Table 1.

Immunological evaluation according to the type of infection, infectious agent and associated manifestations.

Infections	Other manifestations	Suspected IEI	Initial tests
Severe, disseminated by viruses, bacteria, fungi, protozoa, opportunistic microorganisms Cytomegalovirus, Herpesvirus, Mycobacteria Candida sp, Aspergillus sp, Toxoplasmosis P. jirovecii, Cryptosporidium sp Reaction to BCG vaccine	Early onset Growth impairment Chronic diarrhea Absence of thymus Microcephaly, with or without facial dysmorphism	Combined T and B cell immunodeficiencies - SCID	CBC, lymphocyte count (CD3, CD4, CD8, CD19, CD56),TREC, immunoglobulin measurement
	Facial malformations and dysmorphisms Bone dysplasia Fractures Scoliosis Short stature Microcephaly Bruising / bleeding Cerebellar ataxia Oculocutaneous Telangiectasias Global development delay Intellectual deficit Joint hypermotility Extensive eczema Ichthyosis Ectodermal dysplasia	Combined immunodeficiencies associated with syndromes
Severe and / or recurrent bacterial infections, encapsulated respiratory, articular microorganisms, sepsis, Pneumococcus, Hemophilus, Mycoplasma Giardia lamblia Intestinal bacteria: Campylobacter sp, Salmonella sp Enterovirus (polio vaccine) Norovirus	Symptom onset above 6 months Absence of tonsils / adenoids Lymphoproliferation Lymphoid nodular hyperplasia Developmental delay Chromosomal disorders	Predominantly antibody defects	Complete blood count, Immunoglobulin measurements, B lymphocyte count, KREC
Bacterial, encapsulated microorganisms of the respiratory tract, articular or meninges, sepsis Pneumococcus, Neisseria sp, Hemophilus	Manifestations of autoimmunity, lupus-like, glomerulopathy	Complement defects	C3, C4, CH50
Non-significant, non-severe Candidiasis Bacterial infections Epstein-Barr virus	Early onset Lymphoproliferation Hemophagocytic lymphohistiocytosis Partial oculocutaneous albinism Developmental delay Autoimmune cytopenias Autoimmune endocrinopathies Severe inflammatory bowel disease	Diseases with immune dysregulation	Blood count Hematoscopy Autoantibodies
Recurrent skin infections Deep abscesses Necrotizing pneumonia Osteomyelitis Catalase positive microorganisms: Staphylococcus sp, Klebsiella sp, Serratia sp, Pseudomonas sp, Aspergillus sp Candida sp, Burkholderia cepacia, M. tuberculosis	Early onset Granulomas Nonspecific inflammatory bowel disease Pancreatic insufficiency Developmental delay Intellectual deficit Mouth ulcers Delayed umbilical cord fall Poor healing Periodontal disease Pulmonary alveolar proteinosis Lymphedema Myelodysplasia	Numeric or functional phagocyte diseases	Blood count Morphological evaluation of neutrophils in Hematoscopy Neutrophil oxidative burst test (DHR)
Recurrent infections by only one type or few types of microorganism	Little or no fever	Innate immunity deficiency –IRAK4/MyD88 defect	CBC, immunoglobulin measurement, lymphocyte phenotyping, CH50 to rule out other diagnoses,
Bacterial, invasive, sepsis,	Delayed umbilical cord fall		CD62L Shedding assay
meningitis, arthritis,	Improves with age
osteomyelitis
Pneumococcus	Absence of spleen
Recurrent infections by only one type or few types of microorganisms	Reaction to BCG vaccine	Mendelian susceptibility to mycobacteria	Functional assessment of the IFN γ-IL12 axis
Mycobacteria
Intracellular fungi and bacteria
Recurrent infections by only one type or few types of microorganisms	No other manifestations	Innate immunity deficiency with susceptibility to viral infections	Immunoglobulin measurement
HPV-disseminated warts with or without bacterial infections			Blood count
Recurrent herpes simplex encephalitis			Lymphocyte phenotyping to rule out other diagnoses,
Severe reactions to triple viral and yellow fever vaccines			CD62L Shedding assay
Recurrent infections by only one type or few types of microorganisms	Ectodermal dysplasia	Innate immunity deficiencies with susceptibility to fungi	CBC, immunoglobulin measurements, lymphocyte phenotyping, DHR to rule out other diagnoses
Cutaneous and / or invasive fungal infections, mainly Candida sp, with or without cutaneous staphylococcus infections	Autoimmune endocrinopathies
Non-significant, non-severe, nor recurring	Inflammatory manifestations in the absence of infectious agents or autoimmunity	Autoinflammatory diseases	Inflammatory activity test
	Recurrent fever		Autoantibodies, immunoglobulin measurements and lymphocyte phenotyping to rule out other diagnoses
	Urticarial rash without pruritus
	Panniculitis
	Lipodystrophy
	Lytic bone lesions
	Arthritis
	Pyoderma gangrenosum
	Severe acne
	Pustular psoriasis
	Encephalopathy
	Strokes
	Pernio

Sources: Rosenzweig et al., 2020⁵; Tangye et al., 2020²; Bousfiha et al., 2020⁴; Chinen et al, 2019⁷.