Conditions with excessive numbers of warts

In most patients, immunosurveillance and innate immunity contain HPV infection. Excessive numbers of warts are seen in a variety of genetic and acquired conditions (Tab. 4), and may be associated with an increased local risk of cutaneous oncogenesis.

Acquired immunosuppression (Fig. 2) is exceedingly common, whether from transplantation, chemotherapy or acquired immunodeficiency syndrome. Of the acquired conditions, renal transplantation, because it often occurs in younger patients, is associated with a high degree of morbidity

Figure 2. 13 year-old boy with ataxia telangiectasia and extensive warts on the right elbow.

from wart viruses. In fact, estimates on the incidence of warts in allograft recipients range from 17% to 87% [46]. Furthermore, appearance of warts after transplantation is correlated with increased risk of skin cancer development [47]. The incidence of warts in HIV patients ranges from 3.3% to 11.2%. Wart infections in HIV tend to be difficult or impossible to eradicate and quicker to spread [48, 49].

Only a handful of genetic conditions are defined by the presence of viral warts, although viral warts may be seen in almost all immunodeficiencies, particularly those with defects of cell-mediated immunity, the most prevalent being common variable immunodeficiency [50]. The WHIM syndrome (an acronym for warts, hypogammaglobulinemia, recurrent bacterial infections, and myelokathexis) is a form of severe chronic neutropenia with hyperplasia of the mature myeloid compartment in the bone marrow. Recently, a chemokine receptor, CXCR4 has been found to be the causative gene. WHIM syndrome is associated with a heterozygous truncating mutation of the CXCR4 gene. The CXCR4 receptor is bound by CXCL12, a chemokine that regulates cardiogenesis and hematopoiesis among others [51, 52].

EDV is an autosomal recessive genetic condition (2p21-24, 17q25) characterized by disseminated flat warts, which can take on the appear-

Table 5. Malignant conversion of HPV

Malignant diseases caused by HPV infection

Associated HPV viruses

1. Cervical intraepithelial neoplasia Anogenital intraepithelial neoplasia cervical cancer

2. Bowen's disease

3. Bowenoid papulosis

4. Verrucous carcinoma-digital

5. Keratoacanthoma

6. Actinic keratoses Squamous cell carcinoma (head and neck)

7. Malignant proliferating trichilemmal tumor (EDV) 21

8. Carcinoma of internal organs Esophageal carcinoma Anal carcinoma Adenoid cystic carcinoma Ovarian carcinoma

5, 9, 10, 14, 19, 20, 21, 38, 49, 80 3, 5, 8, 10, 16, 33

ance of tinea versicolor-like macules. Rare patients experience neurological changes or ocular squamous cell carcinoma [53]. Malignant conversion of HPV-infected skin, due to UV exposure, is usually seen in early adolescence and continues through the patient's lifetime. Polymorphisms of IL-10 gene promoter causing reduced IL-10 production have been reported in Brazilian EDV patients. These polymorphisms are believed to promote skin cancer development [54].

The most common cutaneous illness associated with abnormal processing of HPV is atopic dermatitis, although some studies have not supported an increased incidence. A recent study from the United Kingdom demonstrated that cervical cancer is more common in eczema patients and patients who acquire common warts. However, this study suggests that non-atopic eczemas, such as seborrheic dermatitis, may be the type associated with cervical cancers, as hay fever, an illness commonly co-morbid with atopic eczema, was not statistically correlated to cervical cancer [31].

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