Edward J. Zabawski

Topical and intralesional cidofovir: A review of pharmacology and therapeutic effects

BACKGROUND Cidofovir is a potent nucleoside analog antiviral drug approved for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. It is currently available only for intravenous infusion. Several small studies and case reports describe the successful use of cidofovir applied either topically or intralesionally in several virally induced cutaneous diseases. OBJECTIVE Our purpose was to review the usefulness of topical and intralesional cidofovir for the treatment of viral infections caused by human papillomavirus, herpesviruses (including acyclovir-resistant strains), Kaposis sarcoma-associated herpesvirus, and molluscum contagiosum. METHODS We performed a review of recent literature. RESULTS Cidofovir is a potent topical intralesional antiviral agent with activity against several DNA viruses that cause cutaneous disease. No significant systemic side effects have been noted, although application site reactions are common and can occasionally be severe. CONCLUSION The effective use of topical and intralesional cidofovir for the treatment of diseases of the skin caused by DNA viruses has been demonstrated in a limited number of patients including those infected with HIV. Although larger studies will be necessary to determine the specific function that topical cidofovir will have in the treatment of cutaneous diseases caused by DNA viruses, the drug offers significant promise.

Incipient intraepidermal cutaneous squamous cell carcinoma: a proposal for reclassifying and grading solar (actinic) keratoses.

Actinic keratoses (AKs) are primarily induced by ultraviolet (UV) radiation and are often identified as premalignant lesions. In our opinion, AKs are proliferations of transformed, neoplastic keratinocytes confined to the epidermis that may eventually extend into the dermis, at which point they are termed squamous cell carcinoma (SCC). In contrast to AKs, SCCs have the potential to metastasize and kill. This process is analogous to that of evolving carcinoma of the uterine cervix that has been termed cervical intraepithelial neoplasia (CIN), a time-tested and reliable classification that provides clinicians with accurate information on which to base treatment decisions regarding cervical neoplasms following biopsy testing. A similar classification scheme could provide guidance to clinicians for the diagnosis and treatment of evolving SCC of the skin and as such, we propose a similar classification using the terminology keratinocytic intraepidermal neoplasia (KIN). This system is more reflective of the histology and natural history of SCC and eliminates ambiguity in the terminology of lesions currently referred to as AKs. The KIN classification defines features by which individual specimens can be objectively graded and specific treatment recommendations are made based on the grade of the lesion. We propose that the term keratinocytic intraepidermal neoplasia (KIN) be used to define and describe evolving SCC of the skin and that the term actinic (solar) keratosis be eliminated.

TOPICAL CIDOFOVIR FOR MOLLUSCUM CONTAGIOSUM IN CHILDREN

To the Editors: Lichen nitidus (LN) is an uncommon cutaneous chronic eruption that usually affects children and young adults. It was described by Pinkus in 1907 (1) and is characterized by the presence of 1 to 2 mm, asymptomatic, skin-colored papules with a flat, shiny surface. Cutaneous lesions of LN are most often localized to the upper extremities, penis, abdomen, chest, and buttocks, but in some cases they can be generalized (2–4). The association with other systemic diseases is extremely rare, and to our knowledge LN has never been described in association with juvenile chronic arthritis. We report a 3-year-old girl who suffered from generalized lichen nitidus and developed polyarticular juvenile chronic arthritis months later. At the age of 11 months the infant began to have a generalized eruption consisting of papular lesions which were diagnosed by biopsy as lichen nitidus. At the age of 15 months, 10 days after receiving a triple viral vaccine, she developed a high fever with swelling and pain in the wrists and ankles for 4 days. When she was 24 months old she had a similar episode without previous infectious or vaccination antecedent that recurred at the age of 28 months, 3 days after she received antimeningococcal A+C vaccine. In spite of clinical improvement observed after these episodes, the swelling and impaired function of the affected joints persisted. Physical examination showed numerous small, flesh-colored papules which were generalized but predominated on the right side of the body, symmetrical polyarthritis of the proximal interphalangeal joints from the second to the fourth, metacarpusphalangical from the first to the fifth, wrists, knees, and ankles. Laboratory findings including complete serologic studies were normal. Rheumatoid factor and antinuclear antibodies were negative. Histologic examination of a skin biopsy specimen revealed a circumscribed lymphohistiocytic infiltrate in the superficial dermis that was characteristic of LN. After treatment with ibuprofen, methotrexate, and prednisone, a good clinical evolution was observed, with an increase in physical activity and improvement of articular function. Most patients suffering from LN have a spontaneous resolution of the lesions after several years, so treatment is not required. Some authors recommend treatment with topical steroids, astemizole, systemic steroids, or PUVA in generalized LN (4,5). Etretinate and acitretin have also been used in palmoplantar LN (6). In our patient, apart from hydration of the skin, specific treatment was not used, the lesions resolving with a residual hypopigmentation 2 years after onset. Familial cases or association with systemic diseases, aside from Crohn disease and atopic dermatitis, have not been reported (7,8). Kano et al. (7) described a 22-yearold man diagnosed with Crohn disease and erythema nodosum who developed LP and LN 2 years later. The clinical course of his LN and LP was independent of intestinal and erythema nodosum lesions. After evaluating immunohistochemical and gene expression studies, these authors suggest that the lesions of LN and LP are likely to be mediated by T cells with antigen specificity distinct from those that cause erythema nodosum and intestinal lesions. The observed association of generalized LN with juvenile chronic arthritis in our patient is the first description in the literature to our knowledge. In spite of the frequency of cutaneous manifestations in the connective tissue diseases, they are not as evident as in juvenile chronic arthritis, excepting the characteristic exanthem of this disease. Recently the development of skin alterations such as a rash in patients being treated with Dpenicillamine and gold salts has been reported (9). Two women suffering from rheumatoid arthritis who developed lesions of LP while being treated with sulfasalazine were described by Kaplan et al. (10). In our patient, the appearance of LN without administration of some type of antirheumatoid drug only a few months before the development of juvenile chronic arthritis, the coexistence of the lesions, and the occurrence of new outbreaks of LN, coinciding with worsening of the arthritis suggest to us that both diseases could be due to the same mechanism, probably immune. However, additional clinical observations and more complete studies are necessary to establish the possible link between these processes.