Abdominal Sonographic Findings in Children With Sickle Cell Anemia

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1 Abdominal Sonographic Findings in Children With Sickle Cell Anemia Journal of Diagnostic Medical Sonography 26(6) The Author(s) 2010 Reprints and permission: sagepub.com/journalspermissions.nav DOI: / Bakhieta Ibrahim Attalla, MD 1 Abstract Sickle cell anemia causes systemic abnormalities related to hemolysis, anemia, and other hemoglobin abnormalities. This review describes the categories relating to abnormalities as well as the sonographic appearance visualized in the liver, gallbladder, spleen, and kidney. Increased awareness of hepatobiliary complications will enable more accurate diagnosis of pathology associated with sickle cell anemia. Keywords sonography, sickle, Sudan Dysfunction of the liver and biliary tract is a common complication of sickle cell anemia (SCA). Hepatobiliary complications of the sickling disorders can be separated into broad categories of disorders related to hemolysis, the problems of anemia and transfusion management, the consequences of sickling and vaso-occlusion, and diseases unrelated to sickle hemoglobin (HbS). This review describes the associated complications related to these categories seen in the liver, gallbladder, spleen, and kidney. Liver Complications The hepatic complications attributed to vascular occlusion encompass a variety of clinical syndromes. In many patients, the liver is generally enlarged throughout life, especially when its measurement is adjusted for body size. Hepatic infarction is seen as a characteristic wedgeshaped, peripherally located hypointense lesion on computed tomography (CT) scan. Single or multiple abscesses have been described with an irregular shape on CT scan. Focal nodular hyperplasia of the liver has been seen angiographically with a characteristic avascular mass. 1 Acute hepatic sequestration, a rarely recognized complication of vaso-occlusion, is characterized by a rapidly enlarging liver accompanied by a decrease in hemoglobin/hematocrit and a rise in reticulocyte count. The liver is smooth and variably tender. Sonography and CT demonstrate only diffuse hepatomegaly. Intrahepatic cholestasis with bile plugs in canaliculi may be seen. Hepatocyte necrosis is unusual. Acute hepatic failure has been reported in several cases where massive hepatic necrosis was seen in the absence of markers for viral hepatitis. 2 There are many causes for liver disease development in sickle cell disease (SCD). Diagnosis and treatment are difficult based on clinical features and laboratory findings. Ten percent of autopsy cases had associated SCD and otherwise unexplained liver cirrhosis. Abnormalities in liver function tests are also frequent in asymptomatic patients. These findings are described as chronic hepatopathy in sickle cell anemia. 3 Traina et al. 4 reported that 67 (96%) patients had some liver abnormality; these included abnormal liver function tests, viral hepatitis, liver sonographic changes, or cholelithiasis. The sickling process was the only explanation for the abnormal liver function tests or liver sonographic changes in 24% of these patients. In one study, the sonographic appearance of the liver in SCD and thalassemia intermedia was described in 105 patients. Hepatomegaly was demonstrated in 70.5% and bright liver in 3.8% of these patients. 5 An autopsy series reported a 91% prevalence of hepatomegaly in patients with SCD. 6 Gallbladder Complications The occurrence of gallstones is one of the most important manifestations of SCD in the digestive tract. Chronic hemolysis, with its accelerated bilirubin turnover, leads to a high incidence of pigment gallstones. 7,8 However, many 1 University of Bahrelghazal, Khartoum, Sudan Corresponding Author: Bakhieta Ibrahim Attalla, University of Bahrelghazal, Khartoum, 1111 Sudan bakhieta@hotmail.com

2 282 Journal of Diagnostic Medical Sonography 26(6) SCD patients with marked hemolysis do not develop gallstones. Thus, abnormalities in gallbladder function or bile acid metabolism may contribute to gallstone formation in these patients. 9 Sonographic surveys of patient populations indicate that the onset of cholelithiasis occurs as early as 2 to 4 years of age and progressively increases in prevalence with age. 8 Nearly 30% of patients develop cholelithiasis by age 18 years. 10 African populations appear to have a substantially lower prevalence than that of Jamaican or North American patients as a low prevalence of cholelithiasis of 6% was reported in Nigeria in patients younger than age 15 years. 11,12 Xenobiotics such as the third-generation cephalosporins may crystallize in the gallbladder, and differences in the use of such antibiotics could account for some of the geographic variation in cholelithiasis frequency. 13 Biliary sludge is a viscous material detectable by nonacoustic shadowing on sonography and may be a precursor of gallstone development. 14 Certain antibiotics such as ceftriaxone seem to promote sludge formation. Studies in patients with SCD indicate that sludge is often found with stones, but sludge alone may or may not progress to stone formation. 11,15 Sonographic appearance of gallstones includes an echogenic shadow that typically casts a strong shadow (Figures 1 and 2). Shadowing may not be demonstrated if the stone is imaged off-axis or when the diameter of the stone is smaller than the width of the beam. With careful scanning using focused high-frequency (5-MHz) probes, shadowing will be visualized with stone sizes as small as a millimeter. Stones are usually found in the dependent part of the gallbladder but can float in concentrated bile and may layer within it. Changes of posture usually cause them to move, but if they become immobile they may adhere to the gallbladder mucosa. Unlike cholesterol deposits or polyps, stones have posterior shadowing, whereas cholesterol and polyps do not usually cast an acoustic shadow. The accuracy of sonography in the diagnosis of gallstones is very high (around 98%) when the classic findings of an echogenic lesion with acoustic shadowing and postural movement are present. When these features cannot be demonstrated, the accuracy falls accordingly. Problems of interpretation may arise at the neck of the gallbladder and cystic duct as the valves of Heister normally return strong echoes and cast a shadow. Cholecystitis produces thickening of the gallbladder wall above the normal 2 to 3 mm (measured in the normally filled gallbladder). 14 In acute cholecystitis, a circumferential lucent zone may be seen in the gallbladder wall. 16 In addition, a striated appearance of the gallbladder wall has been described, consisting of alternating, irregular, discontinuous, and lucent and echogenic bands. 17 In chronic cholecystitis, the fibrosis leads to high-level echoes, and the gallbladder is usually small. 18 Figure 1. Multiple gallbladder stones. Figure 2. Sonogram showing sludge in the gallbladder. Splenic Complications Classically, homozygous SCD patients tend to have small, densely calcified spleens. 19 Splenomegaly appears in the first year of life and should be suspected in children if the spleen is more than 1.25 times longer than the adjacent normal kidney (Figure 3). 20 Pathologically, the endstage spleen is small and fibrotic with marked deposition of hemosiderin and calcium. 21 In patients with SCD, intrasplenic benign nodules corresponding to normal splenic tissue may be identified on imaging studies. 22 Vascular occlusions and repetitive local infarctions tend to cause the so-called autosplenectomy of the spleen in homozygous disease, with splenic function being lost by age five. Rarely, splenomegaly may persist in homozygous patients, but such spleens are also nonfunctional, densely fibrotic, and calcified. Moreover, clinical disappearance of the spleen

3 Attalla 283 Figure 3. Splenomegaly in a patient with sickle cell disease. Figure 4. Sonography showing multiple anechoic areas in the kidney. does not imply atrophy since splenomegaly may recur years later in some patients during intercurrent illness. 21 Fifteen children with SCD undergoing long-term erythrocytapheresis in the Department of Pediatrics at the University of Louisville, Kentucky, were assessed for splenic regeneration using abdominal sonography and radionuclide spleen scans, and it appears that the process of splenic regeneration in these patients is minimal and may depend partly on the intensity of transfusion therapy and the length of time that HbS has been maintained below 20%. 23 Splenic infarcts usually appear as wedge-shaped or rounded hypoechoic areas on ultrasonography. 24 Rests of preserved splenic tissue or regrowth of splenic tissue occasionally may also be seen as hypoechoic areas in patients with SCD. 25 In one study, splenomegaly was detected in 15 patients (17.9%). Shrunken spleen was observed in 5 (6%) of 84 patients. At the time of examination, 36 patients (42.9%) were noted to have autosplenectomy. One patient had multiple punctate echogenic foci in the spleen. Hypoechoic focal parenchymal lesions were observed in 5 patients (6%). 26 Kidney Complications SCD is associated with many structural and functional abnormalities of the kidney, which may progress to chronic renal failure and end-stage renal disease. 27 Clinical and pathologic data indicate that intravascular sickling occurs more readily in the kidney than in any other organ. 28 A series of progressive and random pathologic events involving the kidney begins early in the first decade of life in a patient with SCD and continues throughout life. 29 The combination of hypoxia, hypertonicity, and acidosis in the renal medulla leads to stasis in the vasa recta and Figure 5. Sonography shows an anechoic area in the right kidney of a patient with sickle cell disease. Note also hyperechoic foci in the spleen. to ischemia of the renal medulla and papillary tip, distortion of regional blood flow, focal interstitial nephritis and fibrosis, tubular dysfunction atrophy, and papillary necrosis. 30 Uric acid nephropathy is a rare condition; it is recurrent and may lead to a radiolucent uric acid stone formation, which can be detected by sonography. 31 Several studies have reported a medullary or diffuse increase in reflectivity on renal sonography in patients with SCD. 32 Walker and Serjeant 33 reported increased medullary echogenicity in 5 of 179 patients (2.8%). In the same study, diffusely increased renal echogenicity was reported in 15 of 179 patients (8.4%) (Figures 4 and 5). In one report, increased renal echogenicity was noted in 26 of 189

4 284 Journal of Diagnostic Medical Sonography 26(6) patients with SCD (13.8%). 34 In another study, medullary hyperechogenicity was observed in 6 of 84 patients (7%), and the prevalence of diffusely increased renal echogenicity was 10% in that study. 26 Renal enlargement has been reported in up to 50% of patients with SCD. 35 In one study, the prevalence of renal enlargement was 30.1%. 26 The etiology of renal enlargement in SCD is unknown. However, glomerular hypertrophy and increased renal blood volume have been suggested as likely contributors. 35 One patient in a previous study had typical sonographic findings of renal papillary necrosis, as well as multiple round or triangular cystic spaces communicating with the collecting system in the medullary region without a dilated renal pelvis. 36 Conclusion Abdominal sonographic findings of patients with SCD showed a high incidence of abdominal abnormalities, especially in solid organs such as the liver, gallbladder, spleen, and kidney. Repeated vascular occlusion, chronic hemolysis, and anemia contribute to the pathogenesis of multiple abdominal manifestations of SCD. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the authorship and/or publication of this article. Funding The author(s) received no financial support for the research and/or authorship of this article. References 1. Davies SC, Brozovic M: Acute admissions in patients with sickle cell disease who live in Britain. Br Med J 1987;294: Johnson CS, Omata M, Tong MJ, et al: Liver involvement in sickle cell disease. Medicine (Baltimore) 1985;64: Ahn H, Li CS, Wang W: Sickle cell hepatopathy: clinical presentation, treatment, and outcome in pediatric and adult patients. Pediatr Blood Cancer 2005;45: Traina F, Jorge SG, Yamanaka A, de Meirelles LR, Costa FF, Saad ST: Chronic liver abnormalities in sickle cell disease: a clinicopathological study in 70 living patients. Acta Haematol 2007;118: Papadaki MG, Kattamis AC, Papadaki IG, et al: Abdominal ultrasonographic findings in patients with sickle-cell anaemia and thalassaemia intermedia. Pediatr Radiol 2003;33: Bauer TW, Moore GW, Hutchins GM: The liver in sickle cell disease: a clinicopathologic study of 70 patients. Am J Med 1980;69: West MS, Wethers D, Smith J, Steinberg M; Cooperative Study of Sickle Cell Disease. Laboratory profile of sickle cell disease: a cross-sectional analysis. J Clin Epidemiol 1992;45: Walker TM, Hambleton IR, Serjeant GR: Gallstones in sickle cell disease: observations from the Jamaican cohort study. J Pediatr 2000;136: Everson GT, Nemeth A, Kourourian S, et al: Gallbladder function is altered in sickle haemoglobinopathy. Gastroenterology 1989;96: Galloway SJ, Harwood-Nuss AL: Sickle cell anaemia review. J Emerg Med 1988;6: Nzeh DA, Adedoyin MA: Sonographic pattern of gallbladder disease in children with sickle cell anaemia. Pediatr Radiol 1989;19: Billa RF, Biwole MS, Juimo AG, Bejanga BI, Blackett K: Gall stone disease in African patients with sickle cell anaemia: a preliminary report from Yaounde Cameroon. Gut 1991;32: Comer GM, Ozick LA, Sachdev RK, et al: Transfusionrelated chronic liver disease in sickle cell anemia. Am J Gastroenterol 1991;86: Lee SP, Maher K, Nicholls JF: Origin and fate of biliary sludge. Gastroenterology 1988;94: Al-Salem AH, Qaisruddin S: The significance of biliary sludge in children with sickle cell disease. Pediatr Surg Int 1998;13: Cosgrove DO, McCready VR: Ultrasound Imaging: Liver, Spleen and Pancreas. New York, John Wiley, Barnet E: Liver and biliary tree, in Morley P (ed): Clinical Diagnostic Ultrasound. Oxford, UK, Blackwell Scientific, 1985, pp Cohen RH, Mahony BS, Bowie JD, et al: Striated intramural gallbladder lucencies on US studies: predictors of acute cholecystitis. Radiology 1987;164: Hasan MF, Marsh F, Posner G, et al: Chronic hepatitis C in patients with sickle cell disease. Am J Gastroenterol 1996;91: Serjeant GR: Sickle Cell Disease: The Spleen. New York, Oxford University Press, Loftus WK, Metreweli C: Ultrasound assessment of mild splenomegaly: spleen/kidney ratio. Paediatr Radiol 1998;52: Fischer KC, Shapiro S, Treves S: Visualisation of the spleen with a bone seeking radionuclide in a child with sickle cell anemia. Radiology 1977;122: Jouini S, Sehili S, Mokrani A, et al: Splenic nodules and sickle cell anemia. Radiology 2001;82: Lonergan GJ, Cline DB, Abbondanzo SL: From the archives of the AFIP: sickle cell anemia. Radiographics 2001;21: Dick R, Watkinson A: The liver and spleen, in Sutton D (ed): Textbook of Radiology and Imaging. 7th ed. New York, Elsevier, 2002, pp

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