Table 2.

Infections as general warning signs for primary immunodeficiency.

Type of infection	Characteristics
Otitis media*	• Early onset <3–4 months old • Recurrence after treatment with antibiotics • Complications: mastoiditis • Association with invasive infections • Recurrence after placing of ear tubes • Change to sinusitis after ear tubes • Repeated placement of the ear tube* * The number of otitis episodes that suggest primary immunodeficiency varies with age: ≥3 episodes/year in children aged <5 years; ≥2 episodes/year in children aged ≥5 years
Chronic recurrent rhino sinusitis	• Association with persistent asthma • Need for sinus surgery due to fungal infections
Pneumonia	Evaluate after a single pneumonia if the patient has: • A personal history of recurrent upper respiratory infections (URI) including recurrent otitis media • A personal history of other immunological problems (autoimmunity, chronic diarrhea, recurrent fevers, persistent skin rash, etc.) • Pneumonia requiring hospitalization (any: ICU or regular service) • Persistent pneumonia after adequate antibiotic therapy • Pneumonia requiring IV antibiotics • Bilateral pneumonia • Necrotizing pneumonia • Interstitial pneumonitis Assess patients with 2 or more pneumonias: All patients (preferred option) or assess only if: • X-ray proven pneumonias in different lung locations • Positive family history for early death or primary immunodeficiency (PID) • Pneumonia complicated by pneumatocele or bronchiectasis
Unusual infections or unusual presentations in HIV-negative patients *	• Atypical mycobacteriosis • Resistant tuberculosis • Histoplasmosis • Neurocryptococcosis • Aspergillosis • Leishmaniasis • Blastomycosis * Most relevant signs in developed or non-endemic countries for these diseases
Chronic diarrhea or colitis	Assess whether the patient has: • Rotavirus • Enterovirus • Campylobacteriosis • Cryptosporidium • Persistent Salmonella • Clostridium difficile • Recurrent giardiasis
Chronic dermatitis	• Recurrent staphylococcal infections • Recurrent or persistent candidiasis or fungal infections
Abscesses (liver, lungs, skin)	• Staphylococcus aureus
Central nervous system (CNS) infections	• Meningococcal meningitis • Herpetic encephalitis • Fungal infections
Complications due to live attenuated vaccines	• Disseminated BCG (Mycobacterium bovis; Bacillus Calmette-Guérin) • Poliomyelitis due to the polio vaccine • Diarrhea due to the rotavirus vaccine

Adapted from Costa-Carvalho et al.⁵