Two patients affected by eyelid nodular basal cell carcinomas (BCC) were treated topically with 5% imiquimod. The first case experienced pain, extensive erythema and crusting, retractile medial ectropion and conjuctival mucous secretions during the second week of treatment. These effects improved progressively until the sixth week. Complete clearance of the BCC was also observed. The second case presented during the third week of treatment with pain and a wide crust similar to a third-degree burn. Two months later, complete clearance of the BCC was observed. The total absence of scars in the eyelid skin and absence of cicatricial ectropion were remarkable. Severe reactions may occur during treatment with topical imiquimod for nodular BCC of the eyelids. However, excellent cosmetic results remain after cessation of treatment.
Reversible Severe Reaction to Imiquimod During Treatment of Eyelid Nodular Basal Cell Carcinomas
From the Department of Ophthalmology, Universitary Hospital Arnau de Vilanova, Lleida, Spain.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to V. Huerva, Department of Ophthalmology. University Hospital Arnau de Vilanova. Avda Rovira Roure 80, 25198-Lleida, Spain.
Accepted: March 19, 2009
Posted Online: March 09, 2010
Co-adjuvant treatments have been reported as treatments for eyelid basal cell carcinomas (BCC).1,2 Five percent imiquimod cream has shown efficacy in the treatment of superficial3 and nodular BCC.4 During the past several years, reports have appeared concerning the resolution of eyelid nodular BCC using topical 5% imiquimod.5–8 The most common side effects during the treatment include erythema, erosion, and scabbing or crusting of the lesion; these are felt as a burning or an itching sensation as well as pain.9 Here, we present two cases of severe reversible side effects on the eyelids following the application of 5% imiquimod cream for the treatment of nodular BCC in patients that refuse a surgical procedure.
A 90-year-old woman presented with a nodular lesion at the nasogenian groove. The lesion had been removed in another clinic several years previously (Fig. 1A). A histologic examination had confirmed a BCC with involved margins and that the lesion re-grew progressively. A regimen with 5% imiquimod cream was applied using cotton swabs, once daily, 5 days per week (Monday to Friday) was prescribed for a duration of 6 weeks. After 2 weeks, the patient presented with pain, extensive erythema and crusting, retractile medial ectropion, and conjuctival mucous secretions (Fig. 1B). After this, the cream was applied only at the lesion’s center. The secretions, ectropion, and crusting improved progressively until the completion of treatment at 6 weeks (Figs. 1C and 1D). 6 months later, the BCC resolved completely, as did the abovementioned side effects (Fig. 1E). After a year of follow-up, the lesion had not regrown.
Figure 1. (A) Recurrent Nodular BCC with Superficial Teleangiectasic Vessels at the Nasogenian Groove. (B) Extensive Erythema and Crusting, Retractile Medial Ectropion and Conjuctival Mucous Secretions After Two Weeks of Treatment. (C) Diminution of the Severe Reaction in the Fourth Week of Treatment. (D) Persistence of a Crust in the Primitive Lesion and Clearance of the BCC After Six Weeks. (E) Excellent Clinical and Cosmetic Outcomes Six Months After Treatment Suspension.
A 82-year-old man presented with a crusting nodular lesion below the inferior right eyelid. The lesion was diagnosed as BCC (Fig. 2A). A treatment regimen identical to that in Case 1 was proposed. 3 weeks later, he presented with a wide crust, similar to a third-degree burn (Fig. 2B). Treatment was not halted and, during the following week, the crust extended through most of the lower eyelid’s skin (Fig. 2C). Treatment was then ceased. Two months later, complete clearance of the BCC was observed. The total absence of scars in the eyelid skin and the absence of cicatricial ectropion were remarkable. Only a small crust was noticeable along the primitive zone of the BCC (Fig. 2D). The lesion did not regrow during a year of follow-up.
Figure 2. (A) Nodular BCC with Crusting Below the Inferior Right Eyelid. (B) Wide Crust Similar to a Third-Degree Burn During the Third Week of Treatment. (C) During the Fourth Week, the Crust Extended Through Most of the Lower Eyelid’s Skin Thickness, Similar to a Severe Burn or Necrosis. (D) Excellent Clinical and Cosmetic Outcomes After Two Months of the Treatment.
Durations ranging from 4 to 12 weeks of treatment have been reported for BCC of the eyelids.5–8 In these studies, the frequency of imiquimod application also varies, from 35–6 to 57–8 times per week. The manufacturer recommends 5 times per week for a duration of 6 weeks for superficial BCC located within 1 cm of the eyelids.9 However, as nodular BCC is the most frequent form in this location, similar results for resolution should be expected. There is a lack of clinical trials concerning the treatment of nodular BCC at the periocular region, and experience is based on reported isolated case-series.5–8 Inflammatory skin reactions have been reported following imiquimod application to the eyelids,5–8 where these may persist for the entire duration of the treatment.8 Superficial punctate keratitis associated with conjunctival hyperemia has also been observed.5 The presence of keratitis results in discontinuation of the treatment.5
In the cases reported here, the dosage used was as recommended by the manufacturer and prescribed in previous studies.8,9 However, we observed an intense reaction of the eyelids to treatment, not previously reported. In other patients receiving the same regimen, we did not observe this intense reaction. When a local skin reaction is not observed during the first two weeks of treatment, the patient is declared as a non-responder and further treatment may be cancelled.7 Importantly, severe reactions to imiquimod have been noticed recently.10 Its application around the lesion may produce a reaction in the lax skin of the eyelids, similar to second or third-degree burns. When the application is more localized, as in the first case, the inflammation and crust subside. The use of a shield with a perforation to fit the size of the lesion may prevent the adjacent skin from reacting. It is remarkable that the retractile ectropion in the first case disappeared and that total eyelid apposition was observed. In the second case, the large crust disappeared without scar formation and cicatricial ectropion, thus providing good aesthetic results.
In previous studies, nodular BCC affected the free margin of the eyelid.5–7 At this location, the side effects to the ocular surface may be serious. In the first case, we observed only irritation and secretion, which disappeared by localizing the administration to the lesion’s centre. It is possible that only three applications per week over a 4-week period, without applying the cream around the lesion, is sufficient for the eradication of nodular BCC of the eyelids and avoids adverse reactions. In addition, in the first case, we observed the efficacy of imiquimod for the treatment of recurring nodular BCC of the periocular region. The absence of local recurrences to the eyelids during 3 years7 and 5 years11 of follow-up, in other localizations, has been reported. No follow-up after a year is performed in this study, but our aim was to report on the reversibility of severe side effects, which may occur during this form of treatment.
In conclusion, intense inflammation, conjunctival secretions, extensive crust formation similar to burns, and reversible ectropion may occur during treatment with topical imiquimod for nodular BCC of the eyelids. However, topical imiquimod may represent an alternative modality of treatment in elderly patients who refuse a surgical procedure.
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