Relevance of laboratory testing for the diagnosis of primary immunodeficiencies: a review of case-based examples of selected immunodeficiencies

The field of primary immunodeficiencies (PIDs) is one of several in the area of clinical immunology that has not been static, but rather has shown exponential growth due to enhanced physician, scientist and patient education and awareness, leading to identification of new diseases, new molecular diagnoses of existing clinical phenotypes, broadening of the spectrum of clinical and phenotypic presentations associated with a single or related gene defects, increased bioinformatics resources, and utilization of advanced diagnostic technology and methodology for disease diagnosis and management resulting in improved outcomes and survival. There are currently over 200 PIDs with at least 170 associated genetic defects identified, with several of these being reported in recent years. The enormous clinical and immunological heterogeneity in the PIDs makes diagnosis challenging, but there is no doubt that early and accurate diagnosis facilitates prompt intervention leading to decreased morbidity and mortality. Diagnosis of PIDs often requires correlation of data obtained from clinical and radiological findings with laboratory immunological analyses and genetic testing. The field of laboratory diagnostic immunology is also rapidly burgeoning, both in terms of novel technologies and applications, and knowledge of human immunology. Over the years, the classification of PIDs has been primarily based on the immunological defect(s) ("immunophenotype") with the relatively recent addition of genotype, though there are clinical classifications as well. There can be substantial overlap in terms of the broad immunophenotype and clinical features between PIDs, and therefore, it is relevant to refine, at a cellular and molecular level, unique immunological defects that allow for a specific and accurate diagnosis. The diagnostic testing armamentarium for PID includes flow cytometry - phenotyping and functional, cellular and molecular assays, protein analysis, and mutation identification by gene sequencing. The complexity and diversity of the laboratory diagnosis of PIDs necessitates many of the above-mentioned tests being performed in highly specialized reference laboratories. Despite these restrictions, there remains an urgent need for improved standardization and optimization of phenotypic and functional flow cytometry and protein-specific assays. A key component in the interpretation of immunological assays is the comparison of patient data to that obtained in a statistically-robust manner from age and gender-matched healthy donors. This review highlights a few of the laboratory assays available for the diagnostic work-up of broad categories of PIDs, based on immunophenotyping, followed by examples of disease-specific testing

Periocular capillary hemangioma: management practices in recent years

Jo Anne Hernandez,1,3,4 Audrey Chia,2 Boon Long Quah,1,2 Lay Leng Seah1,2 1Department of Ophthalmology, Kandang Kerbau Women's and Children's Hospital, Singapore; 2Singapore National Eye Centre, Singapore; 3National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; 4Department of Ophthalmology, Cardinal Santos Medical Center, San Juan, Manila, Philippines Purpose: To present a case series on the management options for capillary hemangiomas involving the eyelid and orbit. Methods: This is a retrospective chart review of clinically diagnosed capillary hemangioma cases involving the periocular region treated at two local eye institutions. The patients' demographics and clinical presentation – including visual acuity, refractive error, periorbital and orbital examinations, and ultrasound and magnetic resonance imaging findings – were reviewed. The clinical progression, modalities of treatment, and treatment outcomes were studied. Results: Sixteen cases of capillary hemangiomas involving the eyelid and orbit were studied. The mean age at consultation was 9.6 months (range: 1 month–72 months). The majority were females (75%), with 50% presenting as upper-eyelid hemangiomas and the remaining as lower-eyelid (38%) and glabellar (12%) lesions. Combined superficial and deep involvement was common (64%). Cases whose lesions were located at the upper eyelid or superior orbit led to amblyopia (25%). Fifty-six percent of cases (9/16) were managed conservatively, and 44% (7/16) underwent treatment with either single-agent (n = 4) or combined treatments (n = 3). Conclusion: Close monitoring of visual development and prompt institution of amblyopia therapy for children with periocular capillary hemangiomas generally preserve vision. Extensive lesions that affect the visual axis require local and systemic treatments, alone or in combination, in order to reduce the size and impact of lesions on the eyeball, to reduce induced refractive error and visual occlusion, and to prevent the development of amblyopia, in order to achieve good visual outcomes. Keywords: vascular, vascular malformation, bleomycin, propranolol, prednisolone, amblyopi