Tropical Splenomegaly Syndrome Workup

  • Author: Vikramjit S Kanwar, MD, MBA, MRCP(UK), FAAP; Chief Editor: Robert J Arceci, MD, PhD   more...
 
Updated: May 9, 2012
 

Laboratory Studies

Diagnostic criteria for hyperreactive malarial syndrome

The mere exclusion of other disease processes causing splenomegaly is insufficient to establish a diagnosis of hyperreactive malarial syndrome (HMS). Fakunle was the first to establish diagnostic criteria for the definitive diagnosis of HMS.[3] Bates and Bedu-Addo refined these major criteria in 1997 to the current accepted list.[5] When these stricter criteria are applied, as many as one half of patients with splenomegaly may not have HMS.

Major criteria include the following:

  • Gross splenomegaly 10 cm or more below the costal margin in adults for which no other cause can be found
  • Elevated serum IgM level 2 standard deviations or more above the local mean
  • Clinical and immunologic responses to antimalarial therapy
  • Regression of splenomegaly by 40% by 6 months after start of therapy
  • High antibody levels of Plasmodium species (≥ 1:800)

Minor criteria include the following

  • Hepatic sinusoidal lymphocytosis
  • Normal cellular and humoral responses to antigenic challenge, including a normal phytohemagglutination response
  • Hypersplenism
  • Lymphocytic proliferation
  • Familial occurrence

Hematologic manifestations

  • Normocytic normochromic anemia is almost always present and is related to the degree of splenomegaly. Several factors contribute to its etiology, including pooling of RBCs in the spleen, hypersplenism, and increased RBC destruction and turnover; however, the major factor is increased plasma volume. The reticulocyte count is increased and reflects erythroid hyperplasia. The anemia is Coombs negative. Deficiency of vitamin B12, folic acid, or glucose-6-phosphate dehydrogenase has not been demonstrated.
  • Leukopenia is common and is sometimes associated with lymphocytosis.
  • Thrombocytopenia is generally mild. Both neutropenia and thrombocytopenia are due to splenic trapping.
  • Peripheral smears usually do not reveal the malarial parasite.

Other findings

  • IgM levels are increased. An elevation of 2 standard deviations above the local mean should be present. Serum IgM levels are correlated with the degree of splenomegaly.
  • Patients with HMS have high titers of malarial antibodies.
  • Titers of cold agglutinins, rheumatoid factor, antinuclear factor, cryoproteins, and thyroglobulins may be high.[22]
  • Serologies for cytomegalovirus (CMV), toxoplasmosis, Epstein-Barr virus (EBV), human herpesvirus 6 (HH6), parvovirus B19, and schistosomiasis may be false-positive.[23]
Next

Imaging Studies

  • Imaging tests are of limited value.
  • Ultrasonography of the abdomen may help to document and monitor hepatosplenomegaly.
Previous
Next

Other Tests

  • Polymerase chain reaction (PCR) has been used to detect low-level parasitemia in patients with HMS, and multiplex PCR can identify the species of Plasmodium involved. Because of its cost and complexity, this technique is not in widespread use. Unfortunately, simple rapid malaria tests, such as the ICT Malaria Test, often fail to detect the low level of antigenemia in HMS.[23]
  • A phytohemagglutination stimulation test may be helpful for differentiating HMS from lymphomas and chronic lymphocytic leukemia, for which the result is abnormal.
Previous
Next

Histologic Findings

  • Liver biopsy is rarely indicated.
  • Hepatic sinusoidal lymphocytosis is present in HMS.
  • Unlike with malaria, malarial pigmentation is absent in the macrophages in patients with HMS. This picture may also be present in infectious mononucleosis, hairy cell leukemia, malignant histiocytosis, and Felty syndrome.
  • Kupffer cell hypertrophy and hyperplasia are also present.
Previous
Proceed to Treatment & Management
 
 
Contributor Information and Disclosures
Author

Vikramjit S Kanwar, MD, MBA, MRCP(UK), FAAP  Associate Professor of Pediatric Hematology and Oncology, Department of Pediatrics, Albany Medical Center; Faculty, Alden March Bioethics Institute

Vikramjit S Kanwar, MD, MBA, MRCP(UK), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and Royal College of Physicians of the United Kingdom

Disclosure: Nothing to disclose.

Coauthor(s)

Mundeep K Kainth, DO  Resident Physician, Department of Pediatrics, The Children's Hospital at Albany Medical Center

Mundeep K Kainth, DO is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

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 and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

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; Assistant 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 Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

Helen SI Chan, MBBS, FRCP(C), FAAP  Associate Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto Faculty of Medicine, Canada

Helen SI Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD  King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Mudra Kumar, MD, MBBS, to the original writing and development of this article.

References

  1. Pitney WR. The tropical splenomegaly syndrome. Trans R Soc Trop Med Hyg. 1968;62(5):717-28. [Medline].

  2. Bryceson A, Fakunle YM, Fleming AF, et al. Malaria and splenomegaly. Trans R Soc Trop Med Hyg. 1983;77(6):879. [Medline].

  3. Fakunle YM. Tropical splenomegaly. Part 1: Tropical Africa. Clin Haematol. Oct 1981;10(3):963-75. [Medline].

  4. Facer CA, Crane GG. Hyperreactive malarious splenomegaly. Lancet. Jul 13 1991;338(8759):115-6. [Medline].

  5. Bates I, Bedu-Addo G. Review of diagnostic criteria of hyper-reactive malarial splenomegaly. Lancet. Apr 19 1997;349(9059):1178. [Medline].

  6. Crane GG. Hyperreactive malarious splenomegaly (tropical splenomegaly syndrome). Parasitol Today. Jan 1986;2(1):4-9. [Medline].

  7. Hoffman SL, Piessens WF, Ratiwayanto S, et al. Reduction of suppressor T lymphocytes in the tropical splenomegaly syndrome. N Engl J Med. Feb 9 1984;310(6):337-41. [Medline].

  8. Piessens WF, Hoffman SL, Wadee AA, et al. Antibody-mediated killing of suppressor T lymphocytes as a possible cause of macroglobulinemia in the tropical splenomegaly syndrome. J Clin Invest. Jun 1985;75(6):1821-7. [Medline]. [Full Text].

  9. Singh RK. Hyperreactive malarial splenomegaly in expatriates. Travel Med Infect Dis. Jan 2007;5(1):24-9. [Medline].

  10. Lowenthal MN, Hutt MS, Jones IG, Mohelsky V, O'Riordan EC. Massive splenomegaly in Northern Zambia. I. Analysis of 344 cases. Trans R Soc Trop Med Hyg. 1980;74(1):91-8. [Medline].

  11. Bedu-Addo G, Bates I. Causes of massive tropical splenomegaly in Ghana. Lancet. Aug 10 2002;360(9331):449-54. [Medline].

  12. Pryor DS. Tropical splenomegaly in New Guinea. Q J Med. Jul 1967;36(143):321-36. [Medline].

  13. 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. [Medline].

  14. Fakunle YM, Greenwood BM. Mortality in tropical splenomegaly syndrome. Trans R Soc Trop Med Hyg. 1980;74(3):419. [Medline].

  15. Bates I, Bedu-Addo G, Bevan DH, Rutherford TR. Use of immunoglobulin gene rearrangements to show clonal lymphoproliferation in hyper-reactive malarial splenomegaly. Lancet. Mar 2 1991;337(8740):505-7. [Medline].

  16. 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. Feb 2008;78(2):239-40. [Medline]. [Full Text].

  17. 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. Jan 2006;100(1):68-73. [Medline].

  18. Van den Ende J, van Gompel A, van den Enden E, et al. Hyperreactive malaria in expatriates returning from sub-Saharan Africa. Trop Med Int Health. Sep 2000;5(9):607-11. [Medline].

  19. Allam MM, Alkadarou TA, Ahmed BG, et al. Hyper-reactive Malarial Splenomegaly (HMS) in malaria endemic area in Eastern Sudan. Acta Trop. Feb 2008;105(2):196-9. [Medline]. [Full Text].

  20. Verma S, Aggarwal A. Hyper-reactive malarial splenomegaly: rare cause of pyrexia of unknown origin. Indian J Pediatr. Apr 2007;74(4):409-11. [Medline].

  21. Mitjà O, Hays R, Malken J, Ipai A, Kangapu S, Robson J. HMS-related hemolysis after acute attacks of Plasmodium vivax malaria. Am J Trop Med Hyg. Oct 2011;85(4):616-8. [Medline].

  22. Torres JR, Villegas L, Perez H, et al. Low-grade parasitaemias and cold agglutinins in patients with hyper-reactive malarious splenomegaly and acute haemolysis. Ann Trop Med Parasitol. Mar 2003;97(2):125-30. [Medline].

  23. Mothe B, Lopez-Contreras J, Torres OH, Munoz C, Domingo P, Gurgui M. A case of hyper-reactive malarial splenomegaly. The role of rapid antigen-detecting and PCR-based tests. Infection. Mar 2008;36(2):167-9. [Medline]. [Full Text].

  24. Manenti F, Porta E, Esposito R, Antinori S. Treatment of hyperreactive malarial splenomegaly syndrome. Lancet. Jun 4 1994;343:1441-2. [Medline].

  25. [Best Evidence] Aponte JJ, Aide P, Renom M, et al. Safety of the RTS,S/AS02D candidate malaria vaccine in infants living in a highly endemic area of Mozambique: a double blind randomised controlled phase I/IIb trial. Lancet. Nov 3 2007;370(9598):1543-51. [Medline].

 
Previous
Next
 
Young patient with hepatomegaly and massive splenomegaly.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.