The hyper-reactive malarial splenomegaly: a systematic review of the literature

Abstract

BackgroundThe hyper-reactive malarial splenomegaly syndrome (HMS) is a leading cause of massive splenomegaly in malaria-endemic countries. HMS is caused by a chronic antigenic stimulation derived from the malaria parasite. Classic Fakunle’s major criteria for case definition are: persistent gross splenomegaly, elevated anti-malarial antibodies, IgM titre >2 SD above the local mean value and favourable response to long-term malaria prophylaxis. The syndrome is fatal if left untreated. The aim of this study is to systematically review the literature about HMS, particularly focussing on case definition, epidemiology and management.MethodsThe search strategy was based on the following database sources: Pubmed, EmBase, Scopus. Search was done in March, 2014 and limited to English, Spanish, Italian, French, and Portuguese.ResultsPapers detected were 149, of which 89 were included. Splenomegaly was variably defined and the criterion of increased IgM was not always respected. The highest prevalence was reported in Papua New Guinea (up to 80%). In different African countries, 31 to 76% of all splenomegalies were caused by HMS. Fatality rate reached 36% in three years. The most frequent anti-malarial treatments administered were weekly chloroquine or daily proguanil from a minimum of one month to lifelong. In non-endemic countries, a few authors opted for a single, short anti-malarial treatment. All treated patients with no further exposure improved. Cases not completely fulfilling Fakunle’s criteria and therefore untreated, subsequently evolved into HMS. It seems thus appropriate to treat incomplete or ‘early’ HMS, too.ConclusionsFor patients not re-exposed to endemic areas, a short course of treatment is sufficient, showing that eradicating the infection is sufficient to cure HMS. Longer (probably lifelong) courses, or intermittent treatments, are required for those who remain exposed. Splenectomy, associated with high mortality, should be strictly limited to cases not responding to medical treatment.

Anesthetic Implications of Malarial Infection in a Child

“…The enlarged spleen can be injured in blunt abdominal trauma with splenic rupture presenting as hemoperitoneum or hemothorax. Acute acalculous cholecystitis has been reported in children with falciparum and vivax malaria [16,25,26].…”

Treatment with Doxycycline is Associated with Reduced Spleen Size in Hyper-Reactive Malarial Splenomegaly: A Cohort Study

“…Malaria is sub-acute and patients commonly exhibit pancytopenia in keeping with hypersplenism. The immune impairment and subsequent sepsis, in addition to splenic rupture, is the basis of the high associated mortality (4). This was reported as 37% at 6 years in Papua New Guinea, increasing with spleen size in a case series of 75 adults, and 26% at 10 years in another study (,).…”

Early hyperreactive malarial splenomegaly and risk factors for evolution into the full-blown syndrome: a single-centre, retrospective, longitudinal study

“…Although the exact mechanism is uncertain, evidence suggests that repeated or chronic exposure to malaria elicits exaggerated stimulation of polyclonal B lymphocytes, leading to excessive and partially uncontrolled production of immunoglobulin M (IgM) as the initiating event [ 3 ]. IgM is polyclonal and there is no evidence to attribute the syndrome to any malaria species in particular [ 1 ], although Plasmodium falciparum is by and large the predominant species in the countries where the syndrome has been described [ 4 ]. A history of chronic splenic enlargement [ 5 , 6 ] differentiates HMS from the splenomegaly observed in acute malaria.…”