Eye movement involvement in Parry-Romberg Syndrome: a clinicopathologic case report.

We report the case of a 38-year-old woman who developed a progressive bilateral disease in which the eye motility disorder-diplopia-is the outstanding feature over a period of 12 years. The muscle biopsy of the medial rectus muscle did not show any trace of striated muscle. To the best of our knowledge, this is the first pathological report in an affected extraocular muscle of a patient with Parry-Romberg syndrome (PRS). Previous rare reports of diplopia in PRS have been attributed to enophthalmos, progressive atrophy of the orbit, ocular motor nerve dysfunction, or mechanical restrictions.

Combined treatment with calcipotriol ointment and low-dose ultraviolet A1 phototherapy in childhood morphea.

Various therapies for morphea have been used with limited success, including ones with potentially hazardous side effects. When morphea occurs in childhood it may lead to progressive and long-lasting induration of the skin and subcutaneous tissue, growth retardation, and muscle atrophy. We report an open prospective study in which the efficacy of a combined treatment with calcipotriol ointment and low-dose ultraviolet A1 (UVA1) phototherapy in childhood morphea was investigated. Nineteen children (mean age 8.5 years, range 3-13 years) with morphea were exposed to UVA1 (340-400 nm) phototherapy at a dose of 20 J/cm(2) four times a week for 10 weeks. Forty phototherapy sessions resulted in a cumulative dose of 800 J/cm(2) UVA1. In addition, calcipotriol ointment (0.005%) was applied twice a day. After 10 weeks, palpation and inspection showed a remarkable softening and repigmentation of formerly affected skin resulting in a highly significant (p < 0.001) decrease of the mean clinical score from 7.3 +/- 0.9 at the beginning to 2.4 +/- 0.9 (relative reduction 67.1%) at the end of combined therapy. Our results indicate that a combined therapy with calcipotriol ointment and low-dose UVA1 phototherapy is highly effective in childhood morphea. Further controlled studies are necessary to investigate whether this combined therapy is superior to UVA1 phototherapy alone.

[What remains of the skin after 2000 years in a bog?]. / Was bleibt von der Haut nach 2000 Jahren Moor?

BACKGROUND AND OBJECTIVE: Mummies have an important place in the study of archaeology and paleopathology because they are so well preserved. For the first time skin samples of six 2300-1600 year old bog bodies from North Germany were examined by histology, transmission electron microscopy and immunohistology. METHODS: For histology the samples were stained with H&E and van Gieson elastic stain. Fixation and embedding in epoxy followed for the transmission electron microscopy. Specific antibodies directed to type IV collagen and S-100 were used. RESULTS: Histologically it was possible to observe collagen bundles in the dermis, with a density similar to recently stained samples. Epidermis was not preserved. The electron microscopy showed collagen fibrils with a diameter of 45-110 nm and the characteristic axial periodicity. Throughout the dermis, a number of spores of bacteria with a diameter of 0.83 +/- 0.051 micron and an electron dense core were found. No activity against the used antibodies could be detected. CONCLUSIONS: Histology and electron microscopy demonstrate the excellent conservation of the dermal collagen in the bog. In contrast to ice mummies like "Otzi" and mummies from Egypt, no cellular elements could be found in the skin of bog bodies.

Opposing effects of UVA1 phototherapy on the expression of bcl-2 and p53 in atopic dermatitis.

Recently, medium-dose UVA1 phototherapy (50 J/cm2) has been introduced as an effective treatment for severe atopic dermatitis (AD). In order to further elucidate the mechanisms by which medium-dose UVA1 irradiation leads to an improvement in skin status in patients with AD, biopsy specimens from ten patients before and after treatment were analysed immunohistochemically for features of apoptosis. We sought to determine the extent to which UVA1 irradiation was able to modulate the balance between p53 and bcl-2 expression in vivo using monoclonal antibodies labelling these proteins. As compared with lesional skin of patients with AD before UVA1 irradiation, the number of dermal cells, apparently lymphocytes, that were positive for p53 had significantly increased after treatment and, in addition, some basal keratinocytes showed slight positive staining for p53. An increased expression of the bcl-2 gene before treatment in predominately dermal lymphocytes was significantly downregulated by UVA1 therapy. The increase in p53+ cells and the decrease in bcl-2+ cells were closely linked to a significant reduction in dermal T cells (CD3+) and a substantial clinical improvement in skin condition. In summary, medium-dose UVA1 irradiation led to a marked modulation of the expression of p53 and bcl-2, and this plays a key role in regulating UVA1-induced apoptosis.

[3-dimensional reconstruction in dermatology. Prospects for new possibilities in routine histological diagnosis]. / Dreidimensionale Rekonstruktion in der Dermatologie. Ein Ausblick auf neue Möglichkeiten der histologischen Routinediagnostik.

BACKGROUND AND OBJECTIVE: The combination of digital image-analysis and computer-reconstruction of the three-dimensional architecture of the human skin can make this method usable on an acceptable time scale. PATIENTS/METHODS: We used biopsies of different diseases (malignant melanoma, lichen planus, psoriasis) and of normal skin. Immunohistologically stained sections were digitized and adjusted with respect to features of interest using the interlaced mode of an commercial image analysis system (Lucia G, Nikon GmbH, Düsseldorf). The sections have been segmented and the resulting three dimensional data sets were visualized on a UNIX based work station. RESULTS: Three dimensional reconstruction provides a different view into the architecture of normal and diseased skin: for example, the course of the duct of sweat glands or the perforation of a malignant melanoma through the underlying infiltrate. CONCLUSIONS: A new rapid reconstruction method is presented producing multidimensional histological images of the skin within a few hours. This automation is of interest in basic research and should find its way into routine histological diagnosis.

[An extreme case of environmental neurosis]. / Ein Fall einter "Umweltneurose" skurrilen Ausmasses.

A 64 year old female patient was diagnosed with scleroderma and has been bed-ridden for 25 years. She wears no clothing whatsoever on the grounds of an intolerance to textiles, and has spent the last eight years uninterruptedly in bed in a construction of kitchen paper towels and rubber bed sheets. A somatic disease has been be ruled out and cenesthesic schizophrenia diagnosed. As differential diagnoses, somatization, somatiform disorders and hypochondria were considered. The patient refused any psychiatric treatment.

[Depression and suicidal intentions as a side effect of high dosage interferon-alpha therapy--two cases]. / Depressivität mit Suizidalität als Nebenwirkung der Hochdosistherapie mit Interferon-alpha. Zwei Fallstudien.

Adjuvant therapy with interferon for malignant melanoma causes neurotoxic side effects such as depression. The biochemical mechanisms are unknown. We report two cases with both depression and amnesia. In one case, attempted suicide was accompanied by 7 h of amnesia. The diagnostic classification and possible explanations for the amnesia secondary to interferon therapy are reviewed.

Sweat gland proliferations in scleromyxedema.

Eccrine sweat duct proliferations may be found in various inflammatory and neoplastic skin lesions. We report a patient with scleromyxedema with extensive proliferations of intradermal sweat ducts. Three-dimensional reconstruction demonstrated extensive coiling and branching of the sweat ducts leading into cystic lacunae. In contrast to the basal cell carcinoma that had grown within the scleromyxedematous skin, the ducts close to the lumen stained positive for carcinoembryonic antigen and could therefore be differentiated from basal cell carcinoma. In micrographically controlled surgery of cutaneous epithelial tumors that are located in chronically inflamed skin, such sweat gland proliferations have to be considered as differential diagnosis.

Dose-dependent shift of apoptotic and unaltered melanocytes into the dermis after irradiation with UVA 1.

BACKGROUND: Intense UVA irradiation induces an increase in number, size and activity of intraepidermal melanocytes. The number of melanocytes and the activity of melanogenesis return to normal after cessation of irradiation. OBJECTIVE: In this study, we aimed to clarify the mechanism of reduction of melanocytes by apoptosis to prevent an uncontrolled increase in melanocytes within the epidermis. METHODS: The position of the melanocytes before and after UVA 1 irradiation was controlled by electronmicroscopy and histochemistry using Fontana-Masson staining. The status of apoptosis was demonstrated immunohistologically by the use of p53 and bcl2. RESULTS: A dose-dependent shift of melanocytes into the corium could be demonstrated. At low irradiation doses (20 J/cm2) pendulous melanocytes protrude into the dermis without losing contact to the dermoepidermal basement membrane. Higher irradiation doses (60 J/cm2) lead to a total elimination of fibrillary degenerated, apoptotic or even morphologically intact melanocytes into the corium. Once transported into the corium, the melanocytes can be detected there for more than 4 years. CONCLUSION: This shift mechanism seems to regulate and control UV-induced proliferation of epidermal melanocytes.

[High dosage intravenous immunoglobulin (IVIG) therapy in therapy-refractory ANCA-negative, necrotizing vasculitis]. / Hochdosierte intravenöse Immunglobulin (IVIG)-Therapie bei therapieresistenter ANCA-negativer, nekrotisierender Vaskulitis.

7 patients (5 female, 2 male; age: 22-81 years; average age = 58.1 J) with recurrent necrotizing ANCA-negative, non leucocytoclastic vasculitis, were enrolled into this study. Disease was resistant to prior conservative therapy, and therefore patients received high dose intravenous immuno-globulin (IVIG)--(dose: 1.0 g/kg body weight daily dose 0.25 g/kg body weight over 4 consecutive days). All patients responded rapidly to this therapeutic regimen. Specifically immediate pain relief was striking. Complete clearance of disease was observed in 5 out of 7 patients within 6 months while receiving IVIG (0.5 g/kg body weight) every 4 weeks for one year. In 2 out of 5 patients ulceration and vasculitis healed completely and therapy could be stopped after 6 months. In one patient treatment had to be discontinued due to decreasing kidney function. The data presented demonstrate that IVIG is an effective and valuable therapeutic modality in treatment of severe vasculitis resistant to conventional therapy. However consideration of costs, effectiveness and possible side effects is needed for this therapeutic regime.

[Keratosis palmoplantaris maculosa seu papulosa (Davies-Colley) simulating multiple cornua cutanea]. / Keratosis palmoplantaris maculosa seu papulosa (Davies-Colley) unter dem Bild multipler Cornua cutanea.

Patient with extensive keratosis palmoplantaris maculosa seu papulosa (Davies-Colley) presented with multiple cutaneous horns. The clinical picture, the histology, the electro microscopic examination, the negative tumor screening and the viral classification in the tissue allowed the differentiation from other palmoplantar keratoses. The patient was treated successfully using a combination of acitretin with physical and chemical measures.

In psoriasis the epidermis, including the subepidermal vascular plexus, grows downwards into the dermis.

In psoriatic lesions, capillaries in the papillary bodies seem elongated and increased in number. Most researchers postulate that there is angiogenesis of intrapapillary capillaries in psoriatic plaques. In this study we will show, by means of computer-aided three-dimensional reconstructions in four patients suffering from chronic plaque-type psoriasis, and in a healthy volunteer, that the elongation and increase of intrapapillary capillaries are not the result of angiogenesis. Our three-dimensional reconstructions show that the papillary body of psoriasis contains lymph capillaries besides the blood capillaries. Additionally, an inclusion of two tips of papillary bodies into one papilla at the base of the rete ridges becomes obvious. The vessels of the two tips are connected by a horizontal vessel. At the level of the horizontal connecting vessel there is the blind beginning of a lymphatic vessel. The connecting blood vessel, as well as the lymph capillary, belong to the horizontal subpapillary venous plexus but lie within the papillary body. The three-dimensional reconstructions show that by growing towards the dermis, the rete ridges include the vessels of the horizontal plexus. Surrounded by rete ridges, these vessels appear as intrapapillary capillaries.

The effect of fumaric acid esters and dithranol on acanthosis and hyperproliferation in psoriasis vulgaris.

In this study we investigated the histological changes, regression of acanthosis and rate of proliferation, that accompany the healing of psoriatic lesions after fumaric acid esters and dithranol treatment. Biopsies were taken before and during therapy as well as from neighbouring untreated, clinically uninvolved skin and healthy, non-psoriatic volunteers. Specimens were assessed using computer-supported image analysis and immunohistology. The parameters primarily examined were the height of the rete pegs and of the epithelium above the papillary body, the rate of proliferation, the actual number of cells in the two epidermal compartments and the cellular density in the epidermis. Both fumaric acid esters and dithranol reduce the degree of acanthosis; however, the mechanism and the rate of the reduction differ. While under fumaric acid esters the reduction is more rapid at first but subsequently slows down, dithranol leads to a slow but steady decrease of epidermal thickness, so that at the end of our study the degree of acanthosis was less under dithranol. As an underlying mechanism of action, we found that fumaric acid esters reduce the rate of proliferation and thereby decrease the number of cells per rete peg as well as the size of the individual keratinocytes. Dithranol in contrast does not reduce cell renewal. The decrease of the number of cells in the rete pegs might be caused by an increased differentiation time.

[Large nodular, multicenter, juvenile xanthogranuloma with ulceration]. / Grossknotiges, multizentrisches, juveniles Xanthogranulom mit Ulzeration.

We report on a patient with multicentric juvenile xanthogranuloma, whose unusual clinical and histological pattern initially obscured the diagnosis. Spontaneous remission of the tumour, which has now been maintained for over 2 years, the change from the primary monomorphological fibrocytic appearance to a polymorphological histiocytic picture with multiple fat-storing giant cells, and the lacking dermonstration of specific cell organelles finally allowed the nature of the disease to the definitely diagnosed.

The pseudo-elongation of capillaries in psoriatic plaques.

The intrapapillary vessels in the psoriatic plaque are described as elongated, twisted and multiplied. However there is neither proliferation nor necrosis of vessels in growing and dissolving psoriatic plaques. In 120 patients suffering from psoriasis vulgaris, computer-supported image analysis and in 8 patients additionally 3D reconstructions were made to investigate the regression process of the intrapapillary capillaries in the active and resolving psoriatic plaque. In acanthotic epidermis with a thickness of > 400 microns the first subpapillary horizontally oriented plexus is included in the papilla due to the down-growing of the epidermal rete pegs. In the evaluation of the computer-supported image analysis there is only little variation in the levels of the different vascular plexuses within the dermis, while the epidermis is decreasing from > 600 microns to > 100 microns. In the 3D reconstruction of the transition of a psoriatic lesion into adjacent non-involved skin it could be proved that, apart from the epidermal alterations, there is virtually no difference in the arrangement of the vessels between the psoriatic lesion and the adjacent non-involved skin. In psoriasis the vessels do not proliferate, they rest as resident structures and are embraced by the down-growing rete pegs.

The hyperperfusion of the psoriatic plaque correlates histologically with dilatation of vessels.

We examined psoriatic lesions on the upper legs in 20 patients, using a two-dimensional Laser-Doppler-Scanner (Laser Doppler Perfusion Imager LDI, Lisca Development, Linköping/Sweden). The plaques were evaluated weekly during therapy with dithranol. Five plaques were reconstructed three-dimensionally before and after therapy (reconstruction program ANAT 3D, SIS, Münster, Germany). The psoriatic plaque was represented in the Laser Doppler Perfusion image as a sharply demarcated, hyperperfused area. The perfusion of the plaques dropped during therapy with dithranol to just slightly increased values, compared with normal skin (2.04 arbitrary units AU, healthy skin 1.1 AU). Using three-dimensional reconstruction, we investigated the volume of dermal vessels and the density of papillae. When compared, the volume of papillary vessels was twice as large in psoriatic as in healthy skin. The number of the papillae per square millimetre, detected by three-dimensional reconstruction, was not reduced significantly during therapy. We think that the increased perfusion of the psoriatic plaque is due to the combination of morphological (dilatation of vessels), dynamic (increased blood flow) and optical effects (reduced scattering and increased sampling depth of the laser-beam in acanthotic tissue).

Fumaric acid esters (FAEs) suppress CD 15- and ODP 4-positive cells in psoriasis.

A histological-immunohistological study was conducted to investigate the effect of systemically administered fumaric acid esters (FAEs) on epidermal thickness and composition of the inflammatory infiltrate in psoriatic plaques. The very first effect of systemic therapy with FAEs is the disappearance of CD 15-positive cells in the beneath the epidermis, accompanied by a significant reduction in T-helper cells beneath the epidermis, pointing to an immunosuppressive effect. This is followed after some delay by a reduction in acanthosis and hyperkeratosis. The reduction in infiltrating T-lymphocytes corresponds to that seen after systemic or intralesional therapy with cyclosporin. However, the normalization of the psoriatic plaques takes longer under the influence of FAEs than under cyclosporin.

[The pustular bacterid (Andrews). Are there clinical criteria for differentiating from psoriasis pustulosa palmaris et plantaris?]. / Das pustulöse Bakterid (Andrews). Gibt es klinische Unterscheidungskriterien zu der Psoriasis pustulosa palmaris et plantaris?

A case report on the rare entity of "true" Andrews bacterid and a review of the literature are used to illustrate clinical and morphological criteria that allow discrimination between Andrews bacterid and psoriasis pustulosa palmaris et plantaris. The patient noted the eruption of sterile pustules on palms and soles for the first time in his life at the age of 73 during an attack of acute tonsillitis. He had no history of psoriasis and it was also unknown in the family history. In contrast to psoriasis pustulosa palmaris et plantaris, Andrews bacterid becomes manifest as isolated pustules with an erythematous rim, which do not destroy the ridged skin. On the rest of the integument disseminated pustules are seen but no psoriatic stigmata. Thus, apart from the criterion of coincidence with an infection and the short course, we can also differentiate between Andrews bacterid and psoriasis pustulosa palmaris et plantaris on the basis of clinical criteria.

[Considerations of the pathogenesis of parakeratosis variegata based on morphologic and molecular genetic findings]. / Uberlegungen zur Pathogenese der Parakeratosis variegata anhand morphologischer und molekulargenetischer Befunde.

We report on a 63-year-old woman who had been suffering from generalized parakeratosis variegata since she was 7 years old. Increased tightness of the skin was the only clinical symptom. On the whole integument except for the face, we found a fine network of hyper- and depigmentation and telangiectasias. The skin surface was dry and atrophic with fine lamellar scaling. Histological, immunohistological and ultrastructural findings indicated early infiltration by a cutaneous T-cell lymphoma. However, PCR analysis of the T-cell receptor gamma-chain genes revealed multiple amplification products favouring a polyclonal T-cell proliferation. In light of the clinical history over a period of 56 years, we consider parakeratosis variegata to be a benign, chronic inflammatory condition, as is confirmed by the results of PCR analysis in this patient.