Pediatric Plane Warts Treated With Imiquimod

Viral warts are common, benign lesions caused by human papillomavirus (HPV).¹ They are particularly common in children and adolescents with equal incidence in boys and girls.² Viral warts can be described based on location (eg, cutaneous or mucosal), anatomic site (eg, genital warts), and lesion morphology, which includes shape (eg, filiform) and arrangement (eg, singular, coalescing). The cutaneous warts include palmoplantar warts (ie, verruca plantaris; HPV 1), common warts (verruca vulgaris; HPV 2), and flat or plane warts (verruca plana; HPV 3 and 10).^1,3 In this case report, we highlight the case of a young girl presenting with facial papules and our steps to diagnose her condition and prescribe treatment.

A 9-year-old girl presented to our clinic with multiple skin-colored nonpruritic papules over her right cheek that had been present for 6 months. She had a habit of picking the lesions, and there was evidence of Koebnerization, with linear, slightly raised larger papules (Figure 1).

On physical examination, she had multiple skin-colored, flat-topped, monomorphic papules on her right cheek (Figure 2). They were round to polygonal in shape and varied from 1 to 3 mm in diameter. No similar lesions were noted elsewhere on her body. There were no nail or mucus membrane changes. A review of systems was noncontributory. She was not taking any medications. There was no personal or family history of warts. 

The histopathology stain showed mild hyperkeratosis, hypergranulosis, and acanthosis (Figure 3). Prominent keratohyaline granules with perinuclear vacuolation were noted in the stratum granulosum (Figure 3).

            A clinical diagnosis of plane warts was made based on its typical appearance and location. The diagnosis was confirmed with histopathology examination. The differential diagnosis included lichen nitidus and keratosis pilaris. She was prescribed topical imiquimod, 5% ointment 3 times per week. At the patient’s treatment center (Kuala Lumpur General Hospital), imiquimod is the first-line, off-label treatment for facial plane warts, as imiquimod is convenient and painless. After 3 months, all lesions had resolved, and treatment was discontinued (Figure 4).

Viral warts are common, benign lesions caused by HPV.¹ More than 120 HPV strains have been identified. Besides the HPV strains associated with cutaneous warts, other well-known strains include HPV 6/11, which are associated with more than 90% of anogenital warts (eg, condylomata acuminata), and HPV 16/18, which are associated with cervical, vaginal, and vulvar cancers.^1,3 HPV is acquired by direct skin-to-skin contact; indirect transmission through inanimate objects has not been proven.³ Patients with defective skin barriers or decreased cell-mediated immunity (eg, patients with atopic dermatitis or those taking immunosuppressive medications) are at an increased risk for HPV infection.^1,3 However, an Australian study of 2491 students found there was no significant difference in incidence of warts in children with or without atopic dermatitis.² The incubation period for HPV is 2 to 6 months.³ Most viral warts spontaneously resolve in immunocompetent individuals, but recurrence is very common.^1,3 

Diagnosis of viral warts is typically clinical, and histopathology of a shave biopsy or keratotic debris can aid in diagnosing atypical or recalcitrant cases. Plane warts have a different appearance from common and palmoplantar warts; they are typically small, flesh-colored, flat-topped, round or polygonal papules found in groups on the face, hands, or legs.³ Lesions may sometimes be found in a linear arrangement because of autoinoculation after scratching.³ In our case, the differential diagnosis included lichen nitidus and keratosis pilaris. Lichen nitidus typically presents with numerous, minute, discrete, flat-topped, shiny papules (Figure 2).⁴ Keratosis pilaris presents as minute, discrete, keratotic, follicular papules with variable perifollicular erythema.⁵

Many different treatment options are available for the treatment of cutaneous viral warts and because they often spontaneously resolve, these warts can even be left alone depending on patient preference, symptoms, and cosmesis.^1,3 Definitive treatment is indicated for immunocompromised individuals. Plane warts are treated similar to other cutaneous viral warts.⁶ First-line treatments include topical salicylic acid and cryotherapy but, unfortunately, require multiple visits, and treatment may not be definitive.⁶ The efficacy of cryotherapy is variable, with studies reporting clearance rates of 48% to 68% in children.^6,7 Cryotherapy is more effective than salicylic acid. However, it is painful and causes blistering, making it more difficult to use in children.⁷

Our patient was prescribed imiquimod, an immune-response modifier that is approved for the treatment of anogenital warts.⁸ A research study including 7 participants using off-label imiquimod, 5% ointment 3 times per week for plane warts showed a 57% clearance rate at 16 weeks with no recurrence or systemic adverse effects.⁸ Only 2 other case reports have been documented.^9,10

Management of refractory warts is difficult, as there is no best treatment and management may require consultation with a dermatologist. Additional topical agents such as 5-fluorouracil, cantharidin, and imiquimod may be used with salicylic acid.⁷ Another option is topical immunotherapy with contact allergens, including squaric acid dibutylester (44.7% clearance rate) and diphenylcyclopropenone (88.3% clearance rate).⁷

Intramuscular and intralesional vaccines have recently been studied for both first-line treatment and treatment of recalcitrant viral warts, namely the tuberculin purified protein derivative, measles/ mumps/ rubella, and interferon ß vaccines.¹¹ Newer trials using an intramuscular bivalent HPV vaccine for recalcitrant common warts was 82% effective, and an intramuscular hepatitis B vaccine for first-line treatment of viral warts was 21% effective, with studies reporting the clearance rate at anywhere from 1 to 8 months.^12,13 The proposed mechanism of these vaccines is through stimulation of cell-mediated immunity.¹³

Another recent case outlined a 17-year-old girl with multiple recalcitrant facial plane warts successfully treated with a weekly topical Bacillus Calmette–Guérin vaccine until complete resolution at 6 weeks.¹⁴ Given the safety and availability of these vaccines, vaccines could be considered for off-label treatment of viral warts, particularly in children and young adults who have more robust and responsive immune systems.¹² However, like cryotherapy, pain may be a deterrent to using these vaccines.

The long-term prognosis for viral warts is good, with some studies reporting more than 90% spontaneous resolution at 5 years, but they often recur.⁶ Cutaneous viral warts do not have a predilection for malignant transformation, but cutaneous malignancies should be on the differential diagnosis when presumed-to-be (common) warts do not respond to appropriate therapy.³