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1.
J Clin Invest ; 101(4): 783-94, 1998 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-9466973

RESUMEN

Overexpression of proinflammatory, type 1 cytokines has been demonstrated in psoriasis and is believed to be of pathophysiological importance. IL-10 is a type 2 cytokine with major impact on immunoregulation, since it inhibits type 1/proinflammatory cytokine formation. Therefore, we investigated its role in psoriasis. We found a relative deficiency in cutaneous IL-10 mRNA expression compared with other inflammatory dermatoses. Interestingly, patients during established antipsoriatic therapy showed higher IL-10 mRNA expression of peripheral blood mononuclear cells than patients before therapy. This suggested that IL-10 may have antipsoriatic capacity. Therefore, we performed a phase 2 pilot trial with subcutaneous IL-10 administration (8 microg/kg/d) over 24 d in three patients. Clinical efficiency measured by objective and subjective parameters was found. Immunosuppressive effects (depressed monocytic HLA-DR expression, TNF-alpha and IL-12 secretion capacity, IL-12 plasma levels, and responsiveness to recall antigens) as well as a shift toward a type 2 cytokine pattern (increasing proportion of IL-4, IL-5, and IL-10 producing T cells, selective increase in IgE serum levels) were observed. Remarkably, IL-10 administration also enhanced the intracutaneous IL-10 mRNA expression. Our investigations demonstrate the major importance of IL-10 in psoriasis and show that IL-10 administration represents a new therapeutic approach. This is the first report on IL-10 therapy for cutaneous disorders.


Asunto(s)
Interleucina-10/administración & dosificación , Psoriasis , Adulto , Humanos , Interleucina-10/biosíntesis , Interleucina-10/deficiencia , Interleucina-10/inmunología , Interleucina-4/inmunología , Interleucina-5/inmunología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Psoriasis/patología , ARN Mensajero , Resultado del Tratamiento
2.
J Invest Dermatol ; 109(4): 541-5, 1997 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9326387

RESUMEN

The immunoglobulin VH gene rearrangement in a primary cutaneous, large-cell (centroblastic and immunoblastic) B-cell lymphoma was analyzed using a micromanipulation/single-cell polymerase chain reaction technique. In all single B cells obtained from CD20-stained skin sections that gave a polymerase chain reaction product (eight of 27 in biopsy I), the same VHDJH rearrangement, consisting of DP-54-DIR1-JH3a genes, was detected, with no intraclonal nucleotide diversity. Comparison with the most closely related germline counterpart showed significantly altered complementarity determining gene regions as a result of somatic mutations, suggesting an antigen-driven selection and expansion ofthis particular B-cell clone. Interestingly, in a biopsy obtained from the patient 9 mo later, during disease progression (deep muscle infiltration), the lymphoma cells again contained the same VHDJH gene rearrangement (six of 18 in biopsy II) without any further somatic mutations. Therefore, it is suggested that the cutaneous lymphoma characterized throughout this study descended from postgerminal center B-cells.


Asunto(s)
Reordenamiento Génico , Genes de Inmunoglobulinas/genética , Linfoma de Células B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Neoplasias Cutáneas/genética , Secuencia de Bases , Separación Celular , Femenino , Humanos , Linfoma de Células B/patología , Micromanipulación , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología
3.
J Invest Dermatol ; 115(2): 254-9, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10951243

RESUMEN

Lichen sclerosus et atrophicus is a chronic dermatosis of unknown etiology and pathogenesis. Lichen sclerosus et atrophicus associated skin lesions show T cell enriched infiltrates, sometimes resembling the histologic picture of early mycosis fungoides. It is supposed that the infiltrating T cells participate in the pathogenesis of atrophy and sclerosis. We investigated skin biopsies from 39 lichen sclerosus et atrophicus patients by histology, immunohistochemistry and, in order to establish the status of T cell clonality, by polymerase chain reaction amplifying the T cell receptor-gamma rearrangements. A stage-dependent shift of the CD3-positive T cells was observed from a predominantly CD4-positive to a predominantly CD8-positive phenotype. The increase of CD8-positive cells was associated with more pronounced epidermotropism and basal degeneration. Nearly all CD8-positive cells expressed cytotoxic granules (TIA1), possibly causing the basal destruction. In the late fibrotic stage of the disease, only a weak or no infiltrate was found. Regarding the T cell receptor-gamma polymerase chain reaction, the presence of clonally expanded T cells was demonstrated in 19 of 39 patients (49%) by at least one of two different high resolution electrophoresis techniques applied to separate the amplification products. Thus, for the first time clonally expanded infiltrating T cells were detected in lichen sclerosus et atrophicus. Furthermore, this is one of the first reports on the detection of clonally expanded infiltrating T cells in an inflammatory skin disease. The clonal T cells could not be assigned to the CD4 or CD8 subtype. Most likely, their presence is not the result of a malignant transformation but a response to an as yet unknown lichen sclerosus et atrophicus associated antigen.


Asunto(s)
Liquen Escleroso y Atrófico/metabolismo , Liquen Escleroso y Atrófico/patología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Piel/patología , Linfocitos T/patología , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases/genética , Biopsia , Niño , Células Clonales , Femenino , Reordenamiento Génico/genética , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Receptores de Antígenos de Linfocitos T gamma-delta/genética
4.
J Invest Dermatol ; 113(4): 554-9, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10504440

RESUMEN

The aim of our study was to investigate the metastatic pathways of melanoma cells in sentinel and other regional lymph nodes. The term "sentinel lymph node" means that the first lymph node of the draining site of a primary tumor is never bypassed in malignant melanoma. In this case lymph node dissection would be necessary only when melanoma cells are detected in the sentinel node. Tyrosinase reverse transcriptase-polymerase chain reaction was applied to search for metastatic melanoma in the sentinel lymph node and in further lymph nodes of a complete lymph node basin in patients who underwent lymph node dissection. In 24 patients with malignant melanoma the draining site of the tumor was marked by lymphoscintigraphy and by intraoperative injection of patent blue V in the area around the primary tumor. The lymph nodes of the affected basin were excised and prepared for histopathologic, immunohistochemical, and molecular biologic examinations. Regarding the sentinel lymph node, 10 of 24 patients showed morphologic evidence for metastases, three additional patients showed only tyrosinase transcripts. In 11 of these 13 cases we found one or more nonsentinel lymph nodes with morphologically detectable melanoma cells and/or tyrosinase mRNA. Interestingly, in seven of 24 patients a positive tyrosinase reverse transcriptase-polymerase chain reaction was received in nonsentinel lymph nodes, whereas the sentinel lymph node was negative, not only for all histologic examinations but also by tyrosinase reverse transcriptase-polymerase chain reaction. In five of seven patients of the latter group, gp100 reverse transcriptase-polymerase chain reaction was carried out, showing also gp100 mRNA in nonsentinel lymph nodes only. Our data indicate that the concept of the sentinel lymph node may miss micrometastases. Whether such micrometastases cause a recurrence or a metastasis of malignant melanoma, or can be destroyed by the immune system, remains to be clarified.


Asunto(s)
Ganglios Linfáticos/patología , Melanoma/secundario , Monofenol Monooxigenasa/genética , Reacción en Cadena de la Polimerasa , Adulto , Anciano , Femenino , Humanos , Metástasis Linfática , Masculino , Melanoma/patología , Persona de Mediana Edad
5.
J Invest Dermatol ; 115(4): 620-4, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10998133

RESUMEN

Mycosis fungoides (MF) is a cutaneous T cell lymphoma, clinically characterized by patches, plaques and tumors occurring in successive stages of the disease. In early MF, an infiltrate consisting of mainly reactive T cells is seen in the papillary dermis while tumor cells are mostly confined to the epidermis. By contrast, later stages show nodular infiltrates formed mostly of tumor cells in the dermis while the epidermis is relatively devoid of tumor cells; however, knowledge of the localization of clonal T cells has been based on histomorphologic features and immunohistochemical stainings visualizing certain V-beta subfamilies of the T cell receptor (TCR). As these techniques do not allow for an unequivocal identification of clonal tumor cells, we used micromanipulation and single cell PCR amplifying the TCR chain gene rearrangement. A total number of 387 single T cells was isolated from six skin biopsies in five patients in patch, plaque, and tumor stages. Of these, 180 T cells were picked from the epidermis and 207 from the dermal infiltrate. The rearranged TCR-gamma DNA could be sequenced from 181 of 387 T cells. In three of six patients representing all three stages, epidermal T cells with a clonal rearrangement could be amplified. In early plaque stage a higher degree of epidermal T lymphocytes was found than in initial patch, later plaque, and tumor stages with an inverse distribution found for reactive T lymphocytes. In two patients a biallelic rearrangement was demonstrated that had not been detected in prior PCR analysis from blood and skin samples. These data show that clonal (neoplastic) and non-clonal (reactive) T lymphocytes in MF preferentially infiltrate different microanatomical compartments of the skin, depending on the stage of disease. The microanatomically distinct localization of reactive and clonal T cells suggests that the absence of direct contact between tumor and host-defense lymphocytes may contribute to tumor persistence and progression in epidermis, peripheral blood, and deep dermal tumor cell nests, respectively.


Asunto(s)
Células Clonales/patología , Micosis Fungoide/patología , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T/patología , Anciano , Secuencia de Bases , Femenino , Reordenamiento Génico , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Piel/química
6.
J Invest Dermatol ; 117(6): 1512-20, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11886516

RESUMEN

Primary cutaneous B cell lymphomas are defined as non-Hodgkin lymphomas that occur in the skin without extracutaneous involvement for 6 mo after diagnosis. They are characterized by a less aggressive course and better prognosis than their nodal counterparts. According to the European Organization for Research and Treatment of Cancer classification, the major subentities of primary cutaneous B cell lymphoma are follicle center cell lymphomas, immunocytomas, and large B cell lymphomas of the leg, which differ considerably regarding their clinical behavior, the former two being indolent, the latter being of intermediate malignancy. In this study, we applied a single cell polymerase chain reaction approach to analyze immunoglobulin V(H)/V(L) genes in 532 individual B lymphocytes from histologic sections of four follicle center cell lymphomas localized on the head and trunk, and four large B cell lymphomas on the leg. We found: (i) in six of eight patients a clonal heavy chain, and in seven of eight patients a clonal light chain rearrangement, all being potentially productive; (ii) no bias in VH gene usage, in four of seven light chain rearrangements the V kappa germline gene IGVK3-20*1 was used; (iii) no biallelic rearrangements; (iv) all V(H)/V(L) genes are extensively mutated (mutation rate 5.4-16.3%); (v) intraclonal diversity in six of eight cases (three of each group); and (vi) low replacement vs silent mutation ratios in framework regions indicating preservation of antigen-receptor structure, as in normal B cells selected for antibody expression. Our data indicate a germinal center cell origin of primary cutaneous follicle center cell lymphomas and large B cell lymphomas independent of those belonging to one of these subentities.


Asunto(s)
Centro Germinal/patología , Linfoma de Células B/patología , Linfoma Folicular/patología , Neoplasias Cutáneas/patología , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Linfocitos B/inmunología , Linfocitos B/patología , Biopsia , Células Clonales , Análisis Mutacional de ADN , Femenino , Regulación Neoplásica de la Expresión Génica/inmunología , Reordenamiento Génico de Linfocito B/genética , Centro Germinal/inmunología , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas Ligeras de Inmunoglobulina/genética , Pierna , Linfoma de Células B/inmunología , Linfoma Folicular/inmunología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Neoplasias Cutáneas/inmunología
7.
J Invest Dermatol ; 116(5): 721-7, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-11348460

RESUMEN

Interleukin-10 is an important anti-inflammatory and immunosuppressive cytokine with major impact on several immune reactions, including regulatory mechanisms in the skin. Recently, we performed a phase II trial in psoriatic patients receiving subcutaneously interleukin-10 over 7 wk. The clinical response suggested that interleukin-10 might represent a novel anti-psoriatic drug. In order to understand better the mode of action and to elucidate the effects of systemic interleukin-10 treatment on the skin immune system, skin punch biopsies from sites different from interleukin-10 injection were analyzed. Biopsies were obtained from the patients before, at the end, and 3 wk after interleukin-10 therapy. The results are reported here. Histologic examination showed a decrease of several parameters reflecting the psoriatic disease activity as acanthosis and extension of the horny layer. Immunohistologic examination demonstrated decreasing numbers of infiltrating T cells, dermal CD1a+ cells, and a diminished proliferation of epidermal cells. Using a novel, quantitative reverse transcriptase-polymerase chain reaction approach a significant shift within the cytokine pattern was found. Interleukin-10 therapy led to a decrease of cutaneous interleukin-8 and interleukin-10 mRNA expression. Whereas no significant changes of interleukin-6, tumor necrosis factor-alpha, and interferon-gamma expression were found, interleukin-4 was strongly upregulated suggesting a shift from a type 1 towards a type 2 cytokine pattern. The changes within the local cytokine pattern seem to be disease-related, as an inverse course was found in a single interleukin-10 nonresponding patient. Our findings demonstrate considerable effects of systemic interleukin-10 application on the skin immune systems, which might contribute to the anti-psoriatic activity of interleukin-10.


Asunto(s)
Interleucina-10/uso terapéutico , Psoriasis/tratamiento farmacológico , Piel/efectos de los fármacos , Adulto , Citocinas/genética , Humanos , Inmunohistoquímica , Biología Molecular/métodos , Psoriasis/inmunología , Psoriasis/metabolismo , Psoriasis/patología , ARN Mensajero/metabolismo , Piel/inmunología , Piel/metabolismo , Piel/patología
8.
Immunobiology ; 201(5): 631-44, 2000 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10834319

RESUMEN

B cell neoplasias descending from germinal center cells harbor the hallmark of intraclonal diversity resulting from ongoing mutation in the variable parts of their immunoglobulin-encoding genes. To characterize a primary cutaneous follicle center B cell lymphoma in more detail, we analyzed the respective VH and VL genes in single cells mobilized from four sequential biopsies, three taken from the skin and one obtained after internal dissemination from a retrobulbar infiltrate. The lymphoma cells were found to contain V5-51/D6-12/JH5b (heavy chain) and A27/Jkappa2 (light chain) gene rearrangements detected on both the genomic and the transcriptional level. To provide an accurate mutation analysis, the specific VH gene counterpart (V5-51UK) was cloned from the patient's germline. Analyzing 226 single cells, we found: (i) complete nucleotide identity when VH and VL genes of lymphoma cells from one particular biopsy were compared among each other; (ii) intraclonal diversity due to ongoing mutation comparing the sequences obtained from sequential biopsies; (iii) both VH and VL genes to be highly mutated. Deducing from the sequence data, we propose a scenario of the clonal evolution of the B cell tumor in this patient. From the molecular-biological point of view, this primary cutaneous follicle center B cell lymphoma shows the features of a germinal center cell lymphoma. To draw this conclusion from single cell PCR data, however, a sample of sequential biopsies had to be analyzed.


Asunto(s)
Linfocitos B/inmunología , Genes de Inmunoglobulinas , Linfoma de Células B/inmunología , Linfoma de Células B/patología , Mutación , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Secuencia de Bases , Biopsia , Células Clonales/inmunología , Estudios de Seguimiento , Cabeza , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Cadenas kappa de Inmunoglobulina/genética , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Invasividad Neoplásica , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética
9.
Arch Dermatol ; 135(2): 187-92, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10052405

RESUMEN

OBJECTIVE: To determine the safety and clinical effects of interleukin 10 (IL-10) treatment of psoriasis. DESIGN AND METHODS: In an open-label phase 2 trial, 10 patients with psoriasis subcutaneously received recombinant human IL-10 over a 7-week period in a dosage of 8 microg/kg daily (n=5) or 20 microg/kg 3 times per week (n=5). Patients were followed up for an additional 5 weeks. RESULTS: The treatment was well tolerated. Antipsoriatic effects were found in all but 1 patient. A significant decrease of the psoriasis area and severity index by 55.3% +/- 11.5% (mean +/- SEM) was observed (P<.02). The antipsoriatic efficiency was confirmed by histological examination. Heterogeneity in the effectiveness was found among the patients, but seems to be independent of the dosage regimen. However, a tendency to a better response was found in the patients who received 20-microg/kg IL-10 3 times per week. Decreasing response in the delayed-type hypersensitivity reaction against recall antigens indicated immunosuppressive effects. Moderate effects on hematopoietic cells were observed. CONCLUSIONS: Our data suggest that IL-10 therapy for psoriasis is safe and possibly clinically effective. Consequently, its value in psoriasis and similar immune diseases should be further determined. Dose-finding, placebo-controlled, double-blind trials are necessary now.


Asunto(s)
Interleucina-10/uso terapéutico , Psoriasis/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/patología
10.
Arch Dermatol Res ; 292(12): 583-9, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11214818

RESUMEN

Antibodies such as HMB-45 and anti-S100 protein have been widely used as markers of malignant melanoma despite evidence that HMB-45 has a sensitivity of only 67-93% and S100 is nonspecific for melanoma. Using a subtractive immunization protocol in a mouse model of human melanoma, we have generated several monoclonal antibodies with putative specificity for melanoma. After initial screenings, the antibody SM5-1 was chosen because of its intriguing reactivity with melanocytic tumors in both frozen and paraffin sections. The immunohistochemical staining of SM5-1 was studied in paraffin-embedded specimens of 401 melanomas (n = 401; 250 primary melanomas, 151 metastases), melanocytic nevi of the skin (n = 16), nonmelanocytic neoplasms (n = 84). The results were compared with HMB-45 and anti-S100 staining. All antibodies reacted with nevi and 97-99% with primary melanomas. Whereas both SM5-1 and anti-S100 stained 96% (146/151) of melanoma metastases, HMB-45 correctly identified only 83% (126/151). All HMB-45-negative metastases were positive for SM5-1. Whereas neither SM5-1 nor HMB-45 stained any of 84 specimens from 40 different nonmelanocytic neoplasms, anti-S100 was positive in 21/84 (25%). While the staining pattern of SM5-1 was mostly homogeneous, small tumor areas in some metastases remained unstained. Staining with SM5-1 was also observed in perivascular dendritic cells, in plasma cells, some myofibroblasts and the secretion of eccrine sweat glands. Nonactivated epidermal melanocytes, keratinocytes, endothelial cells, smooth muscle cells and peripheral nerves were all negative for SM5-1. These results suggest that SM5-1 is highly specific, as well as sensitive, for melanocytic lesions and is useful in the immunohistochemical evaluation of melanoma.


Asunto(s)
Anticuerpos Monoclonales , Melanoma/diagnóstico , Animales , Anticuerpos Monoclonales/biosíntesis , Modelos Animales de Enfermedad , Humanos , Hibridomas , Inmunohistoquímica , Metástasis Linfática/diagnóstico , Metástasis Linfática/patología , Melanoma/inmunología , Melanoma/secundario , Ratones , Metástasis de la Neoplasia/diagnóstico , Metástasis de la Neoplasia/inmunología , Nevo Pigmentado/química , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/patología , Sensibilidad y Especificidad , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología
11.
IEEE Trans Biomed Eng ; 44(9): 831-8, 1997 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9282475

RESUMEN

A new approach in radio frequency (rf) electrosurgery, used for tissue treatment, is achieved by using a new process control method. An external control unit allows a commonly available rf-generator to automatically supply the appropriate power for differing tissue types, thus ensuring best cutting quality. The sparks, generated during the scalpel electrode interaction with the tissue, appear statistically distributed. The spark rate depends on various factors and is monotonic with the supplied electrical power. This allows it to be used as the controlled variable in the cutting process. The ac current passing through the tissue is evaluated by an external control unit using an analyzation algorithm to determine the number of sparks. The external unit is comprised of a system, which measures the spark rate, and a subsequent proportional integral (P.I.) controller. The functionality of the control method as well as the electrical circuitry is verified through cuts with different degrees of carbonization and cuts through tissue heterojunctions.


Asunto(s)
Electrocirugia/instrumentación , Tejido Adiposo/cirugía , Animales , Conductividad Eléctrica , Electrodos , Diseño de Equipo , Técnicas In Vitro , Músculo Esquelético/cirugía , Porcinos
12.
Eur J Dermatol ; 13(6): 599-602, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14721786

RESUMEN

Epithelioid sarcoma is a seldom seen tumor characterized by an innocuous presentation of a non tender nodule or cluster of nodules located on a distal extremity with a high propensity for nodal spread as well as relentless local progression. We describe a patient with the neoplasm masquerading as chronic leg ulcers of unknown origin with an unusual immunohistochemical profile. The difficulty of timely clinical and histological diagnosis is a key problem encountered. Better awareness may result in earlier diagnosis and improved prognosis.


Asunto(s)
Úlcera de la Pierna/etiología , Sarcoma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Anciano , Enfermedad Crónica , Errores Diagnósticos , Humanos , Úlcera de la Pierna/diagnóstico , Úlcera de la Pierna/patología , Metástasis Linfática , Masculino , Sarcoma/patología , Sarcoma/secundario , Neoplasias Cutáneas/patología
13.
Int Urol Nephrol ; 23(4): 357-63, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1938232

RESUMEN

The first results of laser surgery in superficial penile tumours are reported. In 2 patients with condylomata acuminata, 2 cases of giant condylomata Buschke-Löwenstein and in 2 patients suffering from early stage penile cancer diagnostic and/or therapeutic treatments using carbon dioxide or neodymium-YAG laser have been performed. In one patient with giant condyloma a recurrent tumour was found 5 weeks after the initial treatment and a second one using CO2 laser was done. All other patients are tumour-free with a follow up of 6-24 months and erectile function is normal. Therefore, in superficial penile tumours laser treatment is an excellent alternative therapeutic approach.


Asunto(s)
Terapia por Láser , Neoplasias del Pene/cirugía , Condiloma Acuminado/cirugía , Humanos , Masculino , Neoplasias del Pene/patología
16.
Br J Dermatol ; 156(3): 486-91, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17300238

RESUMEN

BACKGROUND: Patients with rheumatic diseases receiving antitumour necrosis factor (TNF)-alpha-based treatment may develop cutaneous reactions. OBJECTIVES: To analyse the new onset or aggravation of skin lesions in patients with a rheumatic disease during treatment with TNF-alpha antagonists. METHODS: We conducted a prospective analysis of 35 of 150 patients with a long history of rheumatic disease, including rheumatoid arthritis, ankylosing spondylitis (Bechterew's disease) and psoriatic arthritis, to test for the development of cutaneous manifestations during anti-TNF-alpha (infliximab, adalimumab or etanercept) treatment. RESULTS: Chronic inflammatory skin diseases such as psoriasis and eczema-like manifestations represented the majority of cases (16 of 35). Cutaneous infections caused by viral, bacterial and fungal agents were also observed in many patients (13 of 35). Skin diseases such as dermatitis herpetiformis, leucocytoclastic vasculitis and alopecia occurred in single cases only. CONCLUSIONS: We observed a broad, diverse clinical spectrum with a majority of chronic inflammatory and infectious skin diseases. However, we did not identify individual risk factors and a discontinuation of the anti-TNF-alpha treatment was not necessary if adequate dermatological treatment was performed. The onset of cutaneous side-effects in anti-TNF-alpha-based treatments should be determined by nationwide registries.


Asunto(s)
Antirreumáticos/efectos adversos , Erupciones por Medicamentos/etiología , Factores Inmunológicos/efectos adversos , Enfermedades Reumáticas/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/patología , Erupciones por Medicamentos/patología , Etanercept , Femenino , Humanos , Inmunoglobulina G/efectos adversos , Infliximab , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/inducido químicamente , Estudios Prospectivos , Psoriasis/inducido químicamente , Psoriasis/patología , Receptores del Factor de Necrosis Tumoral , Enfermedades Cutáneas Infecciosas/inducido químicamente
17.
J Eur Acad Dermatol Venereol ; 20(2): 217-21, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16441639

RESUMEN

The presence of ectopic breast tissue is reported in 2-6% of the general population with most cases being located in the axillary region. Although the same pathology occurs in both eutopic and ectopic breast tissue, primary carcinoma of ectopic breast tissue has been reported only in a small number of cases. Because an overlying accessory areola or nipple is often missing and because of a general lack of awareness among physicians and patients concerning these unsuspicious nodules, clinical diagnosis is frequently delayed. Histological diagnosis can also be delayed if ectopic breast tissue is not present or screened for in the biopsy specimens as apocrine glands of the breast and skin, respectively, exhibit striking similarities and immunohistochemistry is of limited help. Diagnostic delay is demonstrated by the case of a 56-year-old patient who underwent a series of four surgical excisions of a primary ectopic breast carcinoma and developed local lymph node metastasis until treatment with tamoxifen was started. As two-thirds of reported cases of primary ectopic breast carcinoma arose within the axillae, this case underlines the importance of a search for ectopic breast tissue in the context of axillary ductal carcinoma.


Asunto(s)
Axila , Neoplasias de la Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Coristoma/diagnóstico , Axila/patología , Axila/cirugía , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/cirugía , Coristoma/patología , Coristoma/cirugía , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad
18.
Ann Rheum Dis ; 65(3): 405-7, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16150791

RESUMEN

BACKGROUND: Blockage of tumour necrosis factor alpha (TNFalpha) is highly effective in rheumatic diseases, especially in rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis. Furthermore, TNFalpha antagonists have also been shown to significantly reduce psoriatic skin lesions. CASE REPORTS: A series of nine patients with RA who were treated with different types of TNFalpha antagonists and who unexpectedly developed either a new onset or an exacerbation of psoriatic skin lesions are reported.


Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Psoriasis/inducido químicamente , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Etanercept , Femenino , Humanos , Inmunoglobulina G/efectos adversos , Infliximab , Masculino , Persona de Mediana Edad , Psoriasis/patología , Receptores del Factor de Necrosis Tumoral
19.
Exp Dermatol ; 14(2): 96-102, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15679578

RESUMEN

The morphology and histology of test sites commonly used to study the penetration of lip products differ significantly from those of the human lip itself. The aim of this study was to investigate whether the porcine snout could serve as an equivalent in vitro model for human lips. The lips of human test subjects and biopsies of porcine snout tissue were compared using histological and microscopic techniques. Using a dermatological laser scanning microscope, the penetration of topically applied fluorescent sodium fluorescein was investigated in vivo on human lips and in vitro on the porcine snout. Biopsies from the in vitro experiments were studied using fluorescence microscopy. Some parts of the porcine snout show a similar morphology and histology as human lips. The stratum corneum (SC) and the epidermis of the porcine snout are thicker than those of human tissue. Both in vivo and in vitro, the topically applied fluorescent dye was detected only on the skin surface and within the uppermost SC layer. These results indicate that porcine snout can be used as an in vitro model for human lips in penetration studies. Both human and porcine tissues exhibit an efficient barrier against the penetration of topically applied substances.


Asunto(s)
Labio/anatomía & histología , Cavidad Nasal/anatomía & histología , Adulto , Animales , Biopsia , Dermatología/métodos , Epidermis/anatomía & histología , Epidermis/metabolismo , Femenino , Fluoresceína/farmacología , Colorantes Fluorescentes/farmacología , Humanos , Microscopía Confocal , Microscopía Fluorescente , Piel , Programas Informáticos , Especificidad de la Especie , Porcinos
20.
Skin Pharmacol Physiol ; 18(4): 175-9, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-15908757

RESUMEN

The removal of the stratum corneum (SC) using adhesive tapes is a common technique in cutaneous studies. The determination of the varying amounts of the SC removed would be a helpful tool in such investigations. In the present study, the cell layers of porcine SC were counted before and after removal of several tape strips using histological techniques. In addition, the pseudo-absorption of the corneocytes reflecting the amount of these cells was determined using spectroscopy. Different amounts of SC were removed using 20 tape strips. The spectroscopically determined data correlate linearly with the number of removed cell layers. Based on these results, the pseudo-absorption of the corneocytes can be used to calculate the absolute number of cell layers removed with a standard deviation of less than 11%. In this way, the SC can be quantified using the procedure of tape stripping in combination with the spectroscopic determination of the corneocytes.


Asunto(s)
Adhesivos , Células Epidérmicas , Epidermis/metabolismo , Absorción Cutánea , Manejo de Especímenes/métodos , Animales , Recuento de Células , Técnicas In Vitro , Espectrofotometría , Porcinos
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