Chapter 061. Disorders of Granulocytes and Monocytes (Part 12)

Patients with leukopenias or leukocyte dysfunction often have delayed inflammatory responses. Therefore, clinical manifestations may be minimal despite overwhelming infection, and unusual infections must always be suspected. Early signs of infection demand prompt, aggressive culturing for microorganisms, use of antibiotics, and surgical drainage of abscesses. Prolonged courses of antibiotics are often required. In patients with CGD, prophylactic antibiotics (trimethoprim-sulfamethoxazole) and antifungals (itraconazole) markedlydiminish the frequency of life-threatening infections. Short courses of glucocorticoids may relieve gastrointestinal or genitourinary tract obstruction by granulomas in patients with CGD. ...
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Chapter 061. Disorders of Granulocytes and Monocytes (Part 12) Chapter 061. Disorders of Granulocytes and Monocytes (Part 12) Patients with leukopenias or leukocyte dysfunction often have delayedinflammatory responses. Therefore, clinical manifestations may be minimaldespite overwhelming infection, and unusual infections must always be suspected.Early signs of infection demand prompt, aggressive culturing for microorganisms,use of antibiotics, and surgical drainage of abscesses. Prolonged courses ofantibiotics are often required. In patients with CGD, prophylactic antibiotics(trimethoprim-sulfamethoxazole) and antifungals (itraconazole) markedlydiminish the frequency of life-threatening infections. Short courses ofglucocorticoids may relieve gastrointestinal or genitourinary tract obstruction bygranulomas in patients with CGD. Recombinant human IFN-γ, whichnonspecifically stimulates phagocytic cell function, reduces the frequency ofinfections in patients with CGD by 70% and reduces the severity of infection. Thiseffect of IFN-γ in CGD is additive to the effect of prophylactic antibiotics. Therecommended dose is 50 µg/m2 subcutaneously three times weekly. IFN-γ has alsobeen used successfully in the treatment of leprosy, nontuberculous mycobacteria,and visceral leishmaniasis. Rigorous oral hygiene reduces but does not eliminate the discomfort ofgingivitis, periodontal disease, and aphthous ulcers; chlorhexidine mouthwash andtooth brushing with a hydrogen peroxide–sodium bicarbonate paste helps manypatients. Oral antifungal agents (fluconazole or itraconazole) have reducedmucocutaneous candidiasis in patients with Jobs syndrome. Androgens,glucocorticoids, lithium, and immunosuppressive therapy have been used torestore myelopoiesis in patients with neutropenia due to impaired production.Recombinant G-CSF is useful in the management of certain forms of neutropeniadue to depressed neutrophil production, especially those related to cancerchemotherapy. Patients with chronic neutropenia with evidence of a good bonemarrow reserve need not receive prophylactic antibiotics. Patients with chronic orcyclic neutrophil counts < 500/µL may benefit from prophylactic antibiotics andG-CSF during periods of neutropenia. Oral trimethoprim-sulfamethoxazole(160/800 mg) twice daily can prevent infection. Increased numbers of fungalinfections are not seen in patients with CGD on this regimen. Oral quinolones suchas levofloxacin and ciprofloxacin are alternatives. In the setting of cytotoxic chemotherapy with severe, persistentneutropenia, trimethoprim-sulfamethoxazole prevents Pneumocystis jirovecipneumonia. These patients, and patients with phagocytic cell dysfunction, shouldavoid heavy exposure to airborne soil, dust, or decaying matter (mulch, manure),which are often rich in Nocardia and the spores of Aspergillus and other fungi.Restriction of activities or social contact has no proven role in reducing risk ofinfection. Cure of some congenital phagocyte defects is possible by bone marrowtransplantation (Chap. 108). However, complications of bone marrowtransplantation are still serious, and with rigorous medical care many patients withphagocytic disorders can go for years without a life-threatening infection. Theidentification of specific gene defects in patients with LAD 1, CGD, and otherimmunodeficiencies has led to gene therapy trials in a number of genetic whitecell disorders. Further Readings Horwitz MS et al: Neutrophil elastase in cyclic and severe congenitalneutropenia. Blood 109:1817, 2007 [PMID: 17053055] Klion AD et al: Approaches to the treatment of hypereosinophilicsyndromes: A workshop summary report. J Allergy Clin Immunol 117:1292, 2006[PMID: 16750989] Nathan C: Neutrophils and immunity: Challenges and opportunities. NatRev Immunol 6:173, 2006 [PMID: 16498448] Puel A et al: Heritable defects of the human TLR signalling pathways. JEndotoxin Res 11:220, 2005 [PMID: 16176658] Rosenzweig SD, Holland SM: Phagocyte immunodeficiencies and theirinfections. J Allergy Clin Immunol 113:620, 2004 [PMID: 15100664] Segal BH et al: Genetic, biochemical, and clinical features of chronicgranulomatous disease. Medicine (Baltimore) 79:170, 2000 [PMID: 10844936] Bibliography Diaz CA, Gulino AV: WHIM syndrome: A defect in CXCR4 signaling.Curr Allergy Asthma Rep 5:350, 2005 [PMID: 16091205] Doffinger R et al: X-linked anhidrotic ectodermal dysplasia withimmunodeficiency is caused by impaired NF-κB signaling. Nat Genet 27:277,2001 [PMID: 11242109] Dorman SE et al: Clinical features of dominant and recessive interferon-γreceptor 1 deficiencies. Lancet 364:2113, 2004 [P ...