U.W. Schnyder

Ultrastructural studies in epidermolysis bullosa hereditaria

SummaryUltrastructural examination was performed in 42 biopsy specimens from 22 patients with the Hallopeau-Siemens types or with the inverse type of epidermolysis bullosa dystrophica recessiva. The patient group consists of 8 cases of the localized Hallopeau-Siemens type, 9 of the generalized Hallopeau-Siemens type and 5 of the inverse type. The origins of the biopsy specimens are involved, intact and experimentally frictioned skin from blister-predilected sites, as well as clinically normal skin from nonpredilection sites. It is confirmed that all the blisters initiate below the basal lamina. Anchoring fibrils are moderately to markedly decreased in most cases, but normal in 3 cases. The collagen fibrils are more or less changed in the majority of cases, while they are normal in 3 other cases. It is thought that secondary degradation of anchoring fibrils and/or collagen fibrils plays an important role in blistering mechanism in the Hallopeau-Siemens and inverse types of recessive dystrophic epidermolysis bullosa, whereas a primary aplasia of anchoring fibrils as causative defect has been out ruled.ZusammenfassungUltrastrukturelle Untersuchungen wurden an 42 Biopsien von 22 Patienten mit einem der Hallopeau-Siemens-Typen bzw. mit dem inversen Typus der rezessiv-dystrophischen Epidermolysis bullosa durchgeführt. Das Patienten-Kollektiv besteht aus 8 Fällen des lokalisierten Hallopeau-Siemens-Typs, 9 des generalisierten Hallopeau-Siemens-Typs und 5 des inversen Typs. Die Biopsien stammen aus befallener, intakter und experimentell traumatisierter Haut von Praedilektionsstellen sowie aus klinisch normaler Haut von Nichtpraedilektionsstellen der Blasenbildung. Es wurde nachgewiesen, daß die Blasenbildung stets unterhalb der Basallamina beginnt. In den meisten Fällen sind die anchoring fibrils mäßig bis stark vermindert, in 3 Fällen jedoch normal. Die Kollagenfibrillen sind in der Mehrzahl der Fälle mehr oder weniger verändert. Es wird angenommen, daß eine sekundäre Degradation von anchoring fibrils und/oder Kollagenfibrillen eine bedeutende Rolle bei der Blasenbildung der Hallopeau-Simens-Typen und des inversen Typs der rezessiv-dystrophischen Epidermolysis bullosa spielt. Dagegen kann eine primäre Aplasie der anchoring fibrils als Ursache ausgeschlossen werden.

Epidermolysis bullosa hereditaria with junctional blistering in an adult

A 38-year-old patient with epidermolysis bullosa is described, in whom junctional blister formation is revealed by electron microscopy. Clinical and ultrastructural differences from the recessive dystrophic type (Hallopeau-Siemens) and from the lethal type (Herlitz) of epidermolysis bullosa are discussed in detail.

Lack of type VII collagen in unaffected skin of patients with severe recessive dystrophic epidermolysis bullosa

Type VII collagen, the major structural component of the anchoring fibrils, was assayed in normal unaffected skin of patients with different forms of hereditary epidermolysis bullosa. Immunofluorescence staining with affinity-purified polyclonal antibodies to type VII collagen revealed a complete absence of staining in the skin of patients with severe dystrophic recessive epidermolysis bullosa. In all other forms, localized recessive dystrophic, dominant dystrophic, junctional and simplex forms there was an intense continuous linear staining of type VII collagen at the dermoepidermal junction. Also, obligate heterozygote carriers of the gene for severe dystrophic recessive form showed a normal pattern of staining. As internal controls and to define the clinical diagnosis, staining with antibodies to type IV collagen, laminin and bullous pemphigoid antigen was also performed. All these antibodies showed a normal staining pattern indicating an intact general morphology of the dermoepidermal junction zone. These results suggest that there is a defect of type VII collagen in patients with severe recessive dystrophic epidermolysis bullosa. The data also suggest that the group of recessive dystrophic epidermolysis bullosa may be heterogeneous not only clinically, but also at the molecular level.

Frequency of congenital nevi, nevi spili and café-au-lait spots and their relation to nevus count and skin complexion in 939 children

To determine the prevalence of congenital melanoevocytic nevi (CMN), of so-called congenital nevus-like nevi (CNLN), nevi spili (NS) and café-au-lait spots (CLS) in childhood, a series of 939 children aged 8-16 years had total skin examination. CMN/CNLN were observed in a frequency of 5.9%, NS in 2.1% and CLS even in 32.7%. Except CLS (which occurred more frequently in boys), all of these lesions were equally represented in both sexes. According to the classification of Kopf and coworkers, 44/55 CNM/CNLN were small and 11/55 medium-sized. CMN/CNLN affected preferentially trunk and upper limbs while head and neck were spared. Such nevi occurred more frequently in dark types of skin complexion and showed a tendency to be more frequent in groups of patients with increased average number of acquired melanonevocytic nevi. Remarkably, CLS were also found in 23/55 (41.7%) children with CMN/CNLN and in 12/20 (60%) children with NS (in a higher frequency than such combinations have to be expected). Compared with the data from other studies, both CMN/CNLN and CLS in our patients were observed in highest prevalence in the literature. Since the frequency of CLS in adults is much lower, it cannot be ruled out that some of the CLS disappear in adolescence.

Type VII collagen is expressed but anchoring fibrils are defective in dystrophic epidermolysis bullosa inversa

A patient with dystrophic epidermolysis bullosa inversa was studied using electron microscopy and indirect immunofluorescence using antibodies to matrix macromolecules of the dermo‐epidermal junction zone. There was splitting below the lamina densa with an apparently normal basement membrane, but a lack of intact anchoring fibrils and with a disarranged papillary connective tissue. Indirect immunofluorescence examination with antibodies to type VII collagen, the major structural protein of anchoring fibrils, showed a normal linear staining pattern. Synthesis of type VII collagen which is unable to form stable, resistant anchoring fibrils may be a distinct feature of this subtype of recessive dystrophic epidermolysis bullosa.

Ultrastructural studies in epidermolysis bullosa hereditaria: I. Dominant dystrophic type of pasini

SummaryUltrastructural examination was performed in 8 biopsies from 4 patients with the Pasini type of epidermolysis bullosa dystrophica dominans. The biopsies were taken from: 1. clinically normal skin from nonpredilection areas, 2. intact skin from predilection areas, 3. involved skin and 4. experimentally frictioned skin. The main ultrastructural alterations detected are as follows: hypoplasia of anchoring fibrils, split or blister formation between basal lamina and dermis, hernia-like protrusion of basal cells, sub- and intraepidermal deposition of fibrillar bodies, and duplications of basal lamina. Among them, the constantly observed finding in all of the four biopsy groups is the structural defect of anchoring fibrils, namely, that the anchoring fibrils are rudimentary and reduced in number. Presence of the structural defect of anchoring fibrils in clinically normal skin fromnonpredilection areas in patients with the Pasini type of epidermolysis bullosa dystrophica dominans indicates that this defect is not a secondary change following repeated mechanical trauma, but a primary, genetically determined event.ZusammenfassungUltrastrukturelle Untersuchungen wurden an 8 Biopsien von 4 Patienten mit dem Typ Pasini der Epidermolysis bullosa dystrophica dominans durchgeführt. Die Biopsiestellen sind 1. klinisch normale Haut aus Nicht-Prädilektionsstellen, 2. intakte Haut aus Prädilektionsstellen, 3. befallene Haut und 4. experimentell geriebene Haut (friction). Die aufgefundenen Hauptveränderungen sind folgende: Hypoplasie der anchoring fibrils, Spalt- oder Blasenbildung zwischen Basallamina und Dermis, Hernienbildung der Basalzellen, sub- und intraepidermale Ablagerung fibrillärer Körper und Duplikation der Basallamina. Der wesentlichste Befund aller vier Biopsiegruppen ist der Strukturdefekt der anchoring fibrils, d. h., daß die anchoring fibrils rudimentär strukturiert und vermindert ausgebildet sind. Der Nachweis dieses Strukturdefekts in klinisch normaler Haut ausNicht-Prädilektionsstellen bei Patienten mit dem Typ Pasini der Epidermolysis bullosa dystrophica dominans zeigt, daß dieser Defekt nicht erst sekundär als Folge mechanischer Belastungen entsteht, sondern eine primäre, genetisch bedingte Veränderung ist.

Soft-X-Ray Therapy in Bowen’s Disease and Erythroplasia of Queyrat

The therapeutic results obtained with soft-X-ray irradiation on 77 lesions in 52 patients are reported. 35 males (67.3%) and 17 females (32.7%) were treated. Clinical and histological features revealed Bowens disease in 73 cases (94.8%) and erythroplasia of Queyrat in 4 cases (5.2%). The primary healing was rated as 100% in all cases up to 6 months after a cumulative dosage of 3,200-5,000 R. 2 cases with a genital localization (2.6% of all sites and 11.1% of anogenital localizations) relapsed after 8 and 16 months, respectively. The follow-up period ranged from 1 to 11 years with a mean of 3 years. In order not to miss the late recurrences, the oncologic follow-up is taken care of by the Dermatology Department of the Zurich University Hospital during 10 years, or longer in some cases. Association with a malignant internal tumour (larynx, bronchi, anus) was found in 3 patients (5.8%).

Epidermolysis bullosa dystrophica dominans – ein Defekt der anchoring fibrils

Ultrastructural studies on a familiar case of Epidermolysis bullosa dystrophica dominans have demonstrated that normal anchoring fibrils are missing in the junctional area beneath the basal lamina; so

Deficiency of arylsulfatase C in cultured skin fibroblasts of X-linked ichthyosis

In October 1978 it was reported by Shapiro et al. [13] that cultured skin fibroblasts of patients with X-linked recessive inherited ichthyosis had a deficiency of steroidsulfatase. The same could be demonstrated for cultured epidermal cells [6]. Such a steroidsulfatase deficiency is also observed in the placenta of mothers with low urinary estriol excretion [1,2,3, 12]. It had also been reported that amnion fluid cells as well as cultured skin fibroblasts from offsprings of mothers with placental steroidsulfatase deficiency showed this inborn enzym defect. This defect of steroidsulfatase activity in the placenta is also associated with low arylsulfatase C activity as shown by biochemical [2, 3, 12] and histochemical methods [4, 5, 7]. Koppe et al. [5] reported three pregnant women with low estrogen excretion due to low placental arylsulfatase C activity. The three boys born were normal at birth but later developed ichthyosis vulgaris of the X-linked inherited type. Histochemical investigations of the skin demonstrated the same deficiency of arylsulfatase C activity in all three children. In conclusion, a deficiency of the two microsomal enzymes steroidsulfatase [2] and arylsulfatase C [10] seems to be associated with X-linked recessive ichthyosis, tough these two enzymes are not identical as demonstrated electrophoretically [3]. The two lysosomal arylsulfatases A and B are not affected [ 12]. The biochemical demonstrat ion of arylsulfatase C deficiency in cultured skin fibroblasts from patients with X-linked ichthyosis has to our knowledge not yet been reported. Skin biopsies from patients with Xlinked ichthyosis were tr immed free of fat, cut into

Nail changes in epidermolysis bullosa : clinical and pathogenetic considerations

Nail changes in epidermolysis bullosa (EB) are common, but although they are highly suggestive of the disease, they are not pathognomonic. They are the result of abnormalities of the nail matrix and nail bed, associated with the pathogenetic alterations of the dermo‐epidermal junction which occur in EB. In addition, secondary trauma in the areas of epidermal‐dermal separation, and chronic inflammation of the nail matrix, are probable contributory factors, even in non‐scarring forms of EB.