Evidence for a causal association for HPV in head and neck cancers.

Current data have now attributed a viral etiology and causality of Human papillomavirus (HPV). Epidemiological analysis of the last decade demonstrates a rapid increase of HPV-associated HNSCC. Genomic detection of HPV DNA in the nuclei of certain oro-pharyngeal cancer cells gives strong evidence of a viral etiology in HNSCC. Non-smokers, non-drinkers, and a sexual debut at a younger age and other sexual risk factors have an increased risk of HPV-positive oropharyngeal cancer. Sexual transmission is considered to play a causal role. In contrast to HPV-negative HNSCC most studies reveal a favorable prognosis for HPV-positive tumors. There is evidence of alterations in the p53 pathway through expression of E6 oncogene with subsequent induction of tumor cell proliferation. Synergies between viral oncogenes and other carcinogens are hypothesized. HPV alone appears to be insufficient as the sole cause of HNSCC; this may explain the long latency period between HPV infection and cancer development. There is now sufficient evidence for a causal role for HPV in HNSCC. As in cervical cancer, HPV requires oncogenes and co-factors for tumor development. Thus, inhibition or loss of such co-factors may lead to tumor regression. The vast amounts of epidemiological, molecular pathological and in vitro experimental data are consistent with the hypothesis that HPV does indeed have a causal role. We await final validation from animal experimentation in which regression of HPV-positive tumors will follow from loss or inhibition of E6 and E7.

Widespread cutaneous carcinomas associated with human papillomaviruses 5, 14 and 20 after introduction of methotrexate in two long-term PUVA-treated patients.

BACKGROUND: PUVA treatment for patients with severe psoriasis has been demonstrated to be highly effective. However, an increased risk of nonmelanoma and melanoma skin cancers has been reported. It is generally accepted that the risk of squamous-cell carcinoma (SCC) is significantly increased in patients with long-term PUVA therapy. The role of methotrexate (MTX) and infection with oncogenic human papillomaviruses which may act as cocarcinogens is poorly documented. CASE REPORTS: Two cases of multiple SCCs associated with numerous PUVA keratoses and PUVA freckles after long-term PUVA therapy and subsequent treatment with MTX are presented. In 1 case, the tumor progressed to metastatic SCC. Tumors and scrapings of psoriatic skin lesions were analyzed for the presence of oncogenic human papillomavirus (HPV) genotypes. The genotype of HPV-5, -14 and -20 was detected in scrapings and skin tumors using PCR amplification. CONCLUSION: These observations support the concept that long-term PUVA treatment is carcinogenic and rise questions concerning an additional influence of MTX in the development and progression of skin cancer. The risk of metastatic SCC seems to be underestimated in high-dose PUVA-treated patients due to longer latency for developing metastases and the small number of studies with long-term follow-up. Treatment with MTX should be considered cautiously in patients previously exposed to high doses of PUVA. The presence of oncogenic HPVs in carcinomas and psoriatic skin lesions detected only with the highly sensitive nested PCR method is not necessarily a proof of their implication in skin carcinogenesis.

Fixed solar urticaria to visible light successfully treated with fexofenadine.

Fixed solar urticaria (FSU) represents an uncommon form of urticaria related mostly to radiation from the ultraviolet (UVB, UVA) and visible spectrum. The exact pathomechanism has so far remained unknown. A 52-year-old woman with a 3-year history of urticated eruptions limited to certain skin areas is presented. Photobiological testing revealed positive reactions limited to the visible light range. The induced lesions appeared only in originally affected skin sites. The particular distribution of whealing supports the concept of specific alteration of mast cells in well defined areas. The clinical findings and the results of phototesting lead to the diagnosis of FSU to visible light. It is recommended to carry out phototesting in patients with FSU in the originally affected skin areas, usually covered and protected by the patient, to avoid false-negative results. Fexofenadine given in the conventional dosage can prevent recurrences and represents a successful treatment measure when dealing with this peculiar form of solar urticaria.

Prolonged photosensitivity following contact photoallergy to ketoprofen.

We report the third case of prolonged photosensitivity secondary to contact photoallergy to topical ketoprofen, a 2-arylpropionic acid derivative. The patient suffered from persistent photosensitivity for more than 1 year after the withdrawal of ketoprofen with recurrent eruptions on sun-exposed skin areas. This photosensitivity was associated with a persistent decrease in polychromatic and UVA minimal erythemal doses. Photobiological testing revealed cross-reactivity with fenofibrate and benzophenones. Photoallergy to ketoprofen is due to the benzophenone structure or to the very similar thiophene phenylketone of tiaprofenic acid, but not to the arylpropionic function. Thus, fenofibrate, tiaprofenic acid and benzophenones should be avoided by patients with a positive history of photocontact dermatitis to ketoprofen.

Delayed-hypersensitivity granulomatous reaction induced by blepharopigmentation with aluminum-silicate.

Blepharopigmentation has been introduced during the last decade as a technique for creating a permanent line along the eyelid margin, thus simulating a cosmetic eyeliner. Complications related to this procedure are mostly reported in the opthalmologic literature describing infectious, allergic, or technical problems. We report a case of a woman who underwent blepharopigmentation with aluminum-silicate and in whom a delayed hypersensitivity granulomatous reaction developed.

Invasive cutaneous squamous cell carcinoma associated with actinic keratosis: a case with orbital invasion and meningeal infiltration.

BACKGROUND: It is suggested that most squamous cell carcinomas in sun-exposed areas arise from preexisting solar keratosis. Actinic keratosis is thought of as being a precursor to squamous cell carcinoma. This form of squamous cell carcinoma has been considered to be a relatively benign lesion. We report a case of invasive squamous cell carcinoma associated with actinic keratosis leading to orbit destruction and meningeal infiltration. OBJECTIVE: To demonstrate that well-differentiated tumors can act extremely aggressively with the potential toward infiltrative growth patterns. METHODS: Histologically controlled surgery along with multiple radiation therapy was performed. RESULTS: The tumor progressed inducing perineural invasion, orbit infiltration, osseous destruction, and meningeal invasion. CONCLUSION: The association of squamous cell carcinoma and actinic keratosis supports the concept of a causal relation. Excision with histologic examination of actinic keratosis seems to be useful for accurate diagnosis. Squamous cell carcinoma can represent an aggressive tumor with infiltrative growth pattern and should not be considered a benign lesion.

Pili torti with congenital deafness (Bjornstad syndrome): a case report.

We report Bjornstad syndrome in a 5-year-old girl with severe bilateral congenital loss of hearing and pili torti. The mode of inheritance of this rare syndrome seems to be heterogeneous. A maternal uncle of the patient was deaf from birth and his hair had shown the same abnormalities at the same age; an autosomal recessive transmission can be assumed.

Frequency of contact allergy in children with atopic dermatitis: results of a prospective study of 137 cases.

The aim of our study was the evaluation of contact sensitization in pediatric patients with atopic dermatitis (AD). It seems that the frequency of contact allergies in the course of AD, and also the frequency of contact allergies in children, is underestimated in general. Our study has been performed by investigating 137 children with AD. The childrens' history was taken according standardized consultation guidelines and followed by a physical examination. Patch testing was performed systematically, including the European standard series, together with tixocortol pivalate, budesonide and the applied emollient. If necessary, optional patch tests were performed according to the child's history. The results demonstrate contact sensitization in 43% of all children tested. The most frequent contact allergens are: metals (19.3%), fragrance (4.4%), balsam of Peru (2.6%), lanolin (4.4%), neomycin (2.6%) and emollients (2.6%). No contact sensitization to corticosteroids nor any induction of active sensitization were seen. Statistical analysis demonstrates that the risk of developing a contact allergy is significantly elevated in children after the age of 5 years. Female sex is a risk factor only for nickel. Age of onset of AD or its severity is not associated with the development of contact allergy. In conclusion, the results indicate the necessity of performing systematic patch testing in the investigation of allergies in children with AD. Preventive measures from an early age are suggested to avoid exposure to the most frequent contact allergens.