Introduction
Tropical splenomegaly syndrome (TSS), also known as hyperreactive malarial splenomegaly syndrome, is a medical condition that affects individuals living in areas where malaria is endemic. The condition is characterized by an enlarged spleen, anemia, and other symptoms that may resemble those of malaria. This article will discuss the causes, symptoms, diagnosis, and treatment of TSS.
What Is the Cause of Tropical Splenomegaly Syndrome?
The exact reason why tropical splenomegaly syndrome (TSS) occurs is not fully known. However, it is thought that repeated malarial infections and other factors in the body can cause the immune system to produce too much of a certain type of antibody called IgM. This IgM then forms clumps with other proteins in the body and gets deposited in certain cells in the liver and spleen. This can cause those organs to become larger than normal and lead to anemia (low red blood cells).
TSS is most commonly found in malaria-endemic areas, and high levels of malarial antibodies can be detected in patients with the condition. Anti-malarial treatment has been shown to reduce the size of the spleen, indicating a response to treatment. However, premature discontinuation of treatment may lead to a relapse of TSS. Effective malarial chemoprophylaxis has been demonstrated to reduce the incidence of TSS as well as spleen rates.
Individuals with sickle cell trait are relatively protected from TSS, as with malaria. Animal models have been developed to show a similar clinical syndrome after malarial infection, further supporting the relationship between TSS and chronic malaria infection.
In summary, while the exact mechanism of TSS remains unclear, evidence suggests that chronic malaria infection, in combination with unknown host factors, may trigger an overactive immune response that leads to the formation of macromolecular aggregates, deposition in the liver and spleen, and subsequent development of TSS. The prevalence of TSS is highest in malaria-endemic areas, and effective anti-malarial treatment and chemoprophylaxis can reduce the incidence of TSS.
What Are the Symptoms?
The symptoms of TSS may vary from person to person and may resemble those of malaria. The most common symptom is an enlarged spleen, which can cause discomfort or pain in the left upper abdomen. Other symptoms may include:
-
Anemia.
-
Weight loss.
-
Night sweats.
-
Chills.
-
Malaise.
-
Joint pain.
-
Abdominal pain.
-
Nausea and vomiting.
-
Enlarged liver.
How to Diagnose This Condition?
Diagnosis of TSS can be challenging as the symptoms may resemble those of other diseases, particularly malaria. The initial stage of diagnosis involves excluding other potential factors that can cause an enlarged spleen, such as liver disease, lymphoma, or leukemia.
The physician performs a physical exam to check for an enlarged spleen and orders blood tests to assess for anemia, liver and kidney function, and the presence of malaria parasites. Imaging tests, such as ultrasound, CT scan, or MRI, may also be used to visualize the spleen and liver and assess for any abnormalities.
A definitive diagnosis of TSS may require a spleen biopsy, which involves the removal of a small tissue sample from the spleen for examination under a microscope. This procedure is generally carried out under local anesthesia and necessitates a hospital stay of a few days.
In addition to the steps mentioned earlier, the following major and minor criteria can help in confirming the diagnosis:
Major Criteria:
-
Gross splenomegaly ten centimeters or more below the costal margin in adults for which no 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 six months after the start of therapy.
-
High antibody levels of Plasmodium species (≥1:800).
Minor Criteria:
-
Hepatic sinusoidal lymphocytosis.
-
Normal cellular and humoral responses to antigenic challenge, including a normal Phyto hemagglutination response.
-
Hypersplenism.
-
Lymphocytic proliferation.
-
Familial occurrence.
What Is the Treatment of Tropical Splenomegaly Syndrome?
- Medical Care: The primary mode of therapy for Tropical Splenomegaly Syndrome (TSS) involves the use of antimalarial drugs. Antimalarial drugs are the only treatment for HMS, but the optimal drug and duration of treatment are unclear. The choice of drug depends on the pattern of drug resistance in the region. Response to treatment may take time, and relapses are common. Chloroquine, Proguanil, and Pyrimethamine have been found to be effective, but drug resistance is a concern. Fixed-dose drug combinations such as Atovaquone-Proguanil or Artemether-Lumefantrine may be used if resistance is suspected. Mefloquine can also be used but may have severe side effects. Chemoprophylaxis in endemic areas and its duration are also unclear.
A retrospective longitudinal study conducted by Bisoffi et al. indicated that patients with early TSS should receive the same treatment as those with full-blown syndrome. This is because early TSS may predispose patients to the more advanced form of the condition. According to the study, it was discovered that patients with early HMS face a substantial risk of TSS progression when re-exposed to malaria. While a single course of antimalarial treatment may be sufficient against early TSS, antimalarial prophylaxis should be used in re-exposed patients to prevent further progression of the condition.
-
Surgical Care: Surgical intervention is not a viable option for treating hyperreactive malarial syndrome (HMS), and splenectomy should be avoided. This is because splenectomy can lead to severe infections with a high mortality rate.
-
Consultations: In order to rule out diseases that resemble hyperreactive malarial syndrome (HMS), it may be necessary to seek consultations with specialists in metabolic and infectious diseases, as well as oncologists.
What Are the Potential Differential Diagnosis for a Patient With Tropical Splenomegaly?
Below are the possible differential diagnoses practitioners and physicians should think of and rule out:
-
Brucellosis
-
B-cell lymphoproliferative
-
Felty syndrome
-
EBV infectious mononucleosis
-
SCD
-
Tuberculosis
-
Leishmania
How to Prevent It?
In order to minimize mosquito exposure and lower the risk of malaria transmission in areas where the disease is prevalent, travelers should adopt various precautionary measures. These include wearing long-sleeved clothing and pants tucked into socks, using N, N-diethyl-meta-toluamide (DEET) spray with a concentration of 25 to 35 percent, utilizing bed nets, and taking prescribed antimalarial medications for chemoprophylaxis. For individuals residing in endemic regions, additional measures such as eliminating stagnant water and employing insecticides near homes can aid in reducing the mosquito population. It is also recommended that the local population follow the same precautions as travelers to prevent malaria.
What Is the Recommended Follow-up Protocol?
It is crucial to schedule regular appointments to track the patient's clinical progress and record reductions in splenomegaly. If chloroquine is administered, ophthalmologic effects should be closely monitored through a slit lamp, funduscopic, and visual field exams. Conduct cardiovascular monitoring with ECG and echocardiography, and other relevant tests periodically. Additional investigation may be necessary to examine myopathy and peripheral neuritis. Liver function tests may also be carried out regularly for those receiving proguanil.
Conclusion
Tropical splenomegaly syndrome (TSS) is a condition that occurs in areas where malaria is common and can cause an overactive immune response leading to macromolecular aggregates in the liver and spleen. Antimalarial drugs are the primary treatment for TSS, and surgical intervention should be avoided. Preventative measures such as wearing protective clothing, applying insect repellent, and taking antimalarial medication can help reduce the risk of developing TSS in endemic areas.
