[Pemphigoid gestationis after egg donation : A case report]. / Pemphigoid gestationis bei Eizellspende : Ein Fallbericht.

Pemphigoid gestationis (PG) is a blistering autoimmune skin disease, typically occurring in the second and third trimester of pregnancy. Aberrant expression of major histocompatibility complex (MHC) class II molecules on the chorionic villi seems to lead to antibody production against bullous pemphigoid (BP)-180. We report a case of PG in a woman whose pregnancy was achieved using egg donation. Since the entire fetal genome is allogeneic to the mother, augmented immune reaction in egg-donated pregnancies appears to trigger the occurrence of PG.

[Adult-onset Still's disease : Rare adult-onset autoinflammatory syndrome]. / Adulter Morbus Still : Seltenes autoinflammatorisches Syndrom im Erwachsenenalter.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease characterized by high spiking fever, arthritis, salmon-pink maculopapular rash and multiple organ involvement. We report a case of an adult-onset Still's disease that meets Yamaguchi's criteria and presented with typical clinical manifestations. AOSD is treated with anti-inflammatory medications. Standard therapy includes corticosteroids. Other medications like azathioprine, methotrexate or interleukin-1 or -6 blockers can be used when standard steroid treatment is not adequate.

Diagnostic approach in lymphoplasmacytic plaque.

BACKGROUND: Lymphoplasmacytic plaque (LPP) is a recently described rare skin disease characterized by a dense dermal lymphohistiocytic infiltrate with polyclonal plasma cells. The clinical picture is distinct with reddish to brownish plaque with a predilection for the lower leg. LPP typically affects children. OBJECTIVE: To define clinical and histologic criteria of LPP and to develop a diagnostic flow chart. METHODS: We investigated six of our own LPP cases. Immunoglobulin light chains, IgG, IgG4, CD31, CD163 as a histiocytic marker were examined by immunohistochemistry. PCR-based molecular studies were conducted for borrelia sp., mycobacterial and leishmania sp. Moreover, 10 cases, which have been reported in the literature, were checked for the same features. RESULTS: We could differentiate three main histological patterns (superficial band-like only, [deep] dermal only and mixed). Acanthosis and interface dermatitis are key features in cases with a superficial band-like or mixed infiltrate. Granulomas and giant cells could be only found in about 30% of the cases. The number of plasma cells was variable accounting for 5-40% of the infiltrate. The number of blood vessels was increased in the majority of the cases. 'Free-floating' collagen bundles surrounded by histiocytes (pseudorosettes) were identified as a new histological feature. An infectious agent could be excluded in all cases. CONCLUSIONS: LPP is a long-standing skin disease, which may also occur in adults and in other body regions than the lower leg. Reproducible clinical and histological criteria allow delineating a diagnostic work-up for LPP.

[Drug reaction with eosinophilia and systemic symptoms (DRESS): a hypersensitivity reaction with various symptoms]. / "Drug reaction with eosinophilia and systemic symptoms" (DRESS): eine Überempfindlichkeitsreaktion mit vielfältiger Symptomatik.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is an illness which is difficult to diagnose because of its various symptoms. In our case, a patient with small spotted exanthema with nearly erythroderma and eosinophilia presented to the emergency room. Systemic steroid therapy was started on suspicion of a drug reaction. Over the course of time, the patient's general condition deteriorated significantly and the patient developed cholecystitis, Staphylococcus aureus bacteremia, pneumonitis and cytomegalovirus reactivation. With this case report, we want to show that DRESS is a disease that is difficult to treat and can develop after a long delay.

[Cutaneous marginal zone lymphoma (SALT) and infection with Borrelia burgdorferi]. / Kutanes Marginalzonenlymphom (SALT) bei chronischer Borrelia-burgdorferi-Infektion.

A relationship between Borrelia burgdorferi and the development of cutaneous B-cell lymphoma (CBCL) has been long discussed. B. burgdorferi DNA has been detected in patients with CBCL and a response of CBCL to antibiotics has been observed. In our patient with a Borrelia infection, a marginal zone lymphoma (SALT) regressed after ceftriaxone therapy. This further case of a combined appearance of CBCL and B. burgdorferi underlines a possible relationship as an example of an infectious trigger in tumorigenesis.

Steven Kossards postmenopausal frontal fibrosing alopecia (PFFA)--a therapeutic dilemma.

Steven Kossard described a new type of hair loss that he named frontal postmenopausal fibrosing alopecia (PFFA). In some of his patients he observed a symmetric regression of the frontal hair line. The eyebrows of the patients were also often affected. The histology of the lesions showed lichen planopilaris. Several cases of frontal fibrosing alopecia have been described- almost all of them in elderly women. We report a women with postmenopausal frontal fibrosing alopecia of Kossard. In our patient there were no other clinical signs of lichen planus on the rest of the body After systemic and local therapy with corticosteroids we were able to observe a termination in the disease. In the subsequent 6-month control period no regrowth of the hair follicles was found. Even if there is no proof for a hormonal basis of the disease, the effectiveness of finasteride in some patients may indicate that androgens might be partially responsible of the pathogenesis of the disease. The local and systemic medication with corticosteroids are not able to bring to a permanent remission and secondary growth of the hair follicles in the affected areas and this brings to the necessity of more invasive or innovative therapeutic methods, like skin transplantation and additional application of medicaments like blockers of the 5/alpha reductase, which have proven their capacity in the androgenetic male alopecia.

Reevaluation of established and new criteria in differential diagnosis of Spitz nevus and melanoma.

The histopathologic differentiation between Spitz nevus and melanoma is of particular interest in routine diagnostic procedures of melanocytic tumors. Atypical Spitz nevi are sometimes difficult to distinguish from melanoma. There is still no single criterion that ensures a distinction of melanoma and atypical Spitz nevus. The aim of this study was to reevaluate established and new criteria to differentiate Spitz nevus from melanoma more reliably. We analyzed 25 melanomas with a Breslow index ≥ 1 mm and 18 classical compound Spitz nevi concerning their histopathologic, immunohistochemical and molecular genetic characteristics. Moreover, clinical follow-up data for 5 years were collected. We found statistically significant differences between Spitz nevus and melanoma for the following features: pagetoid spread, atypia, maturation, elastosis, Kamino bodies, p16 expression, and the staining pattern of HMB45. BRAF was positive in 7/21 melanomas and in 1/14 Spitz nevi. Fluorescence in situ hybridization confirmed the histopathologic diagnosis in 36/37 cases. The established clinical, histopathologic, and immunohistochemical criteria to differentiate Spitz nevus and melanoma could be reproduced in our collective. Especially, the expression of p16, BRAF analysis and fluorescence in situ hybridization proved to be helpful tools to improve the differentiation of Spitz nevus and melanoma in our study. Nevertheless, there is-until now-no reliable histopathologic and immunohistochemical parameter which can discriminate Spitz nevus and melanoma with absolute certainty.

Ultraviolet irradiation induces acute changes in melanocytic nevi.

Ultraviolet (UV) light represents one of the factors that might play a role in the initiation and promotion of malignant transformation of human melanocytes. To determine the short-term effects of UV irradiation on melanocytic nevi in vivo, we investigated one half of symmetric melanocytic nevi after a single UV exposure with double the patient's minimal erythema dose. This half was compared with the nonirradiated, shielded half of the same nevus. The different parts were examined histologically for differences and immunohistochemically for the presence of HMB-45 antigen and proliferating cell nuclear antigen. The features were assessed quantitatively by image analysis. One week after the single UV irradiation, we observed a significant increase of suprabasally located melanocytes and a markedly enhanced expression of HMB-45, whereas proliferative activity of the cells was unchanged. In nevi that were excised 2 or 3 weeks after irradiation, no significant differences were observed between the irradiated and the nonirradiated part. The results indicate that a single UV irradiation may induce transient melanocytic activation with morphologic and histologic changes. Although these data do not formally assess resemblance to melanoma, these changes may be similar to those of melanoma in situ.

Altered x-ray diffraction pattern is accompanied by a change in the mode of cross-link formation in lipodermatosclerosis.

We studied the molecular packing of collagen fibrils by x-ray diffraction in skin specimens of patients with lipodermatosclerosis and in controls. A difference in the tilt angles of the collagen molecules relative to the fiber axis is suggested by a D-stagger that is 1 nm larger in sclerotic skin than in normal skin. In parallel, the collagen cross-links in the skin specimens were analyzed, and a marked increase of both hydroxylysylpyridinoline and lysylpyridinoline, the trivalent mature cross-links characteristic of skeletal tissues, was found. The content of hydroxylysylpyridinoline and lysylpyridinoline was higher in the deep layer of the affected dermis than in the superficial dermis. This increase was always accompanied by an increase in the hydroxylysylpyridinoline/lysylpyridinoline ratio, suggesting that hydroxylysylpyridinoline is a sclerosis-associated cross-link. In addition, lysyl hydroxylation was increased in affected skin, and this increase was apparently restricted to the collagen telopeptides, which are crucial anchoring structures for lysyl dependent cross-links.

Overhydroxylation of lysyl residues is the initial step for altered collagen cross-links and fibril architecture in fibrotic skin.

In fibrotic skin of lipodermatosclerosis a substantial increase of the cross-link hydroxylysylpyridinoline is observed. Hydroxylysylpyridinoline is a typical cross-link of skeletal tissue and is thought to play a major part in the hardening of sclerotic tissue. We investigated whether the increase in hydroxylysylpyridinoline is due to overhydroxylation of lysyl residues in the collagen molecule, which may also be associated with an increase of glycosylated hydroxylysine residues. Furthermore, we determined whether the collagen fibrils in lipodermatosclerosis showed a decrease of the diameter in the tissue as well as in vitro after fibrillogenesis of pepsin-solubilized collagens. Isolated alpha-chains of pepsin solubilized collagen I showed an increase in lysyl hydroxylation (hyl/(hyl + lys)) as compared with normal control [alpha1(I): lipodermatosclerosis 0.18 +/- 0.01; control 0.12 +/- 0.01; alpha2(I): lipodermatosclerosis 0.36 +/- 0.02; control 0. 25 +/- 0.03, p < 0.001]. Furthermore, the content of enzymatic glycosylated hydroxlysine residues increased. This increase is associated with a decrease of fibril diameter of both tissue and fibrils formed in vitro of pepsin-solubilized collagens. In the same pool of collagens an increase in collagen III content was observed as compared with controls (lipodermatosclerosis 14.5% +/- 1.6, control 10.3% +/- 1.6, p < 0.001). Our results showed that the overhydroxylation of lysyl residues, which is required for the generation of hydroxylysylpyridinoline, is not only restricted to the telopeptides but also affects the helical part of the molecule. This process is further associated with an increase of glycosylated hydroxylysyl residues. These changes along with the increase in collagen III content seem to be responsible for the observed alteration in the architecture of collagen fibrils in sclerotic skin.

Enhanced expression of Ki-67, topoisomerase IIalpha, PCNA, p53 and p21WAF1/Cip1 reflecting proliferation and repair activity in UV-irradiated melanocytic nevi.

To investigate the effect of ultraviolet (UV) irradiation on the expression of cell cycle-associated proteins, melanocytic nevi from healthy volunteers were partially covered, irradiated with a defined UV dose, and excised 1 week thereafter. The irradiated and the protected parts were examined separately by conventional microscopy and immunohistochemistry using the antibodies Ki-S11 (Ki-67), Ki-S7 (topoisomerase IIalpha), PC10 (proliferating cell nuclear antigen [PCNA]), DO-7 (p53), 6B6 (p21WAF1/Cip1), and the melanocytic marker HMB-45. DNA nick-end labeling was used as a marker of apoptosis. Irradiation resulted in morphological changes and increased HMB-45 reactivity. Proliferation, as assessed by Ki-67 and topoisomerase IIalpha expression, was also clearly enhanced in the UV-exposed areas. This was confirmed by the appearance of occasional mitotic figures. PCNA expression levels markedly exceeded those of the proliferation markers and did not correlate with the latter in most cases. p21 immunolabeling indices were also consistently augmented after UV exposure; hence it is likely that growth-inhibitory mechanisms partly compensate for the proliferative impulse, and the disproportional rise in PCNA expression probably reflects DNA repair activity. Enhanced p53 immunostaining in four cases suggests that the induction of p21 after irradiation may be p53 mediated, whereas no concomitant apoptotic events were observed. We conclude that UV light can stimulate the proliferative activity of melanocytes in melanocytic nevi, but that simultaneously cell cycle inhibitors are activated to permit DNA repair.

Ultrastructural localization of lectin-binding sites in normal human eccrine and apocrine glands.

The distribution of carbohydrate residues in eccrine and apocrine glands of normal human skin was studied using a post-embedding technique with Lowicryl K4M. Thin sections were incubated with Ulex europaeus agglutinin I (UEA I), wheat germ agglutinin (WGA), peanut agglutinin (PNA), concanavalin A (Con A), soybean agglutinin (SBA), and dolichos biflorus agglutinin (DBA). All lectins except for PNA showed labeling of the plasma membranes of dark cells, clear cells, and apocrine cells. The granules of the eccrine gland were labeled with all lectins except for DBA. The mitochondrial granules of the apocrine gland were not labeled with any lectin, whereas the lysosomal granules showed a positive reaction with all lectins except for PNA. After incubation with PNA, in eccrine glands the granules were the only structure labeled, whereas in apocrine glands the luminal side of the plasma membrane and cytoplasmic vesicles beneath it were the only structures labeled.

Crystalloid inclusion bodies of the endothelial cells in human fetal skin blood vessels and human umbilical cord vessels: a possible relationship to Weibel-Palade bodies?

Crystalloid inclusion bodies (CIB) of the endothelial cells (EC) were investigated in blood vessels of human fetal skin and the umbilical cord by electron- and immunoelectron microscopy. They were found in up to 15% of the investigated EC in various types of vessels. Their sizes ranged from 0.2 microns to 0.6 microns in the largest diameter. Most frequently we observed a laminated pattern of the crystalloid structure with a regular periodicity of dark and light bands. Additionally a honeycomblike pattern was also seen. Measurement of the CIB laminated structure revealed similar dimensions to Weibel-Palade bodies (WPB). In EC of all vessel types we found numerous WPB differing in electron density, shape and size from those of WPB found in adult blood vessels. WPB were found much less frequently in EC with CIB, suggesting that CIB is a precursor of WPB. After incubation with monoclonal antibody against von Willebrand factor (vWf) both WPB and large organelles were labeled. Because of their shape and size the labeled large organelles seemed to represent inadequately preserved CIB. After incubation with anti-lysozyme only the large organelles were labeled. A possible relationship of CIB to WPB is thus suggested. The presence of lysosomal enzymes such as lysozyme suggest that CIB are lysosomal organelle and participate in the uptake of vWf. The crystalloid pattern of CIB may represent an accumulation of a highly condensed form of vWf.

Ultrastructural localization of alpha-L-fucose, factor VIII related antigen and vimentin in endothelial cells of human skin blood vessels using the low temperature embedding technique with Lowicryl K4M.

The present study was performed to investigate the ultrastructural localization of the binding sites of the lectin Ulex europaeus agglutinin, Type I (UEA) and the antibody against factor VIII related antigen (F VIII RAG), both widely used as vascular markers in human skin capillaries at light microscopy level. In addition the ultrastructural localization of vimentin, the major protein of the endothelial intermediate filaments, was demonstrated in human vascular endothelial cells (EC) in situ. The low temperature postembedding technique with Lowicryl K4M with subsequent application of gold labelled antibodies provided both well preserved antigenicity and morphology. The antigenic site of UEA, alpha-L-fucose containing glycohydrate residues, was primarily found in or near the luminal plasma membrane of EC. Gold particles representing the sites of F VII RAG were located in the Weibel-Palade bodies (WPB) of EC. The ultrastructural staining pattern of the anti-vimentin antibody showed an exclusive labelling of the intermediate filaments of EC.

Ultraviolet-induced acute histological changes in irradiated nevi are not associated with allelic loss.

BACKGROUND: Transformed melanocytes in atypical nevi, which are thought to be precursors of melanoma, are frequently deleted on chromosomes 1p, 9q, and 9p21 (p16 locus). Single UV irradiation induces histological changes that are similar to those of atypical nevi and, in part, of melanoma in situ. OBJECTIVE: To determine the effects of UV irradiation on benign melanocytic nevi in vivo. DESIGN: We investigated one half of a symmetric nevus 1 week after a single UV exposure with 4 times the patient's minimal erythema dose and compared it with the nonirradiated, shielded half of the same nevus. Two to 3 areas containing 5 to 30 melanocytes in 7 nevi were microdissected (a total of 18 areas in each nonirradiated and irradiated part), followed by a single-step DNA extraction. Extracted genomic DNA was amplified using a polymerase chain reaction with polymorphic markers D1S450 (1p), D9S12 (9q), IFNA, and D9S171 (9p21) and subjected to autoradiography. OBSERVATIONS: Two, 3, 2, and 2 of 18 areas were homozygous for D1S450, D9S12, IFNA, and D9S171, respectively. No allelic loss could be demonstrated in either nonirradiated or irradiated nevi. CONCLUSIONS: Acute histological changes demonstrated in melanocytic nevi after UV irradiation are not followed by allelic loss on identical chromosomal areas found in dysplastic melanocytes of atypical nevi. This finding supports the hypothesis that initial nonspecific genetic events may occur after UV irradiation, followed by an increase in various repair mechanisms potentially leading to specific genetic damage and loss of heterozygosity; however, loss of heterozygosity is not detectable at an early stage.

[Sweet syndrome and erythema nodosum in ulcerative colitis, refractory to steroids: successful treatment with tacrolimus]. / Sweet-Syndrom und Erythema nodosum bei steroidrefraktärer Colitis ulcerosa. Erfolgreiche Behandlung mit Tacrolimus.

BACKGROUND: Inflammatory bowel disease is accompanied by cutaneous manifestations in about 10% of cases. Erythema nodosum and pyoderma gangraenosum are most frequently observed, which often subside on treatment of the underlying disease. CASE REPORT: A 30-year-old male with a history of long-standing ulcerative colitis experienced an acute attack despite treatment with azathioprine. Further he noticed dull red, elevated and tender maculae on the forelegs. A disseminated and papulosquamous exanthema arose on the back of the trunk and the upper extremities without pruritus. Well-being was compromised and blood sampling revealed an inflammatory response. High-dose steroids with antibiotics were without benefit until they were combined with tacrolimus, an immunosuppressive agent acting similar to ciclosporin. Remission occurred rapidly and the skin lesions resolved. Six months later the patient is currently still in remission and developed no signs of recurrent exanthema. CONCLUSION: The cutaneous lesions are thought to be related to ulcerative colitis and were classified as erythema nodosum and Sweet syndrome. This is the first report on the successful use of tacrolimus in steroid-refractory ulcerative colitis with extraintestinal cutaneous involvement.