Hemophagocytic Lymphohistiocytosis (HLH) is a rare and severe immune disorder in infants, characterized by an overreaction of the body’s immune system. Immune cells become excessively active, leading to widespread inflammation and potential damage to various organs and tissues. Prompt recognition and treatment of HLH are important due to its rapid progression and serious health implications.
Understanding Hemophagocytic Lymphohistiocytosis
HLH is a syndrome where specific immune cells, including T-cells, Natural Killer (NK) cells, and macrophages, become overactive. These cells, instead of targeting only foreign invaders, begin to attack and damage the body’s healthy tissues and organs, such as the bone marrow, spleen, and liver. This uncontrolled activation results in a severe inflammatory response, often referred to as a “cytokine storm,” characterized by an excessive release of chemical messengers called cytokines.
There are two main categories of HLH: primary and secondary. Primary, or familial, HLH is an inherited condition caused by specific genetic mutations that impair the immune system’s ability to regulate itself. These genetic defects often affect proteins involved in the cytolytic pathway, which is how immune cells eliminate infected or abnormal cells. Secondary, or acquired, HLH develops when the immune system becomes strongly activated due to other underlying conditions, such as severe infections (like Epstein-Barr virus), autoimmune diseases, or certain cancers. Both forms lead to similar clinical manifestations due to the overwhelming immune cell activation.
Recognizing Signs in Infants
Identifying HLH in infants can be challenging because its initial symptoms often resemble more common infections. A persistent fever is a frequent early sign, often accompanied by an enlarged liver and spleen, a condition known as hepatosplenomegaly. Babies may also exhibit low blood counts, including anemia (low red blood cells), thrombocytopenia (low platelets), and neutropenia (low neutrophils), which can lead to pallor, easy bruising, or frequent infections.
Skin rashes, which can vary in appearance, may also be observed, potentially mimicking common newborn rashes and delaying diagnosis. Neurological symptoms can also occur, presenting as irritability, seizures, or developmental regression. These symptoms tend to worsen progressively, highlighting the importance of early recognition to prevent further organ damage.
Diagnosing and Treating HLH
Diagnosing HLH involves a combination of clinical findings and laboratory tests. A diagnosis can be confirmed if a genetic mutation associated with HLH is identified, or if at least five out of eight specific clinical and laboratory criteria are met. These criteria include prolonged fever, splenomegaly, and cytopenia affecting at least two blood cell lines, such as low hemoglobin, platelets, or neutrophils.
Further diagnostic indicators include:
- Hypertriglyceridemia (high triglycerides)
- Hypofibrinogenemia (low fibrinogen)
- Elevated serum ferritin levels
- Elevated soluble CD25 (soluble IL-2 receptor) levels
- Low or absent natural killer (NK) cell activity
- Evidence of hemophagocytosis in bone marrow, spleen, or lymph node biopsies
Treatment aims to control inflammation and eliminate overactive immune cells. Initial therapy often involves a combination of chemotherapy agents, such as etoposide, and corticosteroids like dexamethasone, to induce remission. Immunomodulatory drugs, such as cyclosporine, may also be used to suppress the immune system. For infants with central nervous system involvement, chemotherapy may be administered directly into the spinal fluid. For primary HLH, hematopoietic stem cell transplantation (HSCT) is considered a curative option, replacing the defective immune system with healthy cells from a donor.
Outlook and Ongoing Care
With timely diagnosis and appropriate treatment, the outlook for infants with HLH has improved significantly, although it remains a serious condition. Rapid initiation of therapy is important to prevent severe organ damage and improve survival rates. For primary HLH, while chemotherapy and immunotherapy can temporarily control the disease, symptoms often recur, making stem cell transplantation the only curative treatment.
Ongoing monitoring is necessary to detect any potential relapses or long-term complications, especially for those who have received a stem cell transplant. A multidisciplinary care team, including hematologists, oncologists, and other specialists, is often involved in providing comprehensive care and managing potential issues following treatment.