Rapid Diagnosis Crucial for Adults with HLH That Affects Brain

Rapid Diagnosis Crucial for Adults with HLH That Affects Brain

The brain is rarely affected in adult-onset hemophagocytic lymphohistiocytosis (HLH), but its involvement is a serious complication and a quick diagnosis is critical to ensuring best possible outcomes for patients, a case report highlights.

The report, “Severe cerebral involvement in adult-onset hemophagocytic lymphohistiocytosis,” was published in the Journal of Clinical Neuroscience.

HLH is caused by abnormally high activity of inflammatory immune cells. Severe HLH with brain involvement in adults is rare, and can be difficult to diagnose because its symptoms are often non-specific and can resemblance sepsis — an inflammatory condition caused by widespread infection.

Researchers in Massachusetts describe in this report two people with adult-onset HLH and brain involvement.

The first, a 46-year-old woman, was hospitalized after three months of symptoms that included difficulty swallowing (dysphagia), shortness of breath (dyspnea), and a widespread rash. Although an initial neurological examination did not detect abnormalities, the patient’s neurological condition progressively worsened. She was comatose three days later, and life support was initiated.

Blood tests revealed a number of abnormalities, including markers of kidney and liver damage, and a bone marrow biopsy was suggestive of HLH, with a diagnosis confirmed by subsequent testing. Brain imaging was suggestive of acute necrotizing encephalopathy (ANE), where patches of brain tissue die off.

“ANE in children but not in adults with HLH has been reported,” the researchers wrote. “Therefore, we herein describe the first case of an adult patient with HLH presenting with fulminant ANE.”

Despite anti-inflammatory treatment, the patient’s condition continued to worsen, and life support was discontinued five days after her hospital admission.

A 44-year old woman was detailed in the second case. She was hospitalized with symptoms including fever, abdominal pain, acute respiratory distress syndrome (ARDS), and kidney failure, and initially given antibiotics for suspected sepsis.

She, too, went into a coma and required intubation. Brain imaging revealed “innumerable” small hemorrhages, or bleeds within the brain. A bone marrow biopsy was suggestive of HLH, and the patient was started on anti-inflammatory treatment.

She slowly improved; after about three weeks, intubation was no longer required. After two months, she was again living at home and had a modified Rankin score of 2. This score, on a test normally given after a stroke, indicates mild disability — a person able to care for themselves independently but with some loss of abilities in daily life.

These cases illustrate two ways the brain can be affected in HLH, and underscore the importance of timely diagnosis.

“Clinical manifestations, labs and imaging findings of HLH with CNS [brain, central nervous system] involvement are non-specific. Early diagnosis and treatment is important to prevent serious complications and demise,” the team wrote.

HLH “should be considered in patients with sepsis-like illness in the absence of an identifiable infection and disproportionately severe neurological manifestations,” the researchers added.

They also noted that comparable brain injury might be evident in other conditions characterized by excessive inflammation, including  COVID-19.

“Similar brain injury may occur in patients with cytokine storm syndrome due to COVID-19,” they wrote, noting that ANE was reported in a person infected by the SARS-CoV-2 pathogen.

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