Recommended evaluation and management for the immunodeficiency, autoimmunity, and autoinflammation in the immune dysregulation of DS
| Immunologic domain . | Recommended evaluation . | Management recommendations . |
|---|---|---|
| Immunodeficiency | • Quantitative lymphocyte subsets (CD3, CD4, CD8, and CD19) for all DS patients once in early childhood or at initial referral with annual repeat if low counts, other immunologic laboratory abnormalities, or on treatment • Quantitative IgG, IgA, IgM, and IgE for all DS patients once in early childhood or at initial referral with annual repeat if low counts, other immunologic laboratory abnormalities, under age 4, or on treatment • Vaccine-specific antibody titers (ex. pneumococcal, measles, mumps, rubella, varicella, hepatitis B, tetanus, and diphtheria) at age 2 years or at initial referral if older • Consider B cell phenotyping if other immunologic laboratory abnormalities and considering treatment | Vaccination • Ensure complete age-appropriate vaccinations • Live vaccines generally safe but defer if CD4 <400/μl or CD8 <200/μl • RSV, Covid-19, and influenza recommended • Prefer conjugate pneumococcal vaccines; booster schedules for age >2 years per immunocompromised CDC guidance • Nonresponders may benefit from revaccination using conjugate pneumococcal formulations or shortened booster intervals Treatment • Timely and liberal treatment of infections • Low threshold for low-dose antibiotic prophylaxis (ex. azithromycin) for mild/moderate recurrent infections • Low threshold for immunoglobulin replacement in SPAD or CVID-like phenotypes (400–600 mg/kg/mo; target IgG trough ∼800–1,000 mg/dl) • Multidisciplinary care is crucial to optimize anatomic susceptibilities to infection Monitoring • Monitor complete blood cell counts, renal function, and liver function closely on immunoglobulin replacement • Recheck titers 4–8 wk after vaccination to assess response |
| Autoimmunity | • Follow established DS surveillance guidelines (thyroid routinely; symptom-based screening for diabetes, celiac) in collaboration with primary care physician • Baseline autoimmune serologies before IVIG initiation | Treatment • Multidisciplinary management with endocrinology, gastroenterology, rheumatology, neurology, psychiatry, and other specialties as clinically indicated • Immunomodulatory or immunosuppressive therapy when indicated Monitoring • Evaluate new systemic, neurologic, or behavioral symptoms promptly • Recommend heightened infection monitoring when on immunosuppression |
| Autoinflammation | • Regular comprehensive skin examinations • Neuroinflammatory screening and referral when cognitive or behavioral changes present | Treatment • Aggressive control of inflammatory skin disease to reduce infection risk • Escalation to biologics when standard therapies fail as clinically indicated • Consider JAK inhibitors for IFN-driven disease • Supportive care and infection-directed therapy as needed Monitoring • Consider trending inflammatory markers and selected cytokine studies |
| Immunologic domain . | Recommended evaluation . | Management recommendations . |
|---|---|---|
| Immunodeficiency | • Quantitative lymphocyte subsets (CD3, CD4, CD8, and CD19) for all DS patients once in early childhood or at initial referral with annual repeat if low counts, other immunologic laboratory abnormalities, or on treatment • Quantitative IgG, IgA, IgM, and IgE for all DS patients once in early childhood or at initial referral with annual repeat if low counts, other immunologic laboratory abnormalities, under age 4, or on treatment • Vaccine-specific antibody titers (ex. pneumococcal, measles, mumps, rubella, varicella, hepatitis B, tetanus, and diphtheria) at age 2 years or at initial referral if older • Consider B cell phenotyping if other immunologic laboratory abnormalities and considering treatment | Vaccination • Ensure complete age-appropriate vaccinations • Live vaccines generally safe but defer if CD4 <400/μl or CD8 <200/μl • RSV, Covid-19, and influenza recommended • Prefer conjugate pneumococcal vaccines; booster schedules for age >2 years per immunocompromised CDC guidance • Nonresponders may benefit from revaccination using conjugate pneumococcal formulations or shortened booster intervals Treatment • Timely and liberal treatment of infections • Low threshold for low-dose antibiotic prophylaxis (ex. azithromycin) for mild/moderate recurrent infections • Low threshold for immunoglobulin replacement in SPAD or CVID-like phenotypes (400–600 mg/kg/mo; target IgG trough ∼800–1,000 mg/dl) • Multidisciplinary care is crucial to optimize anatomic susceptibilities to infection Monitoring • Monitor complete blood cell counts, renal function, and liver function closely on immunoglobulin replacement • Recheck titers 4–8 wk after vaccination to assess response |
| Autoimmunity | • Follow established DS surveillance guidelines (thyroid routinely; symptom-based screening for diabetes, celiac) in collaboration with primary care physician • Baseline autoimmune serologies before IVIG initiation | Treatment • Multidisciplinary management with endocrinology, gastroenterology, rheumatology, neurology, psychiatry, and other specialties as clinically indicated • Immunomodulatory or immunosuppressive therapy when indicated Monitoring • Evaluate new systemic, neurologic, or behavioral symptoms promptly • Recommend heightened infection monitoring when on immunosuppression |
| Autoinflammation | • Regular comprehensive skin examinations • Neuroinflammatory screening and referral when cognitive or behavioral changes present | Treatment • Aggressive control of inflammatory skin disease to reduce infection risk • Escalation to biologics when standard therapies fail as clinically indicated • Consider JAK inhibitors for IFN-driven disease • Supportive care and infection-directed therapy as needed Monitoring • Consider trending inflammatory markers and selected cytokine studies |