Most children with primary immunodeficiency disorders experience fatigue
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Most children with a primary immunodeficiency experienced fatigue, which can be evaluated via a review of these patients’ charts and use of a generic questionnaire, according to a study published in Journal of Clinical Immunology.
“In our outpatient clinic, a lot of our primary immunodeficiency (PID) patients complain of fatigue, not being able to go to school all the time or play with friends,” Clementien L. Vermont, MD, pediatrician in infectious diseases and immunology at Erasmus MC-Sophia Children’s Hospital in Rotterdam, the Netherlands, told Healio.
“We wanted to quantify and explore the extent of fatigue in these patients to get a better feel for it,” Vermont said.
For the retrospective single-center observational study, researchers reviewed Dec. 1, 2015, to Dec. 1, 2017 medical charts from 54 children with a PID such as hypogammaglobulinemia, common variable immunodeficiency (CVID) or X-linked agammaglobulinemia (XLA).
These patients were being treated with immunoglobulin replacement therapy, with 77% receiving IgG replacement subcutaneously. Also, 39% of these patients had been receiving this therapy for 2 years or less, and 43% had been receiving it for 5 years or longer.
According to the chart review, 64% of the patients had reported fatigue symptoms during one of the consultations conducted during the 2-year study period.
Next, 27 of the patients aged 2 to 18 years (mean age, 10.7 years) and 32 of their parents completed the PedsQL MFS questionnaire, which uses 18 items to classify general fatigue, sleep-rest fatigue and cognitive fatigue over the previous 4 weeks.
The researchers converted questionnaire results into standardized z scores for comparison to reference values, with z scores of less than –1 considered abnormal, or more fatigued compared with healthy peers.
Ninety-one percent of the patient respondents had normal hemoglobulin levels.
The researchers noted that the concordance of scores reported by children and parents was better for older compared with younger children.
Compared with a healthy reference group, children with PID had overall lower scores on all scales, especially in general fatigue. The z scores for general fatigue and total fatigue were significantly lower. For example, the self-reported general fatigue score of the total group was –1.78, and the proxy-reported general fatigue score was –2.45.
The researchers did not find differences in z scores between boys and girls or between the different age groups, although 74% had a z score for general fatigue of less than –1, indicating significantly more fatigue compared with healthy peers. Also, 48% had a total fatigue z score of less than –1.
After reviewing the chart data and PedsQL-MFS scores, the researchers determined an overall fatigue rate of 65% in this population.
“I think the study shows fatigue has a major impact on their daily life, and in quite a few patients, it’s their number one complaint,” Vermont said.
Further, the researchers found that these patients with PID generally reported worse fatigue scores compared with children with multiple sclerosis, cancer or other severe chronic diseases, indicating the high burden that fatigue symptoms have on these patients.
“I think it’s remarkable that the fatigue is as severe or maybe even more than in other severe chronic diseases like childhood cancer and multiple sclerosis,” Vermont said.
The researchers cautioned that fatigue includes psychological and social factors in addition to medical factors and that their study did not include any information about psychiatric comorbidity.
However, these patients reported the most fatigue on the general fatigue subscale, and the least fatigue in the cognitive fatigue subscale, indicating that the fatigue that these children were experiencing primarily was physical.
“Doctors of patients with PID should take the fatigue complaint seriously and be honest in that, despite very good treatment options for their infectious problems, the fatigue often remains in PID patients, and try to help them in coping with that,” Vermont said.
Exercise treatment programs may benefit these patients, the researchers suggested, adding that use of the PedsQL-MFS survey during follow-up also could help determine if medical or psychological interventions could influence fatigue symptoms.
Studies pertaining to these kinds of interventions are warranted and should be pursued, the researchers concluded.
“We would like to proceed with a structured intervention trial in order to cope with and hopefully improve the fatigue complaints. At this moment, however, there is no funding for that,” Vermont said.
“I believe we should do such a trial in a much larger cohort, combining different centers and involve psychologists and physiotherapists. The PedsQL-MFS can be easily used in follow-up of these patients,” Vermont said.
For more information:
Clementien L. Vermont, MD, can be reached at c.vermont@erasmusmc.nl.
Perspective
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Fatigue can be a clinical symptom experienced by patients with immune disorders. The exact cause of fatigue may not be entirely clear, but it is observed more frequently among adults with immune system disorders like autoimmunity and immunodeficiency.
In the recent publication by Visser and colleagues, the authors investigated the prevalence and impact of fatigue in children with PIDs from a single academic center using patient-reported outcome (PRO) measures. This study aimed to address a gap in knowledge by researching how the impact of different types of fatigue affected children with PIDs and their parents.
The study included 56 children aged 2 to 18 years who had a diagnosis of PID related to antibody deficiency and who were on immunoglobulin replacement therapy (IgG-RT). A little over half of the study population (children and parents) returned information from the PRO measure PedsQL-Multidimensional Fatigue Scale (MFS), which is a validated questionnaire for children experiencing fatigue and their parents.
It was not surprising that children with PIDs reported more physical fatigue compared with healthy children, and their parents often concurred. These findings would be consistent with similar studies of adults and small studies of children. Interestingly, children aged younger than 7 years and their parents tended to not agree as well on fatigue scores, whereas children aged 8 years and older had similar perceptions of fatigue as their parents.
The authors concluded that the MFS PRO could be used to assess fatigue in this specific population of children with PID, which may be useful for primary care and other physician providers to assess and monitor fatigue as a symptom. Given differences in child reports under age 8 years, larger studies in PID may be needed to determine whether this is an accurate assessment tool for the younger age group. By better understanding the types of fatigue a patient has and by being able to measure it, there may be opportunities for intervention studies that could show measurable improvement in fatigue over time.
A limitation of this study was that it was limited to one center, to one time point of fatigue assessment and to specific antibody-deficiency PID patients. It would be important to see if fatigue outcomes changed over time and if fatigue was similar in different parts of the country and in more diverse populations of patients with PID.
Another limitation was that all the patients were on IgG-RT, which, as the authors note, is associated with fatigue in certain circumstances. Previous studies have shown that a low IgG level may correlate with increased fatigue, and some studies have shown that patients experience more fatigue after an IV infusion. This study looked at patients on subcutaneous IgG-RT, which, as the authors noted, should have stable antibody levels, but the medication effects cannot be fully discounted.
Half of the patients contacted filled out the MFS survey. Another possible limitation from this is that survey responders versus nonresponders might give different results, which could introduce bias.
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