Darier's sign in cutaneous large T-cell lymphoma.
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Biomedical subjects
Publications and source records attributed to M Bagot.
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BACKGROUND: In the course of mycosis fungoides, pilofollicular manifestations without mucinosis (papules, keratoses, comedones, or epidermal cysts) are rare (15 cases reported). Therefore, histological and clinical diagnoses may be difficult. The clinical course and histopathological and immunohistochemical findings in 9 patients are described. OBSERVATIONS: Pilofollicular lesions were present at the onset (n = 3), before (n = 3), or during a relapse of mycosis fungoides (n = 3). Comedones and epidermal cysts were most frequent (n = 5). They disappeared with lymphoma therapy (n = 4), therapy with isotretinoin (n = 3), or spontaneously (n = 1), or they persisted (n = 1). Clues to the histopathological diagnosis consisted of pilotropism of the infiltrate with minor alteration of the hair follicle walls. The infiltrate was monomorphous and composed of sezariform CD4+ lymphocytes. Pilotropic or peripilofollicular infiltrates, or the absence of infiltrate, were detected in consecutive biopsy specimens obtained from the same patient. The keratinocyte expression of intercellular adhesion molecule type 1 was observed in the hair follicle bulb in front of the pilotropic infiltrate but not in the epidermis. No staining was observed in biopsy specimens of 6 of 7 patients with follicular mucinosis, of folliculitis lesions, or of normal hair follicles. CONCLUSIONS: Our findings indicate the role of adhesion molecules in pilotropism leading to mechanical obstruction of the follicle by tumoral cells followed by hyperkeratosis and cyst formation. It remains to be determined if the expression of intercellular adhesion molecule type 1 is the cause or the consequence of pilotropism. By becoming more aware of it, this variant of mycosis fungoides is probably not so rare.
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In cutaneous T-cell infiltrates, the demonstration of a clonal T-cell receptor (TCR) gene rearrangement has been considered helpful to distinguish Cutaneous T-cell lymphomas from reactive lymphoproliferation. Hence, a polymerase chain reaction (PCR) method using GC-clamp primers and denaturing gradient gel electrophoresis has been developed in our laboratory to analyze the TCR gamma locus configuration. Two hundred eleven cutaneous samples from 155 patients were analyzed. A detectable clonal TCR gamma rearrangement was significantly associated with cutaneous T-cell lymphomas as defined by morphologic and immunologic criteria. A clonal TCR gamma rearrangement was also detected frequently in lymphomatoid papulosis, never in reactive lymphocytic infiltrates and B-cell lymphomas, and rarely in parapsoriasis en plaque and cutaneous lymphoid hyperplasia. Forty five patients had both a cutaneous and a peripheral blood sample. Fifteen had a detectable clonal rearrangement in the two samples and 22 were negative. Six patients had a positive skin sample and a negative blood sample, whereas two patients had a positive blood sample and a negative skin sample. Four lymph node samples were analyzed and the PCR results were the same as in the skin. Finally, 21 patients had sequential samples of recurrent skin lesions. The PCR results were concordant in all and, when detectable, the clonal TCR gamma rearrangement remained unchanged in a given patient. Because of its simplicity and accuracy, the newly designed PCR procedure improves the monitoring of diagnosis, staging, and follow-up in cutaneous T-cell infiltrates.
BACKGROUND AND DESIGN: Cutaneous pleomorphic small T-cell lymphoma is a rare, recently recognized lymphoma, different from mycosis fungoides and Sézary syndrome. Only a few cases have been reported and no treatment modalities have been defined. We reviewed the clinical, histologic, immunohistochemical, molecular biologic, and follow-up data of 11 primary cutaneous pleomorphic small T-cell lymphomas. RESULTS: The lesions presented as red purplish nodules, tumors, or plaques. The infiltrate consisted of small pleomorphic lymphoid cells without epidermotropism in nine patients and with a propensity to infiltrate the dermis and subcutaneous fat. Most cases were CD4+/CD8-. A T-cell clone was detected in the skin lesions of nine patients tested. The mean follow-up was 70.1 months and the median follow-up was 20 months. Ten patients are alive with three having persistent lesions. Interferon alfa-2a induced partial or complete remissions in five patients. Interferon alfa-2a combined with a regimen containing doxorubicin chlorhydrate induced a complete remission in a patient suffering a relapse after cyclophosphamide and interferon alone. CONCLUSIONS: Cutaneous pleomorphic small T-cell lymphoma is a well-defined type of low-grade cutaneous lymphoma with favorable prognosis. Interferon and/or chemotherapy are the treatment of choice in patients with large tumor burden.
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BACKGROUND: Hepatitis C virus (HCV) is the main causative agent of parenterally transmitted non-A, non-B viral hepatitis, Infections with HCV may be associated with disorders of various organs other than the liver, essentially through immunologic mechanisms. OBJECTIVES: To provide an update on HCV and to review and discuss dermatologic disorders directly or indirectly related to HCV-induced liver disease. OBSERVATIONS: The main dermatologic disorders in HCV infection include (1) vasculitis (mainly cryoglobulin-associated vasculitis, the cause of which is HCV in most cases, and, possibly, some cases of polyarteritis nodosa); (2) sporadic porphyria cutanea tarda; (3) cutaneous and/or mucosal lichen planus; and (4) salivary gland lesions, characterized by lymphocytic capillaritis, sometimes associated with lymphocytic sialadenitis resembling that of Sjögren's syndrome. CONCLUSIONS: Hepatitis C virus is the cause of, or is associated with, various dermatologic disorders. In patients with such disorders, HCV infection must be sought routinely because antiviral therapy may be beneficial in some of them.
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BACKGROUND AND DESIGN: Cutaneous adverse drug reactions (ADRs) have been hypothesized to have a metabolic basis. Our aim was to identify detoxification defects involved in toxic epidermal necrolysis and other severe cutaneous ADRs. Lymphoid cells of 33 patients with cutaneous ADRs were challenged with reactive metabolites generated from drugs by a microsomal oxidation system. To be precise in the detoxification defect involved in sulfonamide and anticonvulsant reactions, we challenged lymphoid cells from 11 patients (seven patients with sulfonamide ADRs and four patients with anticonvulsants ADRs) to menadione and formaldehyde. Menadione induces toxic effects by oxygen species; formaldehyde is detoxified by aldehyde dehydrogenase, oxidase, and reductase. RESULTS: When the culprit drug was a sulfonamide or an anticonvulsant (used in 13 and 13 patients, respectively), the toxic effects of culprit drug-reactive metabolites toward patients' lymphoid cells were higher than toward controls'. First-degree relatives of four patients with sulfonamide- and phenobarbital-induced toxic epidermal necrolysis were also tested. In each family, a relative was more susceptible to culprit drug-reactive metabolites than were controls. After incubation with menadione, or formaldehyde, no difference in toxicity was found between patients' and controls' lymphoid cells. CONCLUSIONS: Toxic epidermal necrolysis and other severe cutaneous ADRs to sulfonamides and anticonvulsant drugs may be linked to a highly specific defect in the detoxification of culprit drug-reactive metabolites. Our results suggest that this defect is constitutional and inherited and does not involve oxygen free radicals and/or aldehyde detoxification pathways.
BACKGROUND AND DESIGN: Patients with cutaneous lymphoid infiltrates that appear reactive histologically and immunophenotypically may develop clinically overt cutaneous lymphoma, suggesting the possibility of misdiagnosis by classical methods. We investigated DNA rearrangement in such cases of lymphoid infiltrates of uncertain significance to determine whether this more sensitive method could detect an occult monoclonal lymphoid proliferation. METHODS AND PATIENTS: Skin biopsy specimens were taken from 18 cutaneous lymphoid infiltrates diagnosed as reactive on the basis of clinical, histopathological, and immunohistochemical criteria. Specimens included 12 cases with mixed lymphoid infiltrates rich in polytypic B cells and inconstant follicle formation and 6 cases with exclusive T-lymphoid infiltrates. Southern blot analysis for immunoglobulin and T-cell-receptor beta-chain gene rearrangements was performed in all cases. RESULTS: No specimen showed T-cell-receptor beta-chain gene rearrangement. Clonal immunoglobulin gene rearrangement was demonstrated in one case with polytypic B cells, but no clinical malignancy has appeared 19 years after disease onset duration and 7 years after detection of the B-cell clone. CONCLUSIONS: In the present series, the results suggest that histological and immunohistological criteria are appropriate to establish the diagnosis of most cases of cutaneous lymphoid infiltrates. The detection of a B-cell clone is remarkable by absence of clinical malignancy, suggesting that such a discovery does not necessarily mean an aggressive evolution. Nevertheless, there is presently no way to predict the prognosis of a clonal lymphoid proliferation, indicating that a long-term follow-up is necessary.
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INTRODUCTION: Cutaneous lymphomas occurring in HIV infection are a rare disease. Most of them are high grade lymphomas with fulminant course and poor prognosis. OBJECTIVE: Evaluate clinical and histological aspects as well as immunophenotype and evolution of these lymphomas. PATIENTS AND METHODS: Eight patients with HIV infection were studied between 1992 and 1994. The clinical and histological features were reviewed by the members of the French Study Group for Cutaneous Lymphomas. Staging procedures for lymphomas were performed in 7/8 patients. RESULTS: Seven non epidermotropic lymphomas and one mycosis fungoides were reviewed. Patients were male (6 cases) and female (2 cases); their mean age was 45 years (27-63). The mean level of CD4 T cells/mm3 was 141 (20-380). Only one patient presented with extracutaneous lesions. These lesions were similar to seronegative patients, but unusual features were observed in two cases. Histological classification showed high grade lymphomas in 6/8 cases. The immunophenotype was: T-cell lymphoma in 4 cases, B-cell lymphoma in 3 cases; it could not be determinated in one case. Six patients died. The median of survival is 8 months in this series. DISCUSSION: Our series confirms the predominance of high grade lymphomas presenting in the skin. The T-cell phenotype is more frequent. The onset of a cutaneous lymphoma has a poor prognosis in HIV infection. Most of our patients had localised disease at presentation. Therapeutic management of these lymphomas must be codified.
Human T lymphotropic virus type II (HTLV-II), originally isolated in 1982 from a patient with a "T hairy cell leukemia", has not yet been proven to be the causative agent of any specific hematological disease. In order to screen for such an event, and because HTLV-II has a preferential tropism for OKT8 (CD8) T cells (both in vivo and in vitro), we searched for the presence of HTLV-II in lymphoproliferative diseases (LP) of CD8+ T cells. We report a serological and/or molecular study of 169 patients with a T CD8 LP, including 76 patients with malignant or reactive T CD8 LP (34 lymphomas, 27 large granular leukemias, three prolymphocytic leukemias, one hairy cell leukemia, 11 reactive T CD8 LP) and 93 HIV-1+ patients with a T CD8 peripheral lymphocytosis ( > 1500/mm3) from a prospective HIV cohort involving 1264 individuals. In the first series, the 40 sera available were all HTLV-I/II negative, except a 67-year-old French Guyanan man, with a cutaneous large T CD8 cell lymphoma, HTLV-I+. Furthermore, the molecular analysis of the 69 available DNA samples by PCR failed to detect any proviral HTLV-I/II sequences, except for the HTLV-I+ patient. The serological study of the 93 HIV-1+ individuals with CD8 lymphocytosis, showed that three patients were HTLV-I+, but none was HTLV-II+. Thus, in contrast to HTLV-I, whose etiological role in adult T cell leukemia is now well established, there is neither epidemiological nor molecular evidence that prototypic HTLV-II may be etiologically associated specifically with any of the CD8+ T cell LP investigated in this report.
Pemphigus is a rare autoimmune bullous disease of the skin and mucosae. It has predisposing genetic factors and, in the case of pemphigus foliaceus, environmental factors; some therapeutic drugs may trigger off pemphigus. The disease often begins with painful buccal erosions, followed by flaccid bullae on healthy skin. Some lesions are erythematous plaques involving the seborrheic areas. Cytology shows acantholysis and histology, intraepidermal cleavage. Direct immunofluorescence confirms the diagnosis by showing a network deposit of immunoglobulins and complement. The titres of circulating antibodies to the intracellular substance vary with the course of the disease. The loss of cohesion between keratinocytes is induced by autoantibodies directed against antigens of the epidermal cell junction zone; the molecular weight of these antibodies is 130 and 85 kD for pemphigus vulgaris and 160 and 85 for superficial pemphigus. Paraneoplastic pemphigus is a recently individualized entity. Treatment consists of systematic corticosteroid therapy, sometimes associated with immunosuppressants; it has improved the prognosis of this once lethal disease.
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3; calcitriol) is the biologically active form of vitamin D. This hormone is a potent immunoregulatory agent. Calcipotriol is a synthetic analogue of 1,25(OH)2D3, with similar receptor binding, and comparable effects on cell proliferation and differentiation, but less potent effects on calcium metabolism. As a step towards understanding the mechanisms by which vitamin D compounds affect T-cell activation by epidermal cells (EC), we assessed the effects of 1,25(OH)2D3 and calcipotriol on the human allogeneic mixed epidermal cell-lymphocyte reaction. All experiments were performed both with 1,25(OH)2D3, and calcipotriol, with similar results. Both compounds had potent immunoinhibitory properties on this model, and enhanced the immunosuppressive effects of cyclosporin A. Using preincubation experiments, we found that pretreatment of EC with 1,25(OH)2D3 resulted in a more pronounced inhibition than preincubation of lymphoid cells. The epidermal targets of this inhibitory effect have been further investigated, using cultures with freshly isolated Langerhans cells (LC) or LC-depleted keratinocytes, separated by an immunomagnetic particle technique. Pretreatment of LC induced a 30% decrease of proliferation, compared with vehicle-treated LC. These calcitriol-pulsed LC did not decrease the proliferation induced by unmodified autologous EC. As expected, LC-depleted keratinocytes failed to stimulate allogenic lymphocytes. When added to autologous unmodified EC, however, calcitriol-pulsed keratinocytes induced an 85% decrease of proliferation, compared with vehicle-treated keratinocytes. The phenotypic expression of HLA-DR, -DQ, and -DP antigens on EC, assessed by immunoalkaline phosphatase staining, was not modified after a 2-h or 24-h pulse with 1,25(OH)2D3 or calcipotriol.(ABSTRACT TRUNCATED AT 250 WORDS)