[Intradermal metal deposits in an industrial worker]. / Intradermale Metalleinsprengungen bei einem Industriearbeiter.

CASE REPORT: We describe a 75-year-old patient with asymptomatic grey pigmentation on the face and fingers. He had worked over two decades in cutting high-voltage cables. The cutting procedures were performed without a face shield or protection gloves. The patient presented with gray punctate lesions beside some homogeneously stained zones. DIAGNOSTICS: Histologically, the deposits presented in the dermal tissue in a horse-shoe, oval, or splinter-like shape. The foreign body material was embedded by a few CD68-positive macrophages. Undyed histological sections were investigated via two-dimensional micro-synchrotron X-ray fluorescence analysis (SRXRF). The deposits were identified as zinc (Zn), copper (Cu), nickel (Ni), and strontium (Sr), which were strongly associated with maximal sulfur (S) concentrations. This association is presumably induced by complex binding between thiol groups and metal ions such as Zn, Ni etc. However, the iron (Fe) distribution patterns were quite different to those of Zn, Cu, or Ni. These heavy metals are major components of the metal wires that the patient worked with in his profession. CONCLUSION: To the best of our knowledge, this is the first case report in the dermatological literature of intradermal metal deposits identified via SRXRF analysis.

Seborrhoeic keratoses in patients with internal malignancies: a case-control study with prospective accrual of patients.

BACKGROUND: The association between the eruption of numerous seborrhoeic keratoses as a result of an underlying malignancy is controversially discussed. The aim of this case-control study with prospective accrual of patients was to determine whether a direct association exists between the number seborrhoeic keratoses and internal malignancies. METHODS: The numbers and sites of seborrhoeic keratoses were counted in 150 oncological patients and 150 matched controls. Additionally, the presence or absence of pruritus, acanthosis nigricans, and the sudden appearance of seborrhoeic keratoses were assessed. RESULTS: Seborrhoeic keratoses did not differ significantly between patients with internal malignancies and controls. Only two patients fulfilled the criteria of the Leser-Trélat sign, defined as the eruption of numerous seborrhoeic keratoses as a cutaneous marker of an underlying internal malignancy. CONCLUSION: No association was found between seborrhoeic keratoses and cancer. Furthermore, our data did not provide support to the validity of the Leser-Trélat sign in patients with internal malignancies.

Vascular endothelial growth factor in patients with psoriatic arthritis.

OBJECTIVE: To determine the levels of vascular endothelial growth factor (VEGF) in patients with active psoriatic arthritis, patients with inactive psoriatic arthritis, and healthy controls. Serum VEGF levels were correlated with clinical and laboratory features in patients with active psoriasis arthritis. METHODS: Serum samples from 14 patients with active psoriatic arthritis, 14 patients with inactive psoriatic arthritis, and 9 healthy controls were investigated. VEGF levels in the serum were measured using a sensitive sandwich ELISA. RESULTS: The mean serum VEGF concentration in patients with active PA was 394.4 pg/ml (394 +/- 171.8), in patients with inactive PA 200.4 pg/ml (200.4 +/- 115.7), and in healthy subjects 214.3 pg/ml (214.3 +/- 162.1). Patients with active psoriasis arthritis had significantly higher levels of VEGF compared to patients with inactive psoriasis arthritis and healthy individuals (p > 0.001). In contrast, VEGF levels were comparable in patients with inactive psoriatic arthritis and controls (p =0.659). Furthermore, in patients with psoriatic arthritis, VEGF levels were positively correlated with ESR, HAQ, PASI and VAS. CONCLUSION: VEGF levels may be regarded as a good indicator of active psoriasis arthritis.

Nanocrystalline silver dressings as an efficient anti-MRSA barrier: a new solution to an increasing problem.

The emergence of multi-drug-resistant strains of bacteria represents a particular challenge in the field of wound management. The aim of the current study was to investigate whether nanocrystalline silver dressings possess the physical properties to act as a barrier to the transmission of methicillin-resistant Staphylococcus aureus (MRSA) in the laboratory setting and in a clinical setting. Initially, MRSA suspension and colony culture experiments were performed showing that nanocrystalline silver dressings act as potent and sustained antimicrobial agents, efficiently inhibiting MRSA penetration. Subsequently, a double-centre clinical trial was initiated using nanocrystalline silver dressings as a cover for 10 MRSA colonized wounds in a total of seven patients. By delineating the MRSA load on the upper side of the dressing and the wound bed each time the dressing was changed (i.e. after 1, 24, 48 and 72 h), nanocrystalline silver dressings were found to provide a complete, or almost complete, barrier to the penetration/spread of MRSA in 95% of readings. In addition, 67% of all wound observations showed a decrease in the MRSA load with an eradication rate of 11%. We believe that nanocrystalline silver dressings may become an important part of local MRSA management, with cost benefits to both patients and the healthcare system.

Immunoglobulins coat microorganisms of skin surface: a comparative immunohistochemical and ultrastructural study of cutaneous and oral microbial symbionts.

Only recently have human sweat glands been demonstrated to secrete immunoglobulins (Ig), paralleling Ig secretion in mucosal epithelia. It is well established that Ig protect mucosal membranes against infections by binding to surface structures of microorganisms. In view of these findings immunohistochemical studies were performed to determine if microbes on the skin surface are coated by Ig as proposed for mucosal bacteria and fungi. Smear preparations from the skin and oral cavity rich in micro-organisms were subjected to immunoperoxidase staining using anti-secretory component (SC), -IgA, -IgM, -IgG antibodies. An immunogold labeling technique of microbial suspensions of sweat and saliva was adapted to correlate the results on an ultrastructural level. Negative controls included unsuccessful staining for IgA in preparations obtained from an IgA-deficient patient as well as nonreactivity of subcultured microorganisms for all Ig classes or SC. Smear preparations from both the oral cavity and skin surface exhibited labeling of bacterial or fungal elements with anti-IgA, -IgM, -IgG, and -SC antibodies. Skin bacteria revealed a lower number of reactive microbes as compared to saliva. Staining intensity for the different Ig classes exhibited intra- and interindividual variations. Immunoelectronmicroscopically, Ig and SC could be detected either directly along the cell wall of coccal, coryneform, and fungal elements or on floccular and fimbrial material adhering to the bacterial surface. It is concluded that secretory Ig of the skin cover surface structures of microorganisms and thus modify their adhesional and/or infectious properties, resembling humoral surface immunity on mucous membranes.

Immunohistochemical demonstration of immunoglobulin A in human sebaceous and sweat glands.

Immunoglobulin A (IgA) mediated humoral defense mechanisms have been detected on all mucous membrane surfaces. There are only a few papers about the presence of IgA in human skin. In order to demonstrate the occurrence of IgA in sebaceous and sweat glands, biopsies of normal human skin were investigated and compared to intestinal mucosa. Two different commercially available anti-IgA antibodies were used. For light microscopy peroxidase-anti-peroxidase (PAP) or avidin-biotin complex (ABC) staining was used, and for electron microscopy protein-A-gold (PAG) labeling was performed on tissue sections. Specifically decorated IgA was found in sebaceous glands as well as in various portions of eccrine glands. In sebaceous glands, the maximum of IgA concentration was seen near the mouth of pilosebaceous ducts. Sweat ducts exhibited a continuous coat of IgA, whereas secretory portions contained only singular scattered IgA positive cells. Immunoelectron microscopy suggests endocytotic uptake and processing of IgA in the glandular cells. These results indicate strongly that IgA are secreted by normal human sebaceous and sweat glands. Because it is well known that IgA plays an important role in inactivation of invading viruses, bacteria, and other antigenic structures on mucous membranes, it appears that IgA in sebum and sweat fulfil a similar function on the outer body surface.

Immunohistochemical properties of bone marrow mast cells in systemic mastocytosis: evidence for expression of CD2, CD117/Kit, and bcl-x(L).

In an attempt to identify novel diagnostic markers for mast cell (MC)-proliferative disorders, serial bone marrow (bm) sections of 22 patients with mastocytosis (systemic indolent mastocytosis, n = 19; mast cell leukemia [MCL], n = 1; isolated bm mastocytosis, n = 2) were analyzed by immunohistochemistry using antibodies against CD2, CD15, CD29, CD30, CD31, CD34, CD45, CD51, CD56, CD68R, CD117, HLA-DR, bcl-2, bcl-x(L), myeloperoxidase (MPO), and tryptase. Staining results revealed expression of bcl-x(L), CD68R, and tryptase in neoplastic MCs (focal dense infiltrates) in all patients. Mastocytosis infiltrates were also immunoreactive for CD45, CD117 (Kit), and HLA-DR. In most cases, the CD2 antibody produced reactivity with bm MCs in mastocytosis, whereas in control cases (reactive bm, immunocytoma, myelodysplastic syndrome), MCs were consistently CD2 negative. Expression of bcl-2 was detectable in a subset of MCs in the patient with MCL, whereas no reactivity was seen in patients with SIM or bm mastocytosis. Mastocytosis infiltrates did not react with antibodies against CD15, CD30, CD31, CD34, or MPO. In summary, our data confirm the diagnostic value of staining for tryptase, Kit, and CD68R in mastocytosis. Apart from these, CD2 may be a novel useful marker because MCs in mastocytosis frequently express this antigen, whereas MCs in other pathologic conditions are CD2 negative.

Keratitis, ichthyosis, and deafness syndrome with glycogen storage.

Electron microscopy performed in a young girl suffering from keratitis, ichthyosis, and deafness syndrome showed pathologic storage of glycogen in various types of tissues. This finding may be interpreted as evidence of an underlying inborn error of metabolism.

Decompensation of chronic open-angle glaucoma following mydriasis-induced pigmentary dispersion into the aqueous humour: a light and electron microscopic study.

A patient with well controlled chronic open-angle glaucoma developed after dilatation of both pupils persistent increase in intraocular pressure (IOP) due to extensive pigmentary dispersion into the aqueous humour. Trabeculectomy specimens obtained from both eyes after 3 and 7 weeks were studied by light and electron microscopy. It seems evident that the initial phase of raised IOP was caused by a clogging mechanism to the outflow channels by melanin and phagocytic cells. The permanent increase in IOP is attributed to the damage induced in the fibrous components of the trabecular sheets as a result of a complete breakdown of their endothelial covering.

The relation of nervous elements to intradermal nevi. As electron microscopic study.

Intratumoral nerves of dermal nevi were investigated by electron microscopy in order to elucidate the role of neural elements in the development of these tumors. The following results were obtained: 1. Intratumoral nerves exhibit an increased cellularity, but the number of myelinated fibers is reduced. 2. Nevus cells type B and C are frequently present within nerve fascicles. 3. Unmyelinated axons were found in close relationship to nevus cells. 4. Schwann cells may show proliferations similar to early stages of neurofibroma and can be differentiated from unpigmented tumor cells by their relation to axons only. These findings indicate that identical cell populations are present within the intratumoral nerves and the tumor itself. Therefore, the theory of a neural component in the histogenesis of intradermal nevi is supported.

Human monocytes and keratinocytes in culture ingest hydroxyethylstarch.

Severe itching for unknown reasons has been reported after administration of hydroxyethylstarch (HES) in haemodilution therapy of humans. In skin sections from patients who had received HES for otological reasons HES deposition was found by immunohistochemical methods in keratinocytes, epidermal dendritic cells, endothelial cells and macrophages. The aim of the present investigation was to study the interaction of cultured human monocytes and keratinocytes, normal (HNK) and malignant (KB, A431), with FITC-conjugated HES (200/0.5). Peripheral blood monocytes from healthy donors were isolated by Ficoll-Hypaque gradient centrifugation and adherence to plastic surfaces. Cells were incubated with HES-FITC (1 mg/ml) for 10, 20, 30, 60 and 120 min at 37 degrees C, washed several times to minimize cell-associated HES-FITC. The uptake of HES-FITC (200/0.5) was detected by fluorescence microscopy and flow cytometry. Monocytes and keratinocytes (HNK, KB, A431) acquired significant amounts of HES-FITC after 120 min. Endocytosis was blunted by the addition of unconjugated HES in ten-fold concentration. At 4 degrees C, a further inhibition was achieved, indicating an uptake of HES-FITC by monocytes and keratinocytes in vitro. These results indicate that a connection between the storage of HES by keratinocytes and monocytes and the observed itching in patients might be possible.

Hydroxyethylstarch deposits in human skin--a model for pruritus?

Severe itching for unknown reasons has been reported after administration of hydroxyethylstarch (HES) in haemodilution therapy of humans. After HES treatment, vacuoles in cells of various organs in humans have been shown, predominantly affecting the mononuclear phagocyte system. These vacuoles present indirect evidence for phagocytosis of HES particles. Since phagocytosis is also known to occur in the skin, this organ might represent a target for HES deposition, resulting in subsequent release of mediators responsible for the observed itching. The aim of the present investigation was to study skin biopsies of patients, who had received HES and suffered subsequently from itch. Skin sections were investigated for morphological impairment by means of light and electron microscopy, immunohistochemistry and immunoelectron microscopy using a polyclonal anti-HES antiserum. Storage of HES was demonstrated in the skin of all patients, mainly in dermal macrophages, endothelial cells of blood and lymph vessels, some perineural cells and endoneural macrophages of larger nerve fascicles, some keratinocytes and Langerhans cells. Treatment with antihistaminic agents proved ineffective in these patients; this fits with the observation that morphological signs of histamine release from mast cells were absent. These findings indicate that other mediators from HES-affected cells must be responsible for the development of the itching. Thus, investigation of HES storage may be a useful contribution to the elucidation of release of itch mediators and induction of pruritus.

Tactile corpuscle-like structures in a case of plexiform neurofibromatosis.

Tactile corpuscle-like structures were identified in a plexiform neurofibroma, which was localized on the right cranial hemisphere os a 16-year-old boy and had necessitated repeated surgery. These structures were studied by light and electron microscopy. The origin of their component cells is, however, still controversial. We believe to have accumulated sufficient evidence for a Schwann cell origin of these cells.

Longterm remission of tumor-stage mycosis fungoides following total-skin electron-beam radiotherapy.

We report the case of a patient with mycosis fungoides, stage II B with generalized plaques and ulcerated tumors in a severely reduced general condition, with anemia and extremely poor compliance, who was successfully treated with total-skin electron-beam radiotherapy with a less severe relapse after more than three years.

Crohn's disease masquerading as aphthous ulcers.

Although intraoral involvement in Crohn's disease (CD) is observed in only approximately 9% of cases, oral inflammation precedes intestinal symptoms of CD in about 60% of these patients. We describe a 20-year-old male with recurrent, painful, intraoral lesions who presented no other signs of systemic disease apart from severe loss of body weight. From the routinely screened serological parameters only the erythrocyte sedimentation rate and the acute phase reactants were elevated. A biopsy from the vestibular mucosa revealed a dense mononuclear infiltrate and, focally, small noncaseating granulomas suggestive of CD. Gastrointestinal endoscopy was performed showing mucosal involvement reaching from the esophagus to the descending colon. The diagnosis of active CD was confirmed by histopathology of intestinal biopsy specimens. As oral lesions are sometimes treated without a definite diagnosis, we emphasize the need to search for underlying systemic illness in the differential diagnosis of recurrent inflammatory lesions of the oral cavity.

Sensory recovery in myocutaneous, noninnervated free flaps: a morphologic, immunohistochemical, and electron microscopic study.

The aim of this study was to clarify the following questions: (1) Do newly sprouting axons use the empty neurilemmal sheaths of a flap as conduits? (2) To what extent can sensibility recover? (3) Does sensory recovery occur at the margins of the flap or at its center? (4) Does chemotaxis influence the regeneration process? In 16 free myocutaneous flaps (12 latissimus dorsi, 4 rectus abdominis) we investigated pain (pinprick), constant touch, temperature, 30- and 256-Hz vibration, and static and moving two-point discrimination between 1 1/2 and 8 years after surgery. Four flaps were anesthetic, eight recovered partly, and four had six or more modalities present all over the flap; six of ten flaps with poor recovery showed better sensitivity close to the anastomosis. Nine patients agreed to have two punch biopsies (6 mm) taken from their flaps (seven from areas with different degrees of sensory recovery and two from the center and the periphery when recovery was homogeneous). Biopsies from the areas with better sensory recovery showed slightly more nerves than the other punches in five instances, showed no difference between the two biopsies in one instance, and seemed to have more nerves in the biopsy from the area with less recovery in the last instance. The two pairs of biopsies from the homogeneously recovered flaps showed similar amounts of nerves. S-100 protein-positive neural structures (Schwann cells) were found in 13 biopsies, and neuron-specific enolase-positive nerve fibers (nerve axons) were found in 10 biopsies. Electron microscopy showed mainly unmyelinated fibers, always adjacent to vessels and sometimes with regenerative phenomena. We believe that sprouting axons probably grow into a flap attracted by chemotaxis from hair follicles, the basement membrane, and the laminin contained in the sheath. We recommend maximum scar excision at the recipient site to enhance sensory recovery in flaps. We conclude that (1) the sprouting axons primarily use the empty neurilemal sheaths as conduits, (2) sensory recovery can reach two-point discrimination equal to the donor site of the flap, and (3) sensory recovery occurs mainly from the margin of the flap but also from the bed.

Serum level of VEGF-D in patients with primary lymphedema.

Recent studies have indicated that vascular endothelial growth factor-D (VEGF-D) stimulates lymphangiogenesis in humans. Furthermore, mutations of vascular endothelial growth factor receptor 3 (VEGFR-3) have been observed in families with hereditary lymphedema. The lack of stimulation of lymphangiogenesis could lead to production of even more VEGF-D to obtain stimulation of lymphangiogenesis resulting in a high serum level of VEGF-D. The aim of the present study was to compare the serum level of VEGF-D in patients with primary lymphedema with healthy controls. In a prospective study, the serum level of VEGF-D was determined by a solid phase ELISA in patients with primary lymphedema and compared with healthy controls. In the group of patients with primary lymphedema the serum level of VEGF-D was significantly higher compared with controls (p=0.0047). The increased levels of VEGF-D observed in the present study suggest that primary lymphedema may be based on defective stimulation of VEGFR-3.

[Specific pregnancy dermatoses--a simplified clinical classification]. / Spezifische Schwangerschaftsdermatosen--Eine vereinfachte klinische Klassifikation.

The terminology of the specific pregnancy dermatoses is confusing. Several names have been used for the same clinical conditions or individual reports have been described as special entities. In order to get a more practical classification from the clinical point of view, four broad categories of specific dermatoses of pregnancy are proposed: herpes gestationis, polymorphic eruption of pregnancy, prurigo gravidarum and autoimmune progesterone dermatitis.

[Benzoyl peroxide in the treatment of acne vulgaris (author's transl)]. / Klinische Erfahrungen mit Benzoylperoxyd in der Behandlung der Acne vulgaris.

63 patients suffering from predominantly papulo-pustular acne vulgaris were treated with 5-10% benzoyl peroxidegel over a period of 2-4 months. The skin condition showed marked improvement in 80% of the patients. Two patients developed cutaneous allergy. Benzoyl peroxide is the therapy of choice for the inflammatory form of acne vulgaris. Systemic tetracyclines need not be given concomitantly. Autoradiographic studies revealed that benzoyl peroxide also has a truly sebostatic effect.

[Immunoglobulin A in the sebaceous glands. Light and electron microscopy immunomorphologic detection]. / Immunoglobulin A in Talgdrüsen. Licht- und elektronenmikroskopischer immunmorphologischer Nachweis.

This paper presents evidence for the presence of immunoglobulin A in human sebaceous glands. Light- and electron-microscopic immune cytochemistry techniques revealed secretory IgA in normal sebocytes and within pilosebaceous ducts. The secretory process corresponds to the well-established production of IgA at the site of other internal body surfaces. Basal and suprabasal sebocytes contain IgA in linear extracellular, as well as aggregated intracellular patterns. However, maximal diffuse concentrations are present at the opening of the pilosebaceous duct. This distribution pattern indicates an antimicrobial protective character of IgA, corresponding to similar functions on mucous membrane surfaces. Thus, another important humoral factor contributing to the complex system of skin-associated lymphoid tissue is postulated.