C Nieboer

Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

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Publications (43)146.57 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Recruitment of activated T-cells to the skin is a common feature in a wide variety of inflammatory skin diseases. As CXCR3 activating chemokines CXCL10 (IP-10), CXCL9 (Mig), and CXCL11 (IP-9/I-TAC) specifically attract activated T-cells, this study addressed the question of whether differences in the expression of these chemokines correlate with the site and cellular composition of the skin infiltrates in different types of inflammatory skin disease. Skin biopsies from lichen planus, chronic discoid lupus erythematosus, allergic patch test reactions, psoriasis, and Jessner's lymphocytic infiltration of the skin were investigated for chemokine expression using RNA in situ hybridization, and for the expression of CXCR3 using immunohistochemistry. The results showed differential expression of CXCL10, CXCL9, and CXCL11, which correlated with differences in the localization and cellular composition of the infiltrates. Whereas CXCL10 and CXCL11 were mainly expressed by basal keratinoctyes, CXCL9 mRNA expression was located predominantly in the dermal infiltrates. Correlation with immunohistochemical data suggested that macrophages and activated keratinocytes were the main producers of these chemokines. CXCR3 was expressed by a majority of both CD4+ and CD8+ infiltrating T-cells, suggesting a functional interaction between locally produced chemokines and CXCR3-expressing T-cells. In conclusion, these findings indicate that these CXCR3 activating chemokines play a significant role in the recruitment and maintenance of T-cell infiltrates in the inflammatory skin diseases studied.
    The Journal of Pathology 09/2001; 194(4):398-405. · 7.33 Impact Factor
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    ABSTRACT: The effectiveness of systemic treatment of psoriasis with fumaric acid esters has been proven, but their mode of action at the cellular and molecular level has not yet been fully elucidated. To study the effect of dimethylfumarate (DMF) on the production of the chemokines CXCL1, CXCL8, CXCL9, CXCL10 and CXCL11, formerly known as GROalpha, interleukin-8, Mig, IP-10 and IP-9/I-TAC, respectively, in human keratinocytes and peripheral blood mononuclear cells (PBMC). Cultured keratinocytes were stimulated with interferon (IFN) -gamma to produce CXCL9, CXCL10 and CXCL11 and with phorbol myristate acetate to produce CXCL1 and CXCL8 in the absence and presence of DMF (5, 15 and 45 micromol L(-1)). PBMC were stimulated with either IFN-gamma to produce CXCL9 and CXCL10 or lipopolysaccharide to produce CXCL8, in the absence and presence of DMF (5, 15 and 45 micromol L(-1)). RNA preparations from isolated keratinocytes were analysed by Northern blotting; protein production by keratinocytes and PBMC was monitored by an enzyme-linked immunosorbent assay. Northern blot analysis on isolated keratinocyte RNA preparations showed a dose-dependent inhibition of CXCL1, CXCL8, CXCL9, CXCL10 and CXCL11 transcription by DMF. At 45 micromol L(-1) the inhibition was almost complete. In addition, keratinocytes and PBMC showed in the presence of DMF a dose-dependent inhibition of CXCL8, CXCL9 and CXCL10 protein production. These results show the ability of DMF to inhibit the production of chemokines that may be critically involved in the development and perpetuation of psoriatic lesions. This might explain, at least in part, the beneficial effects of treatment with fumaric acid esters in psoriasis patients.
    British Journal of Dermatology 07/2001; 144(6):1114-20. · 4.10 Impact Factor
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    ABSTRACT: We describe two siblings with late-onset junctional epidermolysis bullosa (JEB) (formerly called epidermolysis junctionalis progressiva). This is a subtype of autosomal recessive JEB characterized by late onset of the symptoms, between the ages of 5 and 8 years. The symptoms are mechanobullous lesions preferentially situated on hands and feet, nail dystrophy, loss of dermatoglyphic pattern, tooth enamel abnormalities and hyperhidrosis. In most forms of JEB a reduction or absence of a specific hemidesmosomal component can be demonstrated by means of immunohistochemical analysis. In this family, all known involved hemidesmosomal components, including uncein, recognized by the monoclonal antibody 19-DEJ-1, appeared to be normally expressed.
    British Journal of Dermatology 06/2001; 144(5):1054-7. · 4.10 Impact Factor
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    ABSTRACT: In two young patients with an elevated temperature, a girl aged 6 months and a boy aged 10 months, purpura and oedema were noticed on the face, ears, arms and legs. On one occasion the boy lost blood anally. A histopathological examination revealed leucocytoclastic vasculitis with fibrin deposits. The diagnosis was 'acute haemorrhagic oedema of infancy' (AHOI), a relatively unknown variant of palpable purpura due to leucocytoclastic vasculitis affecting infants and young children (up to two years of age). AHOI is characterised clinically by marked oedema and fever as well as large palpable purpuric and ecchymotic skin lesions in a target-like pattern mainly on the face, ears and extremities. The skin lesions heal spontaneously within one to three weeks and internal organs are rarely affected. This is in contrast to Henoch-Schönlein purpura, which was observed in a 5-year old boy suffering from similar skin lesions on the legs as well as painful joints, in whom IgA deposits were found in the vasculitis. Henoch-Schönlein purpura is clinically characterised by palpable purpura on the extensor surfaces of the legs and on the buttocks, whereas in AHOI larger purpura and ecchymoses are found on the face, ankles and wrists, with far more extensive oedema. There are also histological differences: in AHOI there is more extensive vasculitis with fibrin deposits and IgA deposits are seen in a minority of cases. Awareness of this relatively unknown form of leucocytoclastic vasculitis will assist in making an early diagnosis possible, thereby avoiding unnecessary treatment and concern.
    Nederlands tijdschrift voor geneeskunde 05/2001; 145(17):834-9.
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    ABSTRACT: Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal bullous disease with heterogeneous clinical manifestations, characterized by linear deposition of IgA along the epidermal basement membrane zone. We report a patient with a metastasized renal cell carcinoma who developed an extensive blistering eruption. The lesions showed immunopathological findings characteristic of LABD. The patient showed a fair response to prednisolone and dapsone. Treatment to control the LABD was no longer required when interferon-alfa was started as palliative therapy for the metastasized renal cell carcinoma. The association of LABD and malignancies has been documented before and is not due to mere chance alone.
    British Journal of Dermatology 05/2001; 144(4):870-3. · 4.10 Impact Factor
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    ABSTRACT: A patient is described who initially presented with pemphigus vulgaris, limited to the oral cavity, and weight loss. Although the various laboratory studies pointed to the diagnosis of paraneoplastic pemphigus (PNP), the underlying neoplasm was not detected until 6 months later, when the patient developed shortness of breath and routine physical examination on admission revealed an abdominal mass, which eventually was proven to be an epithelioid leiomyosarcoma. In spite of radical excision of the tumour and intensive treatment of the dyspnoea, the patient died of respiratory failure 19 months after the PNP had been diagnosed. Early diagnosis of PNP is stressed to possibly prevent fatal pulmonary involvement.
    Oral Oncology 08/2000; 36(4):390-3. · 3.03 Impact Factor
  • Nederlands tijdschrift voor geneeskunde 09/1999; 143(39):1982.
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    ABSTRACT: Objective: To investigate the effect of two Lycra support panty hose (8 and 12 mmHg) on the development of oedema of the lower legs and on feelings such as tiredness, heaviness and burning or pain in the legs.
    Phlebology 01/1999; 14(4):162-166. · 1.92 Impact Factor
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    ABSTRACT: A patient is described who initially presented with an acrovesicular eczema which subsequently developed into erythema multiforme with histopathological features of bullous pemphigoid. Although the various laboratory studies pointed to the diagnosis of paraneoplastic pemphigus (PNP), the underlying neoplasm was not detected until 6 months later, when the biopsies of an oral lesion showed the presence of an underlying non-Hodgkin lymphoma.
    Oral Oncology 12/1998; 34(6):567-70. · 3.03 Impact Factor
  • Acta Dermato Venereologica 12/1997; 77(6):492. · 4.24 Impact Factor
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    ABSTRACT: The expression of IL-8 in psoriasis has been clearly shown with the use of immunocytochemical, RT-PCR and in situ hybridization methods. The presence of its ligand, the IL-8 receptor, has been demonstrated by the RT-PCR technique. We report here a study of the expression of both IL-8 type A and B receptors by immunohistochemical techniques, using one polyclonal and four monoclonal antibodies. By this technique, we found that the neutrophilic granulocytes express the IL-8 type A receptor, whereas the IL-8 type B receptor was present on the keratinocytes. The type B receptor on the keratinocytes was localized in the suprabasal layers of the epidermis. Following therapy, the expression of the IL-8 type B receptor on the keratinocytes was reduced. This could suggest that IL-8 in psoriasis is involved in the disturbed differentiation rather than in proliferation, probably via an autocrine loop.
    Archives for Dermatological Research 08/1997; 289(8):440-3. · 2.27 Impact Factor
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    ABSTRACT: From previous studies, we concluded that the fluorescence overlay antigen mapping (FOAM) technique could be of value to the differential diagnosis of the acquired subepidermal bullous skin disorders, bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA). In these diseases, ultrastructural identification of the site of skin-bound IgG deposits at the epidermal basement membrane zone (EBMZ) may be essential to the correct diagnosis. Since ultrastructural studies are more expensive, time-consuming, and less widely available than immunofluorescence, we addressed the question of whether the FOAM technique can reliably identify the site of IgG deposits at the EBMZ, and distinguish BP from EBA. For this purpose, the technique was applied to perilesional skin from seven patients with BP and six with EBA, using computer-aided imaging of red-stained type VII collagen and green-stained IgG, according to previous findings. Digitized multicolor FOAM images of perilesional skin from patients with BP showed nonoverlap band patterns of green-stained lamina lucida IgG deposits (ultrastructurally proven) and red-stained type VII collagen. By contrast, FOAM images of EBA skin typically showed overlap patterns of green-stained sublamina densa IgG deposits and red-stained type VII collagen. These findings were observed also in skin tissue stored in Michel's transport medium or stored frozen for 15 years. The computer-aided FOAM technique may have great potential in distinguishing between IgG deposits above (BP) and just below (EBA) the lamina densa of the EBMZ in skin tissue. The technique is not as simple as saline-split skin methodology but offers more flexibility, and it certainly is quicker and less expensive than electron microscopy. Furthermore, the use of digitized fluorescence images offers improved possibilities for evaluating the various "linear" patterns of immune reactant deposition at the EBMZ in subepidermal bullous autoimmune skin diseases.
    Archives of Dermatology 03/1996; 132(2):151-7. · 4.31 Impact Factor
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    ABSTRACT: Pemphigus vegetans, a rare form of pemphigus vulgaris, consists of vegetating plaques localized to flexural areas. Two types, the Neumann and the Hallopeau type, are recognized with their own characteristics. Three patients with pemphigus vegetans were examined, two with Hallopeau type and one with Neumann type. The microscopic and immunofluorescence findings were recorded. Two remarkable features were present. In one case pemphigus vegetans was possibly induced by the use of enalapril. Only in three previous cases has enalapril been described in relation to pemphigus. A second case was associated with a malignant lung tumor, a phenomenon which could not be traced in the literature. Two types of pemphigus vegetans must be distinguished. Induction of pemphigus (also vegetans) is an accepted side effect of captopril. The effect of enalapril on pemphigus is still in debate. To the best of our knowledge, this is the first time that a patient with pemphigus vegetans and a simultaneously occurring internal malignancy is described.
    International Journal of Dermatology 04/1994; 33(3):168-71. · 1.23 Impact Factor
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    ABSTRACT: Systemic and sometimes topical therapy with fumaric acid (FA) and its derivatives is used in the treatment of psoriasis. Scattered data show that the topical application of these derivatives elicits side effects. Application of FA and some derivatives on the skin was accompanied by perilesional skin irritation, macular papular rashes and urticarial reactions. In order to determine the irritating and sensitizing properties of FA derivatives we used a cytotoxicity, flank irritation, ear swelling and guinea pig maximization test. The results of the cytotoxicity test demonstrated that dimethylfumarate (DMF) was the most toxic derivative. DMF induced also contact-urticarial reactions in contrast to mono-ethylfumarate (MEF). Challenge experiments with FA, MEF and DMF in MEF- and DMF-sensitized guinea pigs demonstrated that both MEF and DMF are moderate contact sensitizers. In DMF-sensitized animals cross-reactions with MEF were found. As DMF and MEF have cytotoxic, contact-urticarial and/or sensitizing properties, topical application should be avoided.
    Dermatology 02/1994; 188(2):126-30. · 1.69 Impact Factor
  • E M de Boer, C Nieboer
    Nederlands tijdschrift voor geneeskunde 02/1993; 137(1):44; author reply 45.
  • Jim R. Wikler, Cees Nieboer, Rein Willemze
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    ABSTRACT: Previous studies have suggested that Pityrosporum yeasts may be important in the pathogenesis of seborrheic dermatitis (SD). SD occurs more frequently and has a different clinical appearance in patients who are human immunodeficiency virus (HIV)-seropositive than in HIV-seronegative patients. Our purpose was to investigate the role of Pityrosporum yeasts in the pathogenesis of seborrheic dermatitis in HIV-seropositive patients. Twenty-eight HIV-seropositive patients, including seven patients with SD and 21 without SD, and 20 HIV-seronegative patients with SD (n = 10) and without SD (n = 10) were investigated. Quantitative Pityrosporum cultures were taken from the face, chest, and back. None or only a small amount of Pityrosporum yeasts were cultured from SD lesions and SD predilection sites in HIV-seropositive patients. From the SD lesions in the HIV-seronegative control group large amounts of Pityrosporum yeasts were cultured. The results of this and other studies suggest that Pityrosporum yeasts play no role in SD in HIV-seropositive patients and that SD in these patients is a distinct entity to be separated from "classical" SD in HIV-seronegative patients.
    Journal of the American Academy of Dermatology 08/1992; 27(1):37-9. · 5.00 Impact Factor
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    ABSTRACT: The therapeutic efficacy and tolerability of calcipotriol ointment and betamethasone valerate ointment in psoriasis were compared in a multicentre, prospective, randomised, double-blind, right/left trial. 345 inpatients and outpatients with psoriasis vulgaris of symmetrical distribution were treated twice daily for 6 weeks with calcipotriol ointment 50 micrograms/g and betamethasone ointment 0.1% randomly assigned to opposite sides of the body. The main outcome measures--the psoriasis area and severity index (PASI), the investigators' assessments of erythema, thickness, and scaling, and the patients' own assessments of the overall response to treatment--were sought at weeks 2, 4, and 6. Both treatments significantly reduced the PASI scores and the investigator's assessment scores, but at each visit the PASI score was significantly (p less than 0.001) lower with calcipotriol than with betamethasone. At 6 weeks the mean PASI reduction was 68.8% with calcipotriol and 61.4% with betamethasone (95% confidence interval for difference 5.1-9.8, p less than 0.001). The scores for erythema, thickness, and scaling were significantly (p less than 0.001) lower with calcipotriol than with betamethasone at the end of treatment. The patients considered that 82.1% of calcipotriol-treated sides and 69.3% of betamethasone-treated sides had improved greatly or cleared up by the end of treatment (p less than 0.001). 57 adverse events were reported by 52 patients (15.1%). The most common adverse event, lesional/perilesional skin irritation, was slightly but not significantly (p = 0.12) more common with calcipotriol treatment. 15 (4.3%) patients were withdrawn from the study, 3 because of local adverse events. There were no changes in serum calcium during the study. Thus, calcipotriol ointment was superior to betamethasone valerate ointment in psoriasis vulgaris. Though long-term results are not yet available, calcipotriol holds great promise as an antipsoriatic agent.
    The Lancet 02/1991; 337(8735):193-6. · 39.21 Impact Factor
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    ABSTRACT: In the present study a comparative immunohistochemical study was performed on skin biopsies from of patients with Jessner's lymphocytic infiltration of the skin (LIS), polymorphous light eruption (PLE), discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE) using a large panel of monoclonal antibodies against T cell differentiation antigens (CD3, CD4, CD8), immunoregulatory T cell subsets (CD7, 4B4, 2H4, Leu 8), B cells (CD22), activated cells CD25, OKT9, HLA-DR), Langerhans cells (CD1) and macrophages (Leu-M5). The results showed many similarities between LIS and PLE. The most important differences between these conditions and CDLE/SCLE were the high proportions of cells reactive with monoclonal antibody Leu-8 and the absence of T cells expressing HLA-DR antigens in LIS and PLE, suggesting absence of local T cell activation in these conditions. The differential diagnostic and pathogenetic aspects of these findings will be discussed.
    Journal of Cutaneous Pathology 03/1990; 17(1):2-8. · 1.56 Impact Factor
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    ABSTRACT: The effect of UV-light on Pityrosporum yeasts (P.) was studied: P. yeasts cultured from the skin were spread on Dixon plates and irradiated with different UVB-and UVA-light dosages and read after three days, controls were not irradiated. Also P. yeasts, immediately after irradiation, were isolated from the plates and studied with an electron microscope. A significant growth inhibition or no growth at all was seen after 25, 50, 75 J/cm2 UVA and 900 mJ/cm2 UVB, a moderate inhibition after irradiation with 250 mJ/cm2 UVB. The growth inhibition was paralleled by ultrastructural degenerative alterations: clumping of ribosomes and lysis of nuclei. The amount of "stacked material" in the vacuoles was diminished or they were completely empty, the cell wall remained unchanged. Our results imply that the positive effect of sunlight on seborrhoeic dermatitis may well be explained by the direct influence of UV-light on the P. yeasts.
    Acta Dermato Venereologica 02/1990; 70(1):69-71. · 4.24 Impact Factor
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    ABSTRACT: In a 4-month double-blind study the effects of dimethylfumaric acid esters (DMFAE-EC) and DMFAE plus salts of monoethylfumaric acid esters (fumaric acid combination, FAC-EC) in enteric-coated tablets were compared in 22 respectively 23 patients with psoriasis. In both groups about 50% showed a considerable improvement, i.e. the initial score was more than halved. The therapeutic effects showed no significant differences in both groups with respect to the total psoriasis score or the different parameters. In the FAC-EC group the effects were obtained more rapidly. Most frequently observed side effects in both groups were flushings, stomachache and diarrhea. Due to these complaints 3 respectively 8 patients discontinued therapy. Eosinophilia, leukopenia and lymphopenia were the most frequently observed differences in lab tests. It was concluded that FAC-EC had no significantly better effect than monotherapy with DMFAE-EC. Moreover, enteric coating of the tablets did not prevent stomach complaints. Until more information has been obtained about the pharmacokinetics, the toxicity and optimal composition of the drug, the fumaric acid therapy in psoriasis should be seen as experimental.
    Dermatologica 02/1990; 181(1):33-7.

Publication Stats

961 Citations
146.57 Total Impact Points


  • 2001
    • Universitair Medisch Centrum Groningen
      • Department of Dermatology
      Groningen, Groningen, Netherlands
  • 1991–2001
    • VU University Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 1978–1997
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Dermatology
      Amsterdam, North Holland, Netherlands
  • 1988–1990
    • University of Amsterdam
      • Department of Dermatology
      Amsterdam, North Holland, Netherlands
  • 1975–1980
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands