Leukocyte adhesion deficiency type I (LAD-I) is a rare inborn error of immunity affecting approximately 1 in 1 million individuals worldwide. Severe LAD-I is characterized by frequent life-threatening infections and significant pediatric mortality. Although this can have devastating effects on children and their families, there is little research about the lived experience of the disease. To fill this gap, we executed a multi-case study to describe the burden of severe LAD-I from the caregiver perspective.
Caregivers from 5 families with children with severe LAD-I participated in individual, in-depth interviews. Interviews followed a study-specific guide using concept and photo elicitation to obtain descriptions of caring for a child with severe LAD-I. Interview transcripts were analyzed using inductive and deductive approaches to describe the burdens of illness and treatment.
Nine parents were interviewed. Among the 7 children, treatments included: allogeneic hematopoietic stem cell transplantation (alloHSCT; n = 2), investigational gene therapy (GT; n = 4), and antimicrobial prophylaxis (n = 1).
Findings were organized under themes of burden of illness and burden of treatment (Table 1). The burden of illness included challenging journeys to diagnosis and frequent, hard-to-treat infections, leading children and caregivers to isolate physically and socially to reduce infection risk. All caregivers rearranged their jobs or career trajectories substantially to accommodate caregiving. Most parents were frustrated by the absence of LAD-I–specific resources and information. The burden of treatment differed by therapy. AlloHSCT families described difficult recoveries and, for 1 child, only partial success in treating LAD-I. GT families experienced a significant reduction of burden of illness, yet some expressed concerns for their child’s future given the novelty of the treatment. All participants agreed that antimicrobials were not a long-term treatment solution.
Main themes within burden of illness and treatment in severe LAD-I.
| Burden | Themes | Examples |
|---|---|---|
| Illness | Frequent and varied infections | Rashes, skin/mucosal lesions, and infections in the lungs, ears, gums; poorly healing umbilical cords |
| Physical restrictions | Avoiding water parks, beaches, other outdoor activities; limiting sports; preventing contact with pets | |
| Social restrictions | Limiting visitors to the home; avoiding daycare; home schooling | |
| Journey to diagnosis marked by lack of information | Failure of frequent severe infections and slow healing wounds to drive investigation and diagnosis; lack of resources, guidance, and information pre- and post-diagnosis | |
| Treatment | AlloHSCT | Searching for a bone marrow match; complexity of alloHSCT process; managing alloHSCT complications; side-effects from post-transplant treatments; waning efficacy |
| Gene therapy | Generally positive outcomes, despite a long and complex process; required relocation for the duration of treatment; uncertainty about durability and longer-term effects given the novelty of GT | |
| Prophylactic antimicrobials | In 1 case, in the absence of a family donor match for alloHSCT, the clinician recommended this approach; parents indicated it is not a long-term nor complete solution |
| Burden | Themes | Examples |
|---|---|---|
| Illness | Frequent and varied infections | Rashes, skin/mucosal lesions, and infections in the lungs, ears, gums; poorly healing umbilical cords |
| Physical restrictions | Avoiding water parks, beaches, other outdoor activities; limiting sports; preventing contact with pets | |
| Social restrictions | Limiting visitors to the home; avoiding daycare; home schooling | |
| Journey to diagnosis marked by lack of information | Failure of frequent severe infections and slow healing wounds to drive investigation and diagnosis; lack of resources, guidance, and information pre- and post-diagnosis | |
| Treatment | AlloHSCT | Searching for a bone marrow match; complexity of alloHSCT process; managing alloHSCT complications; side-effects from post-transplant treatments; waning efficacy |
| Gene therapy | Generally positive outcomes, despite a long and complex process; required relocation for the duration of treatment; uncertainty about durability and longer-term effects given the novelty of GT | |
| Prophylactic antimicrobials | In 1 case, in the absence of a family donor match for alloHSCT, the clinician recommended this approach; parents indicated it is not a long-term nor complete solution |
Together, the burdens of illness and treatment had profound impacts on these families. The parents’ descriptions also demonstrated that while none of the current treatments for severe LAD-I is perfect, GT shows great potential for improving patients’ health and minimizing disease burden. Moreover, this research provides critical insights for clinicians, whose care of children with severe LAD-I can be informed by understanding the struggles associated with the burdens of illness and treatment.
