Targeting fatigue may improve quality of life for children with primary immunodeficiency

Children with primary immunodeficiency reported fatigue that impacts their quality of life, and targeting this fatigue may improve their well-being, according to a study published in Journal of Clinical Immunology.

Linde N. Nijhof, MSc, of the department of pediatrics at Wilhelmina Children’s Hospital in Utrecht, the Netherlands, and colleagues noted that fatigue is relatively common among children with primary immunodeficiency (PID).

These children often report a lower health-related quality of life (HRQoL) compared with their healthy peers, as well as increased risk for psychological problems and limitations in physical and social activities.

But early detection of fatigue along with timely interventions may improve the well-being of these children in addition to their participation in daily life, the researchers wrote, and may even prevent the persistence of fatigue into adulthood.

The study recruited 79 patients aged 2 to 18 years (mean age, 10.4 ± 4.4 years; 59.5% male) with PID who visited the pediatric immunology and infectious diseases outpatient clinic at Wilhelmina Children’s Hospital, who researchers compared with a group of 504 (mean age, 9.5 ± 4.7 years; 47.6% male) healthy peers.

Researchers used the pediatric quality-of-life multidimensional fatigue scale 3.0 (PedsQL MFS) to assess fatigue — the study’s primary endpoint — and the PedsQL generic core scales (PedsQL GCS) to assess HRQoL. Parents completed questionnaires at home for children aged 2 to 7 years. Children aged 8 to 18 years completed questionnaires themselves, in addition to one parent also completing a questionnaire for the child.

Also, researchers examined each patient’s disease activity — classified as low, moderate or high — and their comorbidities, which included atopic, autoimmune, syndrome, neurological, congenital and psychiatric categories.

According to the study, 18.9% of children with PID were severely fatigued, defined as greater than two standard deviations below the norm of healthy peers, compared with 4.4% of the healthy peer group (P < .005).

Patients with common variable immunodeficiency (CVID), combined immunodeficiency (CID) and selective immunoglobin A deficiency reported severe fatigue, but those with X-linked agammaglobulinemia (XLA) did not.

The researchers suggested that the severe fatigue reported among patients with CVID and CID may be partially related to the immune dysregulation that these patients frequently display, which would be in line with the observation that those with XLA did not report fatigue.

Also, patients aged 8 to 18 years reported significantly more total, general and sleep/rest fatigue than their healthy peers, but reported similar levels of cognitive fatigue.

Parents of patients aged 2 to 7 years reported significantly more fatigue among their children in all PedsQL MFS domains except for cognitive fatigue than parents of the healthy peer group (62.5% vs. 2.7%; P < .005).

Similarly, according to the parents, 38.9% of children aged 8 to 18 years experienced fatigue on all subscales, compared with 2.9% of the healthy peer group (P < .005).

The researchers also associated increased fatigue with lower HRQoL. Each single-point reduction in each child’s general PedsQL MFS score was associated with a 1.1-point (95% CI, 0.9-1.4) mean reduction in total HRQoL score.

Plus, children with lower general fatigue scores (indicating more fatigue) had higher percentages of school absences in the previous 2 weeks and 6 months.

Study participants reported low (72.2%), moderate (26.6%) and high (1.3%) levels of disease activity. Even when their disease was well-managed, some patients reported disabilities associated with fatigue.

However, a multivariable analysis showed no significant association between disease activity with fatigue, even in a subgroup analysis of 16 patients with one or more comorbidities.

The researchers noted the differences between the self-reported and the parent-reported data, indicating that parents tended to underestimate their child’s HRQoL and functioning. The child’s and parents’ perspectives both should be considered, according to the researchers , and parents should be actively involved in treatment.

Overall, the researchers found lower general fatigue scores with respect to total HRQoL and all four PedsQL GCS subscales for both age groups with PID.

“The relatively high prevalence of fatigue in younger children suggests that the focus should shift from treating fatigue to preventing this debilitating symptom,” the researchers wrote, adding that a transdiagnostic approach should be used to address fatigue.

Providers should focus on each patient’s individual needs instead of a specific disease-based approach, the researchers wrote, as long as the disease itself is optimally managed. Doing so would then improve these patients’ functioning, school participation and quality of life.