Health-Related Quality of Life and Emotional Health in X-Linked Carriers of Chronic Granulomatous Disease in the United Kingdom

Alexandra C Battersby,Catherine M Cale,David Goldblatt,Andrew R Gennery,Fiona Mckendrick,Siobhan Burns,Helen Braggins,Mark S Pearce,Mari Campbell

doi:10.1007/s10875-019-00607-6

Abstract

X-linked chronic granulomatous disease (XL-CGD), a rare primary immunodeficiency due to a defect in the gp91phox NADPH oxidase subunit, results in recurrent, severe infection, inflammation, and autoimmunity. Patients have an absent, or significantly reduced, neutrophil oxidative burst. Due to lyonization, XL-CGD carriers have a dual population of functional and non-functional phagocytes and experience a range of symptoms including increased risk of autoimmunity, fatigue, and infection. Patients with CGD have poorer quality of life (QoL) than normal controls. We evaluated QoL and psychological health in UK XL-CGD carriers. Recruited participants completed the Medical Outcomes Study Short Form 36 version 2 (SF-36 V2), providing an overall score for mental and physical health. Psychological health was assessed using the Hospital Anxiety and Depression Scale (HADS) questionnaire. Seventy-five XL-CGD carriers were recruited from 62 families, median age 43 years (range 3–77). Fifty-six were mothers, 6 grandmothers, and 13 siblings. Sixty-two completed the SF36v2 and had reduced QoL scores compared with adult CGD patients and a UK age-matched female control cohort, indicating a reduced QoL. Sixty-one completed a HADS questionnaire. Over 40% experienced moderate or greater levels of anxiety with only one third being classified as normal. Higher anxiety scores significantly correlated with higher depression scores, lower self-esteem, presence of joint or bowel symptoms, and higher levels of fatigue (p < 0.05). This is the first study to evaluate QoL of XL-CGD carriers, and demonstrates high rates of anxiety and significantly reduced QoL scores. XL-CGD carriers should be considered as potential patients and pro-actively assessed and managed.

Highlights

Tyne, United Kingdom (UK)Chronic granulomatous disease (CGD) is a rare inborn error of immunity in which a defect in one of the subunits of NADPH oxidase results in a defective respiratory burst of phagocytic cells, causing recurrent infection, inflammation, and autoimmunity [1]
Eighty families were identified from the UK CGD register, and 75 X-linked chronic granulomatous disease (XL-CGD) carriers were recruited from 62 families
For patients affected by primary immunodeficiencies (PID), research has primarily concentrated on elucidating the pathophysiology of the disease, conducting epidemiological studies to define the prevalence in different populations, and determining the prognosis with different treatment modalities that are available

Summary

Introduction

Chronic granulomatous disease (CGD) is a rare inborn error of immunity in which a defect in one of the subunits of NADPH oxidase results in a defective respiratory burst of phagocytic cells, causing recurrent infection, inflammation, and autoimmunity [1]. Patients with CGD who continue on maintenance prophylactic treatment have poorer quality of life (QoL) than healthy controls or CGD patients who underwent curative hematopoietic stem cell transplantation [2]. CGD can be X-linked or autosomal recessive. Others, have previously described a range of symptoms in XL-CGD carriers. This includes an increased risk of autoimmunity (in particular systemic lupus erythematosus (SLE)–like symptoms), fatigue, and, in some cases, infection, attributed to their dual

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