[Side effects of novel cancer immunotherapies]. / Nebenwirkungen neuer onkologischer Immuntherapien.

Systemic treatment with immune checkpoint inhibitors (ICI) has revolutionized the treatment of hematological and oncological diseases in recent years. The mechanism of action hinges on enhancing the natural ability of the immune system to eliminate malignant cells. The most important substances in this arena include inhibitors of PD­1, PD-L1 and CTLA­4. As a consequence, the spectrum of treatment-associated adverse reactions is shifting away from classical cytotoxic effects (e.g. pancytopenia and polyneuropathy) towards novel entities of immune-mediated complex diseases. These so-called immune-related adverse events (irAEs) can involve any organ system and mimic known classical autoimmune conditions. Timely recognition of irAEs is the key for rapid initiation of a suitable treatment and is especially challenging in the clinical routine as it requires an intensive interdisciplinary management. Nephrologists are particularly confronted with this kind of problem due to the highly interdisciplinary nature of their work. This article summarizes the broad spectrum of currently known renal and more frequently occuring non-renal forms of irAEs and aims to prime the reader on diagnostic and therapeutic options.

The alpha-herpesviridae in dermatology : Varicella zoster virus.

The second part of this publication deals with varicella zoster virus (VZV) and presents an overview of new, rare, and atypical clinical manifestations, including photolocalized varicella, hemorrhagic bullae during varicella, the implication of VZV in immunoglobulin A vasculitis, VZV-related alopecia, ulcerative varicella skin lesions, childhood herpes zoster (HZ), prolonged prodromal pains, recurrent HZ, VZV implication in burning mouth syndrome, verruciform VZV lesions, the significance of satellite lesions during HZ, and late HZ complications, either neurological or internal. Furthermore, certain associations between the occurrence of HZ and subsequent internal pathologies, as well as risk factors for HZ and new developments in vaccination against HZ will be addressed.

The alpha-herpesviridae in dermatology : Herpes simplex virus types I and II.

This review on herpes simplex virus type I and type II (HSV­I, HSV­II) summarizes recent developments in clinical manifestations and treatment interventions for primary and recurrent orolabial and genital herpes, as well as those regarding vaccination issues. Among the clinical presentations, the relationship between pyogenic granuloma and chronic HSV­I infection; HSV-related folliculitis; verrucous HSV­I and HSV­II lesions; the role of recurrent HSV­I infection in burning mouth syndrome; HSV­I and HSV­II infection of the periareolar area; zosteriform HSV; the "knife-cut sign"; and the preferential colonization and infection of preexisting dermatoses by HSV­I or HSV­II are discussed. The usual antiviral treatment regimens for primary and recurrent orolabial and genital herpes are compared to short-term and one-day treatment options. New anti-HSV­I and anti-HSV­II agents include amenavir, pritelivir, brincidofovir, valomaciclovir, and FV-100. Therapeutic or preventive vaccination against HSV­I and HSV­II infections still remains a highly desirable treatment aim, which, unfortunately, has no clinically relevant applications to date.

[The alpha-herpesviridae in dermatology : Herpes simplex virus types I and II. German version]. / Alpha-Herpesviridae in der Dermatologie : Herpes-simplex-Virus Typ I und II.

This review on herpes simplex virus type I and type II (HSV-I, HSV-II) summarizes recent developments in clinical manifestations and treatment interventions for primary and recurrent orolabial and genital herpes, as well as those regarding vaccination issues. Among the clinical presentations, the relationship between pyogenic granuloma and chronic HSV-I infection; HSV-related folliculitis; verrucous HSV-I and HSV-II lesions; the role of recurrent HSV-I infection in burning mouth syndrome; HSV-I and HSV-II infection of the periareolar area; zosteriform HSV; the "knife-cut sign"; and the preferential colonization and infection of preexisting dermatoses by HSV-I or HSV-II are discussed. The usual antiviral treatment regimens for primary and recurrent orolabial and genital herpes are compared to short-term and one-day treatment options. New anti-HSV-I and anti-HSV-II agents include amenavir, pritelivir, brincidofovir, valomaciclovir, and FV-100. Therapeutic or preventive vaccination against HSV-I and HSV-II infections still remains a highly desirable treatment aim, which, unfortunately, has no clinically relevant applications to date.

[The alpha-herpesviridae in dermatology : Varicella zoster virus. German version]. / Alpha-Herpesviridae in der Dermatologie : Varicella-Zoster-Virus.

The second part of this publication deals with varicella zoster virus (VZV) and presents an overview of new, rare, and atypical clinical manifestations, including photolocalized varicella, hemorrhagic bullae during varicella, the implication of VZV in immunoglobulin A vasculitis, VZV-related alopecia, ulcerative varicella skin lesions, childhood herpes zoster (HZ), prolonged prodromal pains, recurrent HZ, VZV implication in burning mouth syndrome, verruciform VZV lesions, the significance of satellite lesions during HZ, and late HZ complications, either neurological or internal. Furthermore, certain associations between the occurrence of HZ and subsequent internal pathologies, as well as risk factors for HZ and new developments in vaccination against HZ will be addressed.

[Buschke-Lowenstein tumors]. / Buschke-Löwenstein-Tumor.

BACKGROUND: A giant condyloma acuminatum which shows destructive growth but lacking invasion is designated as a Buschke-Lowenstein tumor (BLT). OBJECTIVES: Classification of the BLT and therapeutic guidelines are provided. MATERIALS AND METHODS: A MEDLINE literature search from 2006-2016 was performed. RESULTS: Induction through low-risk mucosotropic human papillomavirus (HPV) infection separates BLT from verrucous carcinoma. In the last 10 years, slightly more than 100 new cases have been described. Invasion as a true sign of malignancy was described in 12% of cases. HIV infection was observed in 14%. As invasion often occurs only focally and may only be detected after complete resection, BLT must be treated and considered as a low grade in situ epithelial cancer that evolves from condylomata acuminata. Diagnosis is confirmed by HPV detection and typical histology. CT scans are recommended to rule out deeper invasion. Organ preservation surgery remains the recommended therapy. CONCLUSIONS: Buschke-Lowenstein tumors represent low grade epithelial in situ carcinomas which evolved from condylomata acuminata. Focal invasion is frequent but metastases occur only rarely. Organ preservation surgery is recommended.

Immunotherapy with imiquimod and interferon alfa for metastasized Merkel cell carcinoma.

Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival. We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1-2×10(6) IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 µg weekly, which was then increased to 50 µg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy.

[Extensive fibromata pendulantia. Hydrosurgery as a therapy option using the Versajet technique]. / Flächenhafte Fibromata pendulantia. Hydrochirurgie als Therapieoption mittels Versajet-Technik.

Fibromata pendulantia often appear as small filiform skin tags with a narrow pedicle in the neck, axilla and groin areas. Hitherto, extensive fibromata pendulantia were resected either surgically (curette, scissors, scalpel) or by laser. The present case study of an adipose patient with disseminated fibromata pendulantia in the axillary region in the setting of pseudoacanthosis nigricans introduces the Versajet hydrosurgery technique as an alternative method. It is able to remove tissue and rinse the wound simultaneously by means of a high-pressure water jet.

[Cutaneous cytotoxic T-cell lymphoma]. / Kutanes zytotoxisches T-Zell-Lymphom.

Cutaneous cytotoxic T-cell lymphoma is a rare variant of cutaneous T-cell lymphoma, which shows immunoreactivity for CD56+. We report on an 83-year old woman with numerous skin infiltrates and nodules mainly on her face and trunk. Histopathologic criteria lead to the diagnosis of cutaneous cytotoxic T-cell lymphoma. Bexarotene was not tolerated because of cardiac insufficiency, but treatment with methotrexate (7.5 mg once weekly) led to prompt regression of all lesions.

[Clinical algorithm of cutaneous extragenital wart treatment]. / Klinischer Algorithmus zur Therapie von kutanen, extragenitalen HPV-induzierten Warzen.

Various human papillomavirus of the genera α-, ß-, γ-, µ- and η-papillomavirus induce type-specific extragenital warts. Plantar, common and plane warts are the most common types. The closely related Alpha-papillomaviruses HPV 2, 27 and 57 are responsible for the majority of therapy-resistant common warts. A wide armamentarium of surgical, physical, chemical or drug therapies is available but no modality cures all patients. In order to avoid overtreatment it is mandatory to differentiate between indolent warts which will spontaneously resolve, warts which cause acute discomfort and warts without any tendency to heal spontaneously. HPV type, wart type, localization, size, disease duration as well as age and immune status are parameters influencing self-healing and should be considered when choosing the appropriate wart therapy.

[Pagetoid reticulosis in a patient with mycosis fungoides. Successful therapy with localized electron beam irradiation]. / Pagetoide Retikulose bei einem Patienten mit Mycosis fungoides. Erfolgreiche Therapie mit lokalisierter Elektronenbestrahlung.

Pagetoid reticulosis is a mycosis fungoides subtype. It is characterized by a prominent epidermotropism, localized lesions, slow progression and benign prognosis. We report on a 67-year-old patient with a history of classic mycosis fungoides, who developed pagetoid reticulosis on the right heel. Local electron beam therapy induced a complete remission, with no recurrence over three months of follow-up.

[Primary cutaneous CD30+ ALK(-) anaplastic large cell T-cell lymphoma]. / CD30(+) ALK(-) anaplastisch grosszelliges primär kutanes T-Zell-Lymphom.

Anaplastic large cell lymphomas (ALCL) are characterized by large, pleomorphic cells with a strong expression of cytokine receptor CD 30. We present a 71-year-old patient with several nodules on the right temple extending to his right ear. Based on clinical, histological and immunophenotypic criteria, the diagnosis of a primary cutaneous CD30(+) ALK(-) anaplastic large cell lymphoma was made. After local excision and adjuvant radiotherapy no relapse occurred during a follow-up period of three months.

[Eccrine adenocarcinoma in a patient with familial breast carcinoma]. / Ekkrines Adenokarzinom bei einer Patientin mit familiärem Mammakarzinom.

A 67-year-old patient developed a subcutaneous, non-tender nodule in her left groin over a period of about seven years. The patient underwent surgery and 4 procedures were required to obtain complete excision. The histopathologic findings showed eccrine adenocarcinoma, a member of the heterogeneous group of sweat gland tumors which occur primarily in adults with a peak of 50-60 years of age. Sweat gland carcinomas are extremely rare neoplasms of the skin and exhibit a slow growth rate with a rather high local recurrence rate. The tumor has a disposition to metastasize and shows a poor response rate to adjuvant therapy regimens. Therefore wide, deep surgical excision with an excision margin of 2-3 cm is the treatment of choice. Nevertheless there are some case reports on successful therapy of a metastasized sweat gland carcinoma with 5-fluorouracil and tamoxifen. Here further studies are needed to achieve a better survival rate for patients with metastatic disease.

Molecular analysis of the effect of topical imiquimod treatment of HPV 2/27/57-induced common warts.

Imiquimod is effective in the treatment of genital warts and clinical studies suggest activity against common warts as well. We have analyzed the effect of topical imiquimod on gene expression and virus load in human papilloma virus (HPV) 2/27/57-induced common warts. mRNA was extracted from keratinocyte culture, from normal skin, from three untreated common warts and from three common warts treated topically with 5% imiquimod cream twice daily. Differential gene expression was demonstrated by RT-PCR and by cDNA microarray hybridization. We further analyzed viral DNA content in scales from three superficially pared imiquimod-treated warts by real-time PCR. Comparison of normal skin with wart tissue revealed that HPV 2/27/57 infection led to an induction of IL-6, IL-10 and interferon-gamma inducible protein (IP10) and to an up-regulation of TGF-beta. We could further detect expression of PCTAIRE-3, WNT2B, frizzled-3, notch-2, notch-4 and BRCA2 in normal skin and common warts. Analysis of imiquimod-treated warts demonstrated that imiquimod enhanced IL-6 expression and induced IL-8, GM-CSF, MRP-8 and MRP-14. It could also be shown that imiquimod led to an infiltration of wart tissue with macrophages and to a strong decrease of viral copy number in warts within 3 months of treatment. Our data thus provide molecular proof of principle for imiquimod treatment of cutaneous common warts.