From the Guidelines
Hyperreactive malarial splenomegaly (HMS) is a complex condition that develops through an exaggerated immune response to chronic or recurrent malarial infection, involving polyclonal B-cell activation, excessive production of IgM antibodies, and immune complex deposition in the spleen. The mechanism of HMS is characterized by repeated malaria infections triggering an immune response, particularly in genetically predisposed individuals, as suggested by studies on the aetiology of fever in returning travellers and migrants 1. Initially, the immune response leads to the production of IgM antibodies and immune complexes, which deposit in the spleen, causing persistent activation of splenic macrophages and subsequent splenomegaly.
Key Features of HMS
- The spleen enlarges progressively as it traps and destroys both infected and uninfected red blood cells, resulting in hypersplenism
- Increased levels of circulating cytokines, particularly TNF-alpha, further stimulate B-cell proliferation and IgM production, creating a self-perpetuating cycle
- Clinically, patients develop massive splenomegaly, anemia, and sometimes thrombocytopenia and leukopenia due to hypersplenism The diagnosis of malaria, which is a precursor to HMS, should be considered in any patient presenting with a fever who has ever travelled to an area where malaria is endemic, as outlined in guidelines for the management of severe malaria in children 1.
Treatment and Prevention
- Treatment involves antimalarial prophylaxis with medications like chloroquine or proguanil for at least 6-12 months to break the cycle of HMS
- In some cases, splenectomy may be considered for severe cases unresponsive to medical therapy, though this carries significant risks including overwhelming post-splenectomy infection It is essential to note that the condition is most prevalent in endemic malaria regions, particularly in Africa, Papua New Guinea, and parts of South America, affecting individuals with long-term exposure to malaria parasites.
From the Research
Mechanism of Hyperreactive Malarial Splenomegaly
The mechanism of hyperreactive malarial splenomegaly involves an intense immune reaction, predominantly B cell-driven, to repeated or chronic infections with Plasmodium sp. 2. This aberrant immunological response leads to the production of high levels of total immunoglobulin M and anti-Plasmodium antibodies 2, 3. The chronic antigenic stimulation derived from the malaria parasite causes a massive enlargement of the spleen, resulting in hyperreactive malarial splenomegaly syndrome (HMSS) 4, 5.
Key Factors Contributing to HMSS
- Chronic malaria exposure in endemic areas 6, 2
- Aberrant immunological response to Plasmodium sp. 2
- High levels of total immunoglobulin M and anti-Plasmodium antibodies 2, 3
- Genetic predisposition in some patients 3
- Residence in malaria-endemic countries or areas 4, 5
Diagnostic Criteria for HMSS
- Persistent gross splenomegaly 6, 4
- Elevated anti-malarial antibodies 6, 4
- IgM titre >2 SD above the local mean value 4
- Favourable response to long-term malaria prophylaxis or antimalarial treatment 6, 4
- Exclusion of other causes of splenomegaly or malignancy 6
Treatment and Management of HMSS
- Antimalarial therapy, such as artemisinin-based combination therapy or weekly chloroquine, is effective in treating HMSS 6, 4
- Short-term antimalarial treatment may be sufficient for patients not re-exposed to endemic areas 4
- Longer courses or intermittent treatments may be required for those who remain exposed to malaria-endemic areas 4
- Splenectomy should be strictly limited to cases not responding to medical treatment due to high mortality rates 4