[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.

Accuracy of the non-sentinel node risk score (N-SNORE) in patients with cutaneous melanoma and positive sentinel lymph nodes: a retrospective study.

BACKGROUND: Sentinel node (SLN) biopsy in patients with melanoma permits identification of those at risk for further metastases in non-sentinel lymph nodes (NSLN). However, a mere 20% of SLN-positive patients have metastases in NSLN. Therefore we need criteria to predict NSLN-positivity. A new score system known as the non-sentinel risk score, (N-SNORE) based on five clinical and pathological characteristics (gender, regression in primary melanoma, proportion of SNs containing melanoma, perinodal lymphatic invasion, and SN tumor burden), was first published in 2010. In this study, the accuracy of N-SNORE was validated in melanoma patients with positive SLN. METHODS: A total of 106 melanoma patients with positive SLN, who had undergone complete lymph node dissection (CLND) subsequently, were included in the study. The N-SNORE was calculated in all patients, and the risk was compared to the frequency of NSLN metastases. Statistical analysis of the data was performed. RESULTS: Thirteen patients were at very low risk for NSN metastasis (score 0), 63 patients at low risk (score 1-3), 19 at intermediate risk (score 4-5), 6 at high risk (score 6-7), and 5 at very high risk (score >8). NSLN positivity rates for these 5 risk groups were 7.7%, 18.2%, 21.1%, 33.3%, and 80%, respectively. According to Fisher's exact test, the contingency coefficient was .322; the p-value was .025. CONCLUSION: An increasing N-SNORE was clearly correlated with a higher risk of NSLN positivity. Based on the p-value and the contingency coefficient, the overall accuracy of the N-SNORE was proven on statistical calculation.

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.

Long-term mortality in patients with thrombosis of the inferior vena cava, iliac and femoral veins.

OBJECTIVES: To assess the long-term mortality in patients with thrombosis of the vena cava, iliac and femoral veins. DESIGN: Registry study. MATERIALS: Between 1992 and 2000, 212 consecutive patients with acute pelvic vein thrombosis diagnosed by duplex sonography were examined by magnetic resonance imaging (MRI) to determine the most proximal extent of the thrombus. MRI revealed a thrombosis in the inferior vena cava in 46 patients (22%), in the iliac vein in 142 patients (67%), and in the femoral vein in 24 patients (11%). METHODS: The vital status of the patients was investigated in April 2004 using the Austrian National Registry and the Cause of Death Register. RESULTS: A total of 211 patients of the original 212 patients were monitored over a mean follow-up period of 91 months. Seventy-two of 211 patients (34%) had died. There was no significant difference in the long-term mortality, the survival period or the occurrence of fatal pulmonary embolism (PE) between previously diagnosed vena cava, iliac vein, or femoral vein thrombosis. CONCLUSIONS: Extension of a thrombus into the inferior caval vein in patients considered to have a pelvic vein thrombosis has no impact on long-term mortality or the development of fatal PE compared to those patients with thrombus limited to more distal veins.

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.

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.

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.

Cutaneous dendritic cells are main targets in acute HIV-1-infection.

Acute human immunodeficiency virus (HIV) infection is a transient illness that typically presents with mucocutaneous and constitutional symptoms. It is soon followed by seroconversion with the detection of anti-HIV antibodies in the peripheral blood. To better understand the pathogenetic events leading to this clinical picture, we sought to investigate the (immuno)histologic features of the skin rash occurring in an acutely infected person. A skin biopsy of an acutely infected person was investigated histologically and immunohistologically using paraffin-embedded tissue sections. Interface dermatitis with pronounced vacuolization of the basal keratinocytes was a prominent histological finding. The inflammatory infiltrate was composed of CD3+/CD8+ T cells with coexpression of Granzyme B7 and TIA-1, and CD68+ histiocytes/dendritic cells. CD1a+ intraepidermal Langerhans cells (LC) were significantly decreased and individual LC coexpressed HIV-p24 antigens as evidenced in double labeling experiments. HIV-infected LC were demonstrated in close apposition to cytotoxic T cells. This study provides the first definitive evidence for infection of LC at extramucosal sites in this very early stage of disease. Our findings emphasize the critical role of dendritic cells as a virus reservoir and the skin as a major site of HIV replication during the course of the disease.

Punctate keratoderma-like lesions on the palms and soles in a patient with chloracne: a new clinical manifestation of dioxin intoxication?

We report what we believe to be a novel skin manifestation of dioxin intoxication. A 30-year-old woman with 2,3,7, 8-tetrachlorodibenzo-p-dioxin levels of 144,000 pg g-1 blood fat presented with severe chloracne that affected the entire integument. She also exhibited acral granuloma annulare-like lesions and distal onycholysis and, at a later time point, showed signs of hypertrichosis, as well as brownish-grey hyperpigmentation of the face. In addition, she developed punctate keratoderma-like lesions on the palms and soles. These lesions were negative for human papillomavirus and histologically characterized by cone-shaped hyperkeratoses invaginating, but not penetrating, into the dermis. Squamous syringometaplasia of the eccrine glands was observed in the immediate vicinity of these lesions. Both clinically and histologically these alterations are essentially indistinguishable from what is described as keratosis punctata palmaris et plantaris (KPPP). Although a fortuitous coincidence of chloracne and KPPP cannot be formally excluded, the possibility exists that in our patient toxic levels of dioxin were causally involved in this disorder of keratinization.

Immunoreactivity of B-cell markers (CD79a, L26) in rare cases of extranodal cytotoxic peripheral T- (NK/T-) cell lymphomas.

The monoclonal antibodies L26 (CD20) and CD79a are very useful reagents for the immunohistochemical assessment of B-cell lineage in lymphoproliferative disorders. Although very few CD20-positive peripheral T-cell lymphomas (PTL) have been reported, comprehensive analyses of CD79a reactivity in extranodal PTL and NK/T-cell lymphomas have not been performed previously. This study investigated CD79a (clone JCB117) and CD20 reactivity in 94 extranodal non-B-cell lymphomas (enteropathy-type intestinal T-cell lymphoma [n = 52], nasal NK/T-cell lymphoma [n = 11], and primary cutaneous PTL [n = 31]) and in 17 cases of nodal PTL, unspecified. In four cases (enteropathy-type intestinal T-cell lymphoma [n = 3] and nasal NK/T-cell lymphoma [n = 1]), the majority of tumor cells stained for CD79a (all CD20 negative) and one cutaneous PTL, unspecified, was CD20 positive (CD79a negative). Extensive immunophenotyping and polymerase chain reaction-based molecular analyses revealed that all five B-cell marker-positive extranodal lymphomas had a cytotoxic phenotype and did indeed represent monoclonal peripheral T-cell proliferations. To minimize the risk of misinterpretation of lymphoma cell lineage, especially in cases of extranodal, lymphoproliferative disease, we suggest the use of both CD79a and CD20 in combination with a panel of antibodies reactive to T cells, such as betaF1 and CD5, and to T cells and NK cells, such as CD3, CD2, CD56, and TIA-1.

Effects of interferon-alpha2b treatment on ex vivo differentiation of mast cells from circulating progenitor cells in a patient with systemic mastocytosis.

Interferon (IFN)-alpha, a known inhibitor of myelopoiesis, is increasingly used to treat patients with systemic mastocytosis (SM). However, the mechanisms of IFN-alpha effects on mast cell (MC) growth remain unknown, and the treatment responses may be variable. In the present study, factor-dependent ex-vivo differentiation of MCs from peripheral blood mononuclear cells (PBMNCs) was analyzed in a patient with SM treated with IFN-alpha2b (3 million U/day). The patient exhibited an extensive MC infiltration in his bone marrow (BM) and increasing serum total tryptase levels (spiking to > 1,400 ng/ml). PBMNCs were collected before and during IFN-alpha2b treatment and cultured in the presence or absence of stem cell factor (SCF, 100 ng/ml) for 42 days. In the absence of SCF, no MC growth was detectable. However, in the presence of SCF, MC containing tryptase appeared in the cultures. Treatment with IFN-alpha2b resulted in a time-dependent decrease in SCF-inducible formation of MCs from PB progenitor cells in vitro. Also, during IFN-alpha2b treatment, blood histamine concentrations decreased. Serum total tryptase levels initially increased despite IFN-alpha2b treatment. However, after a latency period of a few months, tryptase concentrations declined and then reached a plateau. In healthy individuals, the SCF-induced in vitro growth of MCs from their progenitor cells was also inhibitable by the addition of IFN-alpha2b. In summary, our data show that IFN-alpha2b can exhibit inhibitory effects on factor-dependent growth of MC progenitor cells. However, it still remains open which of the patients with mastocytosis can benefit from long-term IFN-alpha treatment.

Tissue deposits of hydroxyethyl starch (HES): dose-dependent and time-related.

Tissue deposits occur after administration of plasma substitutes. After hydroxyethyl starch (HES), deposits may last for months, causing pruritus and impairment of function. Because elimination of HES deposits has not been demonstrated in humans, we studied 26 patients, for up to 7 yr after HES administration, to assess HES storage. HES dose ranged from 0.34 to 15.00 g kg-1 body weight, and administration intervals from 1 day to 7 yr. Biopsies of the liver, muscle, spleen, intestine or skin were studied using light and electron microscopy and immunohistochemistry. HES storage was dose-dependent, decreased in all organs with time and was greater in patients suffering from pruritus. We conclude that tissue deposition of HES is transitory and dose-dependent, with differences between subjects in severity and duration.

Increased dermal angiogenesis after low-intensity laser therapy for a chronic radiation ulcer determined by a video measuring system.

Acute and chronic radiation-induced dermatitis can occur after high doses of ionizing radiation of the skin. We describe a patient with a long-lasting radiotherapy-induced ulcer that healed after low-intensity laser therapy. A video measuring system was used to determine the number of dermal vessels in the ulcer before and after laser treatment. We found a statistically significant increase in the number of dermal vessels after low-intensity laser therapy in both the central and marginal parts of the ulcer compared with its pretreatment status.

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.

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.

Immunohistochemistry with monoclonal antibody against Candida albicans mannan antigen demonstrates cutaneous Candida granulomas as evidence of Candida sepsis in an immunosuppressed host.

We report the occurrence of invasive Candida albicans infection with disseminated cutaneous Candida granulomas in a patient with aplastic anaemia after viral hepatitis. Fungal elements in a skin biopsy specimen were detected by PAS stain and identified as Candida sp. by immunohistochemistry directed against the C. albicans mannan surface antigen. Based on rapid diagnosis of Candida granuloma and by Candida-positive cultures of blood and swabs, systemic treatment with liposomal amphotericin B led to survival of the patient.

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.

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.