Splenomegaly in Children: Clinical Case and Viva QnA

Clinical Case of Splenomegaly in Children

Case Presentation

A 7-year-old boy of South Asian descent presents to the pediatric clinic with complaints of progressive abdominal distension and intermittent left upper quadrant pain for the past 4 months. His parents report that he has been experiencing fatigue, decreased appetite, and occasional low-grade fevers, particularly in the evenings. They've also noticed that he bruises easily and has had several nosebleeds in the past month.

Past medical history is significant for recurrent respiratory infections in early childhood. The family recently relocated from a rural area in India six months ago. There's no history of known hematological disorders or liver diseases in the family.

Physical Examination

• General: The child appears pale and tired. Height and weight are at the 25th percentile for age.
• Vital signs: Temperature 37.8°C, Heart rate 100/min, Respiratory rate 24/min, BP 100/60 mmHg
• HEENT: Mild conjunctival pallor, no icterus. Petechiae noted on the hard palate.
• Chest: Clear to auscultation bilaterally
• Cardiovascular: Regular rhythm, no murmurs
• Abdomen: Distended, with visible fullness in the left upper quadrant. Spleen palpable 6 cm below the left costal margin, firm and non-tender. Liver edge palpable 2 cm below the right costal margin. No ascites.
• Skin: Several ecchymoses noted on the shins and forearms. No rash.
• Lymph nodes: Several small (<1 cm), mobile cervical and axillary lymph nodes palpable.

Initial Laboratory Investigations

• Complete Blood Count:
  • WBC: 2.8 x 10^9/L (Normal: 4.5-13.5)
  • RBC: 3.2 x 10^12/L (Normal: 4.0-5.5)
  • Hemoglobin: 8.5 g/dL (Normal: 11.5-15.5)
  • Hematocrit: 25% (Normal: 35-45%)
  • MCV: 78 fL (Normal: 75-90)
  • Platelets: 85 x 10^9/L (Normal: 150-450)
• Peripheral Blood Smear: Pancytopenia confirmed. No abnormal cells or parasites seen.
• Liver Function Tests: Mildly elevated transaminases (AST 65 U/L, ALT 55 U/L)
• Renal Function: Within normal limits
• Coagulation Profile: Slightly prolonged PT and aPTT

Additional Investigations

• Abdominal Ultrasound: Spleen measuring 14 cm in craniocaudal length. Homogeneous echotexture. No focal lesions. Mild hepatomegaly. No portal hypertension or ascites.
• Chest X-ray: Normal
• Serological tests: Negative for EBV, CMV, HIV, and Hepatitis viruses
• Malaria smear: Negative

Differential Diagnosis

Given the clinical presentation, laboratory findings, and recent immigration history, the following differential diagnoses are considered:

1. Visceral Leishmaniasis (Kala-azar)
2. Chronic Malaria (despite negative initial smear)
3. Hematological malignancy (e.g., Leukemia, Lymphoma)
4. Tropical Splenomegaly Syndrome
5. Portal Hypertension (early stage)

Further Management

Based on the high suspicion for visceral leishmaniasis, a bone marrow aspiration is performed, revealing numerous Leishmania amastigotes within macrophages, confirming the diagnosis of Kala-azar.

The patient is started on Liposomal Amphotericin B therapy. Over the course of treatment, his splenomegaly gradually resolves, and his blood counts normalize. He is scheduled for follow-up to monitor for complete cure and potential relapse.

5 Varieties of Presentation of Splenomegaly in Children

1. Infectious Causes

Example: Visceral Leishmaniasis (Kala-azar)

• Gradual onset of fever, weakness, and weight loss
• Progressive abdominal distension due to massive splenomegaly
• Pancytopenia leading to pallor, bleeding tendencies, and recurrent infections
• Hepatomegaly often present
• Hyperpigmentation of skin in chronic cases

2. Hematologic Disorders

Example: Beta-Thalassemia Major

• Presents in infancy or early childhood with failure to thrive
• Severe anemia requiring regular blood transfusions
• Progressive splenomegaly due to extramedullary hematopoiesis
• Skeletal changes (frontal bossing, maxillary prominence) due to bone marrow expansion
• Iron overload complications in older children (cardiac, endocrine)

3. Portal Hypertension

Example: Extrahepatic Portal Vein Obstruction

• Often asymptomatic in early stages
• Splenomegaly may be the initial presenting sign
• Gastroesophageal varices leading to hematemesis or melena
• Hypersplenism causing pancytopenia
• Possible growth retardation due to portosystemic shunting

4. Storage Diseases

Example: Gaucher Disease Type 1

• Variable age of onset, can present in early childhood
• Hepatosplenomegaly, often massive
• Bone pain and pathological fractures
• Pancytopenia due to bone marrow infiltration and hypersplenism
• Growth retardation and delayed puberty in some cases

5. Malignant Infiltration

Example: Acute Lymphoblastic Leukemia (ALL)

• Acute onset of symptoms (weeks to months)
• Fatigue, fever, and bone pain
• Hepatosplenomegaly, often with lymphadenopathy
• Pallor, bruising, and petechiae due to bone marrow failure
• Possible central nervous system involvement (headache, vomiting, cranial nerve palsies)

Viva Questions and Answers on Splenomegaly in Children

1. Q: What is the definition of splenomegaly in children, and how does it differ from adults?
   A: Splenomegaly in children is defined as an enlargement of the spleen beyond its normal size for age. Unlike in adults, where a non-palpable spleen is considered normal, in children, palpability alone doesn't always indicate pathological enlargement. The normal spleen size varies with age:
   • Newborns: Spleen tip may be palpable 0.5-1 cm below the left costal margin
   • By age 3: Usually not palpable in healthy children
   • Older children: Palpable spleen >2 cm below the costal margin is considered enlarged
   Ultrasound measurements provide more accurate assessment, with normal spleen length approximately 0.2 x height (cm) + 1.6 cm, up to a maximum of about 12 cm.
2. Q: Describe the technique for examining the spleen in a child. What precautions should be taken?
   A: The technique for examining the spleen in a child involves:
   1. Position the child supine or in right lateral decubitus position
   2. Begin palpation in the right lower quadrant, moving diagonally towards the left costal margin
   3. Use the palmar surface of the fingers, pressing gently but firmly
   4. Ask the child to take a deep breath, which brings the spleen inferiorly
   5. Note the consistency, tenderness, and distance from the costal margin
   Precautions:
   • Ensure a relaxed abdominal wall (may need to distract younger children)
   • Be gentle to avoid discomfort or potential splenic rupture in massive splenomegaly
   • Warm hands to prevent abdominal muscle guarding
   • Consider examining in both supine and right lateral positions for better assessment
3. Q: What are the major pathophysiological mechanisms leading to splenomegaly in children?
   A: The major pathophysiological mechanisms include:
   1. Congestion: Due to increased blood flow or outflow obstruction (e.g., portal hypertension)
   2. Infiltration: By abnormal cells (e.g., leukemia, lymphoma) or storage materials (e.g., Gaucher disease)
   3. Hyperplasia: Increased demand for splenic function (e.g., hemolytic anemia, infections)
   4. Inflammation: Acute or chronic inflammatory processes (e.g., infectious mononucleosis)
   5. Extramedullary hematopoiesis: Compensatory mechanism in some hematological disorders (e.g., thalassemia)
   Understanding these mechanisms helps in narrowing down differential diagnoses based on clinical presentation and associated features.
4. Q: How does the etiology of splenomegaly vary with age in pediatric populations?
   A: The etiology of splenomegaly varies significantly with age in pediatric populations:
   • Neonates and young infants:
     • Congenital infections (TORCH)
     • Hemolytic disease of the newborn
     • Congenital leukemia
     • Storage disorders (rare)
   • Infants and toddlers:
     • Sickle cell disease
     • Thalassemia
     • Systemic viral infections (e.g., CMV, EBV)
     • Sepsis
   • School-age children:
     • Infectious mononucleosis
     • Malaria (in endemic areas)
     • Leukemia and lymphoma
     • Autoimmune disorders (e.g., SLE)
   • Adolescents:
     • Infectious mononucleosis
     • Lymphoma
     • Portal hypertension (early manifestation)
     • Tropical splenomegaly syndrome
   This age-based variation reflects the changing susceptibility to different conditions and the natural history of various diseases throughout childhood.
5. Q: Discuss the role of the spleen in the immune system and how splenomegaly affects its function.
   A: The spleen plays crucial roles in both innate and adaptive immunity:
   1. Innate immunity:
      • Filters blood, removing aging erythrocytes and blood-borne pathogens
      • Contains a large population of macrophages that phagocytose pathogens
      • Produces tuftsin, an immunomodulating tetrapeptide
   2. Adaptive immunity:
      • Houses B and T lymphocytes in white pulp
      • Site for antigen presentation and initiation of immune responses
      • Production of antibodies, especially IgM
   Effects of splenomegaly on splenic function:
   • Enhanced filtering capacity can lead to cytopenias (hypersplenism)
   • Increased clearance of pathogens, but potential for overwhelming post-splenectomy infection if removed
   • Possible alteration in the balance of immune responses, contributing to autoimmune phenomena in some cases
   • In massive splenomegaly, potential for decreased function due to architectural disruption
   Understanding these functions is crucial for managing patients with splenomegaly and in decision-making regarding potential splenectomy.
6. Q: What is hypersplenism, and how does it manifest in children with splenomegaly?
   A: Hypersplenism is a clinical syndrome characterized by:
   1. Splenomegaly
   2. Cytopenia(s) in one or more cell lines
   3. Compensatory bone marrow hyperplasia
   4. Improvement of cytopenias after splenectomy
   Manifestations in children:
   • Anemia: Fatigue, pallor, decreased exercise tolerance
   • Thrombocytopenia: Easy bruising, petechiae, mucosal bleeding
   • Leukopenia: Increased susceptibility to infections
   • Pancytopenia in severe cases
   Pathophysiology:
   • Increased splenic blood flow and pooling of cells
   • Enhanced phagocytic activity of the enlarged spleen
   • Possible autoimmune component in some cases
7. Q: Describe the approach to a child presenting with splenomegaly. What key elements should be included in the history and physical examination?
   A: The approach to a child with splenomegaly should be systematic: History:
   • Duration and progression of abdominal distension or mass
   • Associated symptoms: fever, weight loss, night sweats, fatigue, bleeding tendency
   • Travel history, especially to endemic areas for infections like malaria or leishmaniasis
   • Family history of hematological disorders or liver diseases
   • History of recurrent infections or autoimmune symptoms
   • Dietary history and exposure to toxins (relevant for liver diseases)
   Physical Examination:
   • General appearance: pallor, jaundice, petechiae, lymphadenopathy
   • Abdominal examination:
     • Liver size and consistency
     • Spleen size, consistency, and tenderness
     • Presence of ascites or dilated abdominal veins
   • Cardiovascular examination: murmurs suggesting portal hypertension
   • Respiratory system: pleural effusion in some systemic diseases
   • Skin: rashes, purpura, café-au-lait spots (neurofibromatosis)
   • Skeletal examination: bone tenderness or deformities in storage diseases
   This comprehensive approach helps in formulating a focused differential diagnosis and guides further investigations.
8. Q: What are the key laboratory and imaging studies you would order in the initial evaluation of a child with splenomegaly?
   A: The initial evaluation should include: Laboratory studies:
   • Complete blood count with differential and reticulocyte count
   • Peripheral blood smear examination
   • Liver function tests including albumin and coagulation profile
   • Renal function tests
   • Lactate dehydrogenase (LDH) and uric acid levels
   • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
   • Serological tests for common infections (EBV, CMV, HIV, hepatitis viruses)
   • Blood culture if fever is present
   • Malaria smear in endemic areas or recent travel history
   Imaging studies:
   • Abdominal ultrasound: To confirm splenomegaly, assess liver size and echogenicity, look for portal hypertension signs, and evaluate for focal lesions
   • Chest X-ray: To evaluate for mediastinal masses or pulmonary infiltrates
   Further specialized tests based on initial findings may include:
   • Flow cytometry of peripheral blood (if leukemia/lymphoma suspected)
   • Hemoglobin electrophoresis (if hemoglobinopathy suspected)
   • Bone marrow aspiration and biopsy (in cases of unexplained cytopenias or suspected malignancy)
   • CT or MRI abdomen (for detailed evaluation of splenic lesions or staging of malignancies)
   This stepwise approach allows for a comprehensive evaluation while avoiding unnecessary invasive procedures.
9. Q: Discuss the pathophysiology and management of portal hypertension leading to splenomegaly in children.
   A: Portal hypertension in children can lead to significant splenomegaly. Understanding its pathophysiology is crucial for management: Pathophysiology:
   • Increased resistance to portal blood flow, leading to elevated portal pressure
   • Causes can be prehepatic (e.g., portal vein thrombosis), intrahepatic (e.g., cirrhosis), or posthepatic (e.g., Budd-Chiari syndrome)
   • Splenomegaly results from:
     • Congestion due to increased portal pressure
     • Hyperplasia of reticuloendothelial cells
     • Increased blood flow through the splenic artery (hyperdynamic circulation)
   • Development of portosystemic collaterals, including esophageal and gastric varices
   Management:
   1. Diagnosis and staging:
      • Doppler ultrasound to assess portal flow and presence of collaterals
      • Endoscopy to evaluate for varices
      • Liver biopsy may be needed to determine underlying cause
   2. Treatment of underlying cause (if possible):
      • Management of chronic liver disease
      • Anticoagulation in cases of portal vein thrombosis
   3. Management of complications:
      • Variceal bleeding: Endoscopic band ligation or sclerotherapy
      • Ascites: Sodium restriction, diuretics
      • Hypersplenism: Consider partial splenic embolization in severe cases
   4. Pharmacological therapy:
      • Non-selective beta-blockers for primary prophylaxis of variceal bleeding in selected cases
      • Octreotide in acute variceal bleeding
   5. Surgical interventions:
      • Portosystemic shunts (e.g., transjugular intrahepatic portosystemic shunt - TIPS)
      • Mesenterico-left portal bypass (Rex shunt) in extrahepatic portal vein obstruction
   6. Liver transplantation in end-stage liver disease
   Management should be individualized based on the underlying cause, severity of portal hypertension, and presence of complications.
10. Q: Explain the concept of 'tropical splenomegaly syndrome' and its relevance in pediatric practice.
    A: Tropical Splenomegaly Syndrome (TSS), also known as Hyperreactive Malarial Splenomegaly (HMS), is an important consideration in pediatric practice, especially in malaria-endemic regions: Key features:
    • Chronic, massive splenomegaly in residents of malaria-endemic areas
    • Associated with repeated malarial infections, particularly P. falciparum
    • More common in adolescents and young adults but can occur in children
    • Characterized by hypergammaglobulinemia, particularly elevated IgM levels
    • Presence of high titers of anti-malarial antibodies
    Pathophysiology:
    • Thought to result from an aberrant immunological response to repeated malarial infections
    • Chronic antigenic stimulation leads to polyclonal B-cell activation and IgM overproduction
    • Deposition of immune complexes in the spleen causing progressive enlargement
    • Genetic predisposition may play a role
    Clinical presentation in children:
    • Massive, non-tender splenomegaly (often extending into the pelvis)
    • Abdominal discomfort and early satiety
    • Anemia and thrombocytopenia due to hypersplenism
    • Recurrent episodes of fever
    • Growth retardation in chronic cases
    Diagnosis:
    • Clinical criteria (Fakunle's criteria) include:
      • Gross splenomegaly (>10 cm below costal margin)
      • Elevated IgM levels (>2 SD above normal)
      • High anti-malarial antibody titers
      • Clinical and immunological response to anti-malarial therapy
    • Exclusion of other causes of massive splenomegaly
    Management:
    1. Long-term antimalarial prophylaxis (e.g., proguanil)
    2. Treatment of acute malarial episodes
    3. Folic acid supplementation for anemia
    4. Regular follow-up to monitor spleen size and hematological parameters
    5. Splenectomy is generally avoided due to increased risk of fulminant malaria
    Relevance in pediatric practice:
    • Important differential diagnosis in children from endemic areas presenting with massive splenomegaly
    • Highlights the need for thorough travel history in immigrant populations
    • Demonstrates the complex interplay between infection and immune response
    • Emphasizes the importance of long-term follow-up and prophylaxis in management
    Understanding TSS is crucial for pediatricians working in or dealing with patients from malaria-endemic regions to ensure proper diagnosis and management.
11. Q: Describe the evaluation and management of a child with suspected visceral leishmaniasis presenting with splenomegaly.
    A: Visceral leishmaniasis (VL), also known as kala-azar, is an important cause of splenomegaly in endemic areas and requires a systematic approach: Clinical presentation:
    • Fever (usually intermittent) for >2 weeks
    • Progressive splenomegaly, often massive
    • Weight loss and anorexia
    • Pallor due to anemia
    • Hepatomegaly (less prominent than splenomegaly)
    • Possible lymphadenopathy (more common in African VL)
    • Skin hyperpigmentation in chronic cases
    Evaluation:
    1. History:
       • Duration of symptoms
       • Travel or residence in endemic areas
       • Previous episodes or treatment
    2. Physical examination:
       • Assessment of spleen and liver size
       • Evaluation for lymphadenopathy
       • Look for signs of malnutrition and secondary infections
    3. Laboratory tests:
       • Complete blood count (typically shows pancytopenia)
       • Liver and renal function tests
       • Serum protein electrophoresis (polyclonal hypergammaglobulinemia)
       • Rapid diagnostic tests (e.g., rK39 immunochromatographic test)
    4. Confirmatory tests:
       • Microscopy of bone marrow aspirate (gold standard)
       • PCR on blood or bone marrow
       • Splenic aspiration (highly sensitive but carries risk)
    5. Additional investigations:
       • HIV testing (due to association)
       • Chest X-ray to rule out tuberculosis
    Management:
    1. Anti-leishmanial therapy:
       • Liposomal amphotericin B: First-line in most cases, especially in developed countries
       • Sodium stibogluconate: Still used in some regions, but increasing resistance
       • Miltefosine: Oral drug, useful in some regions
       • Paromomycin: Used in combination therapy in some areas
    2. Supportive care:
       • Nutritional support
       • Blood transfusion if severe anemia
       • Treatment of secondary infections
    3. Monitoring:
       • Clinical improvement (fever resolution, spleen size reduction)
       • Laboratory parameters (improvement in blood counts)
       • Test of cure (repeat bone marrow examination) at end of treatment
    4. Follow-up:
       • Regular follow-up for at least 6 months post-treatment
       • Monitor for relapse or post-kala-azar dermal leishmaniasis
    Special considerations in children:
    • Dosing of medications should be weight-based
    • Nutritional rehabilitation is crucial
    • Immunization status should be reviewed and updated after treatment
    • Family education about prevention and early recognition of relapse
    A high index of suspicion, prompt diagnosis, and appropriate treatment are key to favorable outcomes in pediatric visceral leishmaniasis.