[Oral lichen planus, amalgam and other restorative materials]. / Orale lichen planus, amalgaam en andere vulmaterialen.

Mucosal lesions in the oral cavity, identical to oral lichen planus (OLP), as a consequence of contact with in particular dental silver amalgam may be due to an allergic reaction to mercury or, possibly, a toxic effect on the oral mucosa. Substitution of amalgam preferably by gold--unless sensitisation to gold exists--often results in remission, which sustains a pathogenic role of amalgam in OLP. Substitution of amalgam should be considered if the mucosal lesions correspond topographically to the restorations and epicutaneous patch testing results in a positive reaction on mercury.

Expression of E-cadherin, alpha- & beta-catenin, and CD44V6 and the subcellular localization of E-cadherin and CD44V6 in normal epidermis and basal cell carcinoma.

Basal cell carcinoma (BCC) of the skin is a locally invasive, rarely metastasizing epithelial tumor. In the current study, the expression of E-cadherin, alpha- and beta-catenin and CD44V6 in normal epidermis and on BCC cells were investigated. A significantly reduced expression of alpha-catenin and CD44V6 and a slightly reduced expression of E-cadherin on BCC cells were observed compared with the overlying epidermis. Immunoelectron microscopy was used to investigate whether the decreased expression of E-cadherin and CD44V6 was due to either an absence or downregulation of specific membrane structures or due to an overall downregulation of these adhesion molecules in all membrane structures in BCC. E-cadherin and CD44V6 were expressed in adherens junctions, desmosomes, and complex interdigitating membrane structures both in normal epidermis and in BCC. A quantitative analysis showed that only a percentage of desmosomes was stained. In addition, the effect of pro-inflammatory cytokines, such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), was investigated in biopsy specimens of normal skin and BCC, using a biopsy culture system and immunohistochemistry. The expression of E-cadherin and CD44V6 was not significantly decreased after culturing BCC or normal skin biopsy specimens for 48 hours with or without recombinant human (rHu)IFN-gamma or rHuTNF-alpha. It may be concluded that the decreased expression of both E-cadherin and CD44V6, observed in light microscopy, was not attributable to the absence of specific specialized structures in BCC and most likely also not caused by downregulation by local cytokines, but rather by generic downregulation of both of these adhesion molecules during malignant transformation.

Interferon-gamma-induced ICAM-1 and CD40 expression, complete lack of HLA-DR and CD80 (B7.1), and inconsistent HLA-ABC expression in basal cell carcinoma: a possible role for interleukin-10?

Basal cell carcinomas (BCCs) of the skin show varying degrees of peritumoural inflammatory infiltrate consisting mainly of T cells, but lack an effective T-cell-mediated immune response. This may be caused by the absence of the major histocompatibility complex (MHC) class I and II antigens, intercellular adhesion molecule-1 (ICAM-1), CD40 and CD80 (B7.1). Interferon-gamma (IFN-gamma) is known to induce or up-regulate their expression on epithelial cells, whereas interleukin-10 (IL-10) down-regulates their expression. The induction and up-regulation of HLA-ABC, HLA-DR, ICAM-1, CD40, and CD80 in BCC and normal skin from BCC patients were investigated in a culture system using recombinant human IFN-gamma (rHuIFN-gamma). The levels of IL-10 were determined in the supernatants after culture. The results showed that only ICAM-1 expression was significantly up-regulated on BCC cells. However, in the normal epidermis of BCC patients and in the epidermis overlying the tumour nests, significant up-regulation of ICAM-1, and CD40, and CD80 and slight up-regulation of HLA-DR were observed. No changes in HLA-ABC expression were observed in either normal skin or BCC. High levels of IL-10 were present in the supernatants of BCC biopsies after culture. It may be concluded that it is highly likely that the presence of IL-10 in BCC is directly or indirectly responsible for the complete lack of expression of HLA-DR, ICAM-1, CD40 and CD80 and the inconsistent expression of HLA-ABC on BCC cells in situ and may be a way of escaping immune survillance.

[Cutaneous and mucosal reactions to dental materials]. / Huid- en slijmvliesreacties door tandheelkundige materialen.

The concentration of substances released by dental materials is usually too low to cause systemic-toxic effects, but there is the potential to induce dermatoses in especially dentists as well as mucositis in mainly dental patients. The cytotoxic irritative and allergic diseases are successively described categorized according to their pathogenesis. The identification of the diseases, which often have a similar appearance, depends on history-taking and patch testing. Non-dental sensitization is of diagnostic importance.

Expression of interferon-gamma receptors and interferon-gamma-induced up-regulation of intercellular adhesion molecule-1 in basal cell carcinoma; decreased expression of IFN-gamma R and shedding of ICAM-1 as a means to escape immune surveillance.

The peritumoural inflammatory infiltrate in basal cell carcinoma (BCC) of the skin consists mainly of T lymphocytes which hardly invade the tumour nests. The absence of intercellular adhesion molecule-1 (ICAM-1) on BCC cells may explain the lack of tumour-infiltrating cells and the lack of an active cell-mediated immune response in this tumour. In this study, the induction of ICAM-1 was investigated in BCC biopsies using recombinant human interferon-gamma (rHuIFN-gamma). The expression of interferon-gamma receptors (IFN-gamma R) in the biopsies was also investigated. The results showed that BCC cells expressed ICAM-1 after incubation with rHuIFN-gamma, but to a lesser degree than normal epidermal cells. The levels of shed ICAM-1 were significantly increased in the culture supernatants of tumour biopsies compared with those from normal skin biopsies, after culturing in the presence of rHuIFN-gamma. The expression of IFN-gamma R was significantly decreased on the tumour cells compared with the overlying epidermis. The decreased expression of IFN-gamma R on the tumour cells and the shedding of ICAM-1 into the peritumoural stroma may be a plausible mechanism by which the tumour cells are protected against an active cell-mediated immune response.

Prevalence of natural rubber latex allergy (type I and type IV) in laboratory workers in The Netherlands.

The objective of the study was to study the prevalence of Type IV and Type I allergy to natural rubber latex (NRL) in a population at risk in the Netherlands. Laboratory workers regularly using gloves were invited to complete a questionnaire and to be tested. We performed patch tests with standard contact allergens, rubber additives, glove powder and pieces of 4 gloves; prick tests with inhalant allergens, glove extracts, glove powder and fruit extracts; and RASTs. Glove-related hand dermatitis was reported in 36.9% of the individuals interviewed. A positive patch test result for rubber additives was seen in only 6.6%. Glove-related urticaria, rhinoconjunctivitis and/or asthma were reported in 24.6% of all cases. Confirmation of an IgE-mediated reaction was achieved in 8.3% by prick test with glove extracts and 5.0% by RAST. No reaction to glove powder was noticed in patch testing or in prick testing. A high prevalence rate of glove-related symptoms and NRL Type I allergy was found in laboratory workers exposed to rubber gloves. Surprisingly, there was no co-existence of Type I and Type IV allergy in this population.

Delayed-type hypersensitivity to contact allergens in psoriasis. A clinical evaluation.

The possibility for patch testing procedures to detect contact allergy was examined in 85 hospitalized patients with forms of psoriasis. Exclusion criteria were active lesions on the back, the use of strong topical corticosteroids, methotrexate, cyclosporin and UV therapy. After screening, a group of 47 patients with different forms of psoriasis were selected for patch testing. Personal history, including topical treatment, occupation and domestic circumstances, were reasons to extend the standard series of allergens. Tars, nickel sulfate, perfume and balsam of Peru scored high. The overall positive rate was 68%. This is higher than that observed in earlier studies. The unexpected results are discussed in the light of the possible mechanism of action.

Erythema multiforme and persistent erythema as early cutaneous manifestations of Lyme disease.

We report two cases of borreliosis (Lyme disease) with unusual cutaneous manifestations, erythema multiforme, and persistent erythema. The lesions in both of our patients had distinctive histopathologic features. To our knowledge, this is the first report of erythema multiforme and persistent erythema as early cutaneous manifestations of Lyme disease.

Allergy to carbamazepine: parallel in vivo and in vitro detection.

PURPOSE: Five to 20% of patients discontinue antiepileptic drug (AED) therapy because of adverse reactions. Careful reintroduction, however, may be considered if true drug allergy can be ruled out. Definitive assessment of such immunologically mediated reactions requires demonstration of either specific antibodies or sensitized lymphocytes. METHODS: We investigated whether skin patch tests (PTs) and in vitro lymphocyte proliferation assays (LPAs) were suitable for detection of allergy to carbamazepine (CBZ) and the possibly cross-reactive oxcarbazepine (OCBZ). Data of 65 patients displaying a wide range of possibly allergic side effects to CBZ were available for analysis. Data of CBZ users without any side effects and healthy volunteers served as controls. Both PTs and LPAs were done with CBZ, OCBZ and three metabolites [CBZ-10,11-epoxide (CBZ-E), 10-monohydroxy-CBZ (MHD), and 10,11-dihydroxy-CBZ (DIOL)]. RESULTS: Positive PTs with CBZ were seen in 20% and with OCBZ in 14% of the patients. Positive LPA results with CBZ and OCBZ, respectively, were found in 40 and 19%. Both tests were positive in 14 and 7% of the patients. Cross-reactivity to OCBZ was seen in -40% of CBZ-reactive patients in both PTs and LPAs. CONCLUSION: These data illustrate the additional value of LPAs in the detection of CBZ allergy while showing that a major part of side effects to CBZ and OCBZ is not immunologically mediated, according to PTs and LPAs.

Somatostatin receptor scintigraphy in cutaneous malignant lymphomas.

BACKGROUND: Lymphoid cells may express somatostatin receptors (SS-Rs) on their cell surface. Therefore radiolabeled somatostatin analogues may be used to visualize SS-R-positive lymphoid neoplasms in vivo. Exact staging is the basis for treatment decisions in cutaneous malignant lymphoma. We considered the possibility that SS-R scintigraphy might offer a clinically useful method of diagnostic imaging in patients with cutaneous malignant lymphoma. OBJECTIVE: We evaluated SS-R scintigraphy in comparison with conventional staging methods in the staging of cutaneous malignant lymphoma. METHODS: We conducted a prospective study in 14 consecutive patients with histologically proven cutaneous malignant lymphoma. SS-R scintigraphy was compared with physical, radiologic, and bone marrow examinations. Lymph node excisions were performed in patients with palpable lymph nodes. RESULTS: SS-R scintigraphy was positive in the lymph nodes in all four patients with malignant lymph node infiltration and negative in the three patients with dermatopathic lymphadenopathy. In two patients, previously unsuspected lymphoma localizations were visualized by SS-R scintigraphy. In only three patients all skin lesions were visualized by SS-R scintigraphy; these three patients had not been treated with topical corticosteroids. SS-R scintigraphy failed to detect an adrenal mass in one patient and bone marrow infiltration in two patients. CONCLUSION: SS-R scintigraphy may help distinguish dermatopathic lymphadenopathy from malignant lymph node infiltration in patients with cutaneous malignant lymphoma.

Increased expression of interleukin-4 receptors on psoriatic epidermal cells.

Abnormal keratinocyte proliferation and differentiation, the main characteristics of psoriasis, may be induced and maintained by cytokines produced by activated resident and recruited inflammatory cells in lesional skin. As the epidermal cytokine profile is clearly altered in psoriasis and because increased expression of interleukin-4 receptor (IL-4R) has been reported in some epithelial proliferative diseases, we investigated the expression of IL-4R on psoriatic epidermal cells (ECs). The expression of IL-4R on freshly isolated ECs from healthy skin and untreated psoriatic lesions was studied by immunostaining using an IL-4R-specific antibody and by examining their capacity to bind biotinylated recombinant human IL-4 using flow cytometry. The number of IL-4R+ ECs and the number of binding sites per cell were significantly increased on psoriatic ECs as compared with healthy control ECs. Immunostaining confirmed these results, whereby staining was mainly observed in the lower epidermal layers. In addition, an increased IL-4R mRNA expression was also observed in psoriatic epidermis using a digoxigenin-labeled IL-4R RNA probe. In short-term in vitro cultures, lipopolysaccharide/phorbol-myristate-acetate-stimulated and unstimulated psoriatic ECs did not produce any immunoreactive IL-4. The results of this study together with the reported increased expression of IL-4R in epithelial neoplasias suggest an association between overexpression of IL-4R and abnormal keratinocyte activation and proliferation.

Adhesion molecules and IL-1 costimulate T lymphocytes in the autologous MECLR in psoriasis.

Membrane molecules such as CD36 (OKM5), intercellular adhesion molecule-1 (ICAM-1, CD54), gamma interferon-induced protein 10 (gamma-IP10) and IL-1 are induced and/or upregulated in psoriatic epidermis. These molecules have important accessory, trafficking or signalling functions in the immune system and also play a role in the pathophysiology of psoriasis. The relevance of adhesion molecules, CD36 and epidermal IL-1 in psoriasis was studied in vitro in the autologous mixed epidermal cell - T lymphocyte reaction (MECLR). Their level of expression was quantitated in epidermal cell suspensions (ECS) from patients with psoriasis and their function was assessed by blocking with specific mAbs and antisera or by depleting CD36+ cells from the ECS prior to the MECLR. ECS from psoriatic lesions contained increased numbers of CD36+ (23 +/- 12%), ICAM-1(+) (31 +/- 14%) and IL-1(+) (57 +/- 21%) cells. The autologous MECLR was inhibited in samples from all patients by mAb to CD2 (LFA-2), CD11a (LFA-1alpha), CD18 (LFA-1beta), ICAM-1, CD58 (LFA-3) and an antiserum to IL-1beta. Thus, adhesion molecules facilitate inflammation in psoriasis not only via adhesion and recruitment of T lymphocyte in psoriatic lesions, but also via activation of T cells. Furthermore CD36 molecules on psoriatic epidermal cells do not costimulate autologous T lymphocytes in psoriasis. The observed costimulatory function of IL-1beta in the MECLR emphasizes its relevance in psoriasis.

Methyldibromoglutaronitrile is an important contact allergen in The Netherlands.

From 15 May to 15 December 1994, 2943 patients suspected of having contact dermatitis (1955 women, 988 men) were patch tested with methyldibromoglutaronitrile 0.3%, 0.1% and 0.05% pet. 119 patients (4.0%; women 4.1%, men 3.8%) proved to be allergic. 71% of the reactions were considered to be relevant. In 2/3 of the patients, causative products were cosmetics, in 1/3 moistened toilet tissues. Testing with methyldibromoglutaronitrile at lower concentrations (0.05% and 0.1%) and with commercial allergens (Euxyl K 400 and methyldibromoglutaronitrile, both containing methyldibromoglutaronitrile 0.1%), resulted in a number of false-negative reactions. All preservatives in the European standard series had lower scores than the 4% positive reactions to methyldibromoglutaronitrile (formaldehyde 2.0%, MCI/MI (Kathon CG) 3.2%, parabens 1.0%, quaternium-15 1.3%). It is concluded that methyldibromoglutaronitrile (present in the commercial preservative Euxyl K 400) is an important contact allergen in the Netherlands in cosmetics and moistened toilet tissues. It should be added to cosmetics series and to proctological series. The optimal test concentration is unknow, but may be 0.3% pet. The concentration of 0.1% methyldibromoglutaronitrile in the currently available commercial allergens appears to be too low, resulting in a number of false-negative reactions.

Cutaneous pathology in primary erythermalgia.

Primary or idiopathic erythermalgia is characterized by recurrent, red, warm, and painful lower extremities. It arises at young age and persists throughout life because no treatment is available. We report the cutaneous pathology of affected skin lesions of three patients with primary erythermalgia. Biopsy specimens showed a mild perivascular mononuclear infiltrate, thickened blood vessel basement membranes, abundant perivascular edema, and moderate endothelial swelling. The thickened basal membrane of the blood vessels showed a laminar structure, and abundant perivascular edema and moderate endothelial cell swelling were evident. These histopathologic findings in primary erythermalgia appear to be nonspecific but allow diagnostic differentiation from erythromelalgia in which fibromuscular intimal proliferation and occlusive thrombi in the endarteriolar capillaries are apparent and from erythermalgia secondary to vasculitis. Histopathologic examination of affected skin lesions in patients with red, congested, warm, and painful burning extremities is a valuable tool in the diagnostic process.

Expression of cytokeratin 8 in basal cell carcinoma: a comparative immunohistochemical and immunoelectron microscopy study.

The comparative study reported here was undertaken in order to resolve the discrepancies in the detection of cytokeratin (Ck) 8 reported in previous studies. The expression of Ck 8 was compared in 6 basal cell carcinomas (BCCs) using immunohistochemical and immunoelectron microscopic techniques and a panel of 4 different commercially available monoclonal antibodies (MoAbs). The results of this comparative study demonstrated not only that the consistent expression of Ck 8 using one of the MoAbs in immunohistochemistry was confirmed by immunoelectron microscopy, but that the inconsistent expression of Ck 8 observed using two other MoAbs was also confirmed. One of the MoAbs did not show any staining at all. The inability of this MoAb to detect the expression of Ck 8 using either of the techniques also indicated that this MoAb may be directed against an epitope of Ck8 that is not detectable in BCC in situ.