Gerhard Kolde

CD1a and CD1c cell sorting yields a homogeneous population of immature human Langerhans cells.

There is increasing evidence that ex vivo generated Langerhans cells (LCs) cannot fully substitute for their physiological counterparts in normal epidermis when studying the immunobiology of this prototype of a tissue-residing immature dendritic cell (DC). Here, we present CD1-based magnetic-activated cell-sorting (MACS) protocols for the effective isolation of human epidermal LCs. CD1c selection yielded a homogeneous population of pure and viable HLA-DR(+)/CD1a(+) DCs, with the ultrastructural features, surface antigen expression and cytokine profile, characteristic of epidermis-resident immature LCs. The immature state and functional integrity were established by allogeneic mixed lymphocyte reactions showing a weak stimulatory capacity of freshly isolated cells and upregulation upon stimulation. Characterizing the cells in more detail, we could demonstrate for the first time that normal human LCs express CXCR4, CD40 ligand (CD40L), and Fas and Fas ligand (FasL). The observed constitutive transcription of TGF-beta suggests that the viability and immature state of epidermal LCs are maintained not only by the TGF-beta production from the microenvironment, but also in an autocrine or paracrine manner. LPS and IFN-omega stimulated the expression of the inflammatory cytokines TNF-alpha and IL-1beta, and there was secretion of IL-12p70 after CD40 ligation. Remarkably, the CD1-sorted LCs showed no loss of their Birbeck granules and CD1a expression upon culturing and no spontaneous phenotypic and functional maturation into potent antigen-presenting cells (APCs). We conclude that human epidermal LCs obtained by the CD1c cell-sorting protocol are optimal candidates with which to elucidate the properties and capabilities of immature cells and to develop immunotherapeutic vaccines.

The pattern of the mononuclear infiltrate as a prognostic parameter in flat superficial spreading melanomas

SummaryThe mononuclear cell infiltrate of 90 superficial spreading melanomas (SSM) op ≦ 1.5 mm thickness was analyzed at different locations around and within the tumors. All patients had been followed for at least 5 years, and 20 (22%) had developed metastases. A correlation between the overall inflammatory response in the histologic sections and the prognosis was not observed, nor could a significant distinction be made between metastasizing and nonmetastasizing melanomas when the mononuclear cell infiltrate was analyzed at different locations. A significant clustering of metastasizing tumors was, however, observed in the subgroup with a relatively strong infiltrate within the tumor compared with the overall infiltrate. From this observation, a semiquantitative description of the pattern of the infiltrate was established. It provides an additional parameter for prognostication in flat SSMs and it raises new questions about the role of the local host-tumor interaction.

The loss of desmosomes after retinoic acid treatment results in an apparent inhibition of HaCaT keratinocyte differentiation

Abstract Epithelial tissue cohesion is based on various types of intercellular adhering junctions of which the desmosomes are particularly abundant in stratified epithelia. The desmogleins (dsg) and desmocollins are their transmembrane components. One or more of the three isoforms of these desmosomal cadherins are coexpressed and specific subtypes prevail at different stages of epidermal differentiation. In HaCaT keratinocytes, desmosomal cadherin expression increased with ongoing differentiation, apart from dsg2. Continuous treatment with retinoic acid (RA) inhibits the differentiation of HaCaT keratinocyte cultures. RA strongly increased the shedding of cells into the culture medium where they quickly underwent cellular death. Electron microscopy showed a marked reduction of desmosomes with nearly complete absence of their structural components, suggesting that RA inhibits their synthesis. RA indeed downregulated the transcript levels of all HaCaT desmosomal cadherins, except dsg2. Immunostaining revealed that desmosomal protein contents corresponded to alterations in transcription rates. Our findings indicate that the RA-induced inhibition of differentiation of keratinocyte cultures results from removal of cells committed to differentiation. In vivo, less adhering but still differentiating cells cannot be removed as easily as they can be in a culture system. The consequence is a sticky and fragile skin.

Erfolgreiche Behandlung des chronisch diskoiden Lupus erythematodes mittels Argon-Laser

ZusammenfassungWir berichten über eine Patientin mit chronisch diskoidem Lupus erythematodes (CDLE), bei der wir erstmals den Argon-Laser zur Lokaltherapie einsetzten. Die Patientin litt unter langjährigen Hautveränderungen, die sich nicht oder nur geringfügig durch etablierte Behandlungsstrategien beeinflussen ließen. Nach Anwendung des Argon-Lasers kam es im Bereich der therapierten Läsionen zu einer vollständigen und dauerhaften Abheilung. Histologische und immunhistologische Befunde sprechen dafür, daß gefäßmediierte Effekte des Argon-Lasers für die beobachtete Wirkung bei LE-bedingten diskoiden Läsionen von Bedeutung sind. Im Rahmen dieser Fallbeschreibungen wird erstmals die Wirksamkeit des Argon-Lasers bei der Behandlung von therapieresistenten diskoiden Hautläsionen beim Lupus erythematodes gezeigt.SummaryWe report on a patient with chronic discoid lupus erythematosus who was treated with argon-laser. The patient suffered from long-standing lesions and had been pretreated with various drugs, with no or slight improvement. After a few argon-laser applications, the treated skin lesions improved dramatically while the untreated lesional skin showed continuous disease activity. Histological and immunohistological investigations of biopsies from treated and untreated lesional skin suggest that endothelial mechanisms play a role in the generation and maintenance of discoid lesions in lupus erythematosus. This is the first reported case of successful treatment of chronic discoid skin lesions of a lupus erythematosus patient with argon-laser.

Oral lichen planus: diagnostic immunofluorescence testing on routine histological material

SIR, A 40-year-old man reported the slow progressive appearance, during the previous 6 years, of pruritic erythematous lesions on the trunk, buttock, abdomen, axilla, genital area and forearm (Fig. 1a). Lesions consisted of follicular papules, comedones, milia and cysts. Lesional areas were alopecic (Fig. 1b), and diffuse alopecia was also present on the scalp and beard area, along with comedones and cysts. The patient reported severe skin dryness, especially in the involved areas. No impairment of salivary or lacrimary function was noted. Serological and haematological tests were all normal or negative. Because of the diffuse presence of cysts and comedones, a diagnosis of chloracne had been made in another institution; the clinical diagnosis was confirmed histologically by the presence of infundibular cysts and a granulomatous foreign body reaction to keratin scales. A further biopsy was performed: the most striking histological feature was a lymphocytic infiltrate involving eccrine glands and coils along with a characteristic epithelial hyperplasia (Figs 1c,d). This picture fits perfectly with that reported in the literature as being characteristic of syringolymphoid hyperplasia, also known as syringotropic mycosis fungoides or syringotropic cutaneous T-cell lymphoma (CTCL). The hair follicles were involved by the lymphocytic infiltrate in a manner similar to that of the eccrine glands. Follicles were surrounded by a dense lymphocytic infiltrate, with extensive exocytosis. Occasional Pautrier microabscesses were evident in the follicular sheath. This pattern is that of pilotropic mycosis fungoides, a form of folliculotropic CTCL. Many follicles were entirely trans-

Mixed response to thalidomide therapy in adults: two cases of multisystem Langerhans' cell histiocytosis.

ant of paraneoplastic autoimmune multiorgan syndrome. 8. Kimyai-Asadi A, Jih MH. Paraneoplastic pemphigus. Int J Dermatol 2001; 40: 367–372. Arch Dermatol 2001; 137: 193–206. 7. Rivollier C, Vaillant L, Machet MC, Martin L, Jan V, 9. Ostezan LB, Fabrè VC, Caughman SW, Swerlick RA, Korman NJ, Callen JP. Paraneoplastic pemphigus in the Huttenberger B, et al. Pemphigus paranéoplastique. Une forme pustuleuse au cours d’une leucémie lymphoide absence of a known neoplasm. J Am Acad Dermatol 1995; 33: 312–315. chronique. Ann Dermatol Venereol 2001; 128: 644–648.

Erythematöse Plaque am Augenunterlid einer 42-jährigen Patientin

Bei der heute 42-jährigen Patientin trat vor 10 Jahren eine gerötete und schuppende Hautveränderung am rechten Augenunterlid auf. Die Läsion nahm in den folgenden Jahren langsam an Größe zu. Während der Sommermonate bemerkte die Patientin eine stärkere Rötung und Schwellung sowie leichten Pruritus.Ansonsten bestanden keine subjektiven Beschwerden. Klinisch waren eine irritative Dermatitis,ein seborrhoisches Ekzem und eine Psoriasis vulgaris diagnostiziert worden. Topische Behandlungen mit Antibiotikaund glukokortikoidhaltigen Externa und bei Verdacht auf aktinische Keratose zwischenzeitlich auch 5-Fluorouracil blieben jeweils ohne Erfolg.

“Selbstheilende” Form eines Kollodiumbabys Transiente Verhornungsstörung oder Minimalform einer lamellären Ichthyose?

ZusammenfassungDas klinische Bild des Kollodiumbabys wird durch verschiedene Verhornungsstörungen hervorgerufen; in der Regel entwickelt sich später eine lamelläre Ichthyose. Eine Selbstheilung wird in bis zu 10% der Fälle beobachtet. Wir berichten über ein männliches Reifgeborenes, welches bei der Geburt vollständig in eine glänzende, kollodiumähnliche Membran gehüllt war. Weiterhin fanden sich ektropionierte Augenlider und evertierte Lippen. In den ersten Lebenswochen löste sich die Membran gänzlich ab und bis zum Alter von 3 Monaten war die Haut des Patienten weitgehend erscheinungsfrei. Die elektronenmikroskopische Untersuchung einer am 20. Lebenstag entnommenen Hautbiopsie zeigte bei unserem Patienten keinen auf eine lamelläre Ichthyose oder eine andere Verhornungsstörung hinweisenden Strukturdefekt der Keratinozyten. Es fanden sich lediglich unspezifische Veränderungen im Sinn einer Abräumreaktion. Diskussion: Unter Berücksichtigung der Literatur läßt sich folgern, daß das klinische Bild eines Kollodiumbabys keine Rückschlüsse auf den weiteren Verlauf zuläßt. Dagegen kann die Elektronenmikroskopie prognostisch richtungsweisende Aussagen beim ätiologisch heterogenen Erscheinungsbild des Kollodiumbabys erlauben.SummaryCollodion baby is a clinical description for a transient condition of the newborn which is caused by various disorders of cornification. The majority of cases are due to autosomal recessive lamellar ichthyosis. In up to 10% of cases „self-healing” of the skin occurs. We report about a mature male baby who at birth was covered entirely with a shining, collodion-like membrane. There also were marked ectropion of the eyelids and eversion of the lips. After shedding of the membrane almost complete clearing of the skin occurred until the age of three months. In the case reported here skin biopsies taken on the 20th day of life showed discrete and non-specific ultrastructural changes, with no features of lamellar ichthyosis or other cornification disorders. Discussion: From these findings and those reported in the literature we conclude that the prognosis of a collodion baby is unpredictable on clinical evaluation. However an ultrastructural examination can contribute to early assessment of prognosis in this heterogeneous neonatal condition.

Nevoid Bag-Like Soft Fibromas

True nevi and nevoid disorders are defined as visible, circumscribed and long-lasting lesions of the skin, reflecting genetic mosaicism. We report on a 17-year-old young man presenting with large pedunculated soft fibromas restricted to a circumscribed area of the right abdomen. We suggest that these nevoid bag-like soft fibromas represent a new malformation in the heterogenous group of nevoid tumors.