Chapter 69: Classification and Clinical Manifestations of Disorders of Monocytes and Macrophages

SUMMARY

Disorders that exclusively result in abnormalities of monocytes, macrophages, or dendritic cells are uncommon and usually are referred to, pathologically, as histiocytosis. These disorders can be inherited, such as familial hemophagocytic lymphohistiocytosis; inflammatory, such as infectious hemophagocytic lymphohistiocytic syndrome; or clonal (neoplastic), such as Langerhans cell histiocytosis. They can result from an inherited enzyme insufficiency in macrophages that lead to exaggerated storage of macromolecules, such as in Gaucher disease. Monocytes are critical sources for proinflammatory and inflammatory cytokines and, when inappropriately activated, can result in the lymphohistiocytic hemophagocytic syndrome with fever, intravascular coagulation, and organ pathology. A variety of hematopoietic neoplasms may have a phenotype characterized by a large proportion of monocytes. Idiopathic (clonal) monocytosis is a rare manifestation of a myelodysplastic syndrome. Some cases of myelogenous leukemia have progenitor cells that mature preferentially into leukemic monocytes, including acute monoblastic or monocytic leukemia, chronic myelomonocytic leukemia, and juvenile myelomonocytic leukemia. Two acquired diseases, hairy cell leukemia and aplastic anemia, result in a severe depression of blood monocytes (along with other blood cell types). Mutations in GATA2 are associated with severe monocytopenia and mycobacterial infections (the MonoMAC syndrome). Inherited disorders affecting white cells, such as chronic granulomatous disease and Chédiak-Higashi syndrome, result in impaired monocyte function. Monocyte dysfunction may accompany a variety of severe illnesses, such as sepsis, trauma, and cancer. Monocytes also contribute to a variety of diseases, such as Crohn disease and rheumatoid arthritis, by virtue of their being a principal source of tumor necrosis factor. Monocytes play a pathogenetic role in other complex, acquired disorders, such as thrombosis and atherogenesis. Table 69–1 catalogues the qualitative and quantitative abnormalities of monocytes, macrophages, and dendritic cells.