Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Objective: The objective of this single-center, open-label trial was to evaluate the percutaneous penetration of Aldara (imiquimod) cream, 5% when applied topically to patients with anogenital warts using a more frequent/aggressive dosing regimen.Methods: Ten otherwise healthy males and six otherwise healthy, nonpregnant, nonlactating females with histology results suggestive of, or diagnostic of, human papilloma virus/condyloma acuminata were enrolled. Females were required to be practicing an acceptable form of contraception control. Patients applied cream daily (8 +/- 2 hours) until complete wart clearance, or for a maximum of 16 weeks. Following the initial dose, at approximately week 4, and at the end-of-treatment, patients were confined for 42 hours in order to obtain a series of blood and urine samples. These samples were analyzed for levels of imiquimod and two metabolites, S-26704 and S-27700. Biological marker levels were not included as a part of this trial.Results: No quantifiable (>/=5 ng/mL) levels of imiquimod or the two metabolites were observed in any of the serum samples collected. Five patients had quantifiable (>/=10 ng/mL) imiquimod, S-26704, or both in urine. No quantifiable levels of S-27700 were observed. Complete clearance of warts occurred in 40% of male patients and 83% of female patients. Erythema was the most frequently observed local skin reaction and was moderate in intensity, although 6 of 16 patients reported a severe erythema reaction at some point in the study. Application site reactions (itching, burning and pain) were the most frequently reported adverse events.Conclusion: The lack of quantifiable levels of imiquimod or metabolites in serum, together with sporadically occurring quantifiable but low levels in urine, indicate that systemic exposure, after daily application of Aldara cream to genital/perianal skin, may occur but is minimal; however, pharmacological (immune marker) effects were not evaluated because cytokine measurements were not obtained. A future trial assessing cytokine levels after topical Aldara therapy with minimal systemic levels of imiquimod would help assess systemic drug and pharmacological effects and utility of this product in pregnant women.
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PMID:Percutaneous penetration of Aldara cream, 5% during the topical treatment of genital and perianal warts. 1083 79

This dose-escalation study was performed to evaluate safety and efficacy of imiquimod 5% cream in the treatment of uncircumcised men with penile warts associated with the foreskin. The cream was applied 3 times/week (n=34) or once per day (n=30) over 8+/-2 h. Imiquimod 5% cream was safe in both treatment groups. However, the 3 times/week regimen was better tolerated with a lower incidence of local skin reactions. In both groups, the 2 most frequently reported local skin reactions were erythema and erosion; they were more severe with the once-daily dosing. The most frequently reported application site reactions were burning, pruritus and irritation or pain (once-daily patients only). Total clearance was achieved in 62% of the patients in the 3 times/week group and by 57% in the once-daily group. Thus, imiquimod 5% cream administered 3 times/week was the optimal dosing regimen in the treatment of penile warts in uncircumcised men.
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PMID:Safety and efficacy of imiquimod 5% cream in the treatment of penile genital warts in uncircumcised men when applied three times weekly or once per day. 1180 42

Imiquimod (1-(2-methylpropyl)-1 H-imidazo[4,5-c]quinolin-4-amine) and its analogues are a class of non-nucleoside imidazoquinolinamines (hetero-cyclic amine) that activate the immune system through localised induction of cytokines, such as IFN-alpha, -beta, and a number of endogenous interleukins. The exact mechanism of its actions are still unexplored, although when tested in a number of cell culture systems, imiquimod demonstrated no inherent antiviral or antiproliferative activity in vitro, whereas, due to its reported ability to produce onsite stimulation and secretion of cytokines in various in vivo studies, such types of immune response modifiers have been shown to cause diverse biological functions, involving immunoregulatory, antiviral, antiproliferative and antitumour activities. These data support a rational justification to consider imiquimod as an innovative topical agent to treat various cutaneous diseases. Since its synthesis in 1980,several studies using animal models and human subjects have been reported substantiating its usefulness as a treatment option for various skin disorders such as genital warts, genital herpes, molluscum contagiosum, basal cell carcinoma and psoriasis. Imiquimod is insoluble in water but in most of the clinical studies its incorporation from 1 - 5% by weight in an oil-into-water cream emulsion has been reported as being well-tolerated with mild-to-moderate drug-related side effects, such as itching, burning sensation, pain, erythema, erosion and oedema. As a potent immune response modifier and an agent stimulating cell-mediated immune responses, imiquimod appears to be a promising drug to treat many skin disorders, infections and neoplasms.
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PMID:A review of the applications of imiquimod: a novel immune response modifier. 1221 23

Perianal Bowen's disease is a uncommon, slow growing, intraepidermal squamous-cell carcinoma (carcinoma in situ) of the anal region and may be a precursor to squamous carcinoma of the anus. It is associated with cervical and vulvar intraepithelial neoplasia and have human papillomavirus as a common cause. Both sexes and all races are affected, with the highest prevalence in patients aged 20 to 45 years. The symptoms of anal Bowen's disease are unspecific and the clinical findings are uncharacteristic and include pain, itching, bleeding and a disturbing lump. Biopsy and histopathologic examination is required for diagnosis and to distinguish other perianal dermatoses; thus an anogenital warts that fail to respond to conventional therapy, or change in appearance, warrant a biopsy and, where the technique is available, DNA typing to identify the viral pathogen. Infact the etiologic agent, the human papillomavirus (HPV), has been classified by DNA techniques into at least 42 types, of which 16 and 18 are considered to carry a high risk for cancer. The intraoperative findings is a lesion at the anocutaneous line: perianal or intra-anal tumor, erosion or ulceration as well as lichenoid lesion or hyperpigmentation. The disease has a proclivity for recurrence and there are many controversies concerning treatment that effectiveness remains uncertain and range from aggressive wide local excision with skin grafting when necessary to laser vaporization (argon or CO2), radiotherapy or a new immune response modifier (Imiquimod). We report a case of a 50-years-old woman with recurrence of Bowen's disease associated with vulvar HPV infection and review the literature.
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PMID:[Perianal Bowen's disease: a case report and review of the literature]. 1290 34

Orf is a zoonosis caused by an epitheliotropic DNA parapox virus. Human orf is a generally benign, self-limiting condition that usually regresses in 6-8 weeks without specific treatment. However, it may be accompanied by local symptoms including pain, pruritus, lymphangitis and axillary adenitis, or less frequently by systemic symptoms such as fever or malaise. Furthermore, it may be complicated by erythema multiforme, Stevens-Johnson syndrome, erysipelas, generalized mucocutaneous eruption, toxic erythema, eyelid oedema and giant, persistent or recurrent lesions in immunocompromised patients. Imiquimod, a potent topical immune response modifier, enhances both the innate and acquired immunity by stimulation of immune system cells resulting in local antiviral, antitumour and immunoregulatory activity. We present, for the first time, four complicated cases of orf successfully treated by topical imiquimod resulting in rapid regression of both orf and associated lesions. Two of the cases were complicated with erythema multiforme, one with recurrent eyelid oedema, and another had giant orf associated with axillary lymphadenitis. We suggest that topical imiquimod may be an effective and safe therapy for complicated orf cases.
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PMID:Rapid improvement of human orf (ecthyma contagiosum) with topical imiquimod cream: report of four complicated cases. 1642 61

A 78-year-old male sought dermatologic consultation for multifocal persistent red lesions of the glans penis. Various topical treatments had proved unsuccessful. Histologic examination revealed penile intraepithelial neoplasia (PIN). Polymerase chain reaction (PCR) showed amplification of human papillomavirus type 16 (HPV-16) DNA. Urological consultants recommended amputation of the glans; the patient rejected this, as well as any other surgical procedure. Therefore, he was treated in our dermatologic practice with imiquimod 5 % cream administered daily over 12 weeks. After therapy was completed, no clinical or histologic evidence of residual tumor was found and HPV-16 DNA was no longer detectable. Local skin reactions such as erosions and edema of the glans accompanied by tingling and itching were well-tolerated by the patient. Imiquimod 5 % cream may represent an alternative local treatment option for multifocal PIN.
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PMID:[Multifocal penile intraepithelial neoplasia--targeted treatment with imiquimod]. 1682 14

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.
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PMID:Topical imiquimod as treatment for different kinds of cutaneous lymphoma. 1857 30

(1) Basal cell carcinoma is a common malignancy that is rarely life-threatening. The aim of treatment is to remove the tumour and prevent local recurrences. Surgical excision is the standard treatment, with a mean relapse rate of about 5% at 5 years. The main alternative is radiotherapy. (2) The Indications section of the Summary of Product Characteristics (SPC) for imiquimod cream in Europe now includes "topical treatment of small superficial basal cell carcinomas in adults". (3) Imiquimod cream was primarily evaluated in 2 double-blind randomised controlled trials versus excipient, in a total of 724 patients. In these trials, small basal cell tumours (maximum 2 cm in diameter) disappeared in three-quarters of patients after imiquimod application 5 or 7 days a week for six weeks. (4) A non comparative trial involving 143 patients showed a relapse rate of 21% at 2 years. Indirect comparisons show that this is a much higher relapse rate than after other well-assessed treatments for basal cell cancer. (5) During clinical trials, nearly one-third of patients who used imiquimod 5 times a week complained of pruritus, a burning sensation, or local pain. Nearly one-half of patients experienced these problems with daily use. (6) Imiquimod cream is relatively inconvenient to use: it has to be applied in the evening; residual cream must be removed the following morning; and baths, showers and direct sunlight must be avoided during treatment.
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PMID:Imiquimod: new indication. Basal cell carcinoma: inferior to other treatments. 1698 24

Genital warts affect at least 1% of sexually active adults. Current therapies are inadequate because they are often painful, may fail to prevent recurrence and transmission of warts, and usually require either surgery or at least application by a physician. Investigation of immunotherapy for genital warts began with interferon. It has been studied in topical, intralesional, systemic and adjuvant applications. We review the major clinical trials of interferon for genital warts, and conclude that intralesional therapy with interferon-alpha or interferon-beta, with complete response rates of 36 to 63%, is the most successful route for interferon monotherapy. In choosing patients for therapy with interferon, major considerations include immune status, pregnancy and ability to return for frequent injections. Imiquimod is a new immune response enhancer that acts through stimulating host cytokine production. Interleukins-1, -2, -6, -8 and -12, interferons alpha, beta and gamma and tumour necrosis factor alpha have all been associated with the mechanism of action of imiquimod. Recently, 3 clinical trials have reported positive results using topical imiquimod to treat genital warts. Complete response rates ranged from 37 to 54% for these controlled trials of 5% imiquimod cream. Adverse effects reported include localised pruritus, erythema, erosion, burning and pain, which were rarely severe enough to cause discontinuation of the medication. Although further trials are necessary to identify the role of imiquimod in the therapy of genital warts, it appears to be an efficacious and well tolerated patient-controlled measure for wart therapy.
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PMID:A guide to immunotherapy of genital warts: focus on interferon and imiquimod. 1803 Nov 42

Despite its clinical importance, the mechanisms that mediate or generate itch are poorly defined. The identification of pruritic compounds offers insight into understanding the molecular and cellular basis of itch. Imiquimod (IQ) is an agonist of Toll-like receptor 7 (TLR7) used to treat various infectious skin diseases such as genital warts, keratosis, and basal cell carcinoma. Itch is reportedly one of the major side effects developed during IQ treatments. We found that IQ acts as a potent itch-evoking compound (pruritogen) in mice via direct excitation of sensory neurons. Combined studies of scratching behavior, patch-clamp recording, and Ca(2+) response revealed the existence of a unique intracellular mechanism, which is independent of TLR7 as well as different from the mechanisms exploited by other well-characterized pruritogens. Nevertheless, as for other pruritogens, IQ requires the presence of transient receptor potential vanilloid 1 (TRPV1)-expressing neurons for itch-associated responses. Our data provide evidence supporting the hypothesis that there is a specific subset of TRPV1-expressing neurons that is equipped with diverse intracellular mechanisms that respond to histamine, chloroquine, and IQ.
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PMID:Analysis of cellular and behavioral responses to imiquimod reveals a unique itch pathway in transient receptor potential vanilloid 1 (TRPV1)-expressing neurons. 2130 Aug 78


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