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Neutropenia is defined as a condition characterized by a depressed neutrophil count and associated with an increased risk of infections. The major causes of neutropenia include hematologic malignancies, metastatic neoplasm involving the bone marrow, irradiation, various drugs, vitamin B12 and folate deficiency, congenital or acquired primary disorders of hematopoiesis, as well as various autoimmune and benign idiopathic disorders.
Individuals with neutropenia often do not exhibit any specific symptoms, thus the condition is diagnosed after adequate blood tests. One of the symptoms can be fever, which constitutes a possibly severe life-threatening situation in which overwhelming infection may ensue rapidly.
The risk for infection in patients with neutropenia is significantly increased with neutrophil counts of 500-200/μL, and starts to get very severe below 200/μL. Bacterial infections represent a major cause of morbidity and mortality in patients who are neutropenic following chemotherapy for malignancy. Skin, mucosa of the oral cavity and lungs are the most frequent sites of infection.
Stomatologic disorders are almost always present after the age of two years in patients with profound neutropenia associated with myeloid cell production, usually characterized by erosive and painful gingivitis with aphthae-like oral furuncles of the tongue and buccal mucosa.
Bacterial infections generally encompass staphylococci, streptococci, enterococci, Pseudomonas aeruginosa and other gram-negative bacilli, whereas Candida or Aspergillusspecies are responsible for fungal infections. A shift has been noted in the epidemiology infectious agents since the widespread use of empiric antibiotic therapy – highly lethal, gram-negative bacilli were superseded by indolent, gram-positive bacterial and fungal pathogens.
The symptoms of infection can have an atypical presentation in patients with neutropenia due to the less local inflammation; hence pus and fluctuance may be absent. It is now evident that patients with neutropenia represent a heterogeneous population with different rates of infection-related morbidity and mortality.
Observant waiting always represents the first option for patients with neutropenia due to a viral infection or medication. Neutropenia that is drug-induced usually resolves within days to weeks upon the discontinuation of treatment, and after viral infection bodies can build up their neutrophil level on their own again.
Cytokines such as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) are occasionally used to treat neutropenia that arises as a result of chemotherapy or radiation. Furthermore, GM-CSF improves the neutrophil count in cyclic neutropenia, severe infantile agranulocytosis (Kostmann syndrome), and idiopathic neutropenias.
Therapeutic use of these cytokines among patients hospitalized for established neutropenia may complement the recommended prophylactic use of these agents for the prevention of neutropenic episodes. American Society of Clinical Oncology endorses such prophylaxis, especially for individuals at high risk for neutropenia developing from cytotoxic drugs in high doses.
Empiric, broad-spectrum antibiotic therapy should be administered swiftly to all patients with febrile neutropenia. The concomitant use of a colony-stimulating factor and antibiotics in individuals with chemotherapy-induced febrile neutropenia did not influence overall mortality, but aids significantly in neutrophil recovery and reduces the length of hospitalization.
Other more aggressive interventions (such as allogeneic marrow transplantation) have been efficacious in individuals with diseases of the bone marrow (i.e. aplastic anemia), as well as in several malignant hematopoietic diseases. Corticosteroid therapy is potentially effective in immune-mediated neutropenia.