Evaluation of warning signs of primary immunodeficiencies

Introduction
Primary immunodeficiencies (PID) are a group of more than 350 rare diseases, which are characterised by a variety of clinical symptoms and are difficult to diagnose. Early diagnosis is very important for improvement of quality of life of the children with PID. The aim of the study was to evaluate the warning signs of PID, taking into account the regional features of PID prevalence to improve early verification of these disorders.

Material and methods
Overall, 107 children aged between two months and 18 years with warning signs of PID, developed by the Jeffrey Modell Foundation Medical Advisory Board, as well as with other warning signs of PID, developed by the Ukrainian Association of Pediatric Immunology, were enrolled in the study. The patients were referred to immunologists by primary care physicians or hospital specialists during the implementation of physician education and a public awareness program of early diagnosis and management of PID.

Results
Among 107 children with warning signs, PID was diagnosed in 19 (17.8%) patients. Chronic diarrhoea with malabsorption was present more frequently in the patients with definable PID (p = 0.0048). Dysmorphic features and/or microcephaly were also more common in the patients with PID (p = 0.0456). More significant differences were found when microcephaly was combined with dysmorphic features (p = 0.0004). Congenital heart disease occurred only in the patients with PID (p = 0.0437), in particular with DiGeorge (22q11.2 deletion) syndrome.

Conclusions
For early detection of PID, it is necessary to take into account regional features of the prevalence of certain PID. Our study has established that such warning signs as chronic diarrhoea with malabsorption, dysmorphic features and microcephaly, and congenital heart disease with/or without seizures with underlying hypocalcaemia were important for PID diagnosis in the studied region.