What is the differential diagnosis for a 14-year-old with sickle cell disease (SCD) and hypersplenism presenting with sore throat, abdominal pain, and headache without fever?

Differential Diagnosis for a 14-Year-Old with Sickle Cell Disease, Hypersplenism, and 6 Days of Sore Throat, Abdominal Pain, and Headache

The most critical diagnosis to exclude immediately is transient aplastic crisis from parvovirus B19 infection, which presents with sore throat (prodromal viral symptoms) and can rapidly progress to life-threatening anemia in patients with sickle cell disease. 1

Life-Threatening Diagnoses Requiring Urgent Evaluation

Transient Aplastic Crisis (Most Likely)

• Parvovirus B19 infection typically presents with prodromal symptoms including sore throat, headache, and malaise before the characteristic anemia develops 1
• The 6-day duration fits the typical timeline for parvovirus infection, which causes profound reticulocytopenia and worsening anemia 1
• Immediate workup must include CBC with reticulocyte count compared to baseline values—reticulocyte count typically drops below 1% 1
• Abdominal pain may reflect worsening anemia and splenic involvement 1
• The absence of fever does not exclude this diagnosis, as parvovirus often presents without the characteristic rash 1
• Siblings and household contacts with sickle cell disease are at high risk for concurrent or subsequent aplastic crisis and require screening 1

Acute Splenic Sequestration Crisis

• Given the patient's known hypersplenism, acute splenic sequestration remains a critical consideration 1, 2
• This presents with rapidly enlarging spleen, acute drop in hemoglobin, and can progress to hypovolemic shock 2
• Abdominal pain would be prominent from acute splenic enlargement 2, 3
• While more common in children under 5 years with HbSS, it can occur at any age, particularly in patients with HbSC genotype who retain splenic function 2, 4
• Physical examination must include careful palpation for acute spleen enlargement beyond baseline 1

Stroke

• Severe headache in sickle cell disease requires urgent neurologic evaluation to exclude stroke 1
• While the patient lacks other neurologic symptoms, stroke can present initially with isolated severe headache 1
• Any headache beyond transient mild headache warrants immediate CBC, reticulocyte count, type and crossmatch, and noncontrast CT or MRI of the brain 1

Infectious Etiologies

Bacterial Sepsis

• Patients with sickle cell disease and hypersplenism have impaired splenic function despite splenomegaly, creating risk for overwhelming bacterial infection 1
• The absence of fever does not exclude serious bacterial infection in immunocompromised patients 1
• Sore throat could represent pharyngitis progressing to bacteremia 1
• Streptococcus pneumoniae and other encapsulated organisms remain high-risk pathogens even with splenomegaly 1

Viral Pharyngitis with Vaso-Occlusive Crisis

• Viral upper respiratory infection (including parvovirus prodrome) can trigger vaso-occlusive pain crisis 1
• Abdominal pain and headache may represent vaso-occlusive pain in multiple sites 1, 3
• However, this diagnosis should not be assumed until life-threatening causes are excluded 1

Other Sickle Cell-Related Complications

Chronic Hypersplenism Complications

• Chronic hypersplenism causes progressive cytopenias (anemia, leukopenia, thrombocytopenia) with compensatory bone marrow proliferation 4
• Abdominal pain may reflect chronic splenic enlargement or splenic infarction 1, 4
• Patients with HbSC genotype rarely undergo auto-splenectomy and maintain large spleens into adulthood 4

Cholelithiasis

• Right upper quadrant abdominal pain with vomiting and worsening jaundice suggests gallstones, which have higher incidence in sickle cell disease 1
• However, the presence of sore throat and headache makes this less likely as the primary diagnosis 1

Immediate Diagnostic Workup Required

The following tests must be obtained urgently:

• CBC with differential and reticulocyte count compared to baseline values 1
• Blood type and crossmatch in preparation for potential transfusion 1
• Parvovirus B19 serology (IgM and IgG) and PCR 1
• Blood cultures if any concern for bacteremia 1
• Comprehensive metabolic panel to assess organ function 1
• Physical examination with careful documentation of spleen size compared to baseline 1
• Noncontrast head CT or MRI if headache is severe or persistent 1

Critical Management Considerations

If transient aplastic crisis is confirmed:

• Isolation from pregnant healthcare workers and other at-risk individuals is mandatory due to high contagiousness of parvovirus 1
• Red blood cell transfusions are often required 1
• Screen household contacts with sickle cell disease 1

If acute splenic sequestration is identified:

• Aggressive fluid resuscitation and transfusion support 2, 3
• Avoid overtransfusion as sequestered cells will be released 2
• Splenectomy is typically performed after recovery from acute episode 2, 5