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1096 Part VIII: Monocytes and Macrophages Chapter 70: Monocytosis and Monocytopenia 1097

Monocytosis occurs in a number of neutropenic states: cyclic neu- A monocytosis in the resolution phase of acute infections has
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tropenia, chronic granulocytopenia of childhood, familial benign been noted, and monocytosis occurs in cases of neonatal, primary,
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chronic neutropenia, infantile genetic agranulocytosis 34,35 and chronic and secondary syphilis. 69,70 Certain viruses, especially cytomegalovirus
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hypoplastic neutropenia. In human cyclic neutropenia, monocyte varicella-zoster virus, and influenza virus induce an increase in blood
oscillation is reciprocal to the neutrophil cycle; the peak monocyto- monocytes. 71–73
sis, which often exceeds 2000/μL (2.0 × 10 /L), occurs at the end of the
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neutropenic period. Monocytes often stay above 500/μL (0.5 × 10 /L) GASTROINTESTINAL DISEASES
throughout the cycle. In the variety of other neutropenias mentioned,
monocytopoiesis often is preserved in the face of neutropenia. Tran- Sprue, ulcerative colitis, regional enteritis, and alcoholic liver disease are
sient elevations of the monocyte count have been reported in the acute associated with monocytosis. 11,74,75
phases of drug-induced agranulocytosis. 37–39 Monocytosis characteristi-
cally appears later in the recovery phase of agranulocytosis and may be NONHEMATOPOIETIC MALIGNANCIES
a harbinger of recovery. 37,40,41 Some observers dispute the validity of the Sixty percent of patients with nonhematologic malignancy exhibit a
latter observation. 42 monocytosis that is independent of the presence or absence of meta-
Monocytosis can occur with lymphomas and can increase with static disease. An inverse relationship of monocyte count (elevated)
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exacerbation of disease activity. Monocytosis has been noted in and T-lymphocyte concentration (decreased) has also been noted in
approximately 25 percent of cases of Hodgkin lymphoma, although it patients with malignant disease. Reports of hematologic values in
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does not correlate with prognosis. 43,44 In contrast, one treatise on the metastatic colon cancer and soft-tissue sarcoma have emphasized the
disease reports the hematologic values of patients with Hodgkin lym- frequency of monocytosis in patients with cancer. 78,79 Consequently, if
phoma at the time of diagnosis; only 4 of 100 have nominal increases in unexplained monocytosis persists, malignancy should be considered.
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absolute blood monocyte counts. A statistically significant increase in
blood monocyte concentration has been reported in myeloma and has
been correlated with the presence of λ light-chain-containing mono- EXOGENOUS CYTOKINE ADMINISTRATION
clonal immunoglobulin. 46,47 Rare cases of M-CSF secreting lymphoid The administration of granulocyte-macrophage colony-stimulat-
tumors have been associated with monocytosis. 48,49 Monocytosis at ing factor (GM-CSF), IL-10, or granulocyte colony-stimulating
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diagnosis has been correlated with decreased survival in several lym- factor (G-CSF) 82,83 may result in mild increases in blood monocyte
phoma types and chronic lymphocytic leukemia. 50,51 Pseudolymphoma counts. Administration of M-CSF 84,85 results in an invariable increase
syndrome, induced by drugs such as carbamazepine, phenytoin, pheno- in blood monocytes. Doses of 40 to 120 mcg/kg per day result in the
barbital, and valproic acid, is associated with monocytosis. 52 peak increase, which may reach three- to fourfold baseline, in approx-
imately 8 days. Administration of human macrophage inflammatory
SPLENECTOMY protein-1α to patients or normal volunteers is associated with a brief
monocytopenia followed by a monocytosis that is proportional to the
Monocytosis is a common feature in individuals who have had dose administered. 86
splenectomy. 53,54
MYOCARDIAL INFARCTION
INFLAMMATORY AND IMMUNE DISORDERS Monocytosis occurs after myocardial infarction, reaching a peak on
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Connective tissue diseases, including rheumatoid arthritis, systemic day 3. A correlation exists between serum creatine kinase activity and
lupus erythematosus, temporal arteritis, myositis, and periarteritis monocyte count, suggesting a relationship between extent of infarction
nodosa, may be associated with monocytosis, although monocytosis is and monocytosis. After myocardial infarction, persistent monocyto-
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not common in these diseases. The usual alterations of the white cell sis is correlated with pump failure. 88–90 Monocytosis is a frequent find-
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count in systemic lupus erythematosus, for example, are neutropenia ing after cardiopulmonary bypass surgery. In the latter circumstance,
and lymphopenia, but 10 percent of patients have a mild monocyto- CD14 (lipopolysaccharide [LPS] receptor) is markedly decreased on the
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sis. An elevation of the blood monocyte count occurs in sarcoidosis monocyte surface and plasma-soluble CD14 is increased, changes com-
and is inversely related to a reduction in circulating T lymphocytes. 58 patible with monocyte activation.
Infectious diseases are an uncommon cause of monocytosis. Only
a few instances of infection were noted in a comprehensive review of
causes of monocytosis, including tonsillitis, dental infection, recurrent MISCELLANEOUS CONDITIONS
liver abscesses, candidiasis, and one instance of tuberculous perito- Other disorders associated with monocytosis include tetrachloroe-
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nitis. Tuberculosis was once a leading cause of monocytosis, because thane poisoning. Monocytosis is a frequent finding at the time of
of the role of monocytes in granuloma (tubercle) formation. Neither parturition. 93,94 An increase in blood monocytes occurs in healthy vol-
the monocyte count nor the ratio of monocytes to lymphocytes cor- unteers 95,96 and in patients with myelodysplastic syndrome (MDS) 97,98
relates with the stage or activity of tuberculosis. 59–61 Mycobacterium for- who are given moderately high, therapeutic-level doses of glucocorti-
tuitum infection, usually in the setting of AIDS, also is associated with coids. Psychiatric depression is associated with a conjoint increase in
monocytosis. 62 neutrophils and monocytes. 99–101 The monocytosis in depressive and
Monocytosis is found in 15 to 20 percent of patients with subacute anxiety disorders is associated with high plasma levels of β endorphins
bacterial endocarditis, 63,64 but is not correlated with the presence of and dysfunctional (hypophagocytic) monocytes. Thermal injury is
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blood macrophages, which may be present in this disease. 65 accompanied by monocytosis. 102,103 Competitive marathon runners have
A number of infections formerly thought to be associated with a monocytosis associated with elevated plasma levels of several cytok-
monocytosis are not, when examined systematically. These include rick- ines, including M-CSF. 104,105 An increase in blood monocytes accompa-
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ettsial diseases, leishmaniasis, typhoid fever, malaria, and disseminated nies several rare syndromes: holoprosencephaly, Kawasaki disease,
candidiasis, brucellosis, and dengue hemorrhagic fever. 67 and Wiskott-Aldrich. 108
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