Chronic mucocutaneous candidiasis (autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy [APECED])is characterized by chronic or recurrent candidal infections of the mucous membranes, skin, and nails (see Table 73-3). There is normal antibody production but significantly decreased or absent lymphocyte proliferation and delayed skin reactivity to Candida. Patients usually do not respond to topical antifungal therapy and must be treated with oral antifungal agents. In most patients, an autoimmune endocrine disorder, such as hypoparathyroidism and Addison disease, develops by early adulthood. Other autoimmune disorders have been reported. The insidious onset requires the need for frequent evaluation for autoimmune endocrine disorders. This disease results from a defect in the gene for the transcription factor autoimmune regulator (AIRE), which is necessary for expression of peripheral tissue antigens in the thymus, resulting in a negative selection in the thymus and in tolerance to these tissues in normal individuals.
Patients with X-linked lymphoproliferative disease (see Table 73-3) have a defect in immune responsiveness to Epstein-Barr virus (EBV). Boys with this disease are normal until infected with EBV, which is acutely fatal in 80% of patients. The disease is caused by a mutation in the gene called SH2D1A at chromosome Xq25, which codes for an adapter protein involved in signal transduction of lymphocytes. With EBV infection, the mutation results in an extensive expansion of CD8 T cells, hepatic necrosis, and death. Boys who survive initial EBV infection have significant hypogammaglobulinemia and are at high risk for developing aplastic anemia and lymphoma. A similar disorder is seen in boys with mutations in XIAP, which results in X-linked lymphoproliferative disorder type 2.
Avoid transfusions with blood products unless they are irradiated and cytomegalovirus-negative.
Avoid live virus vaccines, especially in patients with severe T-cell deficiencies or agammaglobulinemia, and in household members.
Use prophylaxis to Pneumocystis jiroveci (carinii) in T-cell immunodeficiency, and in X-linked hyper-IgM, consider antifungal prophylaxis in T-cell immunodeficiency.
Follow pulmonary function in patients with recurrent pneumonia.
Use chest physiotherapy and postural drainage in patients with recurrent pneumonia.
Consider using prophylactic antibiotics because minor infections can quickly disseminate.
Examine diarrheal stools for Giardia lamblia and Clostridium difficile.
Avoid unnecessary exposure to individuals with infection. Boil water for T-cell defects and hyper-IgM syndrome (Cryptosporidium risk).
Use immunoglobulin for severe antibody deficiency states (400–600 mg/kg q3–4 wk IV).