Tropical Splenomegaly Research Articles

Fatal relapse of Hyperreactive Malarial Splenomegaly (HMS) in a 10-year old Nigerian female: A case report

The Hyperreactive Malarial Splenomegaly Syndrome (HMS) originally called the tropical splenomegaly syndrome (TSS) or Big spleen disease refers to cases of splenomegaly in the tropics for which no cause was found despite thorough investigation. It is restricted to the malarial belt, yet there are few reports on HMS in Nigeria, probably due to a low index of suspicion and non-availability of laboratory facilities to determine titres of malarial antibodies. The objective of this paper is to highlight the features, management, risk of relapse and prognosis of HMS. We present a 10-year old female with recurrent massive splenomegaly with previous clinical response to antimalarials and evidence of hypersplenism. HMS should be suspected in any child with moderate to massive splenomegaly with evidence of hypersplenism and clinical response to antimalarials.

Splenic Pseudocyst With Hypersplenism-Therapeutic Implications Of A Rare Association

Splenic conservation is the standard option in the management of pseudocyst of the spleen to prevent post splenectomy complications. They are usually treated by splenic decapsulation or partial splenectomy. Hypersplenism associated with pseudocyst is very rare and only three cases have been reported in world literature. Presence of hypersplenism necessitates splenectomy. Massive enlargement of spleen predisposes them to trauma and development of pseudocyst. In Countries with a high incidence of malaria and tropical splenomegaly, hypersplenism needs to be excluded, while considering surgical options in the management of pseudocyst of spleen. We report a rare case of a splenic pseudocyst associated with hypersplenism successfully managed by splenectomy.

Hyperreactive malarial splenomegaly in expatriates

Hyperreactive malarial splenomegaly, one of the major causes of splenomegaly in tropics, has been often reported in expatriates of non-tropical settings. Essential features are recurrent malarial infection, overproduction of IgM and hyperplasia of lymphoreticular system. The practice of diagnosing the condition by exclusion of obvious causes of splenomegaly in the tropics has been abandoned. There are specific criteria for the diagnosis. Huge splenomegaly >10 cm below costal margin, serum IgM more than 2 x standard deviation (2SD) above the local mean, high titre of malarial antibodies and response to antimalarial drugs are the cornerstones of the diagnosis. Splenic lymphoma with villous lymphocytes coexists with this condition and it should always be considered in the differential diagnosis of unresponsive or poorly responsive cases of hyperreactive malarial splenomegaly. Condition with fever and acute haemolysis in HMS has been termed as Fulminant tropical splenomegaly syndrome. Treatment of the condition depends on antimalarial (chloroquine/ proguanil/ pyrimethamine) chemoprophylaxis for 1 year or more.

Some Unusual Indications Of Splenectomy

While dealing with various hematological disorders which were subjected to therapeutic splenectomy in our department of general surgery at a tertiary care centre Sher-i-Kashmir Institute of Medical Sciences over a period of more than 20 years, we came across a rare group of diseases in our set up from time to time. This rare group included 5 patients with 1. Hairy cell leukemia -1, 2 Malignant histiocytoma -1, 3 Gaucher's disease -1, 4 Tropical splenomegaly -1, and 5 Splenic hemianginoma-1. All these patients were referred to our department from the department of clinical hematology of the same institute for splenectomy for various types of cytopenias. Response to splenectomy was excellent in malignant histiocytosis, splenic hemiangioma and some of the parameters in hairy cell leukemia and Gaucher's disease, while as an unsatisfactory response was observed in tropical splenomegaly sydrome and in some of the parameters of hairy cell leukemia and Gaucher's disease.

Surgical aspects of malaria

The spread of drug-resistant organisms and increased international travel makes malaria a disorder of ever-increasing importance. This report reviews those aspects of malaria of surgical relevance. The importance of the spleen in host defence against malaria and other infections makes splenic preservation desirable whenever possible after rupture of the spleen. Tropical splenomegaly is caused by an abnormal immune response to malaria and is best managed medically. Careful selection of blood donors is essential to prevent transfusion malaria, and routine antimalarial prophylaxis is indicated for blood recipients in many endemic areas. The risk of postoperative malaria may justify chemoprophylaxis in certain patients.

Massive Tropical Splenomegaly: Malaria and More

Many processes cause massive tropical splenomegaly, but data are lacking on their relative contributions. In this study, investigators sought to define

Causes of massive tropical splenomegaly in Ghana.

The causes and diagnosis of massive tropical splenomegaly are not well studied, especially with modern investigative methods. We aimed to identify features that would help local clinicians differentiate between the underlying conditions. We collected prospective clinical and laboratory data on 221 Ghanaian patients with spleen size of at least 10 cm. We identified conditions associated with massive splenomegaly with molecular and immunological investigations as well as routine tests. Patients were assigned to diagnostic categories on the basis of these test results and predetermined criteria. Hyper-reactive malarial splenomegaly (HMS; 91 patients [41%]) and B-lymphoproliferative disorders (48 [22%]) were the most common disorders associated with massive splenomegaly. Of the remaining patients, 32 (14%) had haematological disorders, and in 50 (23%) we could not identify the cause of splenomegaly. Male sex predominated in all diagnostic groups except HMS and tropical splenic lymphoma. Age less than 40 years and absolute lymphocyte count (less than 10 x 10(9)/L) were the only useful and widely available discriminators for distinguishing patients with HMS from those with lymphoproliferative disorders. B-lymphoproliferative disorders are a previously unrecognised cause of massive tropical splenomegaly. This finding has major implications for management of massive splenomegaly. Diagnosis of the less common causes of this disorder is usually straightforward, but differentiating between B-lympho proliferative disorders and HMS can be difficult. HMS is associated with younger age, a higher proportion of women, and lower absolute lymphocyte counts than lympho proliferative disorders.

Immunoglobulin gene polymerase chain reaction to distinguish hyperreactive malarial splenomegaly from ‘African’ chronic lymphocytic leukaemia and splenic lymphoma

Hyperreactive malarial splenomegaly (HMS) is found in geographical association with B cell lymphoproliferative disorders such as ‘African’ chronic lymphocytic leukaemia (CLL) and splenic lymphoma with villous lymphocytes (SLVL). It is sometimes not easy to make a differential clinical diagnosis between these conditions. We have previously used Southern blotting as a definitive method for the diagnosis of monoclonal lymphoproliferation in these disorders, but this is expensive, lengthy and technically difficult. In the present paper we have compared Southern blotting with polymerase chain reaction (PCR) amplification of the immunoglobulin heavy chain gene. We found an excellent correlation between the 2 methods in demonstrating monoclonal populations of lymphocytes in patients with a clinical diagnosis of CLL or SLVL. We have further demonstrated monoclonality in a patient who could not be classified as CLL or SLVL on clinical criteria alone. In contrast, patients with well defined HMS or with non-B cell proliferations all showed polyclonal rearrangements. We propose that the immunoglobulin gene PCR is a useful tool for the investigation of tropical splenomegaly of uncertain origin.

Non-Invasive Diagnosis of Tropical Splenomegaly Syndrome

A study of 41 clinically diagnosed cases of possible tropical splenomegaly syndrome (TSS) was undertaken in Mulago Hospital, Kampala, Uganda, to determine the appropriateness of liver ultrasonography in confirming a diagnosis of TSS. Definitive diagnosis of TSS was made on liver biopsy in 35 (85%) cases. Abdominal ultrasound showed that 30 of the confirmed cases of TSS had normal liver echo-texture and portal vein diameter, and five had abnormally increased liver echo-texture. The combination of massive splenomegaly and hepatomegaly, together with normal ultrasound features of the liver was highly suggestive of TSS. The sensitivity of this criterion was 86% and the specificity was 83%. This non-invasive approach to the diagnosis of TSS is associated with less hazards than liver biopsy, and a normal echogram could be used to make the diagnosis in over 80% of cases, in the field where histopathology may be lacking.

Tropical splenomegaly syndrome

Tropical splenomegaly syndrome

Use of immunoglobulin gene rearrangements to show clonal lymphoproliferation in hyper-reactive malarial splenomegaly

In Africa, hyper-reactive malarial splenomegaly (HMS), which is also known as tropical splenomegaly syndrome, can be associated with a prominent lymphocytosis in blood and bone marrow that is difficult to distinguish clinically from chronic lymphocytic leukaemia (CLL). The observation that some patients with HMS become resistant to treatment with anti-malarial drugs has led to the suggestion that HMS may evolve into a malignant lymphoproliferative disorder. To test this hypothesis, 22 Ghanaian patients with HMS and/or lymphocytosis were categorised by degree of response to proguanil according to standard clinical criteria, and DNA was extracted from peripheral blood cells and screened for rearrangements of the Jh region of the immunoglobulin gene with a DNA probe. Clonal rearrangements of the Jh region were found in all 3 patients with no response, in none of 13 patients with sustained response, and in 2 of 6 patients with moderate response or relapse on proguanil therapy. The detection of such rearrangements, and hence clonal lymphoproliferation in individuals with clinical features intermediate between HMS and CLL, supports the hypothesis that HMS may evolve into a malignant lymphoproliferative disorder.

Chronic Gaucher's disease masquerading as tropical splenomegaly syndrome in a Nigerian woman

Chronic Gaucher's disease masquerading as tropical splenomegaly syndrome in a Nigerian woman

Existe-t-il des facteurs prédictifs de l'évolution de la splénomégalie idiopathique non tropicale vers un lymphome ?

Idiopathic non tropical splenomegaly is characterized by an increased risk of lymphoma. Seven patients were studied retrospectively to evaluate possible predictive factors. Two patients presented with non Hodgkin lymphoma. The search for predictive criteria was negative except for spleen weight. These results indicate the necessity of long clinical survey and assesment by new biological methods (flow cytometry, molecular biology).

Tropical Splenomegaly Syndrome Associated with Cytomegalovirus Infection

The tropical splenomegaly syndrome (TSS) is characterized by massive splenomegaly with hypersplenism, moderate hepatomegaly, and lymphocytic infiltration of the hepatic sinusoids. In previous reports this syndrome has been shown to be a consequence of a disordered immunologic response of the host to malarial infection. Treatment with antimalarial drugs has resulted in a decrease in malarial antibody titers and a reduction in splenic size. We report a child who had TSS associated with cytomegalovirus infection rather than malaria. Our results suggest that TSS may be precipitated by a variety of infections producing chronic antigenic stimulation and perhaps by autoantigenic stimulation as well.

Absence of cross-reactivity between dengue and human immunodeficiency virus type 1 (HIV-1).

An association between malaria, schistosomia­ sis and tropical splenomegaly and human immunode­ ficiency virus type 1 (HIV-1) seropositivity has been observed in Africa1 2. Recently, the cross-reactivity between infection with Schistosoma mansoni and HIV-1 seropositivity was not confirmed in Brazil5. The potential cros-reactivity among other endemic of epidemic diseases in developing countries and HIV-1 has not been investigated as of yet. We studied the possible cross-reactivity between dengue (break bone fever) and HIV-1. In December, 1986 there were 3000 cases of dengue and 10 cases of Acquired Immunodeficiency Syndrome (AIDS) in Ceara State in Northeast of Brazil3 4. We analyzed sera of 89 individuals with dengue in this State (46 males and 43 females; mean age = 32 ± 16 years). All sera were tested by ELISA (Salk Dupont Laboratories) and all of them were negative for HIV-1 antibodies in at least two of three examinations. This result demonstrates that there was no cross-reactivity between dengue and HIV-1 in the investigated Brazilian patients.

Persistent gross splenomegaly in Nigerian patients with sickle cell anaemia: relationship to malaria

Serum IgM levels, hepatic histopathology, and response to prolonged proguanil treatment were investigated in 15 patients with sickle cell anaemia (SS), aged 8-15 years, with persistent gross splenomegaly (PGS). They were compared with age- and sex-matched SS patients without splenomegaly and with AA controls. The mean +/- SD serum IgM levels were 249.7 (75) mg/100 ml in the SS patients with PGS, 157.6(57.3) mg/100 ml in the SS patients without splenomegaly, and 146.2(48.9) mg/100 ml in the AA controls. The differences between these mean values were statistically significant (P less than 0.05). Hepatic histopathology in 11 of these patients showed moderate to severe sinusoidal dilatation and portal lymphocytic infiltration. Of the 13 patients that were followed on daily proguanil therapy, 10 showed remarkable reduction in splenic size within 6 months. The mean splenic size diminished by 13.8(3.2) cm to 5.6(5.3) cm over the period. The difference was statistically significant (P less than 0.01). This study has confirmed the previous belief that malaria plays a role in the aetiopathogenesis of persistent splenomegaly in sickle cell patients in a fashion similar to, but not quite the same as in, tropical splenomegaly syndrome (TSS). It also underscores the need for malaria chemoprophylaxis in these patients.

6 Tropical splenomegaly syndrome (TSS) and other diseases of the spleen

6 Tropical splenomegaly syndrome (TSS) and other diseases of the spleen

Chronic splenomegaly in Nairobi, Kenya. II. Portal hypertension

Eighty-five patients with chronic splenomegaly and proven oesophageal varices were studied at Kenyatta National Hospital, Nairobi. The major defined groups were hepatosplenic schistosomiasis (24%), cirrhosis (20%) and portal vein occlusion (11%). Hyper-reactive malarial splenomegaly (tropical splenomegaly syndrome) was considered as the cause of oesophageal varices in only one patient. In 26% of cases liver biopsy was non-diagnostic and the extrahepatic portal vein was demonstrated radiologically to be patent. Such patients were thought to be suffering from idiopathic portal hypertension, not previously described elsewhere in Africa. Hepatitis B surface antigen was detected in 12% of controls and in 58% of patients with cirrhosis (p < 0.001). Some serological marker of previous hepatitis B virus infection was present in 92% of patients with cirrhosis and in 79% of controls. Kamba patients from Machakos and Kitui Districts were significantly more prevalent than expected among these 85 cases of portal hypertension.

Chronic splenomegaly in Nairobi, Kenya. I. Epidemiology, malarial antibody and immunoglobulin levels

Chronic splenomegaly in 131 Kenyan patients was investigated at Kenyatta National Hospital, Nairobi. Patients were allocated to diagnostic groups on the basis of clinical, haematological, parasitological, histological, radiological and endoscopic data. The major diagnostic groups were hyper-reactive malarial splenomegaly, our preferred name for tropical splenomegaly syndrome, (31%), hepatosplenic schistosomiasis (18%), visceral leishmaniasis (5%) and “indeterminate splenomegaly”, where no diagnosis could be reached (12%). Another 20% of patients were suffering from various non-schistosomal forms of portal hypertension. A number of specific and rarer causes accounted for the rest of the cases. The tribal and geographical distribution of patients with chronic splenomegaly was compared with the pattern of general medical admissions. Splenomegaly was more frequent than expected in Kamba and Luo patients. Hyper-reactive malarial splenomegaly and hepatosplenic schistosomiasis were common in both groups, whereas visceral leishmaniasis was almost restricted to the Kamba and indeterminate splenomegaly was especially prevalent in the Luo. Malarial antibody and immunoglobulin levels differed significantly between the various diagnostic categories of patients and controls. Malarial serology can be diagnostically useful for chronic splenomegaly, provided results are interpreted in their geographical context.

In vitro growth inhibition of Plasmodium falciparum by sera from tropical splenomegaly syndrome patients.

Sera from tropical splenomegaly syndrome (TSS) and non-TSS patients from the same village were examined for their ability to inhibit the in vitro growth of Plasmodium falciparum. Using synchronized malaria cultures, sera from both groups inhibited parasite development only if added before merozoite reinvasion of erythrocytes had occurred. There was no significant difference in the degree or apparent mechanism of inhibition caused by TSS and non-TSS sera. These results suggest that the aberrant immune response that results in TSS may not be associated with the elaboration of unique serum factors that differentially inhibit growth of the parasite in vitro.