Acta Tropica 101 (2007) 183–186
Evaluation of splenomegaly in the hepatosplenic form of mansonic schistosomiasis ´ Murilo D. Maia a , Edmundo P.A. Lopes a,∗ , Alvaro Antonio B. Ferraz b , F´abio M.R. Barros a , Ana L´ucia C. Domingues a , Edmundo M. Ferraz b a
b
Department of Medicine and Department of Surgery at the Hospital das, Recife, Brazil Department of Surgery at the Hospital das Cl´ınicas of Universidade Federal de Pernambuco (UFPE), Recife, Brazil Received 3 May 2005; received in revised form 21 March 2006; accepted 5 January 2007 Available online 25 January 2007
Abstract This study was aimed to evaluate splenomegaly in patients with the hepatosplenic (HS) form of mansonic schistosomiasis (MS), analyzing the size and weight of the spleen and their relationships with patients’ gender and age. Between October, 1993 to July, 1998, 78 patients with the HS form of MS had undergone splenectomy as treatment of choice for bleeding due to portal hypertension, at Hospital das Cl´ınicas, Pernambuco, Brazil. By means of abdominal palpation, the excess spleen felt below the left costal edge was measured, and the weight was obtained after splenectomy along with the histopathological analysis. Liver biopsy was performed intraoperatively in order to confirm MS and to rule out other liver diseases. The mean age of the 78 patients were 45 years and 41 of them (53%) were female. The average spleen weight was 912 g and the mean spleen size palpable below the left costal edge was 9.1 cm. There was a positive relationship between size and weight (p < 0.001). Spleen weight and size were larger in males (p = 0.007 and p = 0.001, respectively). An inverse correlation between age and spleen weight was observed (p < 0.001). A classification based upon spleen weight showed 53% of patients presenting a moderate (501–1000 g) and 33% a severe (>1001 g) splenomegaly. As for the spleen size, the classification showed 64% of patients presenting moderate (4.1–10 cm below the left costal edge) and 21% severe (>10 cm) splenomegaly. In conclusion, splenomegaly may be considered a key physical finding in patients with HS form of MS, and we found a good correlation between the spleen sizes clinically evaluated with its weight. The majority of cases presents a moderate to severe splenomegaly and spleen size is larger in men and it seems to decrease with aging. © 2007 Elsevier B.V. All rights reserved. Keywords: Splenomegaly; Schistosomiasis mansoni; Splenectomy; Portal hypertension
1. Introduction Mansonic schistosomiasis (MS) manifested by its hepatosplenic (HS) form is the most prevalent liver disease in the Northeast region of Brazil. Secondary ∗
Corresponding author at: Rua Irm˜a Maria David, 154, Ap. 3201, 52061-070 Recife, PE, Brazil. Tel.: +55 81 2126 8534; fax: +55 81 3442 0400. E-mail address:
[email protected] (E.P.A. Lopes). 0001-706X/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.actatropica.2007.01.004
portal hypertension may lead to GI-bleeding, either through gastroesophageal variceal rupture or hypertensive gastropathy (Coutinho, 1979; Coutinho et al., 1997). Noteworthy is that portal hypertension in HS form of MS is not only due to periportal (Symmers) fibrosis as a result of parasite eggs’ deposition within the liver downstream sinusoidal network, but it is also caused by blood overflow induced by splenomegaly. The latter is due to marked hyperplasia of immune cells from long-lasting immunological response against parasite’s
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antigens and to congestion induced by the periportal fibrosis. Splenomegaly leads to an increased blood flow in splenic vein and thereafter to the entire portal territory (Ferraz et al., 2001; Kelner, 1992). Splenomegaly observed in this population may also result in hypersplenism, and a decreased number of total blood cells and an immunosuppressed status may be observed (Ferraz et al., 2001; Kelner, 1992; Pereira et al., 1993). Splenectomy itself is not the treatment of choice for the splenomegaly-induced pancytopenia in asymptomatic patients but most of the times it is performed as a secondary prophylaxis method of digestive bleedings. This surgical procedure effectively reduces blood overflow and thus, portal pressure in about 30% (Ferraz et al., 2001; Kelner, 1992; Raia et al., 1994). Due to its peculiarities, the MS in the HS form has being subject to many publications, with most of them emphasizing its morbidity, mortality and treatment. To date, however, in the western literature, there is no available study evaluating a fair large amount of patients with splenomegaly in the HS form of SM in an orderly way, with diagnosis established by liver biopsy and defined exclusion criteria, especially for chronic viral infections of the liver. Furthermore, the relationship between clinical assessment of spleen size and spleen weight has not been determined in schistosomiasis patients. This study was aimed to retrospectively evaluate splenomegaly in patients with MS in the HS form, taking in account the size and weight of the spleen and their relationships with patients’ gender and age.
During surgery a liver biopsy was performed and analyzed in the Pathology Department at HC of UFPE to confirm the Symmers fibrosis, along with the removed spleen. The exclusion criteria were biopsy reporting the presence of liver disease other than MS, lymphoproliferative disorders and a positive viral hepatitis serological marker (HBsAg or anti-HCV). The spleen was normal when its weight was less than 200 g and above this a splenomegaly was considered. According to the classification criterion proposed by Ferraz et al. (2001), the splenomegaly above 200 g of weight was reported as mild (201–500 g), moderate (501–1000 g) and severe (>1001 g). Spleen size was measured using manual palpation on the left upper quadrant of the abdomen in a systematic way, with the examiner’s fingers used as surrogate marker for a ruler, estimating each finger with 1.5 cm. The fingers were placed in parallel below the left costal edge, at the level of the left hemi-clavicular line, towards its larger axis. Spleen was normal in size when it was not palpable below the left costal edge. Beyond this, splenomegaly up to 4 cm below left costal edge was reported as mild, between 4.1 and 10 cm as moderate, and beyond 10 cm as severe. Central trend measures and variability were used as statistical methods. Student t-test was used for median comparison and qui square for frequency analysis. The significant level adopted was 95%.
2. Patients and methods
Amongst 111 patients initially enrolled, 33 were excluded for the following reasons: non-compliance to the standard protocols, unregistered data, and presence of diseases other than MS in the spleen or in the liver biopsy reports. Effectively, 78 patients were enrolled and 41 (53%) were female. Ages varied between 22 and 71 years (mean of 44.5 and a median of 45 years). Mean male age was 41.6 years, less then the female of 47.1 years (p = 0.004). Mean spleen weight postoperatively was 912 g and mean size observed below the left costal edge preoperatively was 9.1 cm, an highly positive correlation (p < 0.001) was observed between these two parameters. Mean spleen weight was significantly (p < 0.007) higher in 37 male patients (1055 g) than in 41 female’s (783 g), and mean spleen size (p < 0.001) was higher in male patients (10.4 cm) when compared to female’s (7.8 cm). Using the classification criterion defined above, we observed that only one patient had the spleen weight within normal limits. As for the remaining patients, 10
Between October, 1993 and July, 1998, 111 patients were evaluated for enrollment in this study. All of them underwent splenectomy at Hospital das Cl´ınicas (HC) of Universidade Federal de Pernambuco (UFPE), located in the Northeast region of Brazil. Splenectomy was performed in patients who had had a previous episode of digestive hemorrhage aiming a reduction in portal hypertension as secondary prophylaxis of digestive bleeding. It was schedule as elective procedure as soon as patient presented hemodynamic stability and no further signs of ongoing bleeding. All diagnostic and therapeutic approaches followed standard protocols used by the Medicine and Surgery Departments at HC of UFPE. The study was approved by the Human Studies Committee of UFPE. Inclusion criteria were adult patients with MS in the HS form, and all the patients should have annotated in its chart the size of the spleen palpable in excess to the left costal edge, as too the weight of the spleen after its removal in surgery.
3. Results
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Fig. 1. The weight of splenomegaly (mild, moderate or severe), according to age groups of 77 patients with mansonic schistosomiasis in its hepatosplenic form, who underwent splenectomy at Hospital das Cl´ınicas (UFPE), between October, 1993 and July, 1998.
(13%) presented as mild, 41 (53%) as moderate and 26 (33%) as severe splenomegaly. In all 78 patients the spleens were palpable below the left costal edge, including the one presenting normal weight (2 cm below the left costal edge). According to the spleen size below the left costal edge, 12 (15%) were considered as mild, 50 (64%) as moderate, 16 (21%) as severe splenomegaly. The mean spleen weight value showed an inverse correlation with patients’ age. Using the cut-off of 40 years, mean spleen weight was higher (1161.4 g) in the younger group (p < 0.001) when compared to the older (771.8 g). Spleen weight was also analyzed according to age groups classified by decades of life, and an inverse and significant correlation (p < 0.001) between these variables was observed (Fig. 1). The spleen size below the left costal edge did not show a correlation with the patients’ age when the cutoff of 40 years of age was used (p = 0.09). There was, however, a statistical difference when stratified by age groups (p < 0.0001), as shown in Table 1. 4. Discussion Portal hypertension is the most important sequelum of Schistosoma mansoni infection in terms of morbidity
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and mortality. Schistosomiasis is a disease of developing countries and the use of ultrason and computed tomography not always is possible. It is therefore of value if simple clinical examination can be used to assess the size of the spleen. This study has show a very good correlation between the size and weight of the spleen but it be emphasized that all patients in this study had already GIbleeding and were therefore in a state of severe disease. Mean age difference observed between the genders may be the result of the labor and amusement activities linked to male gender, resulting in an earlier and more severe parasitic burden (Coutinho, 1979). Another observation should be that the treatment of schistosomiasis might have been better accepted by women than man, for its staying-at-home activities and thus, accessibility by the health-care workers who offered the anti-parasitic drug door-by-door. The mean weight of 912 g for the spleens detected in this study is accordingly to the previous findings in the literature for schistosomiasis, i.e., varying from 793 to 1000 g (Andrade and Bina, 1983; Domingues and Domingues, 1994) and with others causes of portal hypertension (Bowdler, 1983; Sheth et al., 1995). When we analyzed the spleen weight and size by categories, we found that the majority of patients presented a moderate and severe splenomegaly according to both variables, i.e., 86 and 85%, respectively, showing the advanced stage of the disease. We found that the male gender presented a higher weight and size of the spleen. This finding is also observed in normal subjects. Spleen weight according to the age groups grouped by decades of life, showed a significant decrease in its values the older the individual become. Using a cut-off of 40 years of age, as suggested by Myers and Segal (1974), our results showed an important reduction of the spleen weight amongst the older population. As a matter of fact, this had been already studied by Andrade and Andrade (1965), stating that the reduction of spleen weight increases progressively after the age of 20 years.
Table 1 The size of the spleen (centimeters bellow the left costal edge), according to age groups of 78 patients with mansonic schistosomiasis in the hepatosplenic form, who underwent splenectomy at Hospital das Cl´ınicas (UFPE), between October, 1993 and July, 1998 Spleen size
Age groups (years)
Total (%)
21–30 (%)
31–40 (%)
≤4 cm 4.1–10 cm >10 cm
1 (7.7) 7 (53.8) 5 (38.5)
Total (%)
13 (16.6)
X2 = 318.2, p < 0.001.
41–50 (%)
51–60 (%)
>60 (%)
4 (6.7) 4 (33.3) 7 (60.0)
8 (11.1) 11 (70.4) 8 (18.5)
4 (25.0) 10 (62.5) 2 (12.5)
3 (42.9) 1 (14.3) 3 (42.9)
20 (25.6) 33 (42.3) 25 (32.1)
15 (19.2)
27 (34.6)
16 (20.5)
7 (9.0)
78 (100)
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So, this observation may be due to the natural involution observed in healthy individuals and by the reduction of the immune response to SM observed in older individuals (Zago et al., 1985). The observed reduction of spleen weight related to the older ages might mean the development of larger spleens early in life, when the infection occurs. This was also shown in a 232 autopsy series when the occurrence of HS form of MS was observed mainly in patients between 10 and 40 years of age, and with most becoming infected in childhood (Andrade and Bina, 1983). In addition, the reduction of spleen weight related to the older ages could also be the result of an increasing mortality before the splenectomy among people with severe fibrosis and large spleens. In conclusion, in patients with HS form of MS with a previous episode of digestive bleeding, splenomegaly may be considered a key physical finding, being the majority of patients presenting a moderate to severe one. One of the main finding of the present study is that the clinical assessment of the spleen size is a good predictor of its volume and can be used as a marker of morbidity. Moreover, the spleen maintains the characteristics of “normal” organ, when its size and weight are lower in the female gender and that they decrease with the aging process. References Andrade, Z.A., Andrade, S.G., 1965. The pathology of the spleen in hepatosplenic form of schistosomiasis mansoni. Rev. Inst. Med. Trop. S˜ao Paulo 78, 218–227. Andrade, Z.A., Bina, J.C., 1983. The pathology of the hepatosplenic form of schistosomiasis mansoni in its advanced form (study of
232 complete necropsies). Mem. Inst. Oswaldo Cruz 78, 285– 305. Bowdler, A.J., 1983. Splenomegaly and hipersplenism. Clin. Haematol. 12, 467–487. Coutinho, A.D., 1979. Fatores relacionados com o desenvolvimento das formas cl´ınicas da esquistossomose mansˆonica. Rev. Ass. Med. Brasil 25, 185–188. Coutinho, E.M., Abath, F.G.C., Barbosa, C.S., Domingues, A.L.C., Melo, M.C.V., Montenegro, S.M.L., Lucena, M.A.F., Romani, S.M.A., Souza, W.V., Coutinho, A.D., 1997. Factors involved in schistosoma infection in rural areas of Northeast Brazil. Mem. Inst. Oswaldo Cruz 92, 707–715. Domingues, A.L.C., Domingues, L.A.W., 1994. Forma intestinal, hepatointestinal e hepato-esplˆenica. In: Malta, J. (Ed.), Esquistossomose Mansˆonica. Editora Universit´aria da UFPE, Recife, PE, pp. 91–109. Ferraz, A.A.B., Lopes, E.P.A., Barros, F.M.R., Sette, M.J.A., Arruda, S.M.B., Ferraz, E.M., 2001. Splenectomy plus left gastric vein ligature and devascularization of the great curvature of the stomach in the treatment of hepatosplenic schistosomiasis. Postoperative endoscopic sclerosis is necessary? Arq. Gastroenterol. 38, 84–88. Kelner, S., 1992. Critical evaluation of schistosomiasis portal hypertension surgery. Mem. Inst. Oswaldo Cruz 87, 357–368. Myers, J., Segal, R.J., 1974. Weight of the spleen. Arch. Pathol. 98, 33–35. Pereira, G., Santos, R.P., Alexandre-Neto, J., Azevedo, A.P., Carvalheira, A.E., 1993. Formas graves da esquistossomose mansˆonica: dados de internac¸a˜ o hospitalar em Pernambuco. An. Fac. Med. Univ. Fed. Pernambuco 38, 12–18. Raia, S., da Silva, L.C., Gayotto, L.C., Forster, S.C., Fukushima, J., Strauss, E., 1994. Portal hypertension in schistosomiasis: a longterm follow-up of a randomized trial comparing three types of surgery. Hepatology 20, 398–403. Sheth, S.G., Amarapurkar, D.N., Chopra, K.B., Mani, A.S., Metha, P.J., 1995. Evaluation of splenomegaly in portal hypertension. J. Clin. Gastroenterol. 22, 28–30. Zago, M.A., Figueiredo, M.S., Covas, D.T., Bottura, C., 1985. Aspects of splenic hypofunction in old age. Klin. Wochenschr 63, 590–592.