Investigation of Dental Health in Children With Neutrophil Defects: A Clinical Study

1. BACKGROUND Primary immunodeficiency diseases (PIDs) are a group of rare inherited disorders that are estimated to affect approximately 1 in 2,000 children. In PIDs there is an intrinsic defect in the human immune system, such as a failure to produce enough antibodies to fight infection, or a failure in the cellular defences against infection . These conditions usually manifest themselves early in life and are often life-threatening. Rarer, severe forms of PIDs present in childhood with serious infections and are often associated with additional autoimmune and inflammatory complications. Periodontal diseases are inflammatory diseases of the gingivae (gums) due to an imbalance in the host response to subgingival bacteria and are associated with destruction of the supporting tissues of the teeth and early loss of the dentition and masticatory function. While periodontitis and its non-destructive partner condition, gingivitis (reversible plaque-induced gingival inflammation), are very common, the prevalence of periodontitis in the primary dentition and in the second decade of life appears very low, ranging from 0.1% to 1%. This prevalence increases dramatically in children affected by PIDs, to the point that periodontitis is considered a common feature of syndromic genetic conditions due to single gene defects affecting the host response, such as leukocyte adhesion deficiency (LAD), severe congenital neutropenia, cyclic neutropenia and Chediak-Higashi syndrome. Children with defects in neutrophil activity seem particularly susceptible to develop severe periodontitis, due to the important defensive role of neutrophils against periodontopathogenic bacteria. In such cases, both primary and permanent dentitions are affected, with a devastating effect on mastication, aesthetics and quality of life, also owing to the lack of reliable restorative solutions. Furthermore, oral diseases (in particular periodontitis) may also provide an additional systemic inflammatory burden for these subjects. This could occur since periodontal bacteria have been shown to enter the systemic circulation from inflamed gum tissues even during normal tooth brushing, have been found in atheromatous plaques and in the amniotic fluid of pregnant women.

The treatment of periodontitis involves a non-specific reduction of the bacterial load below the gingival margin, achieved by oral hygiene instructions and non-surgical periodontal therapy (NSPT). More advanced cases need antibiotics, surgical treatment or extractions. In children with PID the response to this treatment is highly variable and the presence of periodontitis often leads to early tooth loss, adding to the poor quality of life of sufferers. Incorporation of periodontal screening has been advocated for early diagnosis and treatment of periodontal diseases in all children and especially for children with neutrophil defects, in order to prevent disease progression and tooth loss. However, most published papers on periodontitis in children with immunodeficiencies are case reports or familial observations or reviews. Therefore, there's a lack of well-designed studies investigating both the prevalence of periodontitis and oral diseases in general in children with neutrophil defects and their response to treatment. In particular, it is not clear which factors determine the onset of periodontitis in a subset of children with PID. Such factors may range from the composition of the subgingival microbiota, the immunological reaction against these bacteria, to the inflammatory response in the periodontium. A better understanding of the causative factors may help in early diagnosis and treatment, reducing the burden on affected children. 2. AIMS AND OBJECTIVES

The hypotheses behind this study are that:

i) Specific microbiological and host response parameters dictate severity of periodontal diseases and associated risk of early tooth loss in children suffering from neutrophil defects ii) Periodontal treatment in children with neutrophil defects and periodontitis can lead to an improvement in their oral health (reduction in periodontal pockets and bleeding scores), which would reduce their risk of tooth loss and potentially improve their future quality of life.

Therefore, the aims of this study are to offer specialist periodontal assessment and treatment to children with neutrophil defects, to determine the impact of neutrophil defects upon gingival health and to assess their response to periodontal therapy. This will facilitate the development of novel therapeutic management pathways specific for these conditions, and will determine whether there is a need for specific care protocols with a consequent improvement in tooth retention, quality of life and systemic health.

• The primary objective of this study is: