History

The most common presenting symptoms of hyperreactive malarial syndrome (HMS) are chronic abdominal swelling (64%) and pain (52%).^[3]Abdominal swelling may wax and wane, and pressure on the abdominal contents may lead to hernias and leg swelling; abdominal pain may be acute.

A history of chronic splenic enlargement differentiates HMS from simple malarial splenomegaly. Extensive travel history should be taken, including travel in the distant past to endemic areas, in patients who present with massive splenomegaly. HMS may develop years after returning home in expatriates and visitors.

Almost all patients report weight loss.

Many patients do not have any symptoms and are capable of normal daily activity. Patients adapt physiologically to chronic anemia and are symptomatic only when it is severe. Weakness, loss of energy, and headache may signify severe anemia.

Rarely, patients have intermittent fever. Persistent, severe fever should raise the possibility of an alternative diagnosis.^[25]

Bleeding complications such as epistaxis are uncommon because thrombocytopenia is usually not severe.

Susceptibility to skin and respiratory infections is slightly increased.

Pregnant women are susceptible to episodes of massive Coombs-negative hemolysis, which are usually preceded by febrile episodes. Coombs-positive hemolysis is associated rarely with acute attacks of Plasmodium vivax malaria.^[26]

Physical

Patients with hyperreactive malarial syndrome (HMS) are usually afebrile at presentation. Pallor is common, and the patient may be malnourished and jaundiced.

In general, tachycardia is absent. If tachycardia is present, it indicates a concurrent complication.

The hallmark of HMS is moderate-to-massive splenomegaly. Few spleens (around one third) are tender, and almost all have a smooth surface, soft consistency, and sharp border.^[24]The enlarged spleen may be seen to protrude against the abdominal wall, and a splenic bruit may be audible. Despite the size of the spleen, splenic rupture is rare.

Extensive travel history should be taken, including travel in the distant past to endemic areas, in patients who present with massive splenomegaly. HMS may develop years after returning home in expatriates and visitors.

Hepatomegaly is common; in a study of 69 Nigerian patients, 93% had accompanying hepatomegaly.^[3] Ascites is uncommon.

Dilatation of the veins, cardiomegaly, low blood pressure, and flow murmurs reflect hypervolemia.

Lymphadenopathy is absent, but bilateral parotid swelling has been described.

Causes

The most important predisposing factor for hyperreactive malarial syndrome (HMS) is residence in or visitation to an area where malaria is endemic. Other risk factors include malnutrition and an as-yet-undefined genetic predisposition.

A study by Gai et al found that in the southern Indian city of Mangaluru (Mangalore), the rate of splenomegaly in patients with malaria caused by Plasmodium falciparum (29.6%) was higher than that in patients with Plasmodium vivax malaria (16.6%).^[27]

Differential Diagnoses

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Bryceson A, Fakunle YM, Fleming AF, et al. Malaria and splenomegaly. Trans R Soc Trop Med Hyg. 1983. 77(6):879. [QxMD MEDLINE Link].
Fakunle YM. Tropical splenomegaly. Part 1: Tropical Africa. Clin Haematol. 1981 Oct. 10(3):963-75. [QxMD MEDLINE Link].
Facer CA, Crane GG. Hyperreactive malarious splenomegaly. Lancet. 1991 Jul 13. 338(8759):115-6. [QxMD MEDLINE Link].
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Alkadarou T, Musa A, Alkadarou A, Mahfouz MS, Troye-Blomberg M, Elhassan AM. Immunological characteristics of hyperreactive malarial splenomegaly syndrome in sudanese patients. J Trop Med. 2013. 2013:961051. [QxMD MEDLINE Link].
David-West AS. Relapses after withdrawal of proguanil treatment in tropical splenomegaly syndrome. Br Med J. 1974 Aug 24. 3(5929):499-501. [QxMD MEDLINE Link].
Singh RK. Hyperreactive malarial splenomegaly in expatriates. Travel Med Infect Dis. 2007 Jan. 5(1):24-9. [QxMD MEDLINE Link].
Pryor DS. Tropical splenomegaly in New Guinea. Q J Med. 1967 Jul. 36(143):321-36. [QxMD MEDLINE Link].
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Crane GG, Wells JV, Hudson P. Tropical splenomegaly syndrome in New Guinea. I. Natural history. Trans R Soc Trop Med Hyg. 1972. 66(5):724-32. [QxMD MEDLINE Link].
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De Iaco G, Saleri N, Perandin F, et al. Hyper-reactive malarial splenomegaly in a patient with human immunodeficiency virus. Am J Trop Med Hyg. 2008 Feb. 78(2):239-40. [QxMD MEDLINE Link].
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Martin-Peprah R, Bates I, Bedu-Addo G, Kwiatkowski DP. Investigation of familial segregation of hyperreactive malarial splenomegaly in Kumasi, Ghana. Trans R Soc Trop Med Hyg. 2006 Jan. 100(1):68-73. [QxMD MEDLINE Link].
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Allam MM, Alkadarou TA, Ahmed BG, et al. Hyper-reactive Malarial Splenomegaly (HMS) in malaria endemic area in Eastern Sudan. Acta Trop. 2008 Feb. 105(2):196-9. [QxMD MEDLINE Link].
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Media Gallery

Young patient with hepatomegaly and massive splenomegaly.

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Author

Mundeep K Kainth, DO, MPH Assistant Professor of Pediatric Infectious Diseases, Cohen Children's Medical Center; City Medical Specialist, Bureau of School Health, Division of Family and Child Health, New York City Department of Health and Mental Hygiene; General Pediatrician, Island Pediatric Associates

Mundeep K Kainth, DO, MPH is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Coauthor(s)

Mudra Kumar, MD, MRCP, FAAP Professor of Pediatrics, Course Director, Course 6 MSII, Preclerkship Director, Clinical Integration, Department of Pediatrics, University of South Florida Morsani College of Medicine

Mudra Kumar, MD, MRCP, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK) Professor Emeritus of Pediatrics, Albany Medical College; Chief of Pediatric Oncology, Homi Bhabha Cancer Hospital, Varanasi, India

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK) is a member of the following medical societies: Children's Oncology Group, International Society of Pediatric Oncology

Disclosure: Nothing to disclose.

Additional Contributors

J Martin Johnston, MD Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Hematology/Oncology, The Children's Hospital at Memorial University Medical Center; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, International Society of Paediatric Oncology

Disclosure: Nothing to disclose.