Hemophagocytic lymphohistiocytosis (HLH) is a rare and severe disorder characterized by excessive activation of macrophages and lymphocytes, leading to abnormal destruction of blood cells. The disease can be either primary or secondary. Primary HLH is usually associated with genetic disorders, while secondary HLH may occur in the context of infections, neoplasia, or autoimmune diseases. The underlying pathophysiological mechanisms include excessive phagocytosis, inflammatory response, and cytokine storm, leading to complications and potentially life-threatening conditions.
History of the disease and interesting historical facts
As early as the beginning of the 20th century, doctors encountered rare cases of manifestations resembling hemophagocytic lymphohistiocytosis. In 1939, Dr. J. Ktsakos first described a case that was later recognized as the classification of HLH. However, it was not until 1991 that the disease was officially recognized after the development of schematic classifications and diagnostic criteria described in the work of an international group of experts. Of interest is that at the beginning of the 21st century, a variety of mutational changes were identified during the study of HLH, which opened up new horizons in understanding the molecular mechanisms and possible directions of therapy.
Epidemiology
Hemophagocytic lymphohistiocytosis is a rare pathological entity, but its frequency varies depending on the geographic region and age. On average, the incidence ranges from 1 to 2 cases per 100,000 population, with the majority of cases being registered in childhood, especially in infancy and early childhood. Statistical studies show that among children, the disease occurs in 7–10% cases, while among adults, this figure is significantly lower. It is also worth noting that secondary HLH is often observed against the background of infectious diseases, such as Epstein-Barr virus infection, which complements the overall picture of the prevalence of the disease.
Genetic predisposition to this disease
Research suggests that hemophagocytic lymphohistiocytosis may be associated with various genetic mutations. The major genes involved include:
- PRF1 (perforins) - mutations in this gene are associated with primary HLH and lead to impaired NK cell function;
- UNC13D - mutations in this gene also lead to a disruption of the exocytotic process in lymphocytes;
- RAB27A - changes in this gene contribute to the disruption of cellular adhesion and migration of macrophages;
- STX11 - mutations cause disturbances in cellular interactions.
These mutations create a predisposition to the disease and can cause its manifestations in various combinations with other genetic abnormalities.
Risk factors for the development of this disease
Hemophagocytic lymphohistiocytosis is associated with several risk factors, which can be divided into physical and chemical. These include:
- Infectious agents (Epstein-Barr virus, cytomegalovirus, group infections);
- Chemotherapy and bone marrow damage;
- Autoimmune diseases (eg, systemic lupus erythematosus, Crohn's disease);
- Long-term use of immunosuppressive therapy.
Paying attention to the listed factors allows you to take measures to prevent the development of the disease.
Diagnosis of this disease
The process of diagnosing hemophagocytic lymphohistiocytosis involves multiple steps and often requires a comprehensive approach. The main symptoms observed in HLH include:
- Fever;
- Hepatosplenomegaly;
- Cytopenia (lack of red and white blood cells, platelets);
- Hypersensitivity rash.
Key laboratory tests are:
- General blood test to detect cytopenia;
- Biochemical analysis, including ferritin levels, which are elevated in HLH;
- Research on the presence of infectious agents using serological and molecular methods.
Radiological examinations (ultrasound, CT) may be necessary to detect enlarged organs (spleen and liver). In some cases, a bone marrow biopsy is required for morphological analysis.
Treatment
Treatment of hemophagocytic lymphohistiocytosis requires an individual approach and is based on the underlying cause of the disease. In the case of primary HLH, the following is most often indicated:
- Immunosuppressive therapy (including glucocorticosteroids, drugs that suppress macrophage function);
- Chemotherapy in the presence of an oncological component;
- Plasmapheresis to reduce the level of free cytokines and correct hemodynamic changes;
- Stem cell transplantation in severe cases.
In secondary HLH, treatment of the underlying disease and the use of symptomatic therapy to manage manifestations are mandatory.
List of medications used to treat this disease
- Methylprednisolone;
- Dexamethasone;
- Cyclophosphamide;
- Vincristine;
- Ethamosin;
- Empirical antibiotics (if there is an infectious factor).
Disease monitoring
Monitoring of hemophagocytic lymphohistiocytosis includes monitoring of the main blood parameters, ferritin level, and organomegaly. It is necessary to regularly evaluate the patient's condition to determine the effectiveness of therapy and develop a further treatment strategy. The prognosis of survival in HLH depends on the timeliness of diagnosis and initiation of treatment, but in general there is a high risk of death, especially in the absence of an adequate approach to therapy. Complications may include multiple organ failure and sepsis, which require immediate action by the treating physicians.
Age-related features of the disease
Hemophagocytic lymphohistiocytosis exhibits different clinical manifestations depending on the age group. Severe forms with pronounced hyperreaction are more often observed in newborns and infants, while in adolescents and adults the disease may occur in a less severe form with fewer symptoms. In the elderly, the risk of secondary HLH against the background of concomitant pathologies increases significantly. Accordingly, approaches to diagnosis and treatment must be adapted in each age group.
Questions and Answers
- What is hemophagocytic lymphohistiocytosis?
Hemophagocytic lymphohistiocytosis is a rare disorder associated with macrophage hyperactivation and suppression of hematopoiesis, leading to multiple systemic abnormalities. - What are the most common symptoms of HLH?
The main symptoms of HLH include fever, hepatosplenomegaly, cytopenias, and general deterioration. - Is there a hereditary predisposition to hemophagocytic lymphohistiocytosis?
Yes, some forms of the disease have a genetic predisposition and are associated with mutations in certain genes. - What are the main diagnostic methods?
Diagnosis includes clinical symptoms, laboratory tests, and bone marrow biopsy to confirm the diagnosis. - Can HLH be treated with medication?
Yes, treatment most often includes immunosuppressive drugs, chemotherapy and support if needed, and may also require a transplant.
Advice from Dr. Oleg Korzhikov
Dr. Oleg Korzhikov recommends the following:
— Be sure to see a doctor if you experience the symptoms listed above. Early detection of HLH increases the chances of successful treatment.
- Support your immune system by avoiding stressful situations and regular check-ups.
— In case of chronic diseases that can contribute to the development of HLH, follow your doctor’s recommendations and monitor the dynamics of the condition.
A visit to a specialist is an important step towards effective treatment of hemophagocytic lymphohistiocytosis.
