Disorders with immunodeficiency

Figure 2.24 A: Werner syndrome (Reprint from Baykal C, Yazganoglu KD. Dermatological Diseases of the Nose and Ears. Berlin: Springer; 2010) B: Progeria (Courtesy of the Howard family) C: Hyper-IgE syndrome (Reprint from Burgdorf WH, Plewig G, Wolff HH, Landthaler M, eds. Braun- Falco’s Dermatology. 3rd ed. Heidelberg: Springer; 2009)

• Recurrent, progressive candidal infections (skin, nails, and mucosa) presenting with recurrent oral thrush, nail dystrophy, crusted cutaneous plaques

• AD, mutation in gene encoding STAT3 (signal transducer and activator of transcription 3), AR (gene encoding tyrosine kinase 2 TYK2)
• ↑ IgE levels, peripheral eosinophilia, cold abscesses, coarse facies, eczematous dermatitis, lung abscesses, pneumonia, retained primary teeth, pneumatocele, otitis media, osteopenia with recurrent fractures

• XLR, WASP gene, encodes WAS protein (controls assembly of actin filaments)
• Thrombocytopenia and platelet dysfunction (since birth) → petechiae and ecchymoses of skin, epistaxis, melena, hematemesis, hematuria
• Atopic dermatitis (face, scalp, flexures), excoriated areas with crust/petechiae, recurrent bacterial infections
• Hepatosplenomegaly, lymphadenopathy, ↑ lymphoma (non-Hodgkin’s lymphoma)
• Death from infections > hemorrhage > malignancy
• Treatment: bone marrow transplantation

• XLR, deficiency of γ chain of IL2 receptor (IL2RG); AR, defect in tyrosine kinase JAK3 or adenosine deaminase (ADA); heterogeneous disorders with severely impaired humoral and cellular immunity
• Deficiency or total absence of circulating lymphocytes

• AR, AIRE gene (autoimmune regulator gene) mutation
• Candidal infections, endocrinopathy (thyroid/parathyroid abnormality, diabetes mellitus, hypoadrenocorticism), cutaneous and other autoimmune disorder (alopecia areata, vitiligo, pernicious anemia)
• Varied cutaneous presentations: seborrheic-like dermatitis or morbilliform eruption, recurrent candidiasis and bacterial infections, chronic diarrhea, failure to thrive