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Enlarged Spleen

Abstract

Tropical splenomegaly syndrome also known as Hyperreactive malarial splenomegaly which happens due to an immune system overstimulation results from repeated malaria infections over an extended period of time, is a rare, chronic condition that is primarily observed in tropical and subtropical regions. Particularly people in habitants of West Africa, Southeast Asia and some parts of South America tend to catch this disease. Its main characterization is a massive enlargement of the spleen which is accompanied by other symptoms such as anemia, fatigue and an enlarged liver known as hepatomegaly. Researchers have linked this disease to immune system dysregulation [1], The disease was first published after several reports in 1979 [2] where it is most common to see individuals living in areas that had high rates of malaria and schistosomiasis as well as other infections that are parasitic. The exact cause of TSS is still unclear but it is believed that it is related to chronic infections particularly that include parasitic and viral agents. Treatment for this typically involves managing the underlying infections or conditions, but there is no specific cure for TSS. Its rarity and the broad spectrum of symptoms often make TSS a diagnostic challenge.

Signs and Symptoms

Tropical Splenomegaly Syndrome has both short term and long term signs and symptoms. In the shorter term of symptoms there's an inclusion of fatigue and general malaise. Temperature can rise resulting in fever (especially if associated with malaria or other infections). Individuals can notice signs of weight loss and poor appetite due to the spleens enlargement. There is feeling of fullness after even eating a little which can stay for periods of time [3]. That can overall lead to abdominal discomfort due to the enlarged organs. The body not having enough space to place the parts becomes harder on the infected person causing issues till it is taken care of. The symptoms can worsen over a long time when left untreated becoming permanent. Including progressive splenomegaly (marked enlargement of the spleen), which become very large and palpable. Hepatomegaly, enlargement of the liver. There is also the risk of Anemia the most common type in TSS is Normocytic normochromic anemia the type where the circulating red blood cells (RBCs) are the same size (normocytic) and have a normal red color (normochromic). Most of the normochromic, normocytic anemias are a consequence of other diseases indicating issues in iron metabolism or erythropoiesis. Some other long term symptoms that may follow are Edema, fluid retention, especially in the lower extremities. Lastly chronic infections remain due to immune system dysfunction [4]. The condition primarily affects the spleen, but can also involve the liver, bone marrow, and immune system. Leading patients to seek medical attention. There are some gaps in knowledge considering the exact pathogenesis of TSS remains unclear, and its connection to chronic parasitic or viral infections is not fully understood despite research efforts.

The spread of malaria shows a trend similar to where Tropical Splenomegaly Syndrome is

Cause

This disease is supposedly a result from immune dysregulation triggered by multiple infections. It is caused by chronic parasitic infections such as malaria, schistosomiasis, and filariasis, though the precise causing agent remains unknown. There are theories that viral infections have a contribution, especially in endemic regions such as tropical Africa, parts of Vietnam, New Guinea, India, Sri Lanka, Thailand, Indonesia, South America, and the Middle East [5]. The disease takes a toll more frequently in individuals living in tropical and subtropical areas with poor access to healthcare.

Like many points in science and research there is gaps in knowledge that the role of viral infections in the development of TSS has not been fully established and research into genetic or environmental risk factors is still ongoing.

Pathophysiology or Mechanism

The spleen and liver are primarily affected, as both organs play key roles in filtering blood and producing immune responses. This response is due to the chronic parasitic which make the immune system become hyperactive. Leading to persistent inflammation and immune cell activation causing the spleen to enlarge. Over time, the immune system becomes less efficient from the large amount of stress impacting it, contributing to the following problems splenomegaly, hepatomegaly, and anemia [6]. With the development of the disease researchers propose that TSS may be due to a genetic proneness because of environmental factors, such as prolonged exposure to infectious agents. It is also hypothesized that TSS may be linked to autoimmune responses, where the body’s immune system attacks its own tissues in response to the constant infections [7]. There is gaps in knowledge which is why the exact mechanisms by which chronic infection leads to splenomegaly and other systemic symptoms are still unclear, further studies are needed to fully understand the disease process [8].

Diagnosis

To diagnose Tropical Splenomegaly Syndrome, healthcare professionals such as general practitioner or tropical medicine specialist would start treatment. Beginning with blood tests that check for anemia, leukopenia and other possible abnormalities. A complete metabolic panel and complete blood count are useful for the initial assessment of potential hepatic and hematologic causes of splenomegaly. If hematologic abnormalities are identified or suspected, a peripheral blood smear would be requested for further evaluation. There would also be Ultrasound or CT scans that can evaluate the size of the spleen and liver [9]. Splenomegaly can commonly be identified during physical examination, though its detection depends on the patient's body type and the extent of spleen enlargement. The spleen is most effectively assessed when the patient is lying supine with knees bent and feet flat on the table, which helps relax the abdominal muscles. Percussion and palpation are useful for detecting splenomegaly, as the spleen cannot be felt if it is not enlarged it should be confirmed with an ultrasonography. As an extra measure parasite testing is also taken, consisting of blood smears and PCR tests help in identifying malaria and schistosomiasis. Another tests that can help is a bone marrow biopsy, it looks for abnormal cell growth and immune system dysfunction. There can be challenges when trying to diagnose the patient due to the nonspecific symptoms of fatigue, fever and weight loss that can overlap with other tropical diseases. Additionally, the rare nature of TSS means it may be misdiagnosed as a common infection or malignancy.

Treatment or Management

There is no specific cure for Tropical Splenomegaly Syndrome itself, therefore treatment is focused on managing the underlying infections or conditions contributing to the disease. Malarial chemoprophylaxis removal efforts have been linked to a reduction in Hyperreactive malarial splenomegaly. Antimalarial treatment have proven effective in reducing splenomegaly, which can correct anemia and lymphocytosis, and lower serum IgM levels in patients. However, discontinuation of prophylaxis in individuals from malaria endemic areas have been associated with relapse, which can occur anywhere from 2 to 18 months after the initial diagnosis [10]. The duration of treatment for malaria prevention depends on whether the patient continues to be exposed to malaria endemic regions. For patients who do not return to these infected states after initial exposure, a short course of antimalarial medication may be sufficient to achieve cure. However, for those who remain at risk due to ongoing exposure to malaria endemic regions, lifelong treatment may be necessary in increments to prevent relapse and manage the risk of infection [11].

Medications: Medication consists of anti-parasitic drugs such as chloroquine for malaria and praziquantel for schistosomiasis [12]. Antibiotics for secondary infections. Corticosteroids to manage inflammation in severe cases. There are surgical options as well for rare cases, splenectomy, removal of the spleen may be considered if the splenomegaly is life threatening and causing severe symptoms. Maintaining a balanced diet and addressing nutrient deficiencies such as iron and folic acid can support overall health. There have been some emerging treatments that research is ongoing into more targeted therapies for immune regulation in TSS.

Prognosis

The prognosis for individuals with TSS depends on several factors: age, the severity of the disease and how well the underlying infections are controlled. The age and stage of disease for younger individuals may have a better prognosis with proper treatment. Meanwhile older individuals may experience more complications. Chronic cases can result in persistent splenomegaly and complications like anemia or infection. The mortality rate ranges from 20% to 57%, with higher rates observed in patients who do not adhere to treatment [13]. In untreated individuals, the primary cause of death is severe infections. Hereditary and environmental factor for those living in endemic regions are at higher risk, and the progression may depend on their access to healthcare and early diagnosis. Development is expected if left untreated, TSS can lead to chronic illness and possibly organ failure in severe cases. A persons quality of life with the disease can significantly impact them due to ongoing symptoms like fatigue, pain from splenomegaly, and recurrent infections [14].

Epidemiology

Primarily found in tropical and subtropical regions, especially in areas endemic to malaria and other parasitic infections. Demographics show that age wise TSS is most commonly seen in young and middle ages adults, though children in endemic areas are also at risk. There is also some correlation seen in more females especially those that breastfeed and are lactating mother showing a 2:1 ratio between female and male. Geographically there is a higher prevalence in areas of West Africa, Southeast Asia, and parts of South America. Indigenous populations in these areas may be more affected due to higher rates of exposure to parasitic infections. By understanding the epidemiology of TSS it helps target public health efforts and reduce the burden of the disease in affected regions [17].

References

1. DO, K. (2023, October 27). Tropical Splenomegaly Syndrome: Practice Essentials, Pathophysiology, Epidemiology. Medscape.com; Medscape. https://emedicine.medscape.com/article/959720-overview?form=social
2. Long, A., Kleiner, A., & R. John Looney. (2023). Immune dysregulation. 151(1), 70–80. https://doi.org/10.1016/j.jaci.2022.11.001
3. Six Spleen Facts Every Myelofibrosis Patient Needs to Know. (2024). Voicesofmpn.com. https://www.voicesofmpn.com/mpn-blog/6-spleen-facts-for-myelofibrosis-patients
4. MARSDEN , P. D. “THE TROPICAL SPLENOMEGAL v SYNDROME a CURRENT APPRAISAL.” THE TROPICAL SPLENOMEGAL v SYNDROME a CURRENT APPRAISAL, www.revistas.usp.br/rimtsp/article/download/198028/182168/556048.
5. Elmakki, E. E. (2012). Hyper-reactive Malarial Splenomegaly Syndrome (HMSS): Review article. Cureus. https://doi.org/10.7759/cureus.72
6. CDC. (2024, May 9). Insecticide-Treated Nets. Malaria. https://www.cdc.gov/malaria/php/public-health-strategy/insecticide-treated-nets.html
7. Cleveland Clinic. (2022, June 5). Antiparasitic Drugs: Malaria, Toxoplasmosis, Parasitic Infection. Cleveland Clinic. https://my.clevelandclinic.org/health/drugs/22945-antiparasitic-drugs
8. Mónica R.A. Pachar-Flores, Suarez, J. A., Chen, R., González, J. A., Iván, N., Naranjo, L., Diaz, Y., & Franco-Paredes, C. (2023). TEMPORARY REMOVAL: Tropical splenomegaly in a migrant-in-transit crossing the Darien gap, Panamá: A probable case of hyper-reactive malarial splenomegaly. IDCases, 34, e01892–e01892. https://doi.org/10.1016/j.idcr.2023.e01892
9. Tropical splenomegaly syndrome. (1970). BMJ, 3(5719), 360–361. https://doi.org/10.1136/bmj.3.5719.360
10. Bedu-Addo, G., & Bates, I. (2002). Causes of massive tropical splenomegaly in Ghana. The Lancet, 360(9331), 449–454. https://doi.org/10.1016/s0140-6736(02)09680-0
11. Aldulaimi, S., & Mendez, A. M. (2021). Splenomegaly: Diagnosis and Management in Adults. American Family Physician, 104(2), 271–276. https://www.aafp.org/pubs/afp/issues/2021/0900/p271.html
12. Okunlola, A. O., Ajao, T. O., Mwila Sabi, Kolawole, O. D., Eweka, O. A., Karim, A., & Adebayo, T. E. (2024). Catastrophic Antiphospholipid Syndrome: A Review of Current Evidence and Future Management Practices. Cureus. https://doi.org/10.7759/cureus.69730
13. Leoni, S., Buonfrate, D., Angheben, A., Gobbi, F., & Bisoffi, Z. (2015). The hyper-reactive malarial splenomegaly: a systematic review of the literature. Malaria Journal, 14(1). https://doi.org/10.1186/s12936-015-0694-3
14. Berberian, D. A., & Dennis, E. W. (1949). The Effect of Chloroquine Diphosphate on Malaria Splenomegaly. The American Journal of Tropical Medicine and Hygiene, s1-29(4), 463–471. https://doi.org/10.4269/ajtmh.1949.s1-29.463
15. McGregor, A., Doherty, T., Lowe, P., Chiodini, P., & Newsholme, W. (2015). Hyperreactive Malarial Splenomegaly Syndrome—Can the Diagnostic Criteria Be Improved? The American Journal of Tropical Medicine and Hygiene, 93(3), 573–576. https://doi.org/10.4269/ajtmh.14-0234
16. Ziegler, J. L., & Stuiver, P. C. (1972). Tropical Splenomegaly Syndrome in a Rwandan Kindred in Uganda. BMJ. British Medical Journal, 3(5818), 79–82. https://doi.org/10.1136/bmj.3.5818.79
17. Allam, M. M., Alkadarou, T. A. M. Y., Ahmed, B. G., Elkhair, I. S., Alansary, E. H., Ibrahim, M. E., Elhassan, A. M., & Elhassan, I. M. (2008). Hyper-reactive Malarial Splenomegaly (HMS) in malaria endemic area in Eastern Sudan. Acta Tropica, 105(2), 196–199. https://doi.org/10.1016/j.actatropica.2007.10.002

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