Multiple and clustered eruptive epidermoid cysts following treatment with topical imiquimod

A 61-year-old woman developed multiple and clustered eruptive epidermoid cysts at the site of treatment of a basal cell carcinoma located on her nose with imiquimod 5% cream (5 times/week for 6 weeks). Clearing was achieved after topical treatment with tretinoin 0.025% cream (1 application/day for 1 month).     

Psoriasis induced by topical imiquimod

We report the provocation of localized psoriasis at the sites of application of topical imiquimod, possibly evolving into a generalized flare. A patient with pre-existing psoriasis that had been stable for 14 years was treated with imiquimod 5% cream daily for 6 weeks to three superficial basal cell carcinomas. During treatment one of the lesions developed severe local skin reactions necessitating rest periods, and received only 18 applications in 6 weeks. The other two lesions were treated for all 42 days. Psoriasiform changes developed at all three application sites. Nine-and-a-half weeks after completing treatment the patient developed disseminated small psoriatic lesions. Other recognized triggers of psoriasis were not identified. The psoriasis resolved slowly with conventional treatment.     

Dermoscopic monitoring of efficacy of ingenol mebutate in the treatment of pigmented and non‐pigmented basal cell carcinomas

Basal cell carcinoma is the most common non‐melanoma skin cancer, and its incidence continues to raise. Although surgery can be considered the mainstay of therapy, new current pharmacological options are available and focus on tumor eradication, maximizing cosmetic results, and functional capacity. Several studies have recently reported on safety and efficacy of topical ingenol mebutate gel, a derivative of the plant Euphorbia Peplus, used to treat actinic keratosis and superficial basal cell carcinoma. In our knowledge, we report for the first time the dermoscopic evaluation of outcome and monitoring of superficial pigmented and non‐pigmented basal cell carcinomas in four patients treated by this novel non‐ablative agent. Ingenol mebutate gel therapy has showed to be effective and without important side‐effects for pigmented and non‐pigmented superficial basal cell carcinomas. We emphasize the usefulness of dermoscopy in supporting the clinical diagnosis and excluding the presence of tumor residue or recurrence. In a future scenario, we hope it will be soon possible to follow‐up the lesions, after treatment, avoiding post‐control biopsy punch.     

Use of 5% imiquimod cream in the treatment of facial basal cell carcinoma: a 3-year retrospective follow-up study

There has been considerable research into the safety and efficacy of topical 5% imiquimod cream for the treatment of skin cancers in recent years, in particular superficial and nodular basal cell carcinomas. However, there are limited long-term follow-up studies. This retrospective study aims to determine the efficacy of 5% imiquimod cream in the treatment of facial basal cell carcinomas over 3 years. Medical records of 12 patients treated with 5% imiquimod cream at a private dermatology practice during 2001 and 2002 were retrospectively reviewed. Target tumours included superficial and nodular basal cell carcinomas, giving a total lesion number of 19. Patients were commenced on a once daily treatment regimen for up to 9 weeks, and given rest periods as required according to the severity of application site reactions. We found that 5% imiquimod cream is an effective treatment option for superficial and nodular basal cell carcinomas, giving a clearance rate of 89.5% at an average of 39 months of follow up.     

The use of topical imiquimod for the treatment of actinic keratosis: a status report

Topical imiquimod 5% cream is approved for the treatment of actinic keratosis (AK), superficial basal cell carcinoma, and external genital warts. The drug's mechanism of action is via stimulation of innate and acquired immune responses, which ultimately leads to inflammatory cell infiltration within the field of drug application followed by apoptosis of diseased tissue. This article reviews available data on the use of topical imiquimod for AK. Topical imiquimod is an effective and safe treatment option for AK that produces complete eradication or marked reduction in the number of lesions in most patients. Subclinical lesions also emerge during treatment of the affected skin region ("field treatment"). In addition, there is evidence that topical imiquimod at least partially reverses some of the cellular, molecular, and genetic photocarcinogenic changes that develop in skin damaged by UV light. Recent evidence suggests that many patients who effectively are cleared of AK lesions after topical imiquimod use remain free of lesions for several months to 2 years or develop a minimal number of new AK lesions.     

Multiple facial basal cell carcinomas in xeroderma pigmentosum treated with topical imiquimod 5% cream

Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by solar sensitivity, photophobia, early onset of freckling, and solar‐induced cutaneous neoplastic changes. Management of patients with XP is a therapeutic challenge as they usually develop multiple cutaneous malignancies, making surgical therapy difficult, and continue to form skin malignancies at a high rate. We describe a 30‐year‐old Chinese man with XP who had been previously treated with excision and dermatoplasty. Upon recurrence of multiple superficial, ulcerative, and pigmented lesions, imiquimod 5% cream was recommended for 4 months. His multiple facial lesions demonstrated an excellent response to topical imiquimod 5% cream with minor side effects. This favorable response indicates that topical application of imiquimod 5% cream is an effective means of treating multiple basal cell carcinomas in XP.     

Successful treatment of basal cell carcinomas in a nevoid basal cell carcinoma syndrome with topical 5% imiquimod

Gorlin-Goltz syndrome, also referred to as naevoid basal cell carcinoma syndrome (NBCCS), is an autosomal dominant skin disease with complete penetrance and inconstancy of the four major findings: multiple naevoid basal cell carcinomas (BCCs), pits on palms and soles, skeletal abnormalities (for example, jaw cysts), and ectopic calcification. The treatment of multiple BCCs is still a matter of debate. We report three cases of multiple BCCs in Gorlin-Goltz syndrome treated with topical 5% imiquimod cream, an immune response modifier. Patients were successfully cleared of BCCs after treatment for 6-8 weeks. Histologically no apparent signs of BCC-persistence could be detected and no recurrences were detected during the 12 month follow up period.     

Use of topical immunomodulators in organ transplant recipients

Solid organ transplant recipients are a growing population at increased risk for the development of cutaneous premalignant and malignant lesions, resulting in significant morbidity and mortality. Topical immunomodulators, in particular imiquimod, have shown efficacy in the management of multiple malignant, precancerous, and viral conditions. The ability to locally induce an immune response, presumably against tumor and viral antigens, and induce apoptosis makes topical immunomodulators a promising therapeutic option in organ transplant recipients. Although limited, data have begun to accumulate on the use of imiquimod in transplant patients for the management of superficial, nodular, and infiltrative basal cell carcinomas; in situ and invasive squamous cell carcinomas; condyloma acuminata; and common warts. As more experience is gathered, the role of imiquimod and other topical immunomodulators in the care of OTRs will be clarified. The authors reviewed the existing data on the use of topical imiquimod in OTRs with mention of its presumed mechanisms of action and other immunomodulators with potential efficacy against cancerous and precancerous lesions.     

Topical imiquimod therapy for basal and squamous cell carcinomas: a clinical experience

Basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) are the most common malignancies in humans. Together, they constitute approximately 95% of nonmelanoma skin cancers (NMSCs). Surgical excision remains the mainstay of therapy of low-risk NMSC, though Mohs micrographic surgery is the gold standard for high-risk NMSC. Both methods produce high cure rates, but they may not be appropriate treatments for elderly patients who are either not surgical candidates or refuse to undergo surgery for their skin cancers. Imiquimod cream 5% is a topical immune response modifier that targets the toll-like receptors 7 and 8 and up-regulates inflammatory pathways targeting diseased tissue. This noninvasive topical therapy may be more appropriate for some patients. Herein, we describe our 5-month clinical experience in mostly elderly subjects with BCC (n=21) or SCC (n= 19) who were not candidates for surgical excision and were treated with topical imiquimod. Most subjects had a history of skin cancer, and the median age of the subjects was 78 years and 79 years in the BCC and SCC groups, respectively. After biopsy alone or biopsy followed by curettage, subjects received imiquimod cream 5% once daily 5 times weekly for 6 weeks. Twenty-three BCC lesions and 22 SCC lesions were included in the analysis. Most of the 45 lesions treated were located on the head and most were in high-risk areas. Approximately 3 months after imiquimod therapy, repeat biopsies showed that only 3 (2 BCCs and 1 SCC) lesion sites had residual tumor. After a median follow-up of 26 months, there was only one additional SCC recurrence. We also present a selection of representative case studies. Imiquimod cream 5% as adjunctive therapy to curettage was safe and well-tolerated in this mostly elderly population. The improved residual tumor and recurrence rates compared with historical rates for electrodesiccation and curettage (ED&C) alone suggest that adjunctive imiquimod therapy may be an appropriate treatment option for patients who desire or require less invasive treatment for NMSCs.     

Efficacy of imiquimod 5% cream for basal cell carcinoma in transplant patients

Imiquimod 5% cream has proven to be effective in superficial and nodular basal cell carcinomas in nonimmunosuppressed patients and treating squamous cell carcinomas in situ in transplant patients. The objective of this open-label study was to determine the efficacy of imiquimod 5% cream in treating basal cell carcinoma in transplant patients. At our unit, four renal transplant patients and one cardiac transplant patient were diagnosed with 10 basal cell carcinomas in 2001. Four tumours were superficial, three nodular and three infiltrative. Five basal cell carcinomas received imiquimod 5% cream at night four times weekly for 6 weeks, without occlusion, and the other five tumours were treated on 5 nights per week for 5 weeks. Biopsies taken 6 weeks after the end of treatment showed no tumour in seven of 10 of the cases. Notably, all four superficial basal cell carcinomas, two of the three of nodular lesions and one of the three of infiltrative cases had completely cleared.     

Multiple basal cell carcinomas in xeroderma pigmentosum treated with imiquimod 5% cream

Abstract:  We report successful treatment of multiple basal cell carcinomas with imiquimod 5% cream in a 16-year-old boy with xeroderma pigmentosum and review the possibility of prophylactic role of imiquimod in the disease. Imiquimod cream was applied uniformly over all the basal cell carcinoma lesions and background pigmented skin, once at bedtime on every alternate day for 12 weeks. Besides the basal cell carcinomas, the background hyperpigmentation and keratotic papules also cleared, and the skin texture improved. The lesions did not recur at the treated sites during the follow up of 1 year.     

Treatment of Keratoacanthoma with 5% Imiquimod Cream and Review of the Previous Report

Keratoacanthoma (KA) is a benign epidermal tumor, characterized by rapid and abundant growth, a tendency toward spontaneous regression and histopathologic similarity to squamous cell carcinoma (SCC). Because KA can be easily misdiagnosed as SCC, surgery is considered the treatment of choice. Recently, regression of KAs following application of 5% imiquimod cream (Aldara®) has been reported. We present 4 cases of KA treated with topical imiquimod, applied 3 to 4 times a week. Obvious improvement was observed after 4 to 6 weeks of application and the lesions were almost cleared leaving scars after 9 to 11 weeks. These results show that topical imiquimod can be an effective option for the conservative management of KA as previously reported. We also suggest that lesions treated with imiquimod cream should be considered for biopsy to judge histopathological remission after 5 to 8 weeks of application to shorten the duration of the treatment.     

Imiquimod in dermatology: an overview

Imiquimod is an immune response modifier commercially available as a 3.75 and 5% cream. Topical imiquimod stimulates the innate and adaptive immune responses and induces cytokine production. This allows its use for the treatment of a wide variety of benign and malignant skin conditions due to its potential antiviral, antitumor, and immunoregulatory effects. Currently, topical imiquimod is US Food and Drug Administration (FDA)‐approved for the treatment of anogenital warts, actinic keratosis, and superficial basal cell carcinomas. However, it has also shown a beneficial effect in the treatment of many other skin disorders. In this review, we describe existing evidence on the mechanism of action of topical imiquimod, its FDA‐approved indications, off‐label uses, and side effects.     

Expression of the hair stem cell-specific keratin 15 in pilar tumors of the skin.

Keratin 15 (K15) was recently shown to be a specific marker of stem cells of the hair-follicle bulge. We studied the reactivity of an antibody to the CD8 antigen (C8/144B), recognizing K15, on 66 cutaneous tumors with known or alleged pilar differentiation, in order to assess its usefulness in the diagnosis of this group of tumors. 2/2 basal cell nevi, 5/8 trichoepitheliomas and 1/3 trichofolliculomas showed substantial reactivity. Much weaker reactivity was observed in cases of trichilemmal tumors (trichilemmomas and trichilemmal cysts); by contrast, all cases of pilomatricomas, basal cell carcinomas and epidermoid cysts were completely unreactive. These results are in keeping with the admitted differentiation of the tumors studied, and suggest further that basal cell carcinomas do not differentiate towards hair bulge cells. From a practical point of view, immunostaining for K15 seems to be an additional useful adjunct for the differential diagnosis between basal cell carcinoma and trichoepithelioma.     

Possible mechanisms in the induction of vitiligo-like hypopigmentation by topical imiquimod

The pathogenesis of vitiligo was examined for clues to the pigmentary changes that may occur after treatment with topical imiquimod. The literature varies on the pigmentary changes induced by topical use of imiquimod. The US Food and Drugs Administration lists 68 reports of pigmentary changes out of a total of 1257 reports related to imiquimod lodged from 1997 to 2003. Some studies describe vitiligo-like hypopigmentation associated with imiquimod treatment of genital warts (as with the patient described in this report), molluscum contagiosum, basal cell carcinoma, extramammary Paget's disease and murine melanoma. Other studies report hyperpigmentation associated with imiquimod. The possible mechanisms of hypopigmentation associated with imiquimod treatment are discussed, including antibodies found in sera of patients with vitiligo to nonpigment cell antigens, cytoplasmic pigment cell antigens and pigment cell-surface antigens; stimulation by imiquimod of both the innate immune response and cell-mediated adaptive immunity; and increased sensitivity of melanocytes to oxidative stress. The vitiligo-like hypopigmentation following topical imiquimod treatment is in line with the mode of action of this drug.     

Imiquimod,a topical immune response modifier,in the treatment of cutaneous metastases of malignant melanoma

BACKGROUND: Imiquimod 5% cream (Aldara, a novel topical immune response modifier, has been approved for the topical treatment of anogenital HPV-induced warts. In addition, several studies have demonstrated antitumoral activity in solar keratoses, superficial basal cell carcinomas and Bowen's disease. AIM: Given the convincing therapeutic results of imiquimod when used for treating selected types of epithelial skin cancer, we became interested to study imiquimod as an adjuvant for treating cutaneous metastases of malignant melanoma. METHODS: Three patients with multiple, i.e. more than 15, cutaneous in-transit metastases of malignant melanoma in unilateral localization on the leg were treated topically with imiquimod 5% cream. RESULTS: Twice daily application under occlusive conditions for a period of 21-28 weeks resulted in >90% regression of cutaneous metastases in 2 patients. The third patient showed marked response only when topical imiquimod was intermittently supplemented by intralesional interleukin (IL)-2 for 2 weeks. Unwanted side effects were mild in all patients. CONCLUSION: Overall, imiquimod as a single agent or in combination with intralesional IL-2 may be a promising immunomodulatory compound for the adjuvant topical treatment of patients with multiple cutaneous metastases of malignant melanoma.     

Hexadaktylie an Hand und Fuß bei einem Patienten mit Basalzellnävussyndrom

A 35-year-old male patient with hexadactyly on the right hand and both feet presented with multiple basal cell carcinomas of the skin. The results of further investigations led to the diagnosis of basal cell nevus syndrome (BCNS). The basal cell nevus syndrome (Gorlin-Goltz syndrome) characterized by multiple basal cell carcinomas, odontogenic cysts, skeletal abnormalities and associated neoplasms belongs to the group of genodermatoses. Reviewing the current literature we discuss aspects of the pathogenesis of the basal cell nevus syndrome as well as diagnosis criteria and treatment options.     

Lichen planopilaris after imiquimod 5% cream for multiple BCC in basal cell naevus syndrome

Basal cell naevus syndrome is an inherited autosomal dominant genetic disorder characterised by multiple basal cell carcinomas (BCC), skeletal, neurological and opthalmological abnormalities. The treatment of choice of the often multiple and large BCC consists of a combined approach including surgery, liquid nitrogen and other topical treatment modalities. Imiquimod 5% cream is an immune–response‐modifying drug with antiviral and anti‐tumour activity. Recent reports have associated the immune‐stimulant properties of imiquimod with the exacerbation of several autoimmune skin diseases, such as eczema, psoriasis, vitiligo and lichenoid dermatitis. Here we report a patient with basal cell naevus syndrome who developed a lichen planopilaris on the same site of the scalp, which had been previously treated with two cycles of imiquimod for multiple BCC.     

Bowen's disease and squamous cell carcinoma in Haber's syndrome: two cases

BACKGROUND: Haber's syndrome is a rare form of autosomal dominant genodermatosis. Clinically, it is associated with rosaceiform dermatosis of the face that begins in childhood, and profuse keratotic lesions resembling seborrheic keratoses, seen predominantly on the trunk, the tops of the limbs and the scalp. We report two cases of Bowen's disease and cutaneous epidermoid carcinoma in Haber's syndrome patients. OBSERVATIONS: A 67 year-old woman with Haber's syndrome and with a familial history consulted for a budding lesion on the abdomen, histological examination of which confirmed epidermoid carcinoma. A 77 year-old woman presented a clinical picture consistent with Haber's syndrome, with three infiltrated erythematosquamous abdominal lesions. Histological examination of a biopsy sample confirmed the clinical diagnosis of Bowen's disease. The patient was successfully treated with imiquimod. DISCUSSION: These two cases appear to indicate the existence of an association between Haber's syndrome and the presence of cutaneous carcinomatous lesions. We propose the hypothesis of transformation of the keratoses seen in seborrheic keratosis. These lesions may be considered as pre-cancerous. Association with skin carcinomas requires regular monitoring of these patients. The use of imiquimod to treat lesions in patients with Bowen's disease resulted in complete cure.     

A pilot study of clinical efficacy of imiquimod and cryotherapy for the treatment of basal cell carcinoma with incomplete response to imiquimod

Background Cryotherapy is a physical procedure whose immunogenic capability enables it to destroy tumour cells, at least partially. Consequently, it can boost the effect of imiquimod. Objective The objective of the present study was to evaluate the efficacy of combining cryotherapy and imiquimod in patients who did not achieve a complete response after treatment of basal cell carcinoma with imiquimod. The study sample comprised 22 patients with 23 basal cell carcinomas. The tumours were treated with liquid nitrogen (one cycle, 20–30 s) before application of imiquimod (five times weekly for 6 weeks). Results A maintained complete clinical response was observed in 19 of the 23 tumours (83%), a partial response in three and no response in one. One tumour presented signs of persistence/recurrence during follow‐up. Conclusions Cryotherapy applied to treat imiquimod‐refractory basal cell carcinoma seems to sensitize the tumour to the effect of the drug, thus reducing the percentage of patients who need surgery after an incomplete response to imiquimod. Further studies are necessary to confirm these findings.