Imiquimod

Imidazo-quinoline derivative with topical immunomodulating, antiviral, tumour-inhibiting effect.

As an agomist of the Toll-like receptor (TLR)7 , imiquimod has an "immunomodulating" effect. Imiquimod activates the NLRP3 inflammasome (see inflammasome below), which responds to cellular stress and tissue damage(Groß C 2016). Imiquimod also activates Toll-like receptors 7 and 8 on dendritic cells, macrophages and monocytes. The stimulation of these receptors triggers a proinflammatory response with the synthesis of IFN-alpha, TNF-alpha, interleukins 1, 6 and 8. Among other things, the phosphorylation of the transcription factor NF kappa B (kappa gene enhancer binding protein) and of transcription factors for interferon is stimulated.

Imiquimod has been shown to reduce the viral load in infected tissue.

Further studies show that Imiquimod can activate Langerhans cells and promote their migration to the draining lymph nodes.

Approved for the topical treatment of condylomata acuminata (external genital warts) in the genital and perianal area in adults.

Approved for the topical treatment of actinic keratoses and small superficial basal cell carcinomas in adults. Topical treatment is a suitable alternative to surgical resection for superficial tumors, especially for multiple basal cell carcinomas of the trunk skin.

Clinical successes (no approval), which are also documented in the literature by individual case reports, have been reported in Bowen's disease(off-label use). Furthermore, smaller studies have described successes in mollusca contagiosa and in therapy-resistant verrucae planae juveniles. Individual observations exist on the successful treatment of lentigo maligna (off-label use) and the plaque stage of mycosis fungoides (off-label use).

For the 5% Imiquimod cream (Aldara), apply a thin layer 3 times/week before going to bed and leave on the skin for 6-10 hours.

For superficial basal cell carcinoma: apply a thin layer once a day for 5 days/week and leave on for 8-10 hours. Treatment over a total of 6 weeks. Numerous studies confirm good healing (80%). However, Imiquimod therapy is not yet covered by all statutory health insurance companies. It is advisable to apply to the insurance provider for cost coverage in advance of a planned therapy. Topical treatment is a suitable alternative to surgical resection for superficial tumors, especially for multiple trunk skin basal cell carcinomas.

For actinic keratoses: application 3 times/week for 4 weeks on the affected areas. Further cycle if required. In an open study with 829 volunteers, a cure rate of 85.4% was reported.

Condylomata acuminata: Apply 3 times/week for a total of 3-4 weeks.

For the 3.75% imiquimod in cream base (Zyklara), the following application applies for actinic keratoses: 1 sachet of the cream is applied once daily in the evening to the face and/or hairless scalp. The first treatment cycle lasts 2 weeks, followed by a treatment break of 2 weeks, then a new treatment phase of 2 weeks (2 on - 2 off - 2 on). If the local skin reactions (possibly also the systemic side effects), which can usually occur at the end of the 2nd and 6th week of treatment, are unacceptable, treatment can be temporarily interrupted. Complete remission is 67% 6 months after the end of treatment.

Important information for the patient: If the skin is still intact, the pathologically altered keratinocytes attacked by the immunomodulation become visible. In this respect, more or larger lesions appear than originally suspected. The patient should be informed of this before the therapy.

Note! According to our own experience, headaches, flu-like symptoms (fever) and myalgia often occur despite topical application (5-10% of patients).

In addition: erythema, erosion, excoriation, scaling and edema in the application areas. Rarely induration, ulceration, scabbing and blistering. In one case, a capillary leak syndrome with fatal outcome (multi-organ failure) was attributed to the use of imiquimod. The tear resistance of condoms and vaginal pessaries may be impaired. In patients with many treated skin lesions, severe manifestations of the mentioned side effects in the sense of a stronger immune induction are known.

Recall dermatitis was described after treatment with imiquimod and subsequent vaccination with an mRNA COVID 19 vaccine (Roshardt Prieto NM et al. 2023)

Aldara 5% cream; Cyclara 3,75% cream (see also http://online.rote-liste.de/suche/stoff/990617)

1. Beutner KR et al. (1999) Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream. J Am Acad Dermatol 41: 1002-1007
2. Cook-Bolden F, Weinberg JM (2002) Topical imiquimod 5% cream in the treatment of Bowen's disease of the penis. J Am Acad Dermatol 46: 146-147
3. Deeths MJ et al. (2005) Treatment of patch and plaque stage mycosis fungoides with imiquimod 5% cream. J Am Acad Dermatol 52: 275-280
4. Diaz-Arrastia C et al. (2001) Clinical and molecular responses in high-grade intraepithelial neoplasia treated with topical imiquimod 5%. Clin Cancer Res 7: 3031-3033
5. Drehs MM et al. (2002) Successful treatment of multiple superficial basal cell carcinomas with topical imiquimod: case report and review of the literature. Dermatol Surg 28: 427-429
6. Epstein E (2003) Extensive lentigo maligna clearing with topical imiquimod. Arch Dermatol 139: 944-945
7. Firooz A et al. (2006) Imiquimod in combination with meglumine antimoniate for cutaneous leishmaniasis: a randomized assessor-blind controlled trial. Arch Dermatol 142: 1575-1579
8. Geisse J et al. (2004) Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol 50: 722-733
9. Gross CJ et al.m(2016) Efflux-Independent NLRP3 Inflammasome Activation by Small Molecules
   Targeting Mitochondria. Immunity 45:761-773.
10. Hengge UR (2001) Topical immunomodulators--progress towards treating inflammation, infection, and cancer. Lancet Infect Dis 1: 189-198
11. Hengge UR, Stark R (2001) Topical imiquimod to treat intraepidermal carcinoma. Arch Dermatol 137: 709-711
12. Kagy MK, Amonette R (2000) The use of imiquimod 5% cream for the treatment of superficial basal cell carcinomas in a basal cell nevus syndrome patient. Dermatol Surg 26: 577-578
13. Mackenzie-Wood A (2001) Imiquimod 5% cream in the treatment of Bowen's disease. J Am Acad Dermatol 44: 462-470
14. Marks R et al. (2001) Imiquimod 5% cream in the treatment of superficial basal cell carcinoma: results of a multicenter 6-week dose-response trial. J Am Acad Dermatol. 44: 807-813
15. Netzwerk aktuell (2004) Capillary leak syndrome under imiquimod (Aldara cream). Drug Telegram 35: 16
16. Oster-Schmidt C (2001) Imiquimod: a new possibility for the treatment-resistant verrucae planae. Arch Dermatol 137: 666-667
17. Roshardt Prieto NM et al. (2023) mRNA COVID 19 vaccine-induced recall dermatitis after topical imiquimod. J Dtsch Dermatol Ges 21:659-660.
18. Smith KJ et al. (2002) Topical 5% imiquimod for the therapy of actinic cheilitis. J Am Acad Dermatol 47: 497-501
19. Sterry W, Ruzicka T et al. (2002) British Journal of Dermatology 147: 1227-1236
20. Stockfleth E et al. (2004) Low incidence of new actinic keratoses after topical 5% imiquimod cream treatment: a long-term follow-up study. Arch Dermatol 140: 1542
21. Stockfleth E et al. (2002) A randomized, double-blind, vehicle-controlled study to assess 5% imiquimod cream for the treatment of multiple actinic keratoses. Arch Dermatol 138: 1498-1502
22. Stockfleth E et al. (2001) Successful treatment of actinic keratosis with imiquimod cream 5%: a report of six cases. Br J Dermatol 144: 1050-1053
23. Wigbels B (2001) Imiquimod: a new treatment possibility in bowenoid papulosis? Dermatologist 52: 128-131