Are hepatomegaly and splenomegaly part of the clinical presentation of Hemophagocytic Lymphohistiocytosis (HLH)?

Hepatomegaly and Splenomegaly in Hemophagocytic Lymphohistiocytosis (HLH)

Yes, hepatomegaly and splenomegaly are key clinical features of Hemophagocytic Lymphohistiocytosis (HLH) and are included in the diagnostic criteria for this condition. 1

Diagnostic Criteria for HLH

According to the HLH-2004 diagnostic criteria, splenomegaly is one of the eight diagnostic criteria used to establish the diagnosis of HLH. While hepatomegaly is not specifically listed as one of the eight main criteria, it is frequently present and considered a significant clinical finding in HLH 1.

The diagnosis of HLH can be established if either:

1. A molecular diagnosis consistent with HLH is made, OR
2. Five of the following eight diagnostic criteria are fulfilled:
   • Fever
   • Splenomegaly
   • Cytopenias affecting ≥2 of 3 lineages in peripheral blood
   • Hypertriglyceridemia and/or hypofibrinogenemia
   • Hemophagocytosis in bone marrow, spleen, or lymph nodes
   • Low or absent NK cell activity
   • Ferritin ≥500 mg/L
   • Soluble CD25 (sIL-2 receptor) ≥2400 U/mL

Importance of Organomegaly in HLH Scoring

In the HScore, which is a scoring system used to estimate the probability of HLH in adults, organomegaly is specifically scored as:

• 0 points: No hepatomegaly or splenomegaly
• 23 points: Hepatomegaly OR splenomegaly
• 38 points: Hepatomegaly AND splenomegaly 1

This scoring system highlights the clinical significance of both hepatomegaly and splenomegaly in the diagnosis of HLH.

Clinical Presentation

In adult patients with HLH:

• Splenomegaly is present in approximately 79.6% of cases
• Hepatomegaly is present in approximately 65.0% of cases 2

These organ enlargements are often accompanied by:

• High fever (96.1%)
• Liver dysfunction (98.1%)
• Cytopenia (99.0%)
• Elevated ferritin levels (98.4%)
• Hypertriglyceridemia (88.5%) 2

Pathophysiology

The hepatomegaly and splenomegaly in HLH result from:

1. Infiltration of these organs by activated lymphocytes and macrophages
2. Tissue inflammation due to excessive cytokine production
3. Hemophagocytosis occurring within these organs 3

Clinical Implications

The presence of hepatomegaly and splenomegaly in patients with suspected HLH has important prognostic implications. Patients who died from HLH were more likely to present with splenomegaly compared to survivors 2, highlighting the importance of recognizing and addressing this clinical feature.

Diagnostic Approach

When evaluating a patient with suspected HLH:

• Physical examination should carefully assess for hepatomegaly and splenomegaly
• Imaging studies (ultrasound, CT, or MRI) may be needed to confirm and quantify organ enlargement
• Additional supportive findings include liver enzyme abnormalities, which are present in most HLH cases 1

Pitfalls and Caveats

1. While organomegaly is common in HLH, its absence does not rule out the diagnosis, especially early in the disease course.
2. Hepatosplenomegaly can be a feature of many other conditions, including infections, malignancies, and autoimmune disorders, requiring careful differential diagnosis.
3. In some patients, hepatomegaly may be more subtle than splenomegaly or vice versa, so thorough examination for both is essential.
4. Hepatomegaly in HLH is often accompanied by liver dysfunction, which can progress to liver failure if HLH is not promptly treated.

In conclusion, hepatomegaly and splenomegaly are integral clinical features of HLH that contribute significantly to both its diagnosis and prognosis. Their presence should prompt consideration of HLH in the appropriate clinical context, particularly when accompanied by other characteristic findings such as fever, cytopenias, and hyperferritinemia.