Two Colleagues, Two Perspectives: Report From the Society for Pediatric Dermatology Annual Meeting, Part 2

Lawrence F. Eichenfield, MD


October 10, 2002

In This Article

Genetic Immunodeficiency Disorders: Cutaneous Findings and Pediatric Dermatologists are Key to Diagnosis and Early Management

Amy Paller, MD,[8] Children's Memorial Hospital and Northwestern University Medical School, Chicago, Illinois, recommended early consultation with a pediatric dermatologist for assessment of children with unusual cutaneous findings that may be features of immunodeficiency. Dr. Paller stressed the historical and physical features of non-AIDS congenital immunodeficiencies.

Several congenital immunodeficiency diseases have characteristic presentations.

A male child presenting with atopic dermatitis, along with petechiae; purpura; a painful, vasculitic rash; and/or bloody diarrhea, should bring up the possibility of Wiskott-Aldrich syndrome. This usually X-linked recessive disorder may also present with spontaneous bleeding after procedures, such as circumcision; failure to thrive; and recurrent infections in early life, commonly bacterial infections but viral or protozoal infections as well. Laboratory findings usually display thrombocytopenia with small platelet size. Wiskott-Aldrich syndrome has been associated with mutations in a protein involved in cytoskeletal organization and signaling, termed WASP, for Wiskott-Aldrich syndrome protein.

Another condition that may present with atopic dermatitis, often with early infantile facial and scalp papulopustules and "cold abscesses," is hyperimmunoglobulinemia E. This autosomal dominant disorder, also known as "Job's syndrome," is usually characterized by the onset of infections within the first few months of life, including Staphylococcus aureus or Haemophilus influenzae infections. Skin features in early life include eosinophilic folliculitis, chronic candidiasis (83% in 1 study), paronychia, cellulitis, lymphangitis, or furuncles. Skin features can precede pneumonia, as well as bronchiectasis and pneumatoceles, which are seen in 77% of patients, with an average age of onset of 3 years. Dental anomalies, with retention of primary teeth, and skeletal disease are very common; more than 3 fractures are seen in 60% of patients. IgE levels are at least 10 times normal for age. Eosinophilia is common, and neutrophil chemotaxis abnormalities contribute to the immunodeficiency. The syndrome has been linked to chromosome 4q.

Chronic mucocutaneous candidiasis is a heterogeneous condition with a great range of immunologic abnormalities. Dr. Paller said that in some patients the immunologic deficit is not demonstrable, while other patients have more extensive defects. In some families with autosomal recessive inheritance, associated endocrinopathy is seen in what is termed autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, known as APECED. Candidal and dermatophyte infections of the skin and mucous membranes are classic findings, although systemic infection is rare. The APECED syndrome is associated with hypoparathyroidism, Addison's syndrome, gonadal abnormalities, alopecia areata, pernicious anemia, and, occasionally, chronic active hepatitis. Dr. Paller related new information that APECED results from mutations in the gene AIRE (autoimmune regulator), which codes for a transcription factor. However, how this results in defective handling of Candida is unknown.

Dr. Paller stressed that children presenting with "silvery hair" should be carefully evaluated for the immune deficiencies associated with Chediak-Higashi and Griscelli syndromes. These rare conditions may present with severe infections in infancy, including infections of the skin, lungs, and upper respiratory tract. Pigment dilution in the skin and eyes may also be evident, and strabismus and nystagmus are common. Examination of the hair shafts displays unevenly clumped pigment in the hair shafts, which causes the silvery sheen, stated Dr. Paller. In Chediak-Higashi syndrome, giant granules may be seen in circulating neutrophils, melanocytes, and central nervous system neurons, among other cell lines, due to mutations in the lysosomal protein LYST1. Griscelli syndrome does not have associated leukocyte inclusions, and has been recently associated with mutations in myosin-Va, involved in membrane transport and organelle tracking.


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