From the Guidelines
Lymphadenopathy in hemoglobin SC disease requires a thorough workup to differentiate between infectious, inflammatory, and malignant causes, with a focus on identifying the underlying cause to guide management and improve patient outcomes. The initial evaluation should include a complete blood count with differential, comprehensive metabolic panel, lactate dehydrogenase, and inflammatory markers like ESR and CRP 1. Specific infectious workup should include blood cultures, HIV testing, EBV, CMV, tuberculosis testing, and consideration of atypical infections, as patients with hemoglobin SC disease are at increased risk of infections due to functional hyposplenism 1.
Differential Diagnosis
The differential diagnosis for lymphadenopathy in hemoglobin SC disease should consider:
- Infections (particularly encapsulated organisms due to functional asplenia)
- Hematologic malignancies (lymphoma risk is increased in hemoglobinopathies)
- Inflammatory conditions related to vaso-occlusive crises
- Medication reactions
Imaging Studies
Imaging studies should begin with ultrasound of affected lymph nodes, followed by CT or PET-CT if malignancy is suspected 1.
Diagnostic Gold Standard
Excisional lymph node biopsy is the gold standard for diagnosis when malignancy is suspected, with samples sent for histopathology, flow cytometry, and microbiology studies 1.
Management
Management should address both the underlying hemoglobinopathy and the specific cause of lymphadenopathy once identified, taking into account the unique pathophysiology of hemoglobin SC disease, which has intermediate disease severity between HbSS and HbAA, characterized by higher hemoglobin levels but still experiencing vaso-occlusive phenomena and increased infection risk due to functional hyposplenism.
From the Research
Differential Diagnoses for Lymphadenopathy in Hemoglobin SC Disease
- Infections (e.g., pneumonia, osteomyelitis) 2
- Sickle cell-related complications (e.g., vaso-occlusive pain, acute chest syndrome) 3, 4, 5
- Hypercoagulability and thromboembolic events 6
- Functional asplenia, which can increase the risk of septicemia 2
- Other conditions that may cause lymphadenopathy, such as malignancies or autoimmune disorders
Workup for Lymphadenopathy in Hemoglobin SC Disease
- Complete blood count (CBC) to evaluate for signs of infection, inflammation, or hematologic abnormalities 3, 4, 5
- Blood cultures and other microbiologic tests to diagnose infections 2
- Imaging studies (e.g., chest X-ray, CT scan) to evaluate for signs of infection, inflammation, or other complications 3, 4, 5
- Coagulation studies to evaluate for hypercoagulability 6
- Pit count or radionuclide liver-spleen scanning to assess splenic function 2
- Other tests as indicated by the patient's clinical presentation and medical history
Considerations for Hydroxyurea Treatment
- Hydroxyurea may be effective in reducing vaso-occlusive pain and other sickle cell-related complications in patients with Hemoglobin SC disease 3, 4, 5
- However, hydroxyurea may also increase the risk of hematologic dose-limiting toxicities (DLTs) 3
- Monitoring of laboratory parameters, including CBC and coagulation studies, is essential for patients receiving hydroxyurea 3, 4, 5