Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome characterized by uncontrolled immune system activation, which leads to hyperinflammation and tissue damage.
Epidemiology
HLH is a rare condition, with an estimated incidence of 1 in 50,000 to 1 in 100,000 individuals. The incidence of HLH varies by age and underlying condition. The most common form of HLH is primary HLH, which is caused by genetic mutations and usually presents in early childhood. Secondary HLH, which is triggered by infections or other underlying conditions, is more common in adults. HLH has a higher incidence in individuals of Asian and African descent.
Etiology
HLH can be caused by a wide range of stimuli, including infections, autoimmune disorders, malignancies, and genetic mutations. Infectious triggers of HLH include viruses (e.g., Epstein-Barr virus, cytomegalovirus, and HIV), bacteria (e.g., Mycobacterium tuberculosis), and fungi (e.g., Histoplasma capsulatum).
Autoimmune disorders that can trigger HLH include systemic lupus erythematosus and rheumatoid arthritis. Malignancies that can trigger HLH include lymphoma and leukemia. Genetic mutations that cause primary HLH affect genes involved in the function of cytotoxic T cells and natural killer cells.
Clinical Presentation
Patients with HLH may also present with neurologic symptoms (e.g., seizures and altered mental status), skin rash, and lymphadenopathy. The symptoms of HLH can be nonspecific, which can make the diagnosis challenging.
Diagnosis
The diagnosis of HLH is based on clinical and laboratory parameters. The HLH-2004 diagnostic criteria, which were developed by the Histiocyte Society, are widely used for the diagnosis of HLH. The criteria include fever, splenomegaly, cytopenias affecting at least two cell lineages, hypertriglyceridemia or hypofibrinogenemia, and evidence of hemophagocytosis (i.e., the phagocytosis of blood cells by macrophages) in the bone marrow, spleen, or lymph nodes.
Additionally, patients must meet at least five of the following criteria: ferritin level >500 μg/L, soluble CD25 level >2,400 U/mL, elevated triglycerides (>265 mg/dL) or low fibrinogen (<150 mg/dL), elevated soluble interleukin-2 receptor (sIL-2R) level, decreased or absent natural killer cell activity, and elevated levels of aspartate aminotransferase or alanine aminotransferase.
Treatment
The treatment of HLH involves controlling the hyperinflammatory state with immunosuppressive therapy. The first-line treatment for HLH is dexamethasone, which is a potent corticosteroid that can suppress the immune system. Other immunosuppressive agents that are used to treat HLH include cyclosporine, etoposide, and intravenous immunoglobulin (IV gamma globulin).
In some cases, HLH may be refractory to first-line treatment, or it may recur after initial treatment. In these cases, second-line therapies may be considered, such as alemtuzumab, rituximab, or stem cell transplantation. Stem cell transplantation can be curative for patients with primary HLH, and it may also be considered in patients with secondary HLH who have a poor response to first-line therapy.
Complications and Prognosis
HLH is associated with a high risk of morbidity and mortality, with a reported mortality rate of up to 50% in untreated patients. The risk of mortality is higher in patients with underlying malignancies or severe infections. Complications of HLH can include multiorgan dysfunction, such as liver failure, acute respiratory distress syndrome (ARDS), and neurologic dysfunction. In addition, HLH can lead to long-term sequelae, such as chronic fatigue and cognitive impairment.
Post-COVID-19 Hemophagocytic Lymphohistiocytosis (HLH) is a rare but severe complication of COVID-19. It is a life-threatening hyperinflammatory syndrome that occurs due to uncontrolled immune activation. This condition can affect multiple organs and can lead to significant morbidity and mortality if not treated promptly. In this report, we will analyze all the research about Post-COVID-19 HLH, describing the nature of the problem, how it is treated, and the organs that are affected by this condition.
Nature of the Problem HLH is a rare but severe condition that occurs due to uncontrolled immune activation. Post-COVID-19 HLH occurs when the immune system overreacts to the virus and triggers a cytokine storm. The cytokine storm is a hyperinflammatory state that can lead to the destruction of multiple organs. The symptoms of HLH can vary, but the most common symptoms include fever, hepatosplenomegaly, cytopenia, and hyperferritinemia. The diagnosis of HLH is based on the HLH-2004 diagnostic criteria, which includes clinical and laboratory parameters.
Treatment
The treatment of Post-COVID-19 HLH involves controlling the hyperinflammatory state with immunosuppressive therapy. The first-line treatment for HLH is dexamethasone, which is a potent corticosteroid that can suppress the immune system. Other immunosuppressive agents that are used to treat HLH include cyclosporine, etoposide, and intravenous immunoglobulin (IVIG). The use of these agents should be closely monitored due to their potential side effects. In severe cases, patients may require treatment with mechanical ventilation and hemodialysis.
Organs Affected and Weaknesses Post-COVID-19 HLH can affect multiple organs, including the liver, spleen, bone marrow, and lymph nodes. The immune system attacks these organs, causing inflammation and tissue damage. This can lead to liver dysfunction, anemia, thrombocytopenia, and renal failure. Patients with HLH may also experience weakness, fatigue, and malaise due to the systemic inflammation.
Conclusion
Post-COVID-19 HLH is a severe complication of COVID-19 that can lead to significant morbidity and mortality. The diagnosis of HLH is based on clinical and laboratory parameters, and the treatment involves controlling the hyperinflammatory state with immunosuppressive therapy. The organs that are affected by HLH include the liver, spleen, bone marrow, and lymph nodes. It is important to monitor patients with COVID-19 for the development of HLH to ensure prompt treatment and reduce the risk of complications.
reference link :
- References
- Al-Samkari H, Berliner N: Hemophagocytic lymphohistiocytosis. Annu Rev Pathol. 2018, 13:27-49. 10.1146/annurev-pathol-020117-043625
- Hayden A, Park S, Giustini D, Lee AY, Chen LY: Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: a systematic scoping review. Blood Rev. 2016, 30:411-20. 10.1016/j.blre.2016.05.001
- Henter JI, Horne A, Aricó M, et al.: HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007, 48:124-31. 10.1002/pbc.21039
- La Rosée P, Horne A, Hines M, et al.: Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019, 133:2465-77. 10.1182/blood.2018894618
- Malinowska I, Machaczka M, Popko K, Siwicka A, Salamonowicz M, Nasiłowska-Adamska B: Hemophagocytic syndrome in children and adults. Arch Immunol Ther Exp (Warsz). 2014, 62:385-94. 10.1007/s00005-014-0274-1
- Stepp SE, Dufourcq-Lagelouse R, Le Deist F, et al.: Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science. 1999, 286:1957-9. 10.1126/science.286.5446.1957
- Sandler RD, Tattersall RS, Schoemans H, et al.: Diagnosis and management of secondary HLH/MAS following HSCT and CAR-T cell therapy in adults; a review of the literature and a survey of practice within EBMT centres on behalf of the Autoimmune Diseases Working Party (ADWP) and Transplant Complications Working Party (TCWP). Front Immunol. 2020, 11:524. 10.3389/fimmu.2020.00524
- Kim YR, Kim DY: Current status of the diagnosis and treatment of hemophagocytic lymphohistiocytosis in adults. Blood Res. 2021, 56:S17-25. 10.5045/br.2021.2020323
- Rouphael NG, Talati NJ, Vaughan C, Cunningham K, Moreira R, Gould C: Infections associated with haemophagocytic syndrome. Lancet Infect Dis. 2007, 7:814-22. 10.1016/S1473-3099(07)70290-6
- Risdall RJ, McKenna RW, Nesbit ME, Krivit W, Balfour HH Jr, Simmons RL, Brunning RD: Virus-associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis. Cancer. 1979, 44:993-1002. 10.1002/1097-0142(197909)44:3<993::aid-cncr2820440329>3.0.co;2-5
- Henter JI, Elinder G, Ost A: Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. Semin Oncol. 1991, 18:29-33.
- Hieber ML, Sprute R, Eichenauer DA, Hallek M, Jachimowicz RD: Hemophagocytic lymphohistiocytosis after SARS-CoV-2 vaccination. Infection. 2022, 50:1399-404. 10.1007/s15010-022-01786-y
- Liu JM, Chi J: Is COVID-19-associated cytokine storm distinct from non-COVID-19 secondary hemophagocytic lymphohistiocytosis?. Exp Biol Med (Maywood). 2022, 247:330-7. 10.1177/15353702211068840
- Ioannou M, Zacharouli K, Doukas SG, et al.: Hemophagocytic lymphohistiocytosis diagnosed by bone marrow trephine biopsy in living post-COVID-19 patients: case report and mini-review. J Mol Histol. 2022, 53:753-62. 10.1007/s10735-022-10088-4
- Kalita P, Laishram D, Dey B, Mishra J, Barman B, Barman H: Secondary hemophagocytic lymphohistiocytosis in post-COVID-19 patients: a report of two cases. Cureus. 2021, 13:e17328. 10.7759/cureus.17328
- Bandaru SS, Capace A, Busa V, Williams A: Secondary hemophagocytic lymphohistiocytosis in a post-COVID-19 patient. Cureus. 2022, 14:e22620. 10.7759/cureus.22620
- Prilutskiy A, Kritselis M, Shevtsov A, et al.: SARS-CoV-2 infection-associated hemophagocytic lymphohistiocytosis. Am J Clin Pathol. 2020, 154:466-74. 10.1093/ajcp/aqaa124
- Schnaubelt S, Tihanyi D, Strassl R, et al.: Hemophagocytic lymphohistiocytosis in COVID-19: case reports of a stepwise approach. Medicine (Baltimore). 2021, 100:e25170. 10.1097/MD.0000000000025170
- Fardet L, Galicier L, Lambotte O, et al.: Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome. Arthritis Rheumatol. 2014, 66:2613-20. 10.1002/art.38690
- Tholin B, Hauge MT, Aukrust P, Fehrle L, Tvedt TH: Hemophagocytic lymphohistiocytosis in a patient with COVID-19 treated with tocilizumab: a case report. J Med Case Rep. 2020, 14:187. 10.1186/s13256-020-02503-9
