[Initially undetected de novo psoriasis triggered by nivolumab for metastatic base of the tongue carcinoma]. / Initial nicht erkannte De-novo-Psoriasis getriggert durch Nivolumab bei metastasiertem Zungengrundkarzinom.

Nivolumab is a monoclonal antibody that binds to the PD-1 receptor on T cells and inhibits the interaction with the PD-L1 and PD-L2 ligands on cancer cells. Thus, nivolumab has immunostimulatory properties. The known side effects of this therapy include fatigue, skin rash, dysfunction of the thyroid gland and colitis, which are explained by the immunoregulatory mechanisms of the drug. Here we report on the case of a 58-year-old man with metastatic base of tongue carcinoma who developed de novo psoriasis triggered by nivolumab. The patient was treated for months with the diagnosis of a generalized mycosis. This case highlights the importance of vigilance for unexpected cutaneous side effects during immune stimulating therapy with checkpoint inhibitors.

[Partial response of solar urticaria to omalizumab therapy]. / Partielles Ansprechen einer Lichturtikaria auf Omalizumab.

The treatment of solar urticaria is regarded as difficult. In some cases good responses to the anti-IgE antibody omalizumab (Xolair®), approved for treatment of chronic spontaneous urticaria, have been reported. We report on a 50-year-old Caucasian woman who for the last 5 years has developed localized itching and stinging erythemas following exposure to sunlight accompanied sometimes by anaphylactic reactions. Oral antihistamines in three- to four-fold doses and a topical sun screen had been only partially effective in long-term use. Positive immediate-type reactions with whealing appeared in phototesting with low doses of UVB and UVA. Three weeks after s. c. injection of 300 mg omalizumab, the minimal urticarial dose (MUD) for UVB was increased at least 20-fold (from <0.001 to 0.02 J/cm2) and for UVA four-fold (from 0.1 to 0.4 J/cm2) and the patient reported no itching at the test area. On the other hand, MUD for UVA1 remained unchanged (5.0 J/cm2). The weekly urticarial activity score (UAS7) was reduced from 30 points before omalizumab administration to 14 points in weeks two and three. Overall, a partial response of solar urticaria to omalizumab therapy could be observed in the present case.

[Phlebology in German departments of dermatology. An analysis on behalf of the German Society of Phlebology]. / Phlebologie an deutschen Hautkliniken. Eine Bestandsaufnahme im Auftrag der Deutschen Gesellschaft für Phlebologie.

BACKGROUND: Phlebologic diseases have become extremely common and have major socio-economic impact. However, the percentage of dermatologists working in phlebology appears to be decreasing according to the data of the German Society of Phlebology (DGP). METHODS: To investigate the reasons for this development, we--on behalf of the DGP--sent a questionnaire to 120 German Departments of Dermatology in autumn 2012. RESULTS: In 76 returned questionnaires, the number of physicians with additional fellowship training in phlebology averaged 1.5; the average number of those who fulfill the criteria for training fellows in phlebology was 0.9. In 71.1 % of the departments there was a phlebologist. A special phlebologic outpatient clinic existed in 73.7 % of the departments. Sonography with Doppler (89.5 %) and duplex (86.8 %) was used as the most frequent diagnostic tool. For therapy, compression (94.7 %), sclerotherapy (liquid 78.9 %, foam 63.2 %, catheter 18.4 %), endoluminal thermic procedures (radio wave 28.9 %, laser 17.1 %) and surgery (especially crossectomy and stripping 67.1 %, phlebectomy of tributaries 75 %) were used. The average number of treatments was very heterogenous in the different departments. CONCLUSIONS: Phlebology definitely plays an important role in dermatology. Most departments fulfill the formal criteria for the license to conduct advanced training in phlebology. A wide spectrum of phlebological diagnostic and therapeutic procedures is available.

[Long term treatment of psoriasis with TNF-alpha antagonists. Occurrence of malignant melanoma]. / Prolongierte Psoriasistherapie mit TNF-alpha-Antagonisten. Entwicklung des malignen Melanoms.

A 51-year-old white man developed de novo a cutaneous malignant melanoma (Stage Ia) after a 30-month treatment period with TNF-alpha-antagonists, consecutively using infliximab, adalimumab and etanercept because of a recalcitrant moderate to severe plaque psoriasis. The patient previously had been treated fumarates for 4 years, cyclosporine A for 2 months and methotrexate for 5 weeks. He also received cycles of cream PUVA and UVB before and then between systemic medications. A possible causal connection between development of melanoma and immunosuppressive treatment is discussed in the light of recent literature. The termination of TNF-alpha-antagonist therapy following development of melanoma is recommended.

Fotemustine and interferon alpha2b in metastatic malignant melanoma.

The efficacy of treatment with fotemustine and interferon (IFN) alpha was evaluated in metastatic melanoma. A group of 50 patients with metastatic malignant melanoma were treated with a combination of IFNalpha2b and the nitrosourea fotemustine. The patients received 10 MU IFN three times weekly for 3 weeks and fotemustine at a dose of 100 mg/m2 on days 8, 15 and 22. After a 5-week rest period, patients with stabilized or responding disease received a maintenance therapy consisting of 10 MU IFN three times a week for 1 week followed by administration of fotemustine (100 mg/m2) on day 8. This cycle was repeated every 4 weeks until progression occurred. If there was complete remission (CR), treatment was stopped after an additional three cycles. Toxicity and clinical response were scored according to WHO criteria. Objective response was seen in 14 patients (28%; 95% confidence interval 15.6%-40.4%) with four CR and ten partial responses (PR). The median duration of CR was 73 weeks, that of PR 26 weeks. Toxicity was acceptable, enabling treatment on an outpatient basis. The combination of fotemustine with IFNalpha is effective and well tolerated, but there is no evident advantage over fotemustine monotherapy in the treatment of metastatic melanoma.

Detection of HHV-8 DNA in a German patient with classical Kaposi's sarcoma may allow an estimation of the incubation period.

DNA of HHV-8 (Kaposi's sarcoma-associated Herpes virus [KSHV]) was detected in a biopsy of a Kaposi's sarcoma in an elderly male patient from Saxony (East Germany). The diagnosis of classical Kaposi's sarcoma was first made in 1986. During World War II, the patient had been on active service on the Greek Islands of Crete and Rhodes only, he did not travel outside East Germany after the war. It is assumed that the patient was infected during his stay on the islands of Crete or Rhodes, where classical Kaposi's sarcoma is endemic. If so, the incubation period of classical Kaposi's sarcoma could be as long as 40 years.

Arabinose furanosyl thymidine: uptake, phosphorylation and incorporation into DNA of mammalian cells.

The naturally occurring nucleoside analogue arabinosyl thymidine is known as an anti-herpes and anti-cancer agent. The biologically active form is arabinosyl thymidine triphosphate (Ara-TTP), which inhibits cellular and viral DNA-polymerases and thus interferes with DNA replication. Using two murine erythroleukemia cell lines, Friend cell clone F4-6 and F4-12N, the latter being thymidine kinase deficient (TK-) cells transformed to a TK+ phenotype with the HSV TK gene, we have determined 1) the role of cellular and herpes simplex virus thymidine kinase (HSV TK) in the uptake of Ara-T into the cells; 2) the subsequent phosphorylation of intracellular Ara-T to Ara-TMP, Ara-TDP and Ara-TTP; 3) the incorporation of Ara-TTP into the DNA. Incorporation into DNA was studied under different conditions, including selective inhibition of the different cellular DNA polymerases by aphidicolin (that inhibits polymerases alpha and delta) and dideoxythymidine (that preferentially inhibits polymerases beta and gamma). The uptake of Ara-T into the methanol soluble pool of the cells depends upon its phosphorylation to Ara-TMP, which is more efficiently performed by the HSV TK than by the cellular TK, thus explaining the sensitivity of HSV infected cells to Ara-T. However, using increasing concentrations of Ara-T, we have shown that phosphorylation also occurs in normal control cells due to the cellular thymidine kinase. More than 90% of Ara-T is phosphorylated in the cell, and more than 60% of total Ara-T(MP, DP, TP) exists in the triphosphate form.(ABSTRACT TRUNCATED AT 250 WORDS)

Photoallergic contact dermatitis from topical diclofenac in Solaraze gel.

Solaraze gel (Shire Deutschland GmbH & Co. KG, Cologne, Germany) containing 3% diclofenac has been licensed in 2001 as a topical treatment for actinic keratoses. It is commonly used in dermatological practice. Undesirable effects are believed to be rare but include pruritus, paresthesia and application-site reactions (dry skin, rash, erythema, contact dermatitis and vesicobullous eruptions). Recently, a few cases of contact dermatitis due to three different allergens including diclofenac have been reported (1,2).

[Granuloma annulare]. / Granuloma anulare.

Granuloma annulare is a benign self-limiting disease of unknown origin, characterized by dermal papules tending to form annular shapes. It belongs to the granulomatous inflammatory skin diseases characterized by histomorphologically detectable granulomas. In addition to localized variants, generalized or disseminated variants also exist. The disease is often asymptomatic and does not require therapy in every case. Established therapies for localized forms of granuloma annulare are glucocorticosteroids, cream PUVA and cryosurgery. Antimalarials, antileprotics, retinoids, fumarates, UVA1 phototherapy and photochemotherapy are of value in disseminated cases. Recent case reports demonstrate the successful treatment of granuloma annulare with topical calcineurin antagonists or imiquimod and with the systemic administration of biologicals.

Clinical experience with topical calcitriol (1,25-dihydroxyvitamin D3) in psoriasis.

The use of vitamin D analogues for the treatment of chronic plaque psoriasis is well documented. Of importance now is their comparability and compatibility with other established treatments for psoriasis. This paper reviews five studies with calcitriol 3 microg g(-1) ointment (Silkis ointment, Galderma Laboratories). Calcitriol applied twice daily was found to be as effective as short-contact dithranol in terms of global improvement and PASI scores. However, patients favoured calcitriol over dithranol when both quality of life and treatment acceptability were assessed. Two studies provide evidence of the benefit of combining calcitriol with other antipsoriatic therapies. Combination with ultraviolet (UV) B phototherapy proved as effective as UVB alone over an 8-week period; however, the combination had a radiation dose-sparing effect, thus reducing the risk of adverse events. Likewise, calcitriol combined with betamethasone valerate (each applied separately, once daily) was as efficacious as twice-daily betamethasone, thereby achieving a corticosteroid-sparing effect. Finally, two studies confirm that calcitriol 3 microg g(-1) ointment can be used safely in patients with psoriasis of the head and confirm the high level of clinical efficacy achieved with this compound.

Acute febrile neutrophilic dermatosis (Sweet's syndrome) caused by minocycline.

Sweet's syndrome (acute febrile neutrophilic dermatosis) occurred in a 29-year-old woman with acne. Although Sweet's syndrome initially seemed to be triggered by an acute acne flare, minocycline could later be identified as the causal agent. Because this could be confirmed in an oral provocation test, this seems to be the first case of a true connection between Sweet's syndrome and its induction by a drug, namely minocycline.

Failure of etretinate in epidermodysplasia verruciformis.

In a patient suffering from benign lesions of epidermodysplasia verruciformis due to human papillomavirus type 5 little clinical improvement could be observed after 6 months of oral etretinate. The drug was given 75 mg/day for 1 month before dosage was reduced to 50 mg/day. Control biopsy after 3 months of treatment still revealed large quantities of virions and typical cytopathic effects in light and electron microscopic examination.

[Human papillomaviruses. Associated diseases of the breast]. / Humane Papillomviren. Assoziierte Erkrankungen der Mamille.

In human papillomavirus-associated acanthomas of the mamilla it was possible to detect DNA of HPV types 41, 6ma and a type related to type 16. The biology of HPV infection resembles that of anogenital lesions. Some of the HPV types found are rare or are thought possibly to have oncogenic potency. Possible evidence for link between HPV and carcinomas of the breast is discussed.

Successful treatment of primary progressive follicular mucinosis with interferons.

Follicular mucinosis is a primary idiopathic disease or a secondary, lymphoma-associated dermatosis. An effective standard therapy for the benign group is unknown. We describe a patient with primary benign disseminated progressive follicular mucinosis who was successfully treated with recombinant interferon alfa-2b and interferon-gamma. Interferons might act by down-regulation of activated inflammatory cells and/or by induction of enhanced elimination of extracellular mucin via increasing phagocytosis by macrophages.

[Sarcoidal allergic contact dermatitis due to palladium following ear piercing]. / Sarkoidale allergische Kontaktdermatitis auf Palladium nach Ohrpiercing.

Granulomatous tissue reactions due to jewelry made of gold, silver, nickel and palladium are rare but nevertheless have been known for a long time. A female patient developed nodular infiltrates after having been pierced with ear stickers containing palladium. A contact allergic reaction could be demonstrated as the underlying cause by inducing similar histological changes following patch testing with palladium.

[Herpes gestationis--oral corticosteroids cannot be avoided]. / Herpes gestationis--an internen Kortikosteroiden führt kein Weg vorbei.

An immunpathologically proven gestational herpes case is presented. Herpes gestationis may begin at any stage of pregnancy but it is usually seen during the second trimester. As a rule oral prednisolone therapy is required. We report on a patient who initially insisted on local therapy only. However this local treatment with steroids proved to be insufficient.

[Cutaneous reactions in Crohn disease. Vasculitis in various skin segments]. / Kutane Reaktionen bei Morbus Crohn. Vaskulitiden verschiedener Etagen des Hautorgans.

Two young female patients presented with recurrent erythema and Henoch-Schönlein purpura respectively. In both cases clinical, histological and radiological showed relatively mild, but previously undiagnosed Crohn's disease as a trigger. We describe the treatment of the underlying disease and the symptomatic treatment of skin lesions. Categories of specific and unspecific skin lesions associated with Crohn's disease, as described in the literature, are presented. Vasculitic changes of the deep versus the superficial dermal plexus are discussed.