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

Abstract

X-linked chronic granulomatous disease (XL-CGD), a rare primary immunodeficiency due to a defect in the gp91 phox 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.

STAT3 Hyper-IgE Syndrome—an Update and Unanswered Questions

“…The largest dataset, from the USIDNET registry, shows that < 25% describe no impact of their health on QOL [ 3 ], though this report was not restricted to patients with STAT3 mutations. Fatigue and depression are common (21%) and associated with skin and pulmonary infection, as is reduced QOL, similarly to chronic granulomatous disease probands, X-linked female carriers, and X-linked agammaglobulinemia patients, demonstrating significant impact of recurrent infection and hospitalization [ 112 – 114 ]. A second series supports the negative impact of pulmonary symptoms on QOL, alone or in combination with dermatological disease [ 43 ].…”

Long Term Outcome and Immune Function After Hematopoietic Stem Cell Transplantation for Primary Immunodeficiency

“…In the X-linked form of chronic granulomatous disease recent data suggest that, because of random lyonisation, female carriers of X-linked chronic granulomatous disease are at significant risk of experiencing autoimmunity, fatigue, anxiety and depression, likely because of inflammation caused by the genetically faulty phagocytes (46–48). Neutrophil function of <10% was highly associated with an increased risk of infection (47).…”

The 49th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Oral Sessions (O009-O172)

“…Ryotaro Nakamura 1 , Bhavisha Patel 2 , Soyoung Kim 3 , Lennie Wong 1 , Saro Armenian 1 , Emma Groarke 2 , Kyle Hebert 3 , Mary Eapen 3 , Neal Young 2 1 City of Hope National Medical Center, Duarte, United States, 2 National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States, 3 Center for International Blood and Marrow Transplantation Registry, Medical College of Wisconsin, Milwaukee, United States Background: Immunosuppressive treatment (IST) and allogeneic hematopoietic cell transplant (HCT) are standard therapies for severe aplastic anemia (SAA). While outcomes after initial IST or HCT have been well described, limited data are available regarding the temporal variations of mortality risks on survivors of SAA after IST or HCT.…”

“…A complex karyotype was defined as three or more structural abnormalities, and a monosomal karyotype as a monosomy with one or more structural abnormalities, excluding WHO-designated recurring translocations or inversions (2017 ELN recommendations). The "other" subgroup included t(6;9), t (3;5), t(9;22), t(8;16), inv (3) or t (3;3), t(16;21), abn(11p15), and del(12p) or abn(12p13). Cytogenetic subgroup, age at HSCT, female donor to male recipient, patient/donor CMV status, time from AML diagnosis to HSCT, and year of HSCT were included as predictors for OS, RI and non-relapse mortality (NRM) in multivariate analysis.…”