[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.

Merkel cell carcinoma: mitoses, expression of Ki-67 and bcl-2 correlate with disease progression.

BACKGROUND: There are conflicting data on markers of disease progression and outcome of Merkel cell carcinoma. OBJECTIVE: We suggest to review histological and various immunohistochemical features of Merkel cell carcinoma specimens, in order to identify prognostic markers of clinical relevance. METHODS: We collected paraffin-embedded blocks from primary tumours from 26 patients diagnosed with Merkel cell carcinoma and determined the following: type and size of the tumour, number of mitoses, proliferation rate (Ki-67 antibody), (anti)-apoptosis rate (bcl-2, p53, p63 antibodies) and lymphatic vessel invasion (D2-40 antibody for podoplanin). Two authors blinded to clinical outcome, independently assessed and scored all samples. The findings were correlated with tumour progression, which was determined by local recurrence, lymph node- or distant metastases. RESULTS: During the average follow-up period of 63.4 months 12 (46%) patients had disease progression. Statistical analysis revealed Ki-67-staining (P = 0.005) as a marker of disease progression, high number of mitoses (P = 0.026) correlated with lymph node metastasis, while a tendency for increased Bcl-2 expression (P = 0.064) was found in patients with local recurrence. A higher number of invaded lymphatic capillaries showed a tendency in correlation with metastases (P = 0.072). CONCLUSION: The findings indicate that high numbers of mitoses, proliferation and survival of tumour cells as marked by Ki-67- and Bcl-2-staining, and infiltration of lymphatic vessels, might correlate with the biological behaviour of Merkel cell carcinoma.

Detection of Borrelia burgdorferi DNA by polymerase chain reaction in the urine and breast milk of patients with Lyme borreliosis.

Current laboratory diagnosis of Lyme borreliosis relies on tests for the detection of antibodies to Borrelia burgdorferi with known limitations. By using a simple extraction procedure for urine samples, B. burgdorferi DNA was amplified by a nested PCR with primers that target the specific part of the flagellin gene. To control possible inhibition of the enzyme (polymerase), a special assay using the same primers was developed. We examined 403 urine samples from 185 patients with skin manifestations of Lyme borreliosis. Before treatment, B. burgdorferi DNA was detected in 88 of 97 patients with Lyme borreliosis. After treatment, all but seven patients became nonreactive. Six of these seven persons suffered from intermittent migratory arthralgias or myalgias, and one from acrodermatitis chronica atrophicans. Two of 49 control patients with various dermatologic disorders and none out of 22 presumably healthy persons were reactive in the PCR. In addition to urine, breast milk from two lactating women with erythema migrans was tested and also found reactive. Borrelia burgdorferi DNA can be detected with high sensitivity (91%) by a nested PCR in urine of patients with Lyme borreliosis. In addition, this test can be a reliable marker for the efficacy of treatment.

Venous thromboembolism at a young age in a brother and sister with coinheritance of homozygous 20210A/A prothrombin mutation and heterozygous 1691G/A factor V Leiden mutation.

We report on members of a Turkish thrombophilic family with coinheritance of the prothrombin mutation PT20210A and the factor V Leiden mutation. The 23-year-old propositus and his elder sister both had episodes of venous theomboembolism at a young age (23 years and 26 years, respectively) and are homozygous for the PT20210A mutation and heterozygous for the factor V Leiden mutation. The 51-year-old father is suffering from coronary heart disease and is heterozygous for both thrombophilic mutations. The asymptomatic 43-year-old mother is heterozygous for the PT20210A mutation, but without activated protein C resistance. Two other children, a 20-year-old girl who is homozygous for the PT20210A mutation and a 13-year-old boy who is heterozygous for the PT20210A mutation, are both free from activated protein C resistance and thrombosis. This report provides further evidence for an early onset of thromboembolic disorders in individuals with an homozygous state of the prothrombin variant 20210A/A and coinheritance of another thrombophilic mutation. Consensus guidelines are required for the treatment and prophylaxis of patients and subjects who remain asymptomatic with homozygous or more than one heterozygous genetic defect associated with thrombophilia.

Functional reconstruction of the upper eyelid after excision of squamous cell carcinoma in xeroderma pigmentosum.

This paper describes a technique for excision of a squamous cell carcinoma of the upper eyelid and subsequent functional reconstruction of the lid in a patient with xeroderma pigmentosum. By applying the modified technique of temporalis muscle flap, the upper eyelid was reconstructed by a skin graft from non-sun-exposed skin and a muscle pocket of the temporalis muscle. For the mucosal layer of the upper eyelid, a transplant of oral mucosa was used. An effective functional and aesthetic outcome has been achieved by this technique.

Erythema migrans and serodiagnosis by enzyme immunoassay and immunoblot with three borrelia species.

There is wide divergence of opinion between physicians regarding the use of serological measures for the diagnosis and treatment of erythema migrans, the hallmark of Lyme borreliosis. We studied the outcome of an enzyme immunoassay and immunoblot (Western blot) used on the sera of patients who had suffered tick bite and erythema migrans, and had been subsequently treated with various antibiotics. Ninety-nine consecutive patients presenting with erythema migrans after tick bite were prospectively recruited at the outpatient department of two Vienna City hospitals and at the consultation office for Lyme borreliosis of the Institute of Hygiene. University Vienna. Blood samples were taken before antibiotic treatment and 3 and 6 months thereafter. Blood samples from 100 blood donors served as controls. Antibodies against Borrelia burgdorferi sensu lato were determined by enzyme immunoassay (IgG and IgM EIA) and by IgG immunoblot. The latter was performed with isolates of B. alzelii (H2) B. burgdorferi sensu stricto (Le) and B. garinii (W) from Austrian patients. The 4 interpretation criteria for immunoblot results were: A (3 bands out of 8), B (2 bands out of 9), C and D (1 band out of 6). In all patients, the erythema resolved within the treatment period. No complications secondary to the borrelia infection were registered. After treatment there was no significant change in titre, nor was there a difference in the immunoblot pattern between the first, second and third serum samples. Serum antibodies to B. burgdorferi were positive by EIA in 22.9% (IgG) and 2.5% (IgM). Immunoblot results offered by borrelia species and by the interpretation criteria, ranging between 8.3% (criterion A, strain Le) and 44.2% (criterion D, strain H2). By EIA, control samples were IgG and IgM positive in 5% and 1%, respectively. Positive immunoblot results with strain H2 were found in 9%, 13%, 18%, and 20% by the criteria A through D respectively. After antibiotic treatment of erythema migrans the immunological response appears to be abrogated. Thus, serological results are not supportive for the diagnosis of erythema migrans, not will they retrospectively prove successful antibiotic treatment of borrelia infection.

[Leucocytoclastic eosinophilic vasculitis with Löffler syndrome]. / Leukozytoklastische eosinophile Vaskulitis bei eosinophilem Lungeninfiltrat "Löffler"

Histologically, leukocytoclastic vasculitis (LV) presents with neutrophilic granulocytes with leukocytoclasia and erythrocyte extravasation, associated with variable counts of lymphocytes, plasma cells and eosinophilic granulocytes. The association of a LV with eosinophilic granulocytes and eosinophilic pneumonia was first described by Chan et al. in 1982. Our case represents the second report in the literature of this rare disease: a 85 year old patient with LV and numerous eosinophilic granulocytes in association with intermittent blood eosinophilia and Löffler syndrome (eosinophilic pulmonary infiltrates). The recurrent episodes were treated successfully with oral corticosteroids.

[Sweet syndrome. Acute neutrophilic dermatosis in multiple myeloma]. / Sweet-Syndrom. Akute neutrophile Dermatose bei multiplem Myelom.

A 64-year-old woman complained of reddish plaques that had suddenly appeared on her upper arms and trunk. Histological investigation revealed perivascular distribution of a neutrophilic infiltrate in the upper and mid-dermis; direct immunofluorescence showed deposits of C3 and fibrin in and around the vessels. Laboratory values in the blood, X-ray of the head and fine-needle biopsy of the hip showed the typical pattern of multiple myeloma. After chemotherapy the dermatological lesions improved rapidly, and the plasmocytoma reached remission stage. The diagnosis of Sweet's syndrome was established on the basis of the clinical and histological changes and the improvement observed after steroid therapy. The coincidence with plasmocytoma confirms the interpretation of Sweet disease as a paraneoplastic syndrome.

[Lymphocyte proliferation test in cutaneous manifestations of Lyme borreliosis]. / Lymphozytenproliferationstest bei kutanen Manifestationen der Lyme-Borreliose.

The humoral immunoreactivity in Lyme borreliosis is a well characterized parameter for establishing the diagnosis of a Borrelia burgdorferi (Bb) infection. Since patients with seronegative Lyme borreliosis have been described, lymphocyte proliferation tests may be used for detecting patients who only develop a cellular immunoreactivity against Bb organisms. We performed a the lymphocyte proliferation assays in order to determine the cellular immunoreactivity to these spirochetes in given patients with histologically confirmed diagnosis of erythema migrans (EM), acrodermatitis chronica atrophicans (ACA), and for control purposes patients with Lyme disease non associated dermatoses (NLDH) and healthy volunteers (G). Stimulation index was defined as 3H thymidine-uptake in peripheral mononuclear cells, calculated as quotient dpm (stimulated cells)/dpm (unstimulated cells) (dpm = disintegrations per minute). Stimulation indices > 10 were considered positive. We detected elevated cellular immunoreactivity of peripheral mononuclear cells in 33% EM-patients (3/9) and in 23% (3/13) ACA patients tested. Patients tested before and after antibiotic therapy showed a significant decrease of stimulation index after antimicrobial treatment (p < 0.05). Patients the EM, who are mostly seronegative at the onset of cutaneous eruption exhibit in a third of patients an elevated cellular immune response to Bb. Therefore lymphocyte proliferation assays can be recommended as an additional test system in case of lack of serological response. The significant decrease of stimulation index after antimicrobial therapy indicates for downregulation of the cellular immune response to these spirochetes investigated, and counts for the specificity of this test system.

Success and failure in the treatment of acrodermatitis chronica atrophicans.

To determine the most effective treatment for acrodermatitis chronica atrophicans, several clinical trials were undertaken in recent years to evaluate whether a 2-week course of ceftriaxone would be superior to oral antibiotics. Of the 46 patients suffering from acrodermatitis chronica atrophicans, 14 were treated with ceftriaxone 2g for 15 days. The remaining patients received either oral penicillin V 1.5 million IU t.i.d. or doxycycline 100 mg b.i.d. for 20 to 30 days. Patients were followed up for at least 1 year. Of the 14 ceftriaxone-treated patients four showed incomplete regression of the inflammatory skin changes after 6 to 12 months. Two out of five patients who were monitored for Borrelia burgdorferi DNA excretion were still positive after 12 months as compared to none of six patients who were treated orally for 20-30 days. Six out of 11 patients treated orally for only 20 days needed retreatment after 6 months because of continuing skin manifestations, neuropathy or arthralgia. A 30-day duration of treatment with oral antibiotics and not the chosen antibiotic is crucial for curing acrodermatitis chronica atrophicans. The duration of treatment with ceftriaxone needed for eradication of Borrelia in acrodermatitis chronica atrophicans has yet to be determined in future studies.

Juvenile hyaline fibromatosis: impaired collagen metabolism in human skin fibroblasts.

Juvenile hyaline fibromatosis (JHF) is inherited as a fatal autosomal recessive disorder characterised by multiple tumorous mucocutaneous proliferations. In this paper a 14 month old girl with JHF is described. For this condition, a malfunction of collagen synthesis is considered as the pathogenetic cause. Recently published data have revealed an absent band for type III collagen (TIIIC) chain in western blot studies of clinically unaffected JHF skin. Therefore supernatants of skin fibroblast cell cultures, obtained from normal human skin, were analysed for type 1 collagen (TIC) and TIIIC metabolites by radioimmunoassays. Besides the typical morphological connective tissue changes in the skin lesions, TIC synthesis and degradation were found increased in JHF fibroblasts compared with control fibroblasts. In contrast, TIIIC overall metabolism was significantly reduced by 36% compared with controls.

Linear focal elastosis (elastotic striae): increased number of elastic fibres determined by a video measuring system.

We present an unusual case of linear focal elastosis occurring exclusively on the legs of a 13-year-old girl. An increase of elastic fibres (EF) was demonstrated histologically, and the number of EF in lesional and normal skin was quantified using a video measuring system. EF were found to be increased by about 100% in lesional skin compared with unaffected skin. EF were elongated, thinned and split at their ends with a paintbrush formation.

Pseudoporphyria cutanea tarda induced by furosemide in a patient undergoing peritoneal dialysis.

We report on a 32-year-old female patient undergoing peritoneal dialysis for diabetic nephropathy who developed blisters and cutaneous fragility on the dorsa of the hands. Histopathology of an early lesion showed a subepidermal cleft under a regular epidermis with single necrotic keratinocytes and normal dermal structures. In an advanced lesion, a subepidermal bulla and caterpillar bodies were found in the epidermis. Dermal vessel walls were normal and surrounded by a discrete lymphocytic infiltrate. Direct immunofluorescence revealed perivascular deposits of C3. Uroporphyrin and coproporphyrin levels of serum, urine and dialysate were repeatedly normal, confirming pseudoporphyria. The patient took furosemide (500 mg daily). Replacement of furosemide by ethacrynic acid led to spontaneous healing of the blisters. The patient was free of further lesions at the 1-year follow-up.

[Lichen striatus or Blaschkitis in the adults. Variations of the same entity?]. / Lichen striatus oder Blaschkitis des Erwachsenen. Variationen derselben Entität?

A 64-year-old woman presented with extensive erythematous papulosquamous lesions along the lines of Blaschko on the right half of the trunk and the right leg. The clinical and histological features led to the diagnosis of lichen striatus, a dermatosis which usually appears during childhood. Treatment with acitretin led to marked improvement. Lichen striatus and its differential diagnoses--particularly "blaschkitis of adulthood" as first described in 1990--are discussed.

Isolation and polymerase chain reaction typing of Borrelia afzelii from a skin lesion in a seronegative patient with generalized ulcerating bullous lichen sclerosus et atrophicus.

A 64-year-old woman presented with bullous and ulcerating lichen sclerosus et atrophicus (LSA) on the neck, trunk, genital and perigenital area and the extremities. Histology of lesional skin showed the typical manifestations of LSA; in one of the biopsies spirochaetes were detected by silver staining. Despite treatment with four courses of ceftriaxone with or without methylprednisone for up to 20 days, progression of LSA was only stopped for a maximum of 1 year. Spirochaetes were isolated from skin cultures obtained from enlarging LSA lesions. These spirochaetes were identified as Borrelia afzelii by sodium dodecyl sulphate--polyacrylamide gel electrophoresis and polymerase chain reaction (PCR) analyses. However, serology for B. burgdorferi sensu lato was repeatedly negative. After one further 28-day course of ceftriaxone the lesions stopped expanding and sclerosis of the skin was diminished. At this time cultures for spirochaetes and PCR of lesional skin for B. afzelii DNA remained negative. These findings suggest a pathogenetic role for B. afzelii in the development of LSA and a beneficial effect of appropriate antibiotic treatment.

Erythema migrans: three weeks treatment for prevention of late Lyme borreliosis.

An open, randomized, prospective study was carried out to compare the clinical efficacy and safety of phenoxymethylpenicillin with that of minocycline in the treatment of erythema migrans. Sixty patients (minocycline 30, penicillin 30) were enrolled in the study. The two groups of patients were statistically homogeneous regarding age and sex distribution. IgG and IgM antibodies against Borrelia burgdorferi were determined by ELISA before and after treatment and 1 year thereafter. Thirty-nine patients completed the study. All these patients (penicillin 21, minocycline 18) who received a 21-day course of treatment were free of clinical symptoms of late Lyme borreliosis after 1 year. Serum antibodies against B. burgdorferi could be detected before treatment in 6/21 patients treated with penicillin and 3/18 patients treated with minocycline. After 1 year 8/39 patients were seropositive without any evidence of ongoing disease. In the remaining 21 patients treatment could not be completed with the initial antibiotic due to side effects (penicillin 9/30, minocycline 12/30). One patient, who stopped penicillin treatment at day 14 and one patient who stopped minocycline at day 4, developed fatigue and memory impairment within the observation period. A 3-week course of treatment with penicillin or minocycline is equally effective in treating patients with erythema migrans and preventing late symptoms of Lyme borreliosis.

Cutaneous malakoplakia on the forehead.

A case of cutaneous malakoplakia in an 81-year-old woman in reported. A reddish slowly growing plaque had appeared on her forehead 13 years previously. Histopathology revealed a dense dermal granulomatous infiltrate consisting of lymphocytes and numerous histiocytes containing Michaelis-Gutmann bodies. Ciprofloxacin treatment resulted in partial involution of the lesion.