Hairy cell leukemia is a rare chronic B-cell lymphoproliferative disorder that is characterized by pancytopenia, monocytopenia, splenomegaly, “hairy cells” on a peripheral smear, “dry tap” on bone marrow aspirate and biopsy, and a characteristic immunophenotype.

The symptoms of hairy cell leukemia can be classified as follows:

1) Cytopenias: The most common symptoms of hairy cell leukemia are attributable to cytopenias that are almost universally present at the time of diagnosis.

a) Anemia: Fatigue, generalized weakness and exertional shortness of the breath, due to anemia, are the most common presenting symptoms of hairy cell leukemia. Although ~75% patients have hemoglobin <12 g/dL at diagnosis, only about a third of patients have severe anemia (defined as hemoglobin <8g/dL). In the vast majority of cases, the anemia is due to bone marrow infiltration or splenomegaly; other causes of anemia such as iron deficiency anemia and autoimmune hemolytic anemia should be excluded, since this has major therapeutic implications.

b) Infections: ~60% patients present with an infection at the time of their initial diagnosis. In contrast to leukocytosis that is seen in most patients with leukemias, patients with hairy cell leukemia present with leukopenia. In fact, severe neutropenia (defined as <0.5 x 109/L neutrophils) is present in ~30% patients at diagnosis. Another important feature is the presence of monocytopenia, a characteristic finding of hairy cell leukemia. The most common infections are due to Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa and Escherichia coli, typically seen in neutropenic patients. Atypical infections caused by mycobacteria, Listeria monocytogenes, Aspergillus species, cytomegalovirus and herpes zoster can also be present at the time of the initial diagnosis.

c) Bleeding: Bleeding due to thrombocytopenia can manifest in ~30% patients at diagnosis, and is directly related to the platelet count. Platelets <100 x 109/L are present in ~75% patients at presentation, and severe thrombocytopenia (<50 x 109/L) are seen in about a third of all patients at diagnosis. The most common bleeding symptoms include ecchymoses, epistaxis, gingival bleeding and menorrhagia.

2) Organomegaly: Although splenomegaly is present on physical examination in most patients with hairy cell leukemia, the vast majority are asymptomatic. Some patients may present with early satiety. Splenic infarcts and splenic rupture have rarely been reported as the presenting features of hairy cell leukemia. Hepatomegaly is seen in ~60% patients at diagnosis, although it is symptomatic in far fewer patients.

3) Autoimmune disease: Patients with hairy cell leukemia may present with concomitant autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. Other less common presentations include diffuse joint pains, polyarteritis nodosa, erythema nodosum or leukocytoclastic vasculitis. Patients may also present with autoimmune hemolytic anemia or immune thrombocytopenia.

4) Other symptoms: Rare symptoms of hairy cell leukemia include:

a) Bulky lymphadenopathy occurs uncommonly, but when present can cause symptoms of compression.

b) Some patients present with bone pain; rarely, imaging studies may reveal destructive bone lesions.

c) Rarely patients present with neurologic involvement – such as meningitis or nerve compression.

5) Asymptomatic presentation: With an increasing use of routine blood tests, a number of patients with hairy cell leukemia are diagnosed incidentally. The vast majority of these patients have cytopenias on complete blood count analysis. Although it is difficult to estimate, it is thought that approximately 25% patients with hairy cell leukemia have no symptoms at diagnosis. It is important to establish the correct diagnosis, and only consider treatment when the indications to treat have been met according to standard guidelines.