Ingolf Franke

Imiquimod, a Topical Immune Response Modifier, in the Treatment of Cutaneous Metastases of Malignant Melanoma

Background: Imiquimod 5% cream (Aldara®), a novel topical immune response modifier, has been approved for the topical treatment of anogenital HPV-induced warts. In addition, several studies have demonstrated antitumoral activity in solar keratoses, superficial basal cell carcinomas and Bowen’s disease. Aim: Given the convincing therapeutic results of imiquimod when used for treating selected types of epithelial skin cancer, we became interested to study imiquimod as an adjuvant for treating cutaneous metastases of malignant melanoma. Methods: Three patients with multiple, i.e. more than 15, cutaneous in-transit metastases of malignant melanoma in unilateral localization on the leg were treated topically with imiquimod 5% cream. Results: Twice daily application under occlusive conditions for a period of 21–28 weeks resulted in >90% regression of cutaneous metastases in 2 patients. The third patient showed marked response only when topical imiquimod was intermittently supplemented by intralesional interleukin (IL)-2 for 2 weeks. Unwanted side effects were mild in all patients. Conclusion: Overall, imiquimod as a single agent or in combination with intralesional IL-2 may be a promising immunomodulatory compound for the adjuvant topical treatment of patients with multiple cutaneous metastases of malignant melanoma.

Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease cases. A mutation in 1 of over 40 monogenic genes can be detected in approximately 30% of individuals with SRNS whose symptoms manifest before 25 years of age. However, in many patients, the genetic etiology remains unknown. Here, we have performed whole exome sequencing to identify recessive causes of SRNS. In 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase. All mutations resulted in reduced or absent SGPL1 protein and/or enzyme activity. Overexpression of cDNA representing SGPL1 mutations resulted in subcellular mislocalization of SGPL1. Furthermore, expression of WT human SGPL1 rescued growth of SGPL1-deficient dpl1&Dgr; yeast strains, whereas expression of disease-associated variants did not. Immunofluorescence revealed SGPL1 expression in mouse podocytes and mesangial cells. Knockdown of Sgpl1 in rat mesangial cells inhibited cell migration, which was partially rescued by VPC23109, an S1P receptor antagonist. In Drosophila, Sply mutants, which lack SGPL1, displayed a phenotype reminiscent of nephrotic syndrome in nephrocytes. WT Sply, but not the disease-associated variants, rescued this phenotype. Together, these results indicate that SGPL1 mutations cause a syndromic form of SRNS.

Successful treatment of angiosarcoma of the scalp by intralesional cytokine therapy and surface irradiation

An 88‐year‐old woman presented to us with angiosarcoma of the scalp that had developed over a 6‐month period following previous trauma. Despite explicit information concerning the extremely malignant potential of the tumour the patient refused any surgical intervention. However, she agreed to receive local, intralesional interferon α‐2b and interleukin‐2 therapy. After partial remission of the tumour, the intralesional cytokine injections were combined with surface radiotherapy. This combination therapy led to a 2‐year remission of both the tumour and sonographically suspicious cervical lymph nodes. Apart from the typical, moderate side‐effects of interferon α‐2b and interleukin‐2 the therapy was well tolerated. In conclusion, in our limited experience intralesional cytokine therapy – alone as well as in combination with surface irradiation – seems to be an alternative therapeutic option for patients who is not a candidate for surgery.

Giant genital variant of folliculosebaceous cystic hamartoma: successful management by CO2 laser and acitretin therapy

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Cutis verticis gyrata secondary to acne scleroticans capitis

We report the case of a 35‐year‐old patient with secondary cutis verticis gyrata (CVG) that histologically presented as acne scleroticans capitis. Clinically, the diagnosis of acne conglobata was made. The CVG developed under systemic corticosteroid treatment of an ulcerative colitis. Corticosteroids were discontinued and a therapeutic attempt was made with isotretinoin. Although under this treatment the conglobate acne healed, the CVG remained unaltered. Dermatosurgical intervention by a scalp reduction plasty finally resulted in a marked improvement of symptoms and acceptable cosmetic outcome.

Cowpox infection transmitted from a domestic cat

A 21‐year‐old immunocompetent woman developed a cowpox infec‐tion,while working as a veterinarians assistant in a rural area.She had never received vaccinia immunization and came in contact with a fatally‐infected house cat. Under symptomatic treatment, the infection remained localized to one cheek and cleared over 3 weeks with substantial dermal‐subcutaneous tissue destruction. Orthopoxvirus detection by PCR is a modern diagnostic standard, in addition to identification by negative‐contrast electron microscopy. A promising therapeutic option is cidofovir, but this virostatic drug is not yet approved for the treatment of cowpox.

High incidence of naevi-associated BRAF wild-type melanoma and dysplastic naevi under treatment with the class I BRAF inhibitor vemurafenib.

There is growing evidence that not only malign keratinocytic but also melanocytic tumours can arise during treatment with vemurafenib. During an on-going early access trial, 13 patients harbouring a BRAF-V600E mutation received vemurafenib (Zelboraf®) 960 mg twice daily to test the safety, tolerability, efficacy and response rate for advanced melanoma. Clinically or dermatoscopically suspicious cutaneous tumours under treatment with vemurafenib were excised. The BRAF-V600E status of confirmed new primary melanoma and dysplastic naevi was tested using a genetic mutation assay and immunohistochemistry. Four of the 13 patients (31%) developed 4 new naevi-associated malignant melanomas and 5 dysplastic naevi between 6 weeks and 6 months after the start of treatment. With the exception of one in situ melanoma, all tumours were BRAF wild-type. Immunohistochemistry revealed increased expression of ERK, pERK and active Rac1-GTP in the naevi-associated melanoma and dysplastic naevi. Careful and continuous skin examination, including dermoscopy, appears to be required during treatment with vemurafenib.

Successful combination therapy of a locally advanced squamous cell carcinoma of the skin with cetuximab and γ-irradiation

Squamous cell carcinoma (SCC) as predominantly UV-induced skin cancer occurs particularly in advanced age. Even though rare on the whole with about 1 % the risk of metastasis increases significantly in dependence on tumor thickness, the degree of differentiation and histological criteria, but also on the horizontal extension of the tumor [1]. Especially in elderly patients cutaneous SCC represents a therapeutic challenge, as due to increased comorbidities larger surgical procedures are associated with considerable risk [2]. An 85-year-old woman presented in our clinic with a 10 12 cm large ulcerated tumor on the Successful combination therapy of a locally advanced squamous cell carcinoma of the skin with cetuximab and -irradiation

Erfolgreiche symptomatische Tazarotentherapie der juvenilen Acanthosis nigricans vom familiär adipositasassoziierten Typ bei Insulinresistenz

ZusammenfassungBei einem 11-jährigen Jungen, der seit dem Kleinkindalter an einer Adipositas permagna litt, war es vor 2 Jahren erstmalig zu braunschwarzen Hyperpigmentierungen und Hyperkeratosen zunächst an Hals und Axillen gekommen. Bei nur geringem Mitbefall der Inguinalregion ließ sich klinisch und histologisch die Diagnose einer Acanthosis nigricans stellen. Aufgrund endokrinologischer Untersuchungen und des Vorkommens gleichartiger Hauterscheinungen bei der ebenfalls sehr adipösen Mutter des Patienten wurde die Erkrankung als eine familiär adipositasassoziierte, mit Insulinresistenz einhergehende Form der Acanthosis nigricans eingeordnet. Im Halbseitenvergleich konnte die lokale Applikation von Tazaroten 0,05% vs. Harnstoff 10% jeweils 1-mal täglich überprüft werden. Es zeigte sich bereits nach 3 Wochen ein deutliches Ansprechen auf der mit Tazaroten behandelten Körperseite, was sich auch histologisch belegen ließ. Unter dem harnstoffhaltigen Externum wurde hingegen keine Besserung des Befundes erreicht. Daraufhin wurde beidseitig mit Tazaroten 0,05% therapiert, was zur deutlichen Rückbildung auch der Restherde führte. Der Befund ist bis zum heutigen Tag bei kontinuierlicher Fortführung der topischen Retinoidtherapie über einen Gesamtzeitraum von 18 Monaten mit vornehmlicher Intervallanwendung (3-mal pro Woche) sehr zufrieden stellend.AbstractAn 11-year-old boy suffering from morbid obesity since infancy developed at age 9 a progressive brown-black hyperpigmentated and hyperkeratotic eruption in the neck and axillary region with minor involvement of both groins. Based on this clinical picture, and confirmed by histopathology, we diagnosed acanthosis nigricans. Following a thorough endocrinological examination and because the patients obese mother showed similar skin lesions, the disease was subclassified as a familial obesity-associated type of acanthosis nigricans associated with insulin resistance. In a right-left-comparison the affected skin of one body side was treated with tazarotene 0.05% versus urea 10%, once daily each. A great benefit for the tazarotene-treated over the opposite side could already be seen after three weeks which was also verified by dermatohistopathology. Three months after topical tazarotene treatment had been extended to both sides, the residual lesions were significantly improved. The highly satisfying, good result has been maintained up to now by a continuous topical retinoid treatment over 18 months, usually with an interval application regimen, i.e., 3× per week.

Topical treatment of extramammary Paget's disease

Dr. M. Arensmeier, Klinik für Hautkrankheiten der Medizinischen Akademie Magdeburg, Leipziger Straße 44, D-39120 Magdeburg Zusammenfassung. Es wird über einen 84jährigen Mann mit ausgedehntem extramammären M. Paget im Genitalbereich berichtet. Der reduzierte Allgemeinzustand des Patienten und die großflächige Ausbreitung der Hautveränderungen ließen als effektivste Therapievariante nur die topische 5-Fluorouracil-Applikation zur Anwendung kommen.Abstract. A case of locally extensive perigenital Pagets disease in an 84-year-old man is presented. Topical application of 5-fluorouracil emerged as the safest and most effective treatment because of the patients poor general condition and the extensive involvement of the pubic and genital skin.