Theodoor van Joost

Patch test reactivity to DMDM hydantoin. Relationship to formaldehyde allergy.

The relationship between contact allergy to formaldehyde and positive patch test reactions to DMDM hydantoin was investigated– 35 formaldehyde‐allergic patients were patch tested with serial dilutions of formaldehyde (0.1% 0.3% 1.0% aq.) and DM hydantoin (the non‐formaldehyde‐containing parent compound of DMDM hydantoin), 21 were also patch tested with MDM hydantoin (1 molecule formaldehyde) in serial dilutions: 7 (33%) reacted to 1 or more concentrations. The other 14 were also tested with DMDM hydantoin (2 molecules formaldehyde) in serial dilutions: 8 (57%) reacted to 1 or more concentrations. Patients patch‐test‐positive to formaldehyde 0.1% and. or 0.3% tended to show more patch test reactivity to (D)MDM hydantoin than those who resided only to 1%. Aqueous solutions of (D)MDM hydantoin in concentrations as used in cosmetic products therefore contain enough fret formaldehyde to cause dermatitis in a patch lost system in some formaldehyde‐allergic patients: 12 such patients applied a cream containing 1% DMDM hydantoin to the flexor aspect of the lower arm twice daily for 1 week; 4 (33%) developed dermatitis. The use of a cream containing 0.25% DMDM hydantoin in these 4 patients still caused dermatitis in I and provoked itching in another. An increase in the use of DMDM hydantoin in cosmetic products will also inevitable increase the risk of cosmetic dermatitis in consumers allergic to formaldehyde.

Idiopathic erythermalgia: a congenital disorder

Idiopathic erythermalgia during early childhood and adolescence is characterized by red, congested, burning pain of the lower extremities provoked by exercise or exposure to warmth. The clinical symptoms of idiopathic erythermalgia in a young woman and her mother are described. Histopathologic and immunofluorescence findings in biopsy specimens of affected areas of skin were consistent with a nonspecific inflammatory process. The condition was completely refractory to any treatment. Even the long-lasting relief of pain with one low dose of aspirin, which is a prerequisite for the diagnosis of thrombocytemic erythromelalgia, was lacking. Idiopathic erythermalgia appears to be a separate clinical entity and congenital disorder.

Expression of interferon‐gamma receptors and interferon‐gamma‐induced up‐regulation of intercellular adhesion molecule‐1 in basal cell carcinoma; decreased expression of IFN‐γR 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‐γ). The expression of interferon‐gamma receptors (IFN‐γR) in the biopsies was also investigated. The results showed that BCC cells expressed ICAM‐1 after incubation with rHuIFN‐γ, 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‐γ. The expression of IFN‐γR was significantly decreased on the tumour cells compared with the overlying epidermis. The decreased expression of IFN‐γR 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.

Interferon-γ-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‐γ(IFN‐γ) 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‐γ (rHuIFN‐γ). 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, 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 surveillance. Copyright

Intralesional treatment of basal cell carcinoma with low-dose recombinant interferon gamma

In this pilot clinical trail the efficacy of intralesional low-dose human recombinant interferon-gamma was investigated in seven outpatients with nodular basal cell carcinoma. There was no antitumor response in any case. Toxic side effects were minimal. All tumors were excised surgically 8 weeks after completion of therapy.

Expression of E-cadherin, α- & β-catenin, and CD44V6 and the subcellular localization of E-cadherin and CD44V6 in normal epidermis and basal cell carcinoma

Abstract Basal cell carcinoma (BCC) of the skin is a locally invasive, rarely metastasizing epithelial tumor. In the current study, the expression of E-cadherin, α- and β-catenin and CD44V 6 in normal epidermis and on BCC cells were investigated. A significantly reduced expression of α-catenin and CD44V 6 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 CD44V 6 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 CD44V 6 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-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), was investigated in biopsy specimens of normal skin and BCC, using a biopsy culture system and immunohistochemistry. The expression of E-cadherin and CD44V 6 was not significantly decreased after culturing BCC or normal skin biopsy specimens for 48 hours with or without recombinant human (rHu)IFN-γ or rHuTNF-α. It may be concluded that the decreased expression of both E-cadherin and CD44V 6 , 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.

Hyposensitization in nickel allergic contact dermatitis: Clinical and immunologic monitoring

BACKGROUND In allergic contact dermatitis (ACD) previously sensitized T cells cause skin damage. If an ubiquitous allergen such as nickel is involved, no effective treatment is available. Down-regulation of this allergic response has been described after antigen presentation in the absence of adequate costimulatory signals. UV exposure can enhance such hyposensitization. OBJECTIVE The aim of this study was to establish the capability of a hyposensitization procedure to induce antigen-specific tolerance. METHODS Twenty-one patients with nickel ACD were randomly assigned to either a hyposensitized or control group. A schedule consisting of UVB treatment and subcutaneous nickel sulfate administration (hyposensitization) or UVB only (control) was applied. During the ensuing 2 years, several clinical and immunologic features were monitored. RESULTS During UVB treatment we observed a significant clinical improvement in both groups that persisted in the hyposensitized group. Except for increased slope variances of specific lymphocyte proliferation in time, no clear changes were seen in the immunologic findings. CONCLUSION Despite significant clinical improvement induced by UVB, hyposensitization did not induce significant changes in the immunologic findings in patients with nickel ACD.

Allergy to Carbamazepine: Parallel In Vivo and In Vitro Detection

Summary: 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.

Subepidermal bullous autoimmune disease associated with immune nephritis: Immunomorphologic studies

There are only a few reports of the association of immune-complex glomerulonephritis with bullous pemphigoid. The occurrence of immune-complex nephritis with linear IgA bullous disease has not been previously reported. We report two cases, one a case of bullous pemphigoid and the other a case of linear IgA bullous disease, both of which were associated with immune-complex glomerulonephritis. The clinical and immunomorphologic data are briefly discussed.

Drug-induced cicatricial pemphigoid and acquired epidermolysis bullosa

A utoimmune diseases probably have a multitude of causes. It is obvious that exogenous agents, particularly drugs, may trigger the development of autoimmune responses leading to bullous eruptions. In the literature several cases of drug-induced (disseminated) bullous pemphigoid (BP) have been reported (see article by Fellner in this issue); however, localized variants of pemphigoid and acquired epidermolysis bullosa, although to a lesser extent, apparently can also be induced by drugs. Important localized variants of pemphigoid are cicatricial pemphigoid (Cl’) (synonyms: mucous membrane pemphigoid [MMP], ocular pemphigoid) and two nonmucosal localized variants: the non-mucosal scarring type pemphigoid (Brunsting-Perry type) and the nonscarring localized-type pemphigoid (LBP). Cicatricial pemphigoid is a rather rare disease of late middle age that occurs particularly on the mucous membranes of the eyes, oropharynx, genitalia, or anus. The characteristic skin picture is that of localized recurrent blisters with the development of scarring.’ The cicatricial process can cause serious adhesions, strictures, and depending on the localization, on the long-term loss of function. Histologically, in contrast to BP, eosinophils in LBP and CP are usually present in significantly small numbers. Particularly in Cl’ lesions, a fairly dense, sometimes predominant lymphocytic inflammatory infiltrate is observed in the dermis. Immunofluorescence (IF) studies in CP show a linear deposition of IgG and complement along the basement