Bowen's Disease Treated with Imiquimod and Cryotherapy.

Sir,

Bowen's disease is a rare, persistent, progressive intra-epidermal carcinoma, which may be potentially malignant, with up to 8% of the cases progressing to squamous cell carcinoma. The various treatment modalities include physical destruction using electrocautery, cryotherapy, curettage, laser therapy or surgical excision, intralesional interferon alpha or bleomycin and noninvasive methods like photodynamic therapy and topical 5-fluorouracil. Most of these therapies are administered by the physician, rather than being self-administered. Imiquimod is a topical immune response modifier with antitumor and antiviral activity. Its utility in Bowen's disease, including penile, facial, vulvar, truncal and recurrent nail disease, has been reported by many authors. Here we report its successful use in an Indian patient with Bowen's disease.

A 39-year-old female, housewife by occupation, presented with persistent, occasionally itchy, progressively enlarging, irregularly shaped, eczematous plaque of nine months’ duration measuring 4×4 cm, on the right lower leg [Figure 1]. It had not responded to topical steroids, salicylic acid, antifungal treatment. With a differential diagnosis of Bowen's disease and lupus vulgaris, a skin biopsy was done and it revealed the features of Bowen's disease [Figure 2]. She was started with 5% topical imiquimod, applied to the plaque on three alternate days in a week, along with liquid nitrogen cryotherapy by dip stick method once weekly. The lesion progressively decreased in size and thickness. At the six-months’ follow-up after starting topical imiquimod, the lesion had flattened with persisting pigmentary changes. Imiquimod was stopped at this stage and cryotherapy was continued for another two months. A repeat biopsy at eight months revealed a normal epidermis. Cryotherapy was stopped and the patient was advised to use topical emollient and regular follow-up every month. After 12 months, the lesion had completely cleared with mild atrophy and pigmentation [Figure 3]. The patient is still under follow-up at six monthly intervals, but there has been no recurrence of the lesion at the end of two years. During treatment with topical imiquimod, patient did not show any side effects except mild irritation and pruritus which were not bothersome to the patient.

Figure 1

Pre-treatment

Figure 2

Histopathology showing typical windblown appearance of Bowen's disease with mitosis (H and E ×40)

Figure 3a

Clinical photograph at the end of one year

Clinical photograph at two-year follow-up

Imiquimod is a potent antiviral and antitumor agent, approved by the US FDA as a topical agent in the treatment of genital and perianal warts.[1] It was later found to be beneficial in a number of cutaneous disorders including many viral infections and malignant as well as premalignant conditions, including Bowen's disease.

In a phase II trial by Mackenzie-Wood et al., the first open labelled study evaluating the use of imiquimod in Bowen's disease, a once daily application of 5% imiquimod for 16 weeks was found to be effective in 14 out of 15 patients.[2] In a randomized, double-blind, placebo-controlled trial involving 34 patients with Bowen's disease, out of 15 patients who were treated with imiquimod 5% cream, 11 achieved resolution of their lesions with no relapse during a follow-up period of nine months.[3] A phase II, randomized, double-blind, vehicle-controlled trial involving 129 patients with histologically proven basal cell carcinoma gave complete response rates of 100, 87.1, 80.8 and 51.7% for patients in twice daily, once daily, five times a week and three times a week dosage schedules of 5% imiquimod, respectively.[4]

Various regimes of topical treatment of cutaneous malignancies with imiquimod include alternate nights to twice daily application from a minimum of six weeks to a maximum of 20 weeks.[2-4] The more frequent the application, the greater the chance for application site reactions, which occur at a frequency of 1% and include pruritus, burning, soreness, erythema, scabbing, flaking, erosion, crusting, edema and induration, which are usually mild-moderate and are dose-dependent. A thrice weekly regime is recommended in most studies because it is the least aggressive treatment which gives the greatest success rate, nearly approaching 100%.

We preferred imiquimod 5% cream over other modalities of treatment because of the easy availability, ease of self-administration, lack of pain, and lack of need for hospitalization and the encouraging reports published in the last few years.