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984 Part VII: Neutrophils, Eosinophils, Basophils, and Mast Cells CHAPTER 64: Classification and Clinical Manifestations of Neutrophil Disorders 985

hairy cell leukemia, and cytotoxic therapy leads to susceptibility to a develop. For example, lack of pneumonic consolidation is characteristic
broader spectrum of infectious agents. Increased concentrations of nor- of pneumonia in granulocytopenic subjects. An exudate, swelling, heat,
mal neutrophils per se are usually not associated with clinical mani- and regional adenopathy are much less prevalent in granulocytopenic
festations; although, increased concentrations of leukemic neutrophil patients. Fever is common, and local pain, tenderness, and erythema
precursors can produce clinical manifestations of microcirculatory leu- nearly always are present despite a marked reduction in neutrophils. 181
kostasis (Chap. 83). Neutrophils also play a role in deleterious vascular The mechanism of neutropenia and the severity of the deficiency
or tissue effects, as noted in the last entries in Table 64–1 (see “Neu- of cells play roles in clinical manifestations. Chronic idiopathic (benign)
trophilia” below). neutropenia is associated with apparent normal granulopoiesis in the
marrow and is asymptomatic even when the neutropenia has been pres-
NEUTROPENIA ent for prolonged periods, sometimes in the face of neutrophil counts
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The lower limit of the normal neutrophil count is approximately approaching zero for prolonged periods. Presumably the delivery of
neutrophils from marrow to tissues is sufficient to prevent infection
1800/μL (1.8 × 10 /L) in subjects of European descent and 1400/μL despite the low blood pool size. Monocyte counts are normal, which
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(1.4 × 10 /L) in subjects of African descent. 174–177 An additional small may aid in host defenses because monocytes are effective phagocytes.
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proportion (~5 percent) of persons of African descent have neutrophil Chronic idiopathic (symptomatic) neutropenia often is associ-
counts between 1000/μL (1.0 × 10 /L) and 1400 (1.4 × 10 /L) without ated with pyoderma and otitis media in children. The former usually
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evidence of associated abnormalities and this finding also may represent is caused by Staphylococcus aureus, Escherichia coli, and Pseudomonas
“ethnic neutropenia.” These findings have not been explained by exag- species, and the latter usually results from infection by pneumococci
gerated margination of neutrophils. Neutropenia is especially striking or Pseudomonas aeruginosa. Unexplained chronic gingivitis may be
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in Yemenite Jews, another ethnic group with very low “normal” neu- a manifestation of chronic neutropenia. Pneumonia, lung abscesses,
trophil counts, and has been reported in West Africans, Caribbean stomatitis, hepatic abscesses, or infections in other sites can occur.
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inhabitants of African descent, Ethiopians, and some Arab groups. 176,177 Chronic cyclic neutropenia is characterized by periodic oscilla-
Persons of African descent do not have the increase of neutrophil count tions in the number of neutrophils, with the nadir occurring at approx-
seen in Europeans who smoke or are administered glucocorticoids; imately 3-week intervals. During a period of neutropenia, patients
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however, they have an appropriate increase of neutrophils in response develop malaise; fever; buccal, labial, or lingual ulcers; and cervical ade-
to infection. Americans of Mexican descent have a slightly elevated neu- nopathy. Furuncles, carbuncles, cellulitis, infected cuts with lymphangi-
trophil count. A decrement in neutrophil concentration to 1000/μL tis, chronic gingivitis, and abscesses of the axilla or groin may occur.
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(1.0 × 10 /L) usually poses little threat in the individual with an intact Although severe infections may be fatal, life-threatening complications
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immune system. If the neutrophil count drops farther, the risk of infec- are uncommon. The cycling involves other hematopoietic cells as well,
tion may increase, if the decrease reflects a decrease in flux rate into but the neutropenia is the most consequential functionally (Chap. 65).
the tissues. Subjects who are chronically neutropenic, as a result of Some individuals have neutropenia because a larger fraction of
severe marrow cell production abnormalities, with counts less than 500 their blood neutrophils is in the marginal rather than the circulating
neutrophils/μL (0.5 × 10 /L) may be at heightened risk for developing pool. The total blood neutrophil pool is normal, and infections do not
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recurrent infections. 179 result from this atypical distribution of neutrophils. This alteration has
The relationship of frequency or type of infection to neutrophil been called pseudoneutropenia. 76–78
concentration is imperfect. The cause of the neutropenia, the coinci-
dence of monocytopenia or lymphopenia, concurrent use of alcohol
or glucocorticoids, exposure to nosocomial infections, and other fac- NEUTROPHILIA
tors influence the likelihood of infection. A breakdown in the barrier An increased neutrophil count can accompany virtually any cause of
function of the skin or circumstances such as indwelling catheters, also, inflammation, especially inflammation caused by bacterial or fungal
increase the risk of infection in severely neutropenic subjects. Lower organisms, and a variety of cancers, especially if metastatic. Certain
neutrophil counts in African (Malawian) mothers infected with HIV drugs, such as glucocorticoids or hematopoietic growth factors and
were associated with an increased risk of HIV in their newborns. 180 minocycline, can induce neutrophilia, as can ethylene glycol intoxica-
Infections in neutropenic subjects who are not otherwise com- tion (see Table 64–1). Acute hemolysis or acute hemorrhage may also
promised usually result from Gram-positive cocci and usually are result in neutrophilia. A notable cause of neutrophilia is cancers that
superficial, involving skin, oropharynx, bronchi, anal canal, or vagina. elaborate granulocyte-colony stimulating factor (G-CSF). Numerous
However, any site can become infected and Gram-negative organisms, cancers are associated with neutrophilia and, in many cases, elabora-
viruses, or opportunistic organisms can be involved. tion of very high concentrations of G-CSF has been documented. In
A decrease in neutrophil count can occur abruptly or gradually these cases, neutrophil counts exceeding 100,000 μL (100 × 10 /L) are
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(Chap. 65). One type of drug-induced neutropenia is distinguished by common. Neutrophilia exceeding 50,000 neutrophils/μL (50 × 10 /L)
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the rapidity of onset. Abrupt-onset neutropenia more likely is severe has been designated a “leukemoid reaction” and reflects an underlying
and leads to symptoms. If the neutrophil count approaches zero (agran- inflammatory (e.g., pancreatitis), infectious (e.g., pneumococcal pneu-
ulocytosis), high fever; chills; necrotizing, painful oral ulcers (agran- monia), or neoplastic (e.g., carcinoma of the lung) cause. A leukemoid
ulocytic angina), and prostration may occur, presumably as a result reaction can mimic rare types of chronic myelogenous or chronic neu-
of sepsis. As the disease progresses, headache, stupor, and rash may trophilic leukemia. The leukemoid reaction classically (1) is composed
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develop. In the preantibiotic era, persistent agranulocytosis had a fatal- largely of mature neutrophils with a low proportion of bands and mye-
ity rate approaching 100 percent. Even with bactericidal, broad-spec- locytes, (2) has increased leukocyte alkaline phosphatase reaction in
trum antibiotics, severe, sustained neutropenia or agranulocytosis is a neutrophils, (3) has increased granulopoiesis with normal maturation
serious illness with a high fatality rate. and morphology of cells in the marrow, (4) has normal cytogenetics of
Pus formation decreases in patients with severe neutropenia. The marrow cells, (5) has polyclonal-derived cells in women in whom such
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failure to suppurate can mislead the clinician and delay identification studies can be conducted (using the human androgen receptor gene
of the infection site because minimal physical or radiographic findings assay), and (6) has cytometric analysis of neutrophils indicating a cluster

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