What are the possible causes of an enlarged spleen and episodic right upper quadrant (RUQ) pain in an otherwise healthy 18-year-old female with no known medical history?

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Enlarged Spleen with Episodic Right Upper Quadrant Pain in an 18-Year-Old Female

In an otherwise healthy 18-year-old female presenting with splenomegaly and episodic right upper quadrant pain, the most critical initial step is obtaining a right upper quadrant ultrasound to evaluate for biliary pathology, followed by comprehensive laboratory workup including complete blood count, liver function tests, and peripheral blood smear to assess for hemolytic disorders, infections, and hematologic malignancies. 1, 2

Initial Diagnostic Imaging Approach

  • Order right upper quadrant ultrasound immediately as the American College of Radiology rates this 9/9 (usually appropriate) for RUQ pain evaluation, providing 96% accuracy for gallbladder pathology without radiation exposure. 1, 3

  • The ultrasound should specifically evaluate for gallstones, gallbladder wall thickening, bile duct dilatation, hepatic abnormalities, and confirm splenomegaly with splenic measurements. 1, 4

  • Do not order CT as initial imaging since CT has only ~75% sensitivity for gallstones, exposes the patient to unnecessary radiation, and is inferior to ultrasound for gallbladder and splenic pathology. 1, 5

Essential Laboratory Studies

  • Obtain complete blood count with differential to assess for anemia, thrombocytopenia, leukocytosis, or abnormal cell morphology that could indicate hemolytic disorders, infections, or hematologic malignancies. 2, 6

  • Order liver function tests including GGT, alkaline phosphatase, AST/ALT, total and direct bilirubin to assess for cholestatic patterns, as GGT elevates earlier and persists longer than alkaline phosphatase in cholestatic disorders. 1, 5

  • Request peripheral blood smear to evaluate for hemolysis, abnormal red blood cell morphology, or circulating blasts. 2

  • Consider reticulocyte count to assess for hemolytic anemia or bone marrow response. 7

Differential Diagnosis Framework

Biliary/Hepatic Causes (Most Common in U.S.)

  • Chronic cholecystitis or biliary dyskinesia can present with recurrent postprandial RUQ pain and may be associated with reactive splenomegaly from chronic inflammation. 1, 2

  • If ultrasound shows gallstones with typical biliary-type pain, consider cholecystokinin-augmented cholescintigraphy with gallbladder ejection fraction calculation; ejection fraction <35% supports biliary dyskinesia diagnosis. 1

Hematologic Causes

  • Hemolytic anemias (including hereditary spherocytosis, sickle cell disease variants like HbSC) cause splenomegaly and can present with episodic pain from splenic sequestration or infarction. 7, 2

  • In sickle cell disease, splenic sequestration presents as rapidly enlarging spleen with hemoglobin decrease >2 g/dL below baseline, though this typically occurs in younger children with HbSS or adolescents with HbSC. 7

  • Lymphoproliferative disorders and leukemias commonly cause splenomegaly and may present with abdominal pain; malignancy is one of the three most common causes of splenomegaly in the United States. 2, 6

Infectious Causes

  • Infectious mononucleosis (Epstein-Barr virus) is extremely common in this age group and causes splenomegaly with abdominal pain; obtain heterophile antibody test or EBV serology. 2

  • Other viral infections, bacterial endocarditis, and parasitic infections can cause splenomegaly, though parasitic causes are more common in tropical regions. 7, 2

Algorithmic Next Steps Based on Initial Results

If Ultrasound Shows Biliary Pathology

  • For diagnostic findings of acute cholecystitis, proceed directly to surgical consultation. 1, 5

  • For equivocal findings, order Tc-99m cholescintigraphy to confirm cystic duct obstruction. 1, 5

  • For suspected bile duct pathology, order MRI with MRCP which has 85-100% sensitivity and 90% specificity for detecting choledocholithiasis and provides superior visualization of the biliary tree. 1

If Laboratory Studies Suggest Hematologic Disorder

  • Hemolysis indicators (elevated reticulocyte count, decreased haptoglobin, elevated indirect bilirubin, abnormal blood smear) warrant hematology consultation and hemoglobin electrophoresis. 7, 2

  • Abnormal white blood cell count or morphology requires bone marrow biopsy consideration and hematology/oncology referral. 2, 6

If Initial Workup is Non-Diagnostic

  • Consider contrast-enhanced CT abdomen and pelvis to evaluate for splenic infarction, abscess, lymphadenopathy, or other occult pathology. 7

  • Abdominal CT and MRI have 90-95% sensitivity and specificity for diagnosing splenic abscess, which can present with episodic pain and fever. 7

Critical Clinical Pitfalls to Avoid

  • Do not dismiss splenomegaly as incidental in a young patient; it is almost always a sign of systemic disease requiring investigation. 2, 8

  • Recognize that RUQ pain can originate from splenic pathology including splenic infarction or abscess, which may present with left upper quadrant, left flank, or referred RUQ pain. 7

  • Do not assume biliary dyskinesia without excluding hematologic causes first, as hemolytic disorders can cause both splenomegaly and biliary symptoms from pigment stone formation. 1, 2

  • Counsel the patient to avoid contact sports until splenomegaly etiology is determined and resolved, as splenic rupture is a serious complication. 2

  • Consider atypical presentations: chronic appendicitis can rarely present with RUQ pain, though this would not explain splenomegaly. 9

Management Considerations

  • Management of splenomegaly involves treating the underlying disease process rather than the splenomegaly itself. 2

  • If splenic sequestration is diagnosed, prompt recognition and careful red blood cell transfusions (3-5 mg/kg aliquots) may be lifesaving, with caution to avoid overtransfusion >10 g/dL. 7

  • Patients requiring splenectomy need increased vaccination and prophylactic antibiotics for respiratory procedures due to limited splenic function. 2

References

Guideline

Diagnostic Approach to Intermittent Right Upper Quadrant Pain

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Splenomegaly: Diagnosis and Management in Adults.

American family physician, 2021

Research

Right Upper Quadrant Pain: Ultrasound First!

Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 2017

Guideline

Best Initial Imaging for a New Soft Lump in the Right Upper Quadrant

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Management of Right Upper Quadrant Pain with Elevated GGT

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Why does my patient have lymphadenopathy or splenomegaly?

Hematology/oncology clinics of North America, 2012

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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