Neutrophil Functional Disorders

Abstract

The phagocytic system is one of the first lines of defence against invading microorganisms. Diseases and disorders that impair phagocyte function can lead to a profound immunodeficiency. Egression from the bone marrow, adhesion, migration, activation, phagocytosis and microorganism killing describe basic mechanisms associated to phagocytic cells. When any of these activities is affected, severe, recurrent and relapsing bacterial as well as fungal infections usually occur. Chronic granulomatous disease is a paradigmatic example of a functional disorder in phagocytic cells. This clinically and genetically heterogenous disease has served during the past 50 years as a model for understanding genotypic–phenotypic correlations of infections susceptibility in primary immunodeficiencies, the utility of anti‐infectious and cytokine prophylactic therapy, hematopoietic stem cell transplantation and gene therapy. Key Concepts Patients with neutrophil functional disorders usually present early in life with recurrent bacterial or fungal infections. Certain infections, such as Burkholderia cepacia , Nocardia , Aspergillus nidulans or nontuberculous mycobacteria should always prompt an inquiry to the possibility of an underlying immune defect. Specific infection locations, such as omphalitis, gingivitis or osteomyelitis, should raise the suspicion of phagocytic cell abnormalities. Abnormal aspects of host response, such as lack of fever, local inflammation or pus, should immediately alert the clinician to the possibility of a neutrophil defect. It is better to perform the right test once than the entire battery of immune defect tests several times. Careful consideration of the clinical and microbiologic presentation usually indicates the right path to pursue. There is no substitute for the right drug, and that requires knowing the pathogen. Because the spectrum of infection in these diseases may range over several microbiologic kingdoms, empiric therapy is to be discouraged in favour of firm diagnoses. Prophylactic antibiotics, antifungal agents and cytokines are highly successful in treating chronic granulomatous disease, and appear to be useful in some other immunodeficiencies as well. A molecular diagnosis should be sought whenever possible. The expanding knowledge of genotype–phenotype relationships suggests that not all defects, even those within the same gene, are created equal. BCG vaccination should be avoided in individuals with CGD, as well as in their newborn close relatives until the defect is ruled out. In general, attenuated viral vaccines are not contraindicated in individuals with primary neutrophil disorders, as antiviral cell‐mediated immunity is intact.

Neutrophil Functional Disorder in Childhood/ Функционални Нарушувања На Неутрофилите Во Детството

“…The treatment includes antibiotic therapy (for therapeutic or prophylactic aims) and surgical interventions and drainage or debridement of infected sites. There is no substitute for the right drug, and that requires knowing the patho-gen. Because the spectrum of infection in these diseases may range over several microbiologic pathogens, empiric therapy is to be discouraged in favor of firm diagnoses [18].…”

“…A molecular diagnosis should be done whenever possible. The expanding knowledge of genotype-phenotype relationships suggests that not all defects, even those within the same gene, are created equal [18].…”