Table 4.
Differential diagnosis of primary immunodeficiencies (PID) presenting with autoimmunity.
| IPEX | CD25 def | STAT5b def | OMENN’S | WAS | HIES | ALPS | APECED | |
|---|---|---|---|---|---|---|---|---|
| Onset | Neonatal, 1 year | <1 year, early infancy | <1 year, infancy | Neonatal, 1 year | 1 year, early infancy | Neonatal, 1 year | Neonatal, 1 year | Infancy, young adulthood |
| Enteropathy | Always | Frequent | Frequent | Frequent | Possible | Not present | Not frequent | Not frequent |
| Endocrinopathy | T1DM ± thyroiditis | Thyroiditis | GH unresponsiveness | Absent | Absent | Absent | Absent | Hypoparathyroidism, adrenal insufficiency ± T1DM, thyroiditis |
| Skin lesions | Eczema, erythroderma | Eczema, erythroderma | Eczema | Erythroderma, alopecia | Eczema | Newborn rash, eczema | Urticarial rash | Alopecia, vitiligo |
| Infections | Rare/secondary to IS | Recurrent/persistent (particularly CMV) | Recurrent (viral), severe varicella | Severe | Frequent | Recurrent pulmonary, cutaneous (S. aureus) | Not frequent | Candidiasis |
| Anemia | Possible | Possible | Rare | Frequent | Possible | Absent | Frequent | Rare |
| Thrombocytopenia | Possible | Possible | Rare | Possible | Always | Absent | Frequent | Rare |
| Neutropenia | Possible | Possible | Rare | Rare | Rare | Rare | Frequent | Rare |
| Others | Failure to thrive, hepatosplenomegaly, lymphoadenopathy, other autoimmune manifestations | Failure to thrive, hepatosplenomegaly, lymphoadenopathy | Growth failure, chronic lung disease, interstitial pneumonia | Failure to thrive, hepatosplenomegaly, lymphoadenopathy, inflammatory pneumonitis and enteritis | Failure to thrive, hemorragies, other autoimmune manifestations, tumors | Characteristic face, cathedral palate, bone fractures | Hepatosplenomegaly, lymphadenopathy, other autoimmune manifestations | Ovarian or testicular failure, gastritis, hepatitis, keratoconjunctivitis |
| Eosinophilia/hyper IgE | Present | Present | Present | Present | Present | Present | Absent | Absent |
| Hereditary pattern | X-linked | AR | AR | AR/unknown | X-linked | AD/AR/unknown | AD/unknown | AR |
| Gene | FOXP3 | IL-2RA (CD25) | STAT5b | RAG1/2 (90%), Artemis/IL7RA/, ADA/DNAligase IV/γc/unknown | WASP | STAT3/TYK2/DOCK8/unknown | FAS/FASL/CASP8/CASP10/unknown | AIRE |
WAS, Wiskott–Aldrich syndrome; HIES, hyper IgE syndrome; ALPS, autoimmune lymphoproliferative syndrome; APECED, autoimmune polyendocrinopathy candidiasis ectodermal dystrophy; def, deficiency; IS, immunosuppression; T1DM, type-1 diabetes mellitus; AR, autosomal recessive; AD, autosomal dominant.