- Multicentric Anogenital Bowen's Disease Treated with Imiquimod and CO2 Laser. [Journal Article]
- SSkinmed 2018; 16(5):333-335
- A 53-year-old white woman presented to our clinic with skin lesions in the anogenital region that had persisted for 1 year. She had a past medical history of total vulvectomy for a vulvar localizatio...
A 53-year-old white woman presented to our clinic with skin lesions in the anogenital region that had persisted for 1 year. She had a past medical history of total vulvectomy for a vulvar localization of Bowen's disease. She was otherwise in good health, with no evidence of illness or immunosuppression. Physical examination revealed multiple erythematous papular lesions located in the anogenital region (Figure 1). Dermatoscopy of the anogenital papules revealed glomerular vessels on an erythematous background typical of Bowen's disease (Figure 2A). There were no palpable inguinal lymph nodes. Rectosigmoidoscopy was normal. The biopsy specimen showed full thickness keratinocyte atypia with loss of normal stratification and was conclusive for Bowen's disease (Figure 2B).
- On "Multicentric Anogenital Bowen's Disease Treated with Imiquimod and CO2 Laser". [Journal Article]
- SSkinmed 2018; 16(5):299-300
- Xeroderma pigmentosum. [Journal Article]
- ADAnn Dermatol Venereol 2018 Nov 05
- Xeroderma pigmentosum (XP) is a form of general dermatosis characterised by photo-induced cutaneous-ocular impairment and by skin cancers. In addition to these signs, there may also be neurological i...
Xeroderma pigmentosum (XP) is a form of general dermatosis characterised by photo-induced cutaneous-ocular impairment and by skin cancers. In addition to these signs, there may also be neurological involvement. This disease is related to a defect in genes within the nucleotide excision repair system for the first seven genetic groups (A-G), and to an abnormality in transcription groups for the eighth group (xeroderma pigmentosum variant - XPV). Cutaneous carcinomas are the most common types of cancer seen. They may begin in childhood. Multiple melanoma commonly occurs during the course of XP but given the frequency of spontaneous regression, the incidence is underestimated. The clinical appearance is characterised by polymorphous lesions with characteristic dyschromia and in most cases it is sufficient to establish the diagnosis. Investigation of unscheduled DNA synthesis (UDS) and cell survival following ultraviolet (UV) radiation were formerly considered the reference examination for laboratory diagnosis. However, these tests are now being replaced by new molecular biology techniques to screen for the genetic mutations characteristic of the disease. These techniques have proved extremely useful in identifying heterozygous patients and in antenatal diagnosis. Photoprotection is the key preventive measure: patients must avoid all exposure to the sun and to artificial sources of UV radiation. The therapeutic arsenal has recently been enriched by several modern therapeutic methods used to destroy cutaneous tumours such as imiquimod and photodynamic therapy (PDT). These approaches are valuable since they eliminate incipient tumours while sparing healthy skin. Surgery and cryosurgery are the most suitable methods for treating cutaneous tumours in children. Chemotherapy may be considered an alternative for the treatment of keratoacanthomas and squamous cell carcinomas (SCC). Cryosurgery may be combined with other therapeutic approaches to eliminate SCC of the lip. Management of these patients in reference centres, coupled with assistance from associations providing support for patients' families, has resulted in improved quality of therapy while slowing down disease progression.
- Human papillomavirus infection: protocol for a randomised controlled trial of imiquimod cream (5%) versus podophyllotoxin cream (0.15%), in combination with quadrivalent human papillomavirus or control vaccination in the treatment and prevention of recurrence of anogenital warts (HIPvac trial). [Journal Article]
- BMBMC Med Res Methodol 2018 Nov 06; 18(1):125
- CONCLUSIONS: The trial is expected to provide the first high-quality evidence of the comparative efficacy and cost-effectiveness of the two topical treatments in current use, as well as investigate the potential benefit of HPV vaccination, in the management of anogenital warts.
- Anal Intraepithelial Neoplasia and Squamous Cell Cancer of the Anus. [Review]
- CCClin Colon Rectal Surg 2018; 31(6):347-352
- Anal intraepithelial neoplasia (AIN) is the premalignant condition of the anal squamous tissue. It is associated with the human papilloma virus and is considered the transition prior to the invasive ...
Anal intraepithelial neoplasia (AIN) is the premalignant condition of the anal squamous tissue. It is associated with the human papilloma virus and is considered the transition prior to the invasive anal squamous cell carcinoma. It is typically asymptomatic and can be either an incidental finding after anorectal surgery or identified when high-risk patient populations are screened. Once AIN is diagnosed, the optimal management remains controversial, partly because the natural history of the disease is unclear. Surgical management of the disease has essentially been replaced by more conservative treatment options and can range from expectant management to topical therapy to photodynamic therapy. The aim of this article is to review the varied treatment options and to briefly review prevention strategies.
- Potentiation of psoriasis-like inflammation by PCSK9. [Journal Article]
- JIJ Invest Dermatol 2018 Nov 02
- Psoriasis is a systemic inflammatory disease, associated with metabolic disorders, including high level of low-density lipoprotein(LDL). Proprotein convertase subtilisin/kexin 9 (PCSK9), promoting th...
Psoriasis is a systemic inflammatory disease, associated with metabolic disorders, including high level of low-density lipoprotein(LDL). Proprotein convertase subtilisin/kexin 9 (PCSK9), promoting the degradation of LDL receptors, and therefore the increased concentration of circulating LDL, is also involved in inflammation. This study aims to examine the role of PCSK9 in psoriasis and to investigate the potential of topically applying siRNA targeting Pcsk9 as a psoriasis treatment. We investigated the expression of PCSK9 in lesions of psoriasis patients, the imiquimod (IMQ) induced psoriatic reactions in Pcsk9 knockout and Pcsk9 siRNA treated mice, and also used cultured human keratinocytes to investigate the role of PCSK9 on regulating cell proliferation and apoptosis. We found that PCSK9 is overexpressed in psoriatic lesions, suppressing Pcsk9 can decrease the inflammatory reaction induced by IMQ treatment and inhibit hyper-proliferation of keratinocytes. We also found that suppressing PCSK9 can significantly alter the cell cycle and induce apoptosis of human keratinocytes. Taken together, our findings indicate that PCSK9 plays an important role in psoriasis, and may be a therapeutic target.
- Guidelines of care for the management of primary cutaneous melanoma. [Journal Article]
- JAJ Am Acad Dermatol 2018 Oct 29
- The incidence of primary cutaneous melanoma continues to increase each year. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is usually curative following early detect...
The incidence of primary cutaneous melanoma continues to increase each year. Melanoma accounts for the majority of skin cancer-related deaths, but treatment is usually curative following early detection of disease. In this American Academy of Dermatology clinical practice guideline, updated treatment recommendations are provided for patients with primary cutaneous melanoma (American Joint Committee on Cancer stages 0-IIC and pathologic stage III by virtue of a positive sentinel lymph node biopsy). Biopsy techniques for a lesion that is clinically suggestive of melanoma are reviewed, as are recommendations for the histopathologic interpretation of cutaneous melanoma. The use of laboratory, molecular, and imaging tests is examined in the initial work-up of patients with newly diagnosed melanoma and for follow-up of asymptomatic patients. With regard to treatment of primary cutaneous melanoma, recommendations for surgical margins and the concepts of staged excision (including Mohs micrographic surgery) and nonsurgical treatments for melanoma in situ, lentigo maligna type (including topical imiquimod and radiation therapy), are updated. The role of sentinel lymph node biopsy as a staging technique for cutaneous melanoma is described, with recommendations for its use in clinical practice. Finally, current data regarding pregnancy and melanoma, genetic testing for familial melanoma, and management of dermatologic toxicities related to novel targeted agents and immunotherapies for patients with advanced disease are summarized.
- Antiviral drugs for varicella-zoster virus and herpes simplex virus infections. [Review]
- MLMed Lett Drugs Ther 2018 Sep 24; 60(1556):153-157
- Ameliorative effects of a fusion protein dual targeting interleukin 17A and tumor necrosis factor α on imiquimod-induced psoriasis in mice. [Journal Article]
- BPBiomed Pharmacother 2018 Oct 06; 108:1425-1434
- In recent decades, biological agents such as tumor necrosis factor-α (TNF-α) inhibitors, have revolutionized the treatment of psoriasis. However, inhibition of a single cytokine may not achieve satis...
In recent decades, biological agents such as tumor necrosis factor-α (TNF-α) inhibitors, have revolutionized the treatment of psoriasis. However, inhibition of a single cytokine may not achieve satisfactory therapeutic results. It is against this background that this research was undertaken to investigate the anti-psoriatic effect of a novel fusion protein (DTF) dual targeting TNF-α and interleukin-17 A (IL-17 A). Imiquimod (IMQ) was topically applied to the skin of mice to develop psoriasis-like skin and treated with etanercept or different doses of DTF. Results showed that DTF treatment (1 mg/kg, 3 mg/kg, 5 mg/kg) significantly attenuated IMQ-induced typical psoriasis-like inflammation, severity score, and epidermis thickening in a dose-dependent manner, and was again more efficient than etanercept (3 mg/kg) in alleviating all these parameters at the same dose. Furthermore, DTF was more potent than etanercept in suppressing the expression of inflammatory factors (IL-17 A, IL-6, IL-1β, IL-23, IL-22 and IL-12) in the serum, spleen and psoriasis-like skin compared with etanercept at the same dose. In addition, DTF was more efficient than etanercept in reducing the expression of keratins, decreasing the mRNA expression of Ly-6 G and Ly-6C, and enhancing the expression of filaggrin and caspase 14 in IMQ-induced psoriasis-like skin. We conclude that DTF alleviates IMQ-induced psoriasis by attenuating inflammatory cascades, reducing keratinocytes proliferation and improving epidermal barrier function through suppressing TNF-α and IL-17 A signal pathways. These data suggest that DTF has potential to be a novel therapeutic candidate for psoriasis.
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- Co-stimulation With TLR7 Agonist Imiquimod and Inactivated Influenza Virus Particles Promotes Mouse B Cell Activation, Differentiation, and Accelerated Antigen Specific Antibody Production. [Journal Article]
- FIFront Immunol 2018; 9:2370
- Current influenza vaccines have relatively low effectiveness, especially against antigenically drifted strains, the effectiveness is even lower in the elderly and immunosuppressed individuals. We hav...
Current influenza vaccines have relatively low effectiveness, especially against antigenically drifted strains, the effectiveness is even lower in the elderly and immunosuppressed individuals. We have previously shown in a randomized clinical trial that the topical application of a toll-like receptor 7 agonist, imiquimod, just before intradermal influenza vaccine could expedite and augment antibody response, including to antigenically-drifted strains. However, the mechanism of this vaccine and imiquimod combination approach is poorly understood. Here, we demonstrated that imiquimod alone directly activated purified mouse peritoneal B cells. When combined with inactivated H1N1/415742Md influenza virus particle (VP) as vaccine, co-stimulation of mouse peritoneal B cells in vitro induced stronger activation, proliferation, and production of virus-antigen specific IgM and IgG. Intraperitoneal injection of a combination of VP and imiquimod (VCI) was associated with an increased number of activated B cells with enhanced expression of CD86 in the mesenteric draining lymph nodes (mesLN) and the spleen at 18 h after injection. Three days after immunization with VCI, mouse spleen showed significantly more IgM and IgG secreting cells upon in vitro re-stimulation with inactivated virus, mouse sera were detected with viral neutralizing antibody. Transfer of these spleen B cells to naïve mice improved survival after lethal dose of H1N1/415742Md challenge. More importantly, the functional response of VCI-induced B cell activation was demonstrated by early challenge with a lethal dose of H1N1/415742Md influenza virus at 3 days after immunization. The spleen and mediastinal lymph nodes (mdLN) in mice immunized with VCI had germinal center formation, and significantly higher number of plasmablasts, plasma cells, and virus-antigen specific IgM and IgG secreting cells at only 3-4 days post virus challenge, compared with those of mice that have received imiquimod, inactivated virus alone or PBS. Serum virus-specific IgG2a, IgG2b, and IgG1 and bronchoalveolar lavage fluid (BALF) virus-specific IgA at 3 or 4 days post challenge were significantly higher in mice immunized with VCI, which had significantly reduced lung viral load and 100% survival. These findings suggested that imiquimod accelerates the vaccine-induced antibody production via inducing rapid differentiation of naïve B cells into antigen-specific antibody producing cells.