From the Guidelines
Management of a 65-year-old female with hemophagocytic lymphohistiocytosis (HLH) and neuropsychiatric symptoms requires prompt, aggressive treatment with immunosuppressive therapy, prioritizing the HLH-94 protocol with etoposide and dexamethasone, as recommended by the most recent guidelines 1. The recommended initial regimen is the HLH-94 protocol, consisting of etoposide (150-300 mg/m² twice weekly for 2 weeks, then weekly) and dexamethasone (10 mg/m² daily for 2 weeks, then tapered over 8 weeks) 1. For neuropsychiatric involvement, intrathecal methotrexate (12 mg weekly) should be added until CNS symptoms resolve. Concurrently, identify and treat the underlying trigger, which is often infection, malignancy, or autoimmune disease in older adults. Supportive care is essential, including:
- Seizure prophylaxis with levetiracetam (500-1000 mg twice daily)
- Management of cerebral edema with mannitol if needed
- Close neurological monitoring Laboratory parameters including ferritin, triglycerides, fibrinogen, and blood counts should be tracked regularly to assess treatment response 1. If the patient fails to respond within 2-3 weeks, consider second-line therapies such as alemtuzumab or ruxolitinib. This aggressive approach is necessary because HLH with neuropsychiatric involvement carries high mortality (50-75%), particularly in older patients, due to the cytokine storm causing multi-organ dysfunction and neurological damage from inflammatory infiltration of the CNS. The use of IV immunoglobulin (IVIG) may be considered, as it has anti-inflammatory potential, but its use has been questioned in certain cases 1. Anakinra may also reduce mortality in sepsis patients with MAS features, and its use could be considered in specific cases 1. It is essential to individualize the treatment approach, taking into account the patient's age, organ function, and underlying trigger, to minimize toxicity and optimize outcomes 1.
From the Research
Managing a 65-Year-Old Female Patient with HLH and Neuropsychiatric Symptoms
- The patient's condition is a rare multisystem disorder characterized by proliferation and diffuse infiltration of multiple organs with histiocytes, including the central nervous system (CNS) 2.
- CNS involvement in adults with HLH is less frequent than in children, but can still occur, with symptoms including disturbance of consciousness, cranial nerve palsies, seizures, headache, limb paralysis, irritability, meningism, and memory loss 2.
- The diagnosis of HLH is often challenging due to diverse clinical manifestations and the presence of several diagnostic mimics, and the prognosis is generally poor, warranting rapid diagnosis and aggressive management 3.
- Treatment of HLH is primarily based on suppressing the inflammatory response, but the treatment needs to be modified in adults depending on the underlying cause and comorbidities 3.
- In some cases, adult-onset CNS-HLH can occur with predominantly CNS involvement, and this diagnosis should be considered in the differential diagnosis of adults presenting with progressive brain lesions, even in the absence of typical systemic signs of HLH 4.
- A comprehensive review of the patient's medical history, laboratory tests, and imaging studies is necessary to determine the underlying cause of HLH and to develop an effective treatment plan 5, 6.
Key Considerations
- CNS involvement in HLH can be diverse and may include neurological manifestations such as seizures, headache, and limb paralysis 2, 6.
- The diagnosis of HLH requires a high index of suspicion and a comprehensive evaluation of the patient's clinical and laboratory findings 3.
- Treatment of HLH should be individualized based on the underlying cause and comorbidities, and may involve immunosuppressive therapy, chemotherapy, or other interventions 5, 3.
- Close monitoring of the patient's condition and adjustment of the treatment plan as needed is crucial to improve outcomes 2, 4.