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LETTER TO EDITOR
Year : 2022  |  Volume : 23  |  Issue : 2  |  Page : 183-184

Imiquimod-Induced vulval erosions in a child


1 Department of Dermatology, Bhojani Clinic, Mumbai, Maharashtra, India
2 Department of Dermatology, Dr. Save's Clinic, Mumbai, Maharashtra, India

Date of Submission09-Sep-2021
Date of Decision14-Jan-2022
Date of Acceptance16-Jan-2022
Date of Web Publication30-Mar-2022

Correspondence Address:
Dr. Resham Vasani
Department of Dermatology, Bhojani Clinic, Matunga, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.ijpd_128_21

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How to cite this article:
Vasani R, Save S. Imiquimod-Induced vulval erosions in a child. Indian J Paediatr Dermatol 2022;23:183-4

How to cite this URL:
Vasani R, Save S. Imiquimod-Induced vulval erosions in a child. Indian J Paediatr Dermatol [serial online] 2022 [cited 2022 May 17];23:183-4. Available from: https://www.ijpd.in/text.asp?2022/23/2/183/341459



To the Editor,

A 6-year-old girl was brought with complaints of multiple painful raw areas over the genitalia for 3 days with associated urinary retention for the past 16 h. There were no other systemic complaints. The parents were applying 5% imiquimod cream twice daily over the warts present over the groin for the past 16 days as advised by the treating dermatologist. The application was stopped after the appearance of lesions. They confirmed the application of the cream precisely over the affected areas and denied the possibility of direct contact of the cream with the vulvovaginal area. There was no history suggestive of sexual abuse, however, the female caretaker of the child had palmar warts.

Cutaneous examination showed multiple well-defined irregularly shaped erosions 1–3 mm in size, over an erythematous base on the inner aspect of the labia majora and minora [Figure 1]a and [Figure 1]b. Bilateral subcentimeter-sized nontender inguinal lymphadenopathy was present. Both sides of the groin showed the presence of flat warts. There was no inflammation of the skin overlying and surrounding warts. The rest of the cutaneous examination including that of the oral cavity, palms, soles was normal.
Figure 1: (a and b) Multiple irregularly shaped ulcerations on the inner aspect of the labia majora and minora over an erythematous base. Multiple flat warts on the bilateral groins

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A diagnosis of imiquimod-induced mucositis distant to the site of application was made by excluding two likely differential diagnoses. Herpes genitalis was ruled out by lack of preceding vesiculation and the absence of history and clinical findings suggestive of sexual abuse. The young age of the patient and absence of fever made the diagnosis of Lipschultz ulcer unlikely. Since there was a temporal relation of application of Imiquimod cream and the appearance of the lesions, with no other disease or drug likely to be responsible for the appearance of lesions as well the positive response seen on withdrawal of the drug made Imiquimod the "probable" or "likely" drug as per the WHO-UMC scale with a score of 6 on the Naranjo adverse drug reaction probability scale. The parents did not consent for a rechallenge.

A Tzanck smear from the base of the erosion did not show multinucleated giant cells. The parents refused a biopsy. Complete blood count, erythrocyte sedimentation rate, urine routine, and screening for herpes antibodies, HIV, VDRL, and HBsAg were negative.

Symptomatic treatment was advised with wet compresses with oral cefadroxil and topical mupirocin that resulted in complete healing of the erosions within 5 days. Podophyllin (20%) was applied weekly over warts till complete resolution. The palmar warts of the caretaker were treated with topical keratolytic.

Imiquimod belongs to a class of immune-response modifiers.[1] It is a toll-like receptor (TLR) agonist and induces innate immune response.[2] Local inflammatory reactions such as pruritus, tenderness, burning, edema, and ulcerations are known and are considered pharmacological effects.[3] Intriguingly, in this patient, the imiquimod application site remained completely unaltered.

Although the development of mucositis at sites distant to the application of imiquimod has been described in adults, there is only one case documented in the pediatric age group by Smith et al.[4] Paradoxical distant site aphthous-like ulcerations have been described with imiquimod in adults, but since the morphology, in this case, did not match the morphology of aphthous ulcers, we preferred to keep the term mucositis. Approximately 1% of the applied imiquimod is said to get absorbed into the skin.[5] The amount of absorbed drug is likely higher considering the thin skin in the inguinal region in the child. It takes around 15 days to attain the maximum serum concentration in the case of imiquimod[5] and this patient developed the said lesions on the 16th day of imiquimod application explaining the chronology of presentation.

The mucosal epithelial cells specifically express the TLRs and the application of imiquimod induces the production of proinflammatory Th1 cytokines such as Tumor necrosis factor-alpha, interferon gamma, interleukin-12 (IL-12), IL-1, and IL-6, enabling the migration of leukocytes and lymphocytes leading to the appearance of erosive mucosal lesions.[5]

This phenomenon is rare in the pediatric age group. The increased absorption of the drug from the thin inguinal skin of a child can well explain this phenomenon in children. Close vigilance of the adjacent and distant mucosae is recommended while applying imiquimod in flexures such as groin in children.

Declaration of consent

The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s) of the patient. In the form the parent(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Gupta AK, Cherman AM, Tyring SK. Viral and nonviral uses of imiquimod: A review. J Cutan Med Surg 2004;8:338-52.  Back to cited text no. 1
    
2.
Harrison CJ, Miller RL, Bernstein DI. Post-therapy suppression of genital herpes simplex virus (HSV) recurrences and enhancement of HSV-specific T-cell memory by imiquimod in guinea pigs. Antimicrob Agents Chemother 1994;38:2059-64.  Back to cited text no. 2
    
3.
Cantisani C, Lazic T, Richetta AG, Clerico R, Mattozzi C, Calvieri S. Imiquimod 5% cream use in dermatology, side effects and recent patents. Recent Pat Inflamm Allergy Drug Discov 2012;6:65-9.  Back to cited text no. 3
    
4.
Smith WA, Siegel D, Lyon VB, Holland KE. Psoriasiform eruption and oral ulcerations as adverse effects of topical 5% imiquimod treatment in children: A report of four cases. Pediatr Dermatol 2013;30:e157-60.  Back to cited text no. 4
    
5.
Hammerl V, Parlar B, Navarini A, Gantenbein L, Väth H, Mueller SM. Mucosal side effects in patients treated with topical imiquimodA scoping review of the literature. Dermatol Ther 2021;34:e14355.  Back to cited text no. 5
    


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