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J Thivolet

Publications and source records attributed to J Thivolet.

At least 19 recordsLinked to original sources
PubMed1997

External anogenital lesions in organ transplant recipients. A clinicopathologic and virologic assessment.

BACKGROUND AND DESIGN: In a series of patients treated at a university department of dermatology, we assessed the clinicopathologic features of external anogenital lesions in organ transplant recipients. For 6 years, 1002 recipients with various dermatologic problems underwent assessment for the presence of proliferative external anogenital lesions; these lesions were examined histologically and virologically for the presence of human papillomaviruses (HPV). RESULTS: Twenty-three patients (2.3%) presented with anogenital lesions, women being more often involved. Clinicopathologic examination revealed 18 anogenital warts, 3 cases of bowenoid papulosis, 1 giant condyloma, and 1 in situ carcinoma. Other viral coinfections were frequent. The lesions were extensive and refractory to treatment in 13 patients, but lesions in 7 were cured alter the immunosuppressive treatment was tapered of discontinued. Dysplastic changes were frequent on histologic examination. Twenty-one lesions contained HPV; 6 of 13 patients with HPV DNA in their lesions harbored oncogenic types that predominated in dysplastic lesions. In some patients, the same HPV types were detected within cutaneous and anogenital lesions, suggesting self-contamination. CONCLUSIONS: External anogenital lesions are more rare than cutaneous lesions in organ transplant recipients. These lesions may represent a marker of immunosuppression, especially when they are extensive. Their clinical aspect is often misleading; furthermore, because of the presence of dysplastic histologic aspects and oncogenic HPV types, they could be susceptible to malignant transformation, necessitating regular surveillance.

Adult↗
PubMed1995

Comparative epidemiologic study of premalignant and malignant epithelial cutaneous lesions developing after kidney and heart transplantation.

BACKGROUND: Cutaneous carcinomas are the most frequent cancers in organ transplant recipients. OBJECTIVE: Our purpose was to compare the epidemiologic data of cutaneous premalignant and malignant epithelial lesions in kidney and heart transplant recipients. METHODS: A total of 580 kidney and 150 heart transplant recipients were examined for the presence of premalignant and malignant epithelial lesions. RESULTS: A twofold increase in incidence of premalignant and malignant epithelial lesions was found in heart compared with kidney transplant recipients. Heart transplant recipients were older at transplantation, received more intense immunosuppressive treatment, and had a shorter delay from transplantation to the development of the first lesion. The squamous cell carcinoma/basal cell carcinoma ratio was 2.37:1 in kidney and 1.08:1 in heart transplant recipients. The extracephalic location represented 60% of the premalignant and malignant epithelial lesions in kidney and 30% in heart transplant recipients. CONCLUSION: Cutaneous premalignant and malignant epithelial lesions in kidney and heart transplant recipients show epidemiologic differences that can tentatively be explained by the older age and the more intense immunosuppressive treatment of heart transplant recipients.

Adult↗
PubMed1995

Major antigenic epitopes of bullous pemphigoid 230 kDa antigen map within the C-terminal end of the protein. Evidence using a 55 kDa recombinant protein.

In order to obtain greater insight into the nature of B-cell epitopes in bullous pemphigoid (BP), we generated a BP recombinant protein of 55 kDa M(r) (rBP 55) from a cDNA sequence encoding for the carboxyterminal region of the 230 kDa BP antigen. Serum IgG from guinea-pigs immunized with rBP 55 stained the basement membrane zone of normal human skin and immunoprecipitated the rBP 55 protein, and also the 230 kDa BP antigen recovered from extracts of cultured keratinocytes, thus confirming that the rBP 55 amino acid sequence is present in native BP antigen. The reactivity of sera from 60 patients with BP was analysed using an immunoblot assay on epidermal protein extracts and on the rBP 55 protein. Forty of the 60 BP sera (66%) contained autoantibodies to the 230 kDa polypeptide in an epidermal extract, and 37 of these 40 sera (92%) recognized the rBP 55 protein. In contrast, no reactivity against rBP 55 was detected with 20 BP sera devoid of autoantibodies against the 230 kDa antigen. Likewise, sera from patients with autoimmune blistering skin disorders other than BP (epidermolysis bullosa acquisita or pemphigus vulgaris), and control sera, were unreactive to rBP 55. These results clearly demonstrate the immunogenicity and antigenicity of the C-terminal end of the 230 kDa BP antigen. They confirm that this 555 amino acid segment, corresponding to rBP 55, contains major epitopes which can bind BP patients' autoantibodies, and suggest that the rBP 55 protein could be useful for further characterization of these B-cell epitopes.

Animals↗
PubMed1995

["Francophony"].

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Dermatology↗
PubMed1994

Human monoclonal autoantibodies specific for the bullous pemphigoid antigen 1 (BPAg 1).

Bullous pemphigoid (BP) is an acquired blistering skin disease associated with the production of IgG autoantibodies to the 230-kDa BP Ag (BPAg1). To better characterize the epitopes of BPAg1, we generated immortalized B cell lines secreting human mAbs (HumAbs) to BPAg1 from two BP patients whose sera reacted with native BPAg1 but not with a recombinant BP55 carboxyl-terminal peptide. Ab-producing B cell lines were established by EBV infection of CD40-activated PBMCs. Three independent clonal lines were obtained that secreted IgG HumAbs, including one IgG1 kappa (BP3) and two distinct IgG4 kappa (BP1 and BP2). These three HumAbs immunoprecipitated BPAg1. Blocking immunofluorescence experiments and phylogenetic studies showed that these Abs recognize different epitopes of BPAg1. This analysis with HumAbs further extends the serologic demonstration of the wide variety of epitopes recognized by BPAg1 autoantibodies which contrasts with the limited number of epitopes recognized by thyroid peroxidase monoclonal autoantibodies.

Antibodies, Monoclonal↗
PubMed1994

Comparative study of indirect immunofluorescence and immunoblotting for the diagnosis of autoimmune pemphigus.

The diagnosis of pemphigus relies on immunopathological criteria including the detection of circulating autoantibodies to desmosomal components. In the present work we compared the usefulness of immunoblotting (IB) and indirect immunofluorescence (IIF) in the diagnosis of pemphigus using monkey oesophagus (MO) and rabbit lip (RL) as epithelial substrates. Among 54 sera from patients with well-documented pemphigus (40 pemphigus vulgaris, PV, and 14 pemphigus foliaceus, PF), 46 (85%) proved positive by IIF (46 on MO and 41 on RL) as compared with 44 (81.5%) positive by IB. IIF and IB were equally sensitive (90%) for the diagnosis of PV whereas IIF (on RL) was more sensitive (71%) than IB (57%) for the detection of PF autoantibodies. However, when the two techniques were considered in combination, the sensitivity of the detection of pemphigus autoantibodies rose to 94.5%. An IB study would therefore be warranted in the presence of an (alleged) pemphigus serum that was IIF-negative since approximately 10% of these were found to be positive. Furthermore, the pattern of IB reactivity may assist in classification, since the 130- and the 160-kDa antigens seem specifically correlated with PV and PF, respectively.

Adult↗
PubMed1994

The effect of anti-CD4 monoclonal antibody treatment on immunopathological changes in psoriatic skin.

Recent clinical studies which showed the therapeutic effect of cyclosporin A and of anti-CD4 MoAb emphasized the role of activated CD4+ T cells infiltrating the lesional skin in the pathogenesis of psoriasis. The aim of the present study was to analyze the mode of action of anti-CD4 MoAb in 3 psoriatic patients who experienced an anti-CD4 MoAb-induced clinical improvement maximal 3-4 weeks after the onset of an 8-day therapy. We evaluated the effect of anti-CD4 MoAb treatment on the phenotype of resident and passenger inflammatory skin cells in lesional skin samples. We observed a gradual improvement of 3 out of 4 histopathologic features including parakeratosis, papillomatosis and acanthosis. In the dermis there was no modification in the density of the dermal mononuclear cell infiltrate, which consisted mainly of CD3+, CD45RO+, TCR alpha beta+, CD11a+, HLA-DR+T cells with a CD4/CD8 cell ratio of 1.5/1. Therefore as previously observed for peripheral blood mononuclear cells, the number of CD4+ T cells infiltrating the dermis remained unaffected by the treatment. In contrast, CD4 MoAb treatment was associated with drastic changes in the epidermis. These included a decrease in both CD4+ and CD8+ epidermal T cell infiltrate, diminished numbers of ICAM-1+ and HLA-DR+ keratinocytes and restored numbers of CD1a+ epidermal Langerhans cells. We conclude from this study that clinical improvement of psoriasis by anti-CD4 MoAb therapy paralleled: (1) a decrease in epidermal T cells, and (2) a down-regulation of keratinocyte activation markers (ICAM-1 and HLA-DR). These results suggest that the observed changes are secondary to down-regulation of inflammatory cytokine production by T cells in situ.

Adult↗
PubMed1994

Pseudo oral hairy leukoplakia in a renal allograft recipient.

Oral hairy leukoplakia (OHL) is a disorder of the tongue associated with Epstein-Barr virus (EBV). OHL is seen mainly in HIV infection but is also rarely seen in the course of iatrogenic immunosuppression, especially in kidney transplantation; OHL is even more rarely seen in immunocompetent hosts. Lesions that clinically and histologically mimicked OHL but were not associated with EBV were recently characterized as pseudo hairy leukoplakia. We present such a case that occurred in a renal allograft recipient; light and electron microscopy, immunohistochemistry, and in situ hybridization were used to examine the patient for the presence of EBV and human papillomavirus. Two independent treatments with topical retinoid and oral amoxicillin resulted in complete remission. Pseudo hairy leukoplakia may correspond, at least in some cases, to the conditions known as leukoedema and white sponge nevus; the distinction of these diseases from OHL is of importance because OHL is a hallmark of severe immunosuppression.

Cytoplasm↗
PubMed1994

A novel therapeutic approach to psoriasis with combination calcipotriol ointment and very low-dose cyclosporine: results of a multicenter placebo-controlled study.

BACKGROUND: Recent advances in the treatment of psoriasis include both the topical vitamin D analogue calcipotriol and cyclosporine. Combined treatments have been sought to decrease the incidence of side effects while maintaining efficacy in the treatment of severe chronic plaque psoriasis. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of the combination of 2 mg/kg/day of cyclosporine with calcipotriol ointment (50 micrograms/gm) in the treatment of severe plaque psoriasis. METHODS: Sixty-nine patients were randomly selected for this double-blind, multicenter study to receive cyclosporine (2 mg/kg/day) combined with calcipotriol ointment (50 micrograms/gm) or cyclosporine (2 mg/kg/day) combined with placebo ointment (vehicle of calcipotriol) for a 6-week period. RESULTS: Complete clearing or 90% improvement in Psoriasis Area and Severity Index score occurred in 50.0% of patients in the calcipotriol/cyclosporine group in comparison with 11.8% of patients treated with placebo/cyclosporine (p = 0.0019). The confidence interval for the difference ranged from 17.8% to 58.7%. No difference was found between the two groups with respect to side effects. CONCLUSION: The calcipotriol/cyclosporine combination was more effective than placebo/cyclosporine. Further studies are needed to establish the long-term efficacy and safety profile of this combination therapy.

Adult↗
PubMed1994

Disseminated superficial porokeratosis in a patient with AIDS.

We report the case of a 50-year-old male homosexual suffering from AIDS, who developed diffuse annular hyperkeratotic lesions on the arms and legs. Histopathological examination revealed typical features of porokeratosis, which clinically was of the disseminated superficial type. Ultrastructural examination showed a paucity of keratohyalin granules and lamellar bodies. Immunohistochemical studies showed an almost complete absence of Langerhans cells in lesional epidermis. Involucrin and filaggrin expression were altered in areas of cornoid lamella formation, whereas basal keratinocytes in these areas expressed PCNA/cyclin and, to a lesser degree, p53 protein. Porokeratosis may affect immunocompetent patients, but has also been reported in the setting of immunosuppression following organ transplantation. As far as we are aware, the development of porokeratosis during the course of HIV infection has not been reported previously.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Pemphigus: past, present and future.

Pemphigus remains the archetype of the autoimmune bullous diseases with circulating and skin antibodies in patients as well as in animal models. Pemphigus antigens are desmosomal-associated glycoproteins of 130 kD in pemphigus vulgaris (desmoglein 3) and of 160 kD (desmoglein 1) in pemphigus foliaceus (fogo selvagem in Brazil, pemphigus seborrheicus in other countries). Pemphigus may be associated to drugs and/or immune system related tumors (e.g. thymoma). Two new forms of pemphigus have been described: IgA pemphigus and paraneoplastic pemphigus. Targets of the autoantibodies are various desmosomal and cellular adhesion molecules. Even if each main pemphigus variant corresponds to specific antibodies, association of various antibodies may be found, leading to the concept of dysimmunoreactivity.

Animals↗
PubMed1994

Immunohistopathological study of autoimmune pemphigus. Lack of strictly specific histological and indirect immunofluorescence criteria for paraneoplastic pemphigus.

Paraneoplastic pemphigus (PNP) is a form of pemphigus considered to bear characteristic immunohistopathological features (vacuolar-interface dermatitis, keratinocyte dyskeratosis and reactivity of patients' sera with transitional epithelia). The present study was undertaken in order to investigate whether these criteria are specific enough so as to allow the diagnosis of PNP in the absence of clinical data. A retrospective study of 66 biopsies of pemphigus revealed that one third of them comprised histological signs of PNP; one of the corresponding sera reacted with mouse bladder epithelium. However, no evidence of a neoplastic disease was present in any of the patients, and Western blotting further excluded the diagnosis of PNP. These results suggest that some of the features considered characteristic of PNP are not strictly specific for this variety of pemphigus; hence this diagnosis cannot be reliably established by histology or immunofluorescence but requires biochemical studies.

Acantholysis↗