H. Hamm

Ichthyosis bullosa of Siemens: A unique type of epidermolytic hyperkeratosis

We report the second family of ichthyosis bullosa, an entity that was first described by Siemens in 1937 and since then has fallen into oblivion. Clinically, ichthyosis bullosa is characterized by blistering resembling epidermolysis bullosa simplex and by generalized, yet circumscribed dark gray hyperkeratoses covering mainly the arms and the legs. Lichenification and superficially denuded areas (mauserung) are further prominent features. Histology disclosed intracorneal blister formation corresponding to the mauserung phenomenon and epidermolytic hyperkeratosis that was confined to the granular layer and to the uppermost layers of the prickle cells. On electron microscopic examination the keratinocytes of these layers displayed structural alterations of tonofilaments as usually observed in epidermolytic hyperkeratosis. Thus ichthyosis bullosa shares with bullous ichthyosiform erythroderma blistering and epidermolytic hyperkeratosis, but can be distinguished from this wellknown disease by the lack of erythroderma, by the mauserung phenomenon, by the confinement of acanthokeratolysis to the superficial layers of the epidermis, and by intracorneal blistering.

A novel missense mutation in GJB2 disturbs gap junction protein transport and causes focal palmoplantar keratoderma with deafness

Gap junctions are intercellular channels that mediate rapid intercellular communication. They consist of connexins, small transmembrane proteins that belong to a large family found throughout the animal kingdom. In the skin, several connexins are expressed and are involved in the regulation of epidermal growth and differentiation. One of the skin expressed gap junction genes is GJB2, which codes for connexin 26 and is associated with a wide variety of keratinisation disorders. Here, we report on a family with a novel GJB2 mutation (p.His73Arg) causing a syndrome of focal palmoplantar keratoderma with severe progressive sensorineural hearing impairment, a phenotype reminiscent of Vohwinkel syndrome. Using fluorescent connexin fusion proteins, we show that the mutation induces a transport defect similar to that found for the Vohwinkel syndrome mutation p.Asp66His. Co-transfection into cells expressing wild type connexin26 shows that the mutant has a dominant negative effect on connexin trafficking. We suggest that there may be a weak genotype–phenotype correlation for mutations in GJB2.

Multiple agminate Spitz naevi: review of the literature and report of a case with distinctive immunohistological features.

We describe a 13‐year‐old girl with multiple pigmented nodules and plaques arranged in a cluster in the right lumbar region, which had developed since infancy.

Epidermolytic Palmoplantar Keratoderma of Vörner: Is It the Most Frequent Type of Hereditary Palmoplantar Keratoderma?

In a retrospective study, we reevaluated the biopsies that had been obtained, during the past 11 years, from 26 patients presenting with hereditary palmoplantar keratoderma (PPK). Twelve out of 26 biopsies disclosed the histological features of epidermolytic hyperkeratosis, consistent with the diagnosis of epidermolytic PPK of Vörner. A review of the histologically examined cases of the literature revealed a comparable predominance of this hereditary PPK. We conclude that, in contrast to the current opinion, epidermolytic PPK of Vörner represents the most frequent type of hereditary PPK.

Congenital Atrichia with Nail Dystrophy, Abnormal Facies, and Retarded Psychomotor Development in Two Siblings: A New Autosomal Recessive Syndrome?

Abstract: We cared for two sisters, ages 3 and 4 years, who suffered from congenital atrichia. Scalp biopsies performed on both children revealed a marked atrophy of hair follicles with rudimentary hair shafts. The absence of peribulbar infiltrates ruled out alopecia areata. Dystrophy of all nails, distinctive facies, retarded psychomotor development, and a delay in speaking were additional symptoms. The unique combination of findings excludes wellestablished syndromes such as atrichia with papular lesions, GAPO syndrome, and dominant hidrotic ectodermal dysplasia, as well as X‐linked hypohidrotic ectodermal dysplasia. We therefore conclude that we may be dealing with a new genetic entity. The occurrence of the disorder in two siblings with unaffected parents suggests an autosomal recessive mode of inheritance.

HLA-DR and HLA-DQ antigen expression of anagen and telogen hair bulbs in long-standing alopecia areata.

Hair bulb keratinocytes normally lack expression of major histocompatibility (MHC) class I and class II antigens [5]. In alopecia areata (AA), however, both HLA-A, B, C and HLA-DR antigens were found to be expressed in diseased anagen hair bulbs [2, 8, 9]. We studied HLA-DQ in anagen hair bulbs of longstanding AA in order to determine whether this MHC class II antigen is coexpressed with HLA-DR. Furthermore, we were interested to know to what extent MHC class II antigen expression is maintained in hair bulb epithelium after entering the telogen phase. Cryostat sections of scalp biopsy specimens from 33 patients with long-standing AA (> 12 months duration) and five healthy volunteers were immunohistologically investigated using an indirect immunoperoxidase technique. Anti-HLA-DR antibody D 1 12 was kindly provided by Dr. S. Carrel, Lausanne, Switzerland. Anti-HLA-DQ antibody Leu 10 was purchased from Becton-Dickinson, Heidelberg, FRG. Adjacent sections of the same hair bulbs were stained with both antibodies. The extent of positive staining of bulb keratinocytes was evaluated by three independent observers. Staining of single dendritic cells within the hair bulb epithelium was regarded as negative. Complete, partial or at least focal staining of hair bulb epithelium was observed in 41 of 61 anagen hair bulbs (67%) for HLA-DR and in 32 of 61 anagen bulbs (52%) for HLA-DQ. If only focal staining occurred this was predominantly present in the area of the precortical matrix and presumptive cortex (Fig. 1).

Topical immunotherapy with contact allergens in alopecia areata: evidence for non-specific systemic suppression of cellular immune reactions.

Topical immunotherapy of alopecia areata (AA) with obligate contact sensitizers, such as diphenylcyclopropenone (DCP) or squaric acid dibutylester (SADBE), may induce regrowth of hair [2, 3, 9, 10]. The mechanisms of the treatment response are unknown. Repeated application of DCP was shown to alter the composition of peribulbar lymphocytic infiltrates in AA towards a relative increase of CD8-positive T cells [4], as well as to reverse the pathological expression of MHC antigens in hair bulb epithelium [1]. Here we show that long-term topical treatment of AA patients with contact sensitizers leads to a significant non-specific systemic suppression of delayed type hypersensitivity (DTH) reactions. The patients (46 males and 55 females, age range 14 57 years) with long-standing AA (1 year duration or longer) were treated once weekly with DCP or SADBE in doses that elicited a mild contact dermatitis on the scalp. Before the first application of the contact allergen and after 6 months of treatment a M6rieux multitest with seven recall antigens [5] was performed on the inner aspect of the forearm. As a control, 14 healthy volunteers (7 males and 7 females, age range 2 3 49 years) underwent two M6rieux multitests with an interval of 6 months between. The number of positive reactions and the score (the sum of the mean diameters) of all positive reactions were determined after 48 h [6]. Evaluation of the data was done using non-parametric statistical methods (Wilcoxon test, Mann-Whitney test).

Hornstein-Knickenberg-/ Birt-Hogg-Dubé-Syndrom Fallbericht mit Spontanpneumothorax und Aplasie der linken A. carotis interna

ZusammenfassungBei einem 36-jährigen Patienten bestanden seit einigen Jahren zentrofazial, am Hals und am Rücken multiple hautfarbene Papeln. Auch bei seinem Vater, der Schwester und fraglich auch beim Großvater väterlicherseits wurden auswärtig ähnliche Hautbefunde erhoben. Die histologische Begutachtung der Hautveränderungen in allen 3 Fällen ergab Fibrofollikulome. Zusätzlich trat bei dem Patienten im Alter von 33 Jahren ein linksseitiger Spontanpneumothorax und ein Jahr später eine Subarachnoidalblutung bei Aplasie der linken A. carotis interna auf. Der Großvater väterlicherseits war an einem metastasierenden Rektumkarzinom verstorben.Wir diagnostizierten ein Hornstein-Knickenberg-/Birt-Hogg-Dubé-Syndrom, das durch das gemeinsame Auftreten von Fibrofollikulomen und Kolonadenomen charakterisiert ist. Die vorgestellte Familie stützt die Annahme eines autosomal-dominanten Erbgangs dieses Syndroms. Neben Haut und Darm können noch weitere Organsysteme, nämlich Nieren- und Genitaltrakt, Augen und Endokrinium betroffen sein. Lungenveränderungen wurden bislang bei 6 Patienten mit diesem Syndrom beschrieben. Wir möchten mit dieser Beobachtung auf die charakteristischen Hautveränderungen des Hornstein-Knickenberg-/Birt-Hogg-Dubé-Syndroms hinweisen, die Leitsymptom maligner Tumoren und anderer Begleitsymptome sein können.AbstractA 36-year-old man presented with multiple skin-colored papules on his face, neck and back of several years duration. His father, sister and probably his grandfather suffered from similar skin lesions. The histological examination revealed fibrofolliculomas in all three cases. At the age of 33 years the patient developed a spontaneous pneumothorax, and one year later a subarachnoidal hemorrhage due to aplasia of the left carotid artery. His grandfather had died from metastatic rectal carcinoma. A diagnosis of Hornstein-Knickenberg-/ Birt-Hogg-Dubé syndrome was made, which is characterized by fibrofolliculomas and colon adenomas. Our familial observation speaks in favor of autosomal dominant transmission of the Hornstein-Knickenberg-/ Birt-Hogg-Dubé syndrome. Apart from the skin several other organs may be involved, including the kidneys, urogenital tract, eyes and endocrine system. By this report we wish to draw intention to the typical skin lesions which can be the marker for neoplasia and other characteristic associated findings.

Macrophages in melanocytic naevi

SummaryWhereas the inflammatory infiltrates of malignant melanoma have been widely investigated, little is known about the infiltrates accompanying benign melanocytic naevi. Using monoclonal antibodies directed against HLA-DR antigens, the CD1 antigen, the transferrin receptor and functionally divergent macrophage subpopulations, frozen fresh material of 87 melanocytic naevi (MN), ten primary cutaneous melanomas (PCM) and ten samples of normal skin were studied. Compared with normal skin, abundant HLA-DR+ cells were found in the stroma of MN equivalent to the quantity present in PCM. In MN we found higher numbers of dermal CD1+ dendritic cells compared with PCM and normal skin. There were more macrophages that expressed the transferrin receptor or the antigens 27E10, RM3/1 and 25F9 in MN than in normal skin but fewer than in PCM. No significant differences were found between congenital MN (n=40), common acquired MN (n=27) and dysplastic MN (n=20) macrophage subpopulations. Also, no correlations were evident between macrophage infiltrates and naevus location or patients age. Our data show that potential melanoma precursors among melanocytic naevi cannot be identified by the pattern of macrophage infiltrates.

Subepidermal blasenbildende Autoimmundermatose mit linearen Ablagerungen von IgA und IgG

ZusammenfassungWir berichten über eine 29jährige Patientin mit einer subepidermal blasenbildenden Autoimmundermatose, die durch lineare Ablagerungen von IgA- und IgG-Antikörpern an der dermoepidermalen Junktionszone gekennzeichnet ist. Klinisch fanden sich pralle Bläschen im Gesicht, am Stamm, an den Extremitäten und an der Mundschleimhaut. Histologisch sahen wir eine subepidermale Blasenbildung und ein neutrophilenreiches Entzündungsinfiltrat. Mittels direkter Immunfluoreszenz fanden sich in der Haut der Patientin lineare IgA-Ablagerungen an der Basalmembranzone. Ungewöhnlich war jedoch der gleichzeitige Nachweis von linearen IgG- und C3-Ablagerungen, die typischerweise beim bullösen Pemphigoid vorkommen. Auch im Serum der Patientin fanden sich Autoantikörper sowohl der IgA- als auch der IgG-Klasse. Der Fall dieser Patientin bestätigt frühere Berichte, daß es bei den subepidermal blasenbildenden Autoimmundermatosen eine Untergruppe von Patienten mit gleichzeitigem Nachweis von IgA- und IgG-Antikörpern gibt, bei denen sich klinische, histologische und immunpathologische Merkmale von linearer IgA-Dermatose und bullösem Pemphigoid überlappen.AbstractA 29-year-old female patient with an autoimmune subepidermal blistering disease had linear deposits of both IgA and IgG at the basement membrane zone. Clinically, the patient presented with tense blisters on the face, trunk, extremities and oral mucosa. Histologically, we found a subepidermal blister formation and a predominantly neutrophilic infiltrate. Direct immunofluorescence showed linear deposits of IgA along the basement membrane zone, as well as linear deposits of IgG and C3 as typically found in bullous pemphigoid. Indirect immunofluorescence demonstrated circulating IgA and IgG autoantibodies. This case extends previous reports on a subgroup of patients with subepidermal blistering diseases characterized by the presence of both IgA and IgG anti-basement membrane antibodies. These patients reveal clinical, histological and immunopathological features of linear IgA disease and bullous pemphigoid.