cysts, or perihepatic abscesses may be mistaken for .... multi-organ involvement including the lymph nodes, ... hepatosplenomegaly, lack of lymphadenopathy,.
APPROACH TO A CHILD WITH PALLOR AND HEPATOSPLENOMEGALY Anirban Das, MD, DM Introduction Pallor and hepatosplenomegaly in a child are frequent causesof referralto the pediatrician. Causes are diverse and vary with the age and clinical condition of the child. Co-existence of other signs and symptoms often help narrow the multiple diagnostic possibilities. A systematic approach is needed to clinically differentiate the provisional diagnoses and order relevant investigations to conrm the etiology. Pathophysiology Palloris dened as the perceptible reduction of the color or tone of the skin and mucosa. While anemia is the most important cause of pallor, decreased perfusion (eg. hypotensive shock, vasoconstriction following hypoglycemia) and tissue edema leading to alteration of the consistency of the subcutaneous tissue (eg. hypothyroidism, hypoalbuminemia, congestive cardiac failure) can also result in pallor. Anemia, the most important cause of pallor, is dened as hemoglobin (Hb) concentration or red blood cell (RBC) mass less than the 5th percentile for age. Hb levels vary by age, and hence the child's Hb level must be compared with age-based norms to diagnose anemia. Pallor is generally appreciated when the Hb is below 9-10g%. Anemia might be result from blood loss, hemolysis or due to inadequate production. Hepatomegaly: The mere presence of a palpable liver does not dene hepatomegaly. While in neonates the liver may be palpable 2-3 cm below the costal margin, this is usually 3.5 cm in newborns and > 2 cm in children suggests enlargement. Liver span is determined by measuring the distance between the upper edge, determined by percussion, and the lower edge, determined by palpation, in the midclavicular line. The liver span increases with body weight and age. The normal range for liver span by percussion at 1 week of age is 4.5-5 cm. In the preterm infants the span varies between 4-5 cm and in term infants between 5-6.5 cm. This increases to 6-7 cm between 1-5 years, 7-9 cm between 5-10 years and 810 cm between 10-16 years. Hepatomegaly generally occurs via one of the
CHAPTER 18
following ve mechanisms: inammation, excessive storage, inltration, congestion, and obstruction. However, the liver can also be displaced inferiorly by the diaphragm, thoracic organs, or presence of uid or air in the thorax, giving the impression of hepatomegaly. Retroperitoneal masses, choledochal cysts, or perihepatic abscesses may be mistaken for hepatomegaly. Children with chest wall deformities can erroneously appear to have hepatomegaly. The Riedel lobe may be palpable in normal persons and be confused as pathologic hepatic enlargement. However, there would be no sign, symptom, or laboratory evidence of disease. Splenomegaly is detected by physical examination. The normal spleen lies entirely within the rib cage and is usually not palpable. However, one third of newborns, 5-15% of children and 3% of young adults may physiologically have a palpable spleen. The tip of the normal, palpable spleen is soft, smooth, nontender and < 1-2 cm below the left costal margin.Inspection may reveal fullness in the left upper quadrant that descends on inspiration indicating massive splenomegaly. Bimanual palpation, ballotment, and palpation from above (Middleton maneuver) are used in examination. Percussion for splenic dullness is performed by one of the several methods(described by Nixon, Castell, or Barkun, percussion of Traube's semilunar space). Studies have demonstrated sensitivity of 56-71% for palpation and 59-82% for percussion. Splenomegaly is usually secondary to one of the following mechanisms: sequestration, reticuloendothelial hyperplasia, congestion, or inltration. However, a palpable spleen might also be the result of visceroptosis, pushed down in conditions s u c h a s h y p e r- r e a c t i v e a i r w a y d i s e a s e o r pneumothorax, or secondary to malnutrition and rickets. The spleen may be palpable in endemic areas for infections like malaria, and in some tropical countries like New Guinea, the incidence of splenomegaly may be up to 60%. The pathological spleen is usually rm, might have an abnormal surface, and is often associated with signs and symptoms of the underlying disease. Sometimes gastric or colonic masses and pancreatic or renal cysts or tumors can mimic splenomegaly.
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APPROACH TO A CHILD WITH PALLOR AND HEPATOSPLENOMEGALY
Clinical evaluation History a detailed history provides important clues. Acuity of symptoms helps in triaging priorities for evaluation and investigations. A child with acute leukemia is often symptomatic for 4-6 weeks prior to presentation. Among anemia presenting in infancy, the chronology of normal hematopoiesis often correlates with the age of onset of symptoms. Anemia with hepatosplenomegaly diagnosed at 4-6 months of agemight point towards a -chain hemoglobinopathy, detected only after the switch from fetal to adult Hb. History and severity of neonatal jaundice needs to be enquired in detail for diagnosing hemolytic anemias. Fever might not point towards infection alone, as autoimmune disorders as well as malignancies present with febrile episodes. History of travel to endemic areas for specic infections (malaria, leishmaniosis, rickettsia infection) should always be enquired. Documentation of transfusions received previously is important. A history of bleeding might help identify the involvement of the hematopoietic system, either suggestive of marrow involvement or associated coagulopathy. However, the sites of hemorrhage help identify a generalized or a local cause (eg. isolated hematemesis in portal hypertension). Specic intake of drugs can precipitate a clinical manifestation in both immune-mediated hemolysis or in underlying enzyme (glucose-6-phosphate dehydrogenase) deciency. An affected family member mandates documenting a detailed pedigree analysis to diagnose inheritance patters, which may be either autosomal dominant (hereditary spherocytosis) and recessive (storage disorders). Clues may also be provided by a history of jaundice, anemia, gallstones and early deaths in the family. Examination: Signs which need to be looked for on clinical evaluation and provide important clues to diagnosis include the following: Icterus in hemolytic anemias and liver diseases. Facial changes in chronic hemolytic disorders and inltrative disorders. Ophthalmological manifestations, with (osteopetrosis) and without affecting vision (cherry red spot in storage disorders, KF ring in Wilson disease). Lymphadenopathyin inltrative disorders or related to reticuloendothelial hyperplasia. Cutaneous bleeding in inltrative and autoimmune
disorders. Cutaneous rash in multisystem disorders like histiocytosis or as an autoimmune manifestation. Cutaneous nodules in infancy may be present in leukemia, neuroblastoma and Langerhans cell histiocytosis. Musculoskeletal involvement might be in the form of skeletal pain (inltrative disorders) or arthritis (infection, autoimmune), which might be difcult to distinguish clearly in a small child. Neurological manifestations might include developmental delay in storage disorders or a vascular event in specic hematological disorders (sickle cell disease, paroxysmal nocturnal hemoglobinuria). Cardiac murmurs in infective endocarditis and autoimmune disorders. Table I: Selected clinical ndings and diagnostic considerations in a child with pallor and hepatosplenomegaly Clinical nding
Diagnostic consideration(s)
Icterus Facial changes
hemolytic anemias, liver diseases
Ophthalmological manifestations Lymphadenopathy Cutaneous bleeding Cutaneous rash Cutaneous nodules Musculoskeletal involvement
Neurological manifestations
Cardiac murmurs
chronic hemolytic disorders, inltrative disorders Visual loss (osteopetrosis), cherry red spots (storage disorders), KF ring (Wilson disease) inltrative disorders, reticuloendothelial hyperplasia Inltrative disorders, autoimmune disorders Histiocytosis, autoimmune disorders leukemia, neuroblastoma, Langerhans cell histiocytosis skeletal pain (inltrative disorders) or arthritis (infection, autoimmune), which might be difcult to distinguish clearly in a small child developmental delay in storage disorders or a vascular event in specic hematological disorders (sickle cell disease, paroxysmal nocturnal hemoglobinuria) infective endocarditis, autoimmune disorders
Investigations Hematology: A complete blood count with a meticulous examination of the peripheral smear is the most important investigation. The type of anemia, microcytic, normocytic or macrocytic, provides a clue
APPROACH TO A CHILD WITH PALLOR AND HEPATOSPLENOMEGALY
to the pathology. Reticulocytosis points towards hemorrhage or hemolysis. A high white cell count with thrombocytopenia might point towards a hematological malignancy, whereas bi/pancytopenia can be a manifestation of a severe infection, malignancy or autoimmune process. The leukemoid reaction is characterized by a high leukocyte count of 30,000–50,000/L and signicant increase in mature neutrophils in the peripheral blood and a differential count showing marked left shift. This term is often used to distinguish this degree of neutrophilia from leukemia. In a leukemoid reaction, the circulating neutrophils are usually mature, not clonally derived and include promyelocytes, myelocytes, and metamyelocytes. Important causes of leukemoid reaction include severe infections, malignancies, severe hemorrhage or acute hemolysis. Traditionally a high leukocyte alkaline phosphate score has been used to distinguish a leukemoid reaction from chronic myeloid leukemia. A leukoerythroblastic picture is dened as the presence of immature red blood cells and granulocytes in the peripheral blood and bone marrow. This usually signies bone marrow inltration by malignancy, or conditions such as osteopetrosis and myelobrosis, with the marrow elements being 'pushed out' into the peripheral blood. However, especially in children this can also signify increased demands for production in the marrow following hemorrhage, hemolysis, or, recovery from bone marrow suppression after a severe infection, and may be seen in varied conditions including thalassemia major, sickle cell crisis, and systemic lupus erythematosus. Examination of the bone marrow is a part of evaluation for not only hematological malignancies, but also might help in the diagnosis of infections and storage disorders. Flow cytometry aids in diagnosing subtypes of leukemia. Coagulation abnormality may be detected in severe sepsis, hemophagocytic lymphohistiocytosis, acute promyelocytic and monocytic leukemia and liver inltration leading to synthetic dysfunction. Biochemistry: The liver function tests provide an important clue towards the pathology. The type of jaundice points towards hemolysis or a primary hepatobiliary involvement. Calcium, phosphate, and
uric acid are deranged in presence of tumor lysis in a hematological malignancy. Lactate dehydrogenase is elevated in presence of malignancy. Radiology: A chest x-ray can demonstrate enlarged mediastinal nodes in a hematological malignancy. The lung parenchyma can be involved in tuberculosis. Ultrasound of the abdomen can corroborate the clinical ndings of organomegaly, as well as show enlarged lymph nodes in case of infections like tuberculosis, and more commonly malignancy. Normative sizes of liver and spleen in Indian children (n=597) have been established. Doppler studies help diagnose portal hypertension. Focal changes in the liver (in histiocytosis) and spleen (in Hodgkin lymphoma) can be detected. Anemia and hepatosplenomegaly in infants The main causes in infants can be subdivided into the following 3 groups, viz., (A) Infections Intrauterine infections, including cytomegalic inclusion disease, disseminated toxoplasmosis, syphilis, rubella, herpes simplex and human immunodeciency viral infections can present with anemia, hepatosplenomegaly and jaundice. Stigmata, including cataracts, developmental delay and microcephaly often co-exist. Severe bacterial sepsis may present with organomegaly, cytopenia and deranged liver function. Associated hemolysis, if present, is postulated to be associated with macrophage activation and red cell sequestration secondary to infection. Congenital malaria: The clinical features of malaria in neonates and young infants are non-specic and overlap with those of sepsis. Congenital malaria is dened as the presence of asexual stages of the parasite in cord blood at the time of delivery or in the peripheral smear of the infant in the rst seven days of life. While malaria caused by Plasmodium falciparum has been implicated in most studies from Africa, Plasmodium vivax associated disease has been described from elsewhere, including the Indian subcontinent. Disseminated tuberculosis presents with fever and multi-organ involvement including the lymph nodes, lungs, liver, spleen, skin, kidneys, bones and the central nervous system.
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APPROACH TO A CHILD WITH PALLOR AND HEPATOSPLENOMEGALY
Disseminated histoplasmosis can present in infants and immunocompromised children with hepatosplenomegaly, lymphadenopathy, anemia, thrombocytopenia, mucocutaneous manifestations and pneumonia. (B) Haemolysis and extramedullary haematopoiesis Approach to an infant with a suspected haemolytic disorder involves conrming evidence of increased red cell destruction and accelerated production. The next step is to identify the mechanism of destruction, which might be either extrinsic or intrinsic to the red cells.Extrinsic or extracellular factors are usually acquired. Acquired disorders include those that are associated with infection, immune-mediated (blood group incompatibilities, T-antigen activation), or are secondary to some other underlying pathology (microangiopathic anemia, vitamin E deciency). Intrinsic red cell defects are more likely to be genetic in origin. Inherited disorders are due to defects in cell membrane (hereditary spherocytosis, elliptocytosis, stomatocytosis), abnormalities in red cell metabolism (deciency in glucose-6-phosphate dehydrogenase, pyruvate kinase), or a consequence of a haemoglobin chain defect (thalassemia, sickle cell anemia, unstable haemoglobin defects). Haemolysis may be associated with extramedullary haematopoiesis in disorders like thalassemia. Congenital dyserythropoietic anemia can also present in infancy with anemia and a disproportionately low reticulocyte response, and organomegaly, with (type 2) or without jaundice (type 1,3) depending on the co-existence of hemolysis. (c) Infiltrative disorders Inltrative disorders may be non-neoplastic or malignant. Storage disorders form an important subgroup among the non-malignant conditions.Gaucher disease type 1 is the most frequent of these disorders can present at any age with anemia and splenohepatomegaly. Gaucher disease type 2 presents in infancy with extensive visceral involvement and neurodegeneration and is fatal within the rst years of life. Depending on the type, Niemann–Pick disease has classic signs, including hepatosplenomegaly, cherry red spots in macula, psychomotor deterioration, reticular pulmonary inltrates and foamy cells in the bone marrow. In storage diseases, a diagnosis is
established on the basis of the clinical picture, enzyme assays of white cells or cultured broblasts and bone marrow aspiration revealing the characteristic cells of the disorder. Osteopetrosis in infancy usually presents with severe disease with macrocephaly, hepatosplenomegaly, failure to thrive, deafness and blindness due to cranial nerve compression, and severeanemia. Radiographs reveal diffuse bone sclerosis and subsequently bonewithin-bone appearance. Dental problems,osteomyelitis of the mandible, and pathologic fractures are common. Hemophagocytic lymphohistiocytosis: Any infection in a genetically predisposed infant can progress to hemophagocytic lymphohistiocytosis. Typical ndings include fever, hepatosplenomegaly and cytopenia, with or without lymphadenopathy, skin rash, jaundice, edema and neurological manifestations. Investigations reveal hypertriglyceridemia, coagulopathy with hypobrinogenemia, hyperferritinemia, liver dysfunction with elevated transaminases and evidence of hemophagocytosis in the marrow. Infant leukemia is an important differential diagnosis among malignant disorders. Unique features in infant leukemia include extra-medullary involvement of skin (leukemia cutis) and lungs, bulky hepatosplenomegaly, lack of lymphadenopathy, central nervous system involvement, high leucocyte counts at presentation, pro-B cell immunophenotype in lymphoblastic leukemia, and presence of mixed lineage leukemia (MLL) gene rearrangements. Langerhans cell histiocytosis is currently classied as a myeloid neoplasm and can present with seborrheic rash, otorrhea and jaundice, in addition to pallor, bleeds and hepatosplenomegaly. It can affect many different organs, including the skeleton, skin, lymph nodes, liver, lungs,spleen, haematopoiesis, or central nervous system. Biopsy demonstrates inammatory lesions that include CD1a+/CD207+ dendritic cells. Juvenile myelomonocytic leukemia presents in young children, generally < 2years, with cutaneous ndings (eczema, maculopapular rash) and respiratory symptoms along with pancytopenia and spleno-hepatomegaly. Monocytosis (>1000/mm3) and elevated fetal haemoglobin are characteristic ndings. About 15% of children may have associated neurobromatosis type 1.
APPROACH TO A CHILD WITH PALLOR AND HEPATOSPLENOMEGALY
(A) Infections Viral infections: Common viral Illnesses including Epstein-Barr virus (EBV) among others can present in an older child with pallor, lymphadenopathy and h e p a t o s p l e n o m e g a l y. M a n i f e s t a t i o n s c a n includeatypical lymphocytosis, acquired immune hemolytic anemia, immune thrombocytopenia or even aplastic anemia. Human immunodeciency viral infections can present with fever, lymphadenopathy, hepatosplenomegaly, anemia and thrombocytopenia. Bacterial infections: Severe disseminated bacterial infections, in particular by Salmonella and Rickettsia can present with multi-organ involvement. Infective endocarditis can present with fever, anemia, hepatosplenomegaly and hemorrhages.Among chronic infections,hematologic manifestations of tuberculosis include leukemoid reaction, monocytosis and rarely pancytopenia, with hepatosplenomegaly being present in disseminated disease. Parasitic infections: Malaria is a frequent cause of fever with anemia and splenomegaly (with or without hepatomegaly) in tropical countries. Leishmania causes progressive splenomegaly and pancytopenia (anemia,neutropenia and thrombocytopenia). The bone marrow is usually hypercellular with hemophagocytosis. Some children may show coagulopathy. (B) Hematological causes Thalassemiais the most commonhemoglobino-pathy presenting with anemia and hepatosplen-omegaly. While thalassemia major presents in infancy, nontransfusion dependent thalassemia can present in older children with anemia, jaundice, hepatosplenomegaly, growth failure and skeletal changes. Diagnosis is conrmed by high perfor-mance liquid chromatography by demonstrating elevated fetal hemoglobin in the child, followed by genetic studies to identify specic mutations that alsohelps in antenatal diagnosis. Sickle cell anemia: Many Indian children with sickle cell anemia have persistence of splenomegaly, along with early and severe anemia, jaundice, and hepatomegaly. They may present with vaso-occlusive crises. Diagnosis is conrmed using hemoglobin high performance liquid chromatography. Indian children are recognized to have higher fetal hemoglobin levels and a milder clinical phenotype.
Hereditary spherocytosisis the most common red cell membrane disorder. It is a heterogeneous disorder in which abnormalities of RBC structural proteins lead to loss of erythrocyte membrane surface area, resulting in spherical-shaped, hyper-dense, poorly deformable red cells with a shortened life span. Children present with a triad of anemia, splenomegaly and jaundice. Although this is an autosomal dominant disorder, in India, family history is present in approximately one-third of patients. Diagnosis is suspected by presence of microspherocytes in the peripheral smear and an elevated mean corpuscular haemoglobin concentration >36 g/dL and conrmed using an eosin-5-maleimide (EMA) binding assay. The osmotic fragility test has fallen into disfavour. Congenital dyserythropoietic anemias (CDA) are a group of heterogeneous disorders with abnormality in late erythropoiesis, presenting with anemia with an inappropriately low reticulocyte response, jaundice and hepatosplenomegaly. Bone marrow examination demonstrates erythroid hyperplasia, with megaloblastosis and chromatin bridges in CDA type I, and binucleate late polychromic erythroblasts in CDA type II. Electron microscopy conrms the 'Swiss cheese' appearance in type I and vesicles under the plasma membrane in type II. The latter condition used to be diagnosed by the acidied serum lysis test, and the demonstration of red cell membrane abnormality in CDA type II is often demonstrated using the EMA binding assay. A u t o i m m u n e h e m o l y t i c a n e m i a (AIHA) is characterized by antibodies that target red cells and present with clinical evidence of acute hemolysis. Subtypes include warm-reacting AIHA, cold agglutinin disease (diagnosed by variations of the direct antiglobulin test), and paroxysmal cold hemoglobinuria (Donath Landsteiner test). In children, the latter classically presents within several weeks after a viral infection with the sudden onset of hemoglobinuria, accompanied by fever, pallor, and jaundice. (C) Liver disease Macrocytic anemia may be present in chronic liver disorders; hepatosplenomegaly might be a part of the primary disorder. Liver disease is often accompanied by increased portal pressures, with the resultant
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APPROACH TO A CHILD WITH PALLOR AND HEPATOSPLENOMEGALY
congestive splenomegaly potentially creating any combination of anemia, leukopenia, or thrombocytopenia. Wilson disease can present with a severe hemolytic anemia. Similarly, autoimmune hepatitis can have associated immune hemolysis. Several viruses can simultaneously affect the liver and cause anemia due to either myelosuppression or associated hemolysis. (D) Congestive causes Congestive heart failure of any etiology can have pallor (and not necessarily anemia) and congestive hepatomegaly. Extrahepatic/intrahepatic portal venous obstruction presents with splenomegaly without or with hepatomegaly and jaundice, and anemia secondary to variceal bleeding. (E) Immune disorders Autoimmune disorders like systemic onset juvenile idiopathic arthritis may present with anemia, hepatosplenomegaly and arthralgia, closely mimicking hematological malignancies. Macrophage activation syndrome present with fever and pancytopenia and might need a bone marrow examination to aid diagnosis and rule out malignancy. Anemia in systemic lupus erythematosus might be related to the chronic disease itself or due to associated immune hemolysis. Common variable immunodeciency may also present with autoimmune manifestations including hemolytic anemia and thromb-ocytopenia. (F) Marrow infiltrative disorders Storage disorders: Patients with type 1 Gaucher disease can present with asymptomatic splenomegaly, pancytopenia secondary to hypersplenism (rarely from inltration of the bone marrowwith Gaucher cells), growth retardation, and skeletal manifestations.The Erlenmeyer askdeformity is seen from bone marrow expansion; generalized bone mineral loss and infarction are visible on radiographs and can lead to pathologic fractures. Diagnosis is reached by demonstrating typical Gaucher cells in the bone marrow and decreased glucocerebrosidase activity of white cells and conrmed by molecular testing. Osteopetrosis: The autosomal dominant form of osteopetrosis presents later in childhood with fractures and mild anemia, with or without mild hepatosplenomegaly. Cranial nerve dysfunction, dental abnormalities, or osteomyelitis of the mandible
are seen less frequently. X-ray demonstrates increased bone density, clubbing of metaphyses and alternate bands of lucent and dense bands. Acute Leukemia: The leukemia are the most common malignant neoplasms in children. Acute leukemia can present with fever, bone pains, lymphadenopathy, pallor, bleeds and hepatosplenomegaly. Testicular involvement may be present in males. Central nervous system involvement with cranial neuropathies, headache and seizures may be present. Gum hypertrophy and chloromas may be manifestations of acute myeloid leukemia. However, extramedullary deposits can also be present in some forms of acute lymphoblastic leukemia. Diagnosis is conrmed by a bone marrow examination followed by ow cytometry and cytogenetic studies. Children with acute leukemia may present with an oncologic emergency like respiratory failure due to superior mediastinal syndrome, renal failure secondary to tumor lysis or hypercalcemia and hyperviscosity symptoms in the lungs and brain secondary to hyperleukocytosis. Chronic myeloproliferative neoplasms: Chronic myeloid leukemia presents with generalized weakness and fatigue due to anemia and massive splenomegaly. The diagnosis is suggested by a high white blood cell count with myeloid cells at all stages of differentiation in the peripheral blood and bone marrow. The diagnosis is conrmed by cytogenetic and molecular studies that demonstrate the presence of the characteristic Philadelphia chromosome and the BCR-ABL gene rearrangement. Juvenile myelomonocytic leukemia presents in younger children with anemia, thrombocytopenia with massive splenomegaly. Langerhans cell histiocytosis may present in older children with involvement of the liver, spleen and hematopoietic system as risk organs in multisystem disease, along with disease in the bones, skin, lymph nodes and lungs. Hemophagocytic lymphohistiocytosis may present in older children following severe infections with or without a genetic predisposition. Hyperferritinemic sepsis-related multi-organ dysfunction syndrome and macrophage activation syndrome are differential diagnoses to consider in such children, as many of the features may be overlapping.
APPROACH TO A CHILD WITH PALLOR AND HEPATOSPLENOMEGALY Fig.1. Simplied algorithmic approach to a child with anemia and hepatosplenomegaly (Abbreviations: EBV, Epstein Barr virus; HLH, Hemophagocytic lymphocytosis; AIHA, Autoimmune hemolytic anemia; LCH, Langerhans cell histiocytosis; HIV, Human immunodeciency virus; HS, Hereditary spherocytosis; CDA , Congenital dyserythropoietic anemia; CML, Chronic myeloid leukemia; JMML, Juvenile myelomonocytic leukemia; SOJIA, Systemic onset juvenile idiopathic arthritis; SLE, Systemic lupus erythematosus; CVID, Common variable immunodeciency. Child with pallor and hepatosplenomegaly
Acute presentation
Fever
Infection
Chronic history
Bledding
Severe anemia
Systematic approach and targeted investigations aid diagnosis. Many children with febrile illnesses due to infections may develop mild anemia and hepatosplenomegaly. Appropriate diagnosis and management leads to resolution of symptoms. Emergent manifestations of less common but serious disorders warrant recognition and treatment to stabilize and refer to the specialist in a timely manner. Persistence of symptoms, progressive increase in organ size or change in consistency, development of serious symptoms like bleeding would warrant a referral to the specialist for comprehensive evaluation and management. Suggested Reading
2. Dhingra B, Sharma S, Mishra D, et al Normal values of liver and spleen size by ultrasonography in Indian children. Indian Pediatr. 2010;47:487-92. 3. Wolf AD, Lavine JE. Hepatomegaly in neonates and children. Pediatr Rev. 2000;21:303-10.
Inltration
4. Bricks LF, Cocozza AM, Resegue R, et al Experience in the evaluation of children with hepatosplenomegaly at a teaching ambulatory, São Paulo, Brazil. Rev Inst Med Trop Sao Paulo. 1998;40:269-75.
Severe leukemia, LCH sepis OsteoMalaria petrosis
Infection
Pallor and hepatosplenomegaly may be manifestations of a wide spectrum of disorders in children.
1. Janus J, Moerschel SK. Evaluation of anemia in children. Am Fam Physician. 2010;81:1462-71.
MaligImmune nancy
EBV leukemia HLH Enteric NeuroblRicket- astoma tsia Infective Infeendoction carditis
Take home messages
Storage Hematodisorders logocal
Tuberc- Gaucher Thalasulosis semia NiemKala azar, ann Sickle HS, HIV CDA Pick Histoplasmosis
Myeloproliferative neoplasm
CML, JMML
ImmOthers une SOJIA, Chronic liver SLE disease, CVID Portal hypertension, Congestive heart failure
5. Anusha G, Somaiah G, Siddique AM, et al. Study of etiological and clinical prole of hepatosplenomegaly in children between 1 month and 15 years of age. Sch J App Med Sci. 2014;2:554-557.
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