Can Angioimmunoblastic T cell lymphoma cause flu-like symptoms and fluctuations in white blood cell count?

Angioimmunoblastic T-Cell Lymphoma and Clinical Manifestations

Yes, angioimmunoblastic T-cell lymphoma (AITL) characteristically causes both flu-like symptoms and fluctuating white blood cell counts as part of its core clinical presentation. 1

Flu-Like Symptoms in AITL

AITL presents with a constellation of systemic symptoms that mimic flu-like illness:

• Fever is a hallmark feature of AITL, occurring as part of the classic presentation alongside generalized lymphadenopathy 1
• B symptoms (fever, night sweats, weight loss) are extremely common and should prompt investigation for opportunistic infections as well as the underlying lymphoma 1
• Skin rashes frequently accompany the systemic symptoms, contributing to the flu-like presentation 1
• The disease creates what has been termed an "immunodysplastic syndrome" with exacerbated inflammatory response and immune dysregulation 2

These systemic manifestations result from the secretion of cytokines and chemokines (IL-6, IL-21, CXCL-13, VEGF) by the malignant T-follicular helper cells, which modulate complex interactions within the tumor microenvironment 2.

White Blood Cell Count Fluctuations

AITL causes variable and fluctuating white blood cell abnormalities through multiple mechanisms:

• Eosinophilia is frequently associated with AITL and can fluctuate during the disease course 1
• Peripheral blood involvement occurs in AITL, with documented cases showing peripheral blood plasmacytosis and variable lymphocyte counts 3
• Bone marrow infiltration is common, affecting hematopoiesis and causing cytopenias that may fluctuate 4, 3
• Autoimmune cytopenias can develop, including autoimmune hemolytic anemia and immune thrombocytopenia, which cause fluctuating blood counts 5

The white blood cell count may show paradoxical patterns—some patients present with leukopenia despite having a lymphoproliferative disorder, while others show elevated counts with eosinophilia 4, 3.

Critical Diagnostic Considerations

When evaluating a patient with flu-like symptoms and fluctuating WBC:

• AITL typically presents in advanced stage (III or IV) at diagnosis, with most patients showing systemic involvement 1, 4
• Associated findings that distinguish AITL from simple viral illness include: hepatomegaly or splenomegaly, polyclonal hypergammaglobulinemia, pleural effusion, and ascites 4, 3
• EBV-positive B cells are frequently present in the tumor microenvironment and should be assessed 1
• The median age at presentation is around 60 years, occurring mainly in older patients 1, 4

Important Clinical Pitfalls

• Do not dismiss persistent flu-like symptoms in older adults with lymphadenopathy and fluctuating blood counts as simple viral infection 4, 3
• Opportunistic infections must be excluded when B symptoms are present, as AITL patients have severe immune dysregulation and predisposition to recurrent infections 1, 2
• The differential diagnosis is broad, including viral infections, collagenosis, and adverse drug reactions—AITL has been called a "many-faced lymphoma" for this reason 2
• Autoimmune phenomena can complicate the clinical picture, with predisposition to autoimmunity being a characteristic feature of AITL 2

Prognosis and Urgency

The prognosis of AITL is poor, with 5-year overall survival around 30-40% even with aggressive treatment 2. Early diagnosis is crucial, as the disease follows an aggressive, potentially fatal course—one reported case resulted in death within 2 months of diagnosis 3. The median survival time ranges around 20 months, though some patients achieve long-term survival exceeding 10 years 4.