Overview
Definition:
Recurrent infections in children refer to frequent episodes of common or unusual infections that are more severe, prolonged, or incompletely resolved than typically expected for age and immune status
Suspecting immune deficiency is crucial when these infections suggest a defect in the host defense mechanisms.
Epidemiology:
Primary immunodeficiency disorders (PIDs) affect approximately 1 in 2,000 live births, with some PIDs being much rarer
Many PIDs remain undiagnosed or are diagnosed late, leading to significant morbidity and mortality
Recurrent infections are the most common presenting complaint.
Clinical Significance:
Timely recognition of recurrent infections as a sign of potential immune deficiency is paramount
Early diagnosis and appropriate management can prevent severe complications like sepsis, chronic organ damage, autoimmunity, and malignancy, significantly improving long-term outcomes and quality of life for affected children.
Clinical Presentation
Symptoms:
Frequent ear infections (otitis media) requiring more than 4 antibiotic courses per year
Recurrent sinusitis requiring more than 2 courses of antibiotics per year
Pneumonia occurring more than twice in a lifetime
Persistent thrush beyond 6 months of age
Deep skin or soft tissue infections (e.g., cellulitis, abscesses)
Recurrent severe gastroenteritis or failure to thrive
Sepsis or meningitis
Chronic diarrhea
Autoimmune phenomena
Family history of PID or early childhood deaths.
Signs:
Poor growth or failure to thrive
Ocular abnormalities
Eczema or dermatitis
Generalized lymphadenopathy or splenomegaly
Recurrent oral ulcers
Absent or small tonsils/lymphoid tissue
Recurrent fevers without a clear source
Chronic cough with poor weight gain
Evidence of opportunistic infections.
Diagnostic Criteria:
No single universal diagnostic criterion exists for suspecting PID
rather, a constellation of clinical features, infection patterns, and family history triggers a high index of suspicion
Several scoring systems exist (e.g., the 10 Warning Signs of PID) to aid in identification.
Diagnostic Approach
History Taking:
Detailed history of infection pattern: number, frequency, severity, site, and response to treatment
Specific pathogens involved
History of prematurity, congenital anomalies, consanguinity
Family history of recurrent infections, autoimmune diseases, allergies, or early deaths
Maternal history of infections during pregnancy
Medications taken by child and family
Vaccination history
Growth parameters: weight, height, head circumference.
Physical Examination:
Assess growth and nutritional status
Examine skin for lesions, eczema, or signs of chronic infection
Palpate for lymphadenopathy and organomegaly
Inspect oral cavity for thrush and ulcers
Assess ears, nose, throat, and lungs for signs of acute or chronic infection
Examine joints and eyes
Perform a thorough neurological exam.
Investigations:
Screening tests: Complete blood count (CBC) with differential, Quantitative immunoglobulins (IgG, IgA, IgM), Specific antibody titers (e.g., post-vaccination titers to tetanus, pneumococcus)
Further testing: Neutrophil function tests (e.g., DHR assay), Complement levels (CH50, C3, C4, C1 esterase inhibitor), Lymphocyte subset analysis (flow cytometry for T, B, NK cells), Genetic testing for suspected specific PIDs
Imaging: Chest X-ray for pneumonia or bronchiectasis.
Differential Diagnosis:
Common infections with typical courses
Other causes of failure to thrive (e.g., malnutrition, malabsorption)
Allergies and asthma
Cystic fibrosis
Neutropenia of other causes
Transient hypogammaglobulinemia of infancy
Secondary immunodeficiencies (e.g., due to HIV, chemotherapy, immunosuppressive drugs, malignancy).
Management
Initial Management:
Prompt and aggressive treatment of acute infections with appropriate antibiotics
Hospitalization for severe infections or sepsis
Nutritional support and growth monitoring
Isolation to prevent exposure to pathogens in severely immunocompromised individuals.
Medical Management:
Immunoglobulin replacement therapy (IVIG or SCIG) for antibody deficiencies
Prophylactic antibiotics or antivirals for certain PIDs
Hematopoietic stem cell transplantation (HSCT) for severe PIDs
Gene therapy is emerging for specific PIDs
Management of autoimmune complications.
Surgical Management:
Surgical intervention may be required for complications like abscess drainage or removal of infected organs, but only after appropriate antimicrobial therapy and consultation with the immunology team
Avoid live vaccines in severely immunocompromised patients
Splenectomy is generally contraindicated in PIDs due to increased risk of overwhelming sepsis.
Supportive Care:
Education of family regarding the condition, treatment, and infection prevention strategies
Vaccination counseling
Psychological support for the child and family
Regular follow-up with the pediatric immunology team
Monitoring for complications.
Complications
Early Complications:
Sepsis, meningitis, pneumonia, osteomyelitis, severe gastroenteritis leading to dehydration and electrolyte imbalance, overwhelming post-splenectomy infection (if spleen is involved).
Late Complications:
Chronic organ damage (e.g., bronchiectasis, liver cirrhosis, neurological deficits)
Autoimmune disorders (e.g., hemolytic anemia, thrombocytopenia, arthritis)
Increased risk of malignancies (e.g., lymphomas, leukemias)
Growth failure.
Prevention Strategies:
Strict adherence to prophylactic treatments
Early recognition and treatment of infections
Strict hygiene measures
Avoiding exposure to known sources of infection
Careful vaccination policies
Genetic counseling for affected families.
Prognosis
Factors Affecting Prognosis:
Type and severity of PID
Age at diagnosis
Promptness and efficacy of treatment
Development of complications (e.g., chronic organ damage, malignancy)
Availability of definitive treatments like HSCT
Adherence to management protocols.
Outcomes:
Prognosis varies widely
With early diagnosis and optimal management, many children with PIDs can lead healthy and productive lives
Severe PIDs, especially if diagnosed late or with complications, can have significant morbidity and mortality
Advances in HSCT and gene therapy are improving outcomes.
Follow Up:
Lifelong or long-term follow-up with a pediatric immunologist is essential
Regular monitoring of immune function, infection status, growth, and development
Screening for complications such as autoimmunity and malignancy
Management of associated conditions.
Key Points
Exam Focus:
Remember the "10 Warning Signs of PID" for quick screening
Be familiar with common PIDs like XLA, SCID, CVID, CGD, and their characteristic infection patterns
Understand the initial diagnostic workup: CBC, Ig levels, and specific antibody titers
Recognize the importance of family history, especially consanguinity.
Clinical Pearls:
A child with recurrent infections not responding adequately to standard treatment should raise suspicion for PID
Don't attribute recurrent severe infections solely to environmental factors without considering underlying immune deficits
Always consider PID in infants with failure to thrive and recurrent serious infections
Early referral to a pediatric immunologist is crucial.
Common Mistakes:
Delayed diagnosis due to underestimating the significance of recurrent infections
Inadequate workup or misinterpretation of laboratory results
Treating infections without considering the underlying immune defect
Prescribing live vaccines to immunocompromised children
Failure to refer to a specialist promptly.