Topical treatment of melanoma skin metastases with imiquimod

The treatment of skin metastases of melanoma can be difficult in many cases because of the patients age, as well as the number, size and location of the lesions. We present the case of an 82-year-old male with melanoma skin metastases on the scalp, which responded satisfactorily to treatment with 5 % imiquimod cream. Imiquimod is a topical immunomodulator with antiviral and antineoplastic action. This case, along with others that have recently been published, supports the usefulness of this treatment in selected cases of melanoma skin metastases, at least for palliative purposes.     

Topical treatment with imiquimod may induce regression of facial keratoacanthoma

Keratoacanthoma (KA) is a rapidly growing tumour histologically resembling squamous cell carcinoma. Although it may regress spontaneously, KA is routinely treated by excision or radiation therapy. Here we report on the successful therapeutic use of imiquimod for the treatment of KA. Four patients with a one to six week history of facial KA were treated with imiquimod cream 5 % every second day for four to 12 weeks. In each patient, KA fully regressed under topical treatment with imiquimod. In three of the patients, KA had disappeared within four to six weeks. In two patients, disappearance was confirmed histologically. No recurrence occurred during a four- to six-month follow-up-period. Our observations indicate that topical immunostimulation with imiquimod may induce or promote immune defence mechanisms leading to KA regression. Imiquimod might therefore prove to be an effective non-invasive treatment modality for KA that warrants more extensive evaluation by clinical studies.     

Topical imiquimod as treatment for different kinds of cutaneous lymphoma

Imiquimod as a topical immune response modifier leads to a localized production of interferon and other cytokines. Apart from its use for genital warts it has therefore been used as treatment for different cutaneous neoplasms, including a few cases of cutaneous T-cell lymphoma. We treated 8 patients (4 with mycosis fungoides, 1 with CD30+ anaplastic large cell lymphoma and 3 with primary cutaneous B-cell lymphoma) with topical imiquimod. Therapy was started three times per week, in cases without response, the frequency was increased to a daily application. Two patients with mycosis fungoides and the patient with the CD30+ anaplastic large cell lymphoma had a complete clinical remission, the other two patients with mycosis fungoides did not show a response to imiquimod. Of the patients with cutaneous B-cell lymphoma, two reached a partial remission, one did not respond to therapy. Two patients had side effects such as erythema and pruritus which disappeared when the frequency of therapy was reduced. Our preliminary data show that imiquimod might be effective in some cases with therapy resistant lesions of cutaneous T-cell lymphoma as well as of cutaneous B-cell lymphoma, but more controlled studies are needed.     

Inhibition of UV‐induced uric acid production using Allopurinol prevents suppression of the contact hypersensitivity response

Exposure to solar ultraviolet (UV) radiation suppresses adaptive immune responses. This contributes to skin carcinogenesis but may protect from some autoimmune diseases. However, the molecular changes occurring within UV‐exposed skin that precipitate the downstream events leading to immune suppression are not fully understood. Using a combination of in vitro and in vivo mouse models, we have discovered that UV induces significant cutaneous production of immune suppressive uric acid. The ability of UV‐induced uric acid to inhibit a contact hypersensitivity response was successfully blocked by the gout‐treating drug Allopurinol. Up‐regulation of NLRP3 mRNA by UV was also found to be dependent on UV‐induced uric acid. This suggested that the target of UV‐induced uric acid included proteins involved in the formation and activation of the NLRP3‐inflammasome. However, in contrast to NLRP3, the adaptor protein ASC, which is required for formation of the NLRP3‐inflammasome, was significantly down‐regulated. Furthermore, this down‐regulation was not dependent on UV‐induced uric acid production because Allopurinol treatment failed to prevent the reduction in ASC. Hence, our results identify uric acid as an important molecule involved in sterile UV‐induced inflammation and immune suppression. UV‐induced uric acid may therefore offer a unique therapeutic target for preventing and treating skin cancer.     

Topical imiquimod treatment of aciclovir-resistant herpes simplex disease: case series and literature review

Infection with herpes simplex virus (HSV) is extremely common worldwide. In immunocompromised patients anogenital HSV disease may have atypical features and may be very severe. Treatment of aciclovir-resistant anogenital HSV disease is challenging, as resistance to alternative treatments may occur, and effective treatment generally involves intravenous therapy with relatively toxic agents such as foscarnet. This case report presents three immunocompromised patients with presumed aciclovir-resistant anogenital HSV disease who were successfully treated with topical imiquimod. Imiquimod promotes local immune activation, which results in resolution of viral lesions such as anogenital warts and HSV disease. It is convenient to use and avoids the necessity for intravenous treatment with substantial systemic toxicity. In addition, as the mode of action of imiquimod is related to immune stimulation rather than direct antiviral activity, it may be used repeatedly without resistance developing.     

Suprathreshold doses of hapten are required to induce both contact hypersensitivity and tolerance

Whereas both high (conventional) and low (optimal) doses of epicutaneously applied hapten induce contact hypersensitivity in normal mice, only conventional doses retain their capacity to induce contact hypersensitivity after acute, low dose ultraviolet B radiation in UVB-resistant mice. Recent evidence indicates that conventional doses of hapten as well as acute, low dose ultraviolet B radiation destroy virtually all epidermal Langerhans cells, which leads to the conclusions that (a) dermal antigen presenting cells have a prominent role to play in contact hypersensitivity induction, and that (b) Langerhans cell provide this function only in normal skin, and only if non-toxic amounts of hapten are present. We have now explored the ability of suprathreshold, threshold, and sub-threshold doses of hapten to induce tolerance when painted on or injected into normal skin or skin exposed to ultraviolet B radiation. Our results indicate that a single exposure of low dose, ultraviolet B radiation generated tolerance-promoting signals within the epidermis when a threshold dose of hapten was painted on the exposed site. By contrast, suprathreshold doses of hapten painted on skin after four consecutive daily doses of ultraviolet B radiation led to tolerance that arose exclusively from cells within the dermis. In absence of ultraviolet B radiation, epicutaneously applied hapten failed uniformly to induce tolerance, whether applied at suprathreshold, threshold or sub-threshold doses. We conclude that normal skin lacks cells with inherent tolerance-promoting capacity, but that cells of this type can emerge within either epidermis or dermis after exposure to acute, low dose ultraviolet B radiation.     

Topical antifungal treatment prevents recurrence of toenail onychomycosis following cure

Recurrence rates are high for onychomycosis, with prophylactic topical antifungal use proposed to counter recurrence. Although this is a reasonable action for many clinicians, few studies have been conducted on the efficacy of topical prophylaxis. A retrospective chart review (2010–2015) was conducted in patients receiving oral terbinafine or itraconazole for toenail onychomycosis. Following complete cure, a topical antifungal (amorolfine, bifonazole, ciclopirox olamine, or terbinafine spray) was used weekly as prophylaxis. Recurrence was recorded along with patient characteristics including demographics and concomitant medical conditions. Data from 320 patients were collected. Recurrence was significantly lower in patients receiving topical antifungal prophylaxis than in no prophylactic treatment following oral terbinafine (p < .001), but not itraconazole (p = .185). Regardless of oral treatment, the use of topical antifungals as prophylaxis (p < .001) decreased, and the number of affected toenails (p = .048) and family history of fungal infections (p < .001) increased the likelihood that recurrence would occur. This study supports the use of topical antifungal medications as prophylactic treatment to help prevent recurrence of toenail onychomycosis and suggests that those with a family history of fungal infections should be closely monitored.