otitis media (22.7%) . It can also affect the lungs and the central nervous system (CNS). Diagnosis of LCH is confirmed with positive staining of biopsy sample with immunohistochemistry staining of CD1a, S100, and CD207 (Langerin). BRAFV600E mutations are common in pediatric LCH patients as well [4-5]. Treatment of LCH is typically a combination of prednisone and vinblastine. In addition to treatment side effects, other morbidities depend on whether the disease affects a single system (24% incidence of long-term problems) or multiple systems (71% incidence of long-term problems) . While other histiocytic diseases have been known to cause CNS vasculitis and stroke [7-8], this is the first documented case of LCH presenting with an acute ischemic stroke.
A 16-month-old male presented to the emergency department (ED) with tachypnea and dyspnea. Left-sided lymphadenopathy was found on examination, as well as a large mass was found on the lateral frontal bone just above the orbit. The patient’s mother noted that it had been growing for six weeks; and, ultrasound of the mass showed it was cystic in nature. On history, the patient had seven to eight documented ear infections within the previous year. Chest X-ray (CXR) found indications of heart failure (HF) (enlarged heart and interstitial edema typical of HF); however, echocardiogram demonstrated normal heart structure and function. Computed tomography (CT) showed hilar and subcarinal lymphadenopathy (Figure 1).
The patient was treated with ceftriaxone and zithromax. After treatment showed limited effectiveness (persistent infection and fever of 103°F), the patient underwent bronchoalveolar lavage (BAL). BAL indicated airways with no active infection or malignant cells; however, there were signs of inflammation. Head CT showed sharply defined lytic lesion of the left orbit region, concerning for eosinophilic granuloma or hematologic malignancy (Figure 2).
Biopsy was performed; immunohistochemistry was positive for CD1a, S100, CD68, and CD207 (Langerin). The patient was also positive for the BRAFV600E mutation. With this information a diagnosis LCH was confirmed and therapy was initiated with vinblastine and prednisone. After his first dose of chemotherapeutic treatment, he was discharged from the hospital.
Approximately one week after initiating chemotherapy, the patient was re-admitted to the hospital with left brain stroke. Head and neck magnetic resonance imaging/magnetic resonance angiogram (MRI/MRA) found large left middle cerebral artery (MCA) territory infarction, with acute cutoff of left MCA and significant decrease in caliber of the left internal carotid artery (ICA) throughout its intracranial course (Figures 3-4).
Echocardiogram demonstrated a functionally and structurally normal heart with intact atrial septum; and, no thrombus or vegetation was noted. Following an extensive workup and ruling out all other possible causative factors, the etiology of stroke was attributed to secondary CNS vasculitis. This was possibly secondary to his primary diagnosis of LCH.
Though uncommon in the pediatric population, there are reports in adults of histiocytic disorders leading to CNS vasculitis (Table 1) [9-10]. Vasculitides in children is a rare condition as a whole, occurring in no more than 53 in 100,000 (12401245, 15517648). LCH is even rarer still [TF1] with reports of nine cases per million in this age group (16652350).
Therefore, it is extremely unlikely that these two medical conditions occurred independently of each other. Finally, vasculitis secondary to chemotherapy has been documented with gemcitabine but not with vinblastine . Therefore, the likelihood that vinblastine contributed to the stroke is unlikely. Hence this would be the first case describing vasculitis in the setting of LCH and a subsequent stroke in a 16-month-old child.
This would be the first case in pediatrics or adults describing vasculitis in the setting of LCH and a subsequent stroke. Clinicians should be aware that this devastating outcome can be a rare presentation in the setting of LCH.
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Langerhans Cell Histiocytosis Causing Central Nervous System Vasculitis Leading to Stroke in a Two-year-old Boy: A Case Report
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Cite this article as:
Froelich N T, Rizk E (January 24, 2019) Langerhans Cell Histiocytosis Causing Central Nervous System Vasculitis Leading to Stroke in a Two-year-old Boy: A Case Report. Cureus 11(1): e3951. doi:10.7759/cureus.3951
Received by Cureus: September 11, 2018
Peer review began: November 07, 2018
Peer review concluded: January 09, 2019
Published: January 24, 2019
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Froelich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 3.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.