This 14-year-old boy with cartilage hair hypoplasia (CHH), Blackfan-Diamond anemia, and chronic immune deficiency developed disseminated flat warts and granulomatous violaceous rubbery plaques on both elbows. Cartilage hair hypoplasia (CHH) is a form of short-limbed dwarfism characterized by T-cell immunodeficiency and fine, sparse hair. The genetic deficiency has been mapped to chromosome 9p13 and some patients have mutations in the RNA component of ribonuclease mitochondrial RNA processing (RNAse MRP). Along with hematologic abnormalities and immune deficiency, clinical manifestations may include short hands, brachydactyly, fine blond hair, notched incisors, and microdontia. Although severe viral infections and opportunistic infections (Candida, Pneumocystis, and CMV) have been associated with CHH, epidermodysplasia verruciformis (EDV) has not been previously reported among these patients.
EDV is an autosomal recessive (and sometimes X-linked) inherited disease associated with a specific immune defect in the recognition of certain human papilloma viruses (HPV). The warty growths typically begin in the first 5 years of life on the hands, trunk and face but can be delayed until puberty in approximately 20 percent of cases. Typically a persistent and chronic infection, residence of tumorigenic HPV strains may predispose to malignant transformation to squamous cell carcinoma especially in the 3rd to 5th decade. Cancer risk is markedly increased in the HPV strains 5, 8 and 47 (although reported I many other strains) due to there ability to express E6 and E7 despite immune attack. Cancers develop mostly in sun-exposed areas indicating that both specific HPV strains and damaging UV radiation is needed to create tumors. Therapy for EDV involves avoidance of UV and X-ray radiation. Systemic and topical retinoids as well as interferon-alpha have been reported with variable success.
Granulomatous plaques (often of a sarcoidal nature) have been reported in immunodeficiency diseases such as common variable immunodeficiency (up to 10 percent of patients) and ataxia-telangiectasia. It is hypothesized that poor T-cell immune response and not true sarcoidosis may be responsible for the granuloma formation. By contrast, patients with X-linked agammaglobulinemia, a disorder associated more with B-cell dysfunction rather than T-cells, do not develop these granulomas. It is our suspicion that the granulomatous plaques of cartilage-hair hypoplasia may likewise result from the T-cell dysfunction described above. References:
1. Majewski S, Jablonska S: Epidermodysplasia verruciformis as a model of human papillomavirus-induced genetic cancer of the skin. Arch Dermatol. 1995;131(11):1312-8.
2. Mechanic LJ. Dikman S. Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Ann Int Med. 1997;127(8 Pt 1):613-7.
3. Murakawa GJ, McCalmot T, Frieden IJ. Chronic plaques in a patient with ataxia telangiectasia. Cutaneous granulomatous lesions in a patient with AT. Archives of Dermatology. 1998;134(9):1145,1148.
4. Ridanpaa M, Suslisalo T, de la Chapelle A: Genetic and physical mapping of the cartilage-hair hypoplasia locus on 9p13. Am J Hum Genet. 1995;57:A201.
annular violaceous rubbery plaque with pink border