Wide-area 308-nm phototherapy with nonlaser light in the treatment of psoriasis: results of a pilot study.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to N Pimpinelli.
Explore the source record for details and available documents.
The combination of PEG-interferon and ribavirin is currently recommended for the treatment of chronic hepatitis C, which is a common cause of morbidity and mortality worldwide. Hair disorders have often been described during interferon therapy, which include reversible hair discoloration, hypertricosis and alopecia. Ribavirin is reported to cause photoallergic reactions. We report two cases of alopecia universalis, with complete hair loss extended to the whole body, secondary to PEG-interferon and ribavirin combination therapy for chronic hepatitis C virus infection. Both female patients were infected by genotype 1 and presented alopecia during the second half of a 48-week therapy, concurrently with low levels of ferritin and thyroid dysfunction (patient 1) or depression (patient 2). Patient 1 withdrew from the therapy on week 26 and, due to the occurrence of maculo-erythematous cutaneous eczema, underwent corticosteroid therapy with complete hair regrowth. Patient 2 completed the scheduled therapy and showed a spontaneous complete hair regrowth. It should be noted that in spite of an early (within 4 weeks of therapy) virological response, patient 1 had a disease relapse after therapy withdrawal and corticosteroid therapy, while patient 2 maintained a sustained virological response. In conclusion, interferon therapy may trigger reversible alopecia universalis in susceptible patients. However, given the benign and reversible nature of this side effect, patients who achieve a virological response should be strongly advised to complete the treatment in order to prevent disease relapse.
Chromosomal translocations affecting the IGH locus and various oncogene loci are recurrent in many types of systemic B-cell lymphomas. Hardly any data exist, however, on such translocations in primary cutaneous B-cell lymphomas (PCBCL). Here, a series of 29 PCBCL was investigated by interphase fluorescence in situ hybridization with probes for the IGH, MYC, BCL6, and MLT1 loci. None of the six follicle center cell lymphomas and nine marginal zone lymphomas showed evidence for any translocation affecting these loci. In contrast, 11 of 14 large B-cell lymphomas of the leg harbored breakpoints in at least one of the loci. Translocations involving the MYC locus were detected in six cases, five of them derived from a MYC/IGH juxtaposition and one from a translocation involving a non-IG gene partner. Rearrangements of the BCL6 locus were detected in five B-cell lymphomas of the leg, and involved IGH (two cases), IGL (one case), and non-IG genes (two cases). This study shows that large B-cell lymphomas of the leg display a pattern of chromosomal translocations similar to their systemic counterparts whereas primary cutaneous follicle center cell lymphomas and marginal zone lymphomas lack these typical chromosomal translocations.
Explore the source record for details and available documents.
We analysed the immunophenotypic and molecular expression of BCA-1 (B-cell-specific chemokine) and CXCR5 (BCA-1 receptor) in normal skin and different cutaneous lymphoproliferative disorders (cutaneous T-cell lymphoma (CTCL); cutaneous B-cell lymphoma (CBCL); cutaneous B-cell pseudolymphoma (PCBCL)), with the aim of investigating their possible involvement in the pathogenesis of cutaneous B-cell disorders. BCA-1 and CXCR5 were constantly expressed in CBCL and PCBCL, but not in normal skin and CTCL. BCA-1 and CXCR5 were constantly coexpressed by CD22+ B-cells, while CD35+ follicular dendritic cells coexpressed BCA-1 in PCBCL cells only. In low grade CBCL, as compared with high grade CBCL, the intensity of CXCR5 expression on neoplastic CD22+ cells was lower than that of BCA-1. The image analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products showed a significant quantitative difference between PCBCL/low grade CBCL and high grade CBCL. The above findings, although only observed in a small series of patients, are in keeping with findings in MALT gastric and gastric MALT lymphomas, adding further evidence of the close similarities between CBCL and MALT lymphomas.
Explore the source record for details and available documents.
Xeroderma pigmentosum (XP) is a rare autosomal recessive photosensitive disorder, which results in multiple face, neck and head basal cell carcinomas (BCCs), squamous cell carcinomas and melanomas. A 15-year-old boy with XP presented with multiple facial BCCs previously treated by surgical excision. Standard BCC treatments such as surgery are not ideal for patients with several facial BCCs because of the risk of scarring, and the patient refused further surgery. As an alternative, three times weekly application of imiquimod 5% cream in combination with oral acitretin (20 mg daily) was prescribed for 4-6 weeks. No adverse events were reported during treatment and all tumours had resolved at the 6-month follow up visit, highlighting the therapeutic potential of imiquimod 5% cream.
We report two cases of cutaneous B-cell pseudolymphoma (PCBCL) induced by intradermal antigen injections for specific immune therapy (SIT). In both cases, the lesions had first developed on the area of injection; years later, new lesions appeared far from the original site. The histological, immunohistochemical, and molecular findings of the lesions showed features consistent with the diagnosis of PCBCL in both cases. In particular, the staining for sIg light chains showed a polyclonal pattern, and the molecular analysis by reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot showed a germ-line configuration of the Ig heavy chain genes. While the development of PCBCL related to a specific stimulus is well known and widely reported, the development of histologically and immunohistologically identical lesions far from the injection site is definitely worthy of note. This behaviour might be due to the presence of retained antigens in the injection site. This chronic antigenic stimulation could induce the progressive selection--and subsequent dissemination--of antigen-specific B cell clones.
The survival of patients affected by cutaneous melanoma has improved dramatically in the last 10 years, because of earlier diagnosis. Despite this, the therapeutic results obtained in metastatic melanoma (MM) are very disappointing due to its poor responsiveness to cytotoxic agents. In this type of solid tumor, tumor chemosensitivity assays have been suggested to be an important tool to predict clinical responsiveness to therapy. Metastatic melanoma cells (MMCs) were obtained from subcutaneous melanoma metastases of five patients and cultured for several consecutive passages. An immunofluorescence and an electron microscopic study were performed in order to establish the ultrastructural and physiopathological features of MMCs. A sulphorodamine-B test was used to measure in vitro sensitivity of MMCs to temozolomide, cisplatin, vindesine, taxol and interpheron alpha-2a. Following a 72 h exposure, maximum activity was obtained with vindesine (median inhibitory concentration, IC(50), 0.23 nM) and taxol (median IC(50) 0.31 nM). Cisplatin median IC(50) values were higher (4.6 microM) than taxol and vindesine, but still in the range of clinically achievable plasma concentrations. Temozolomide inhibited cell proliferation only at very high concentrations (median IC(50) 228 microM). No significant cell growth inhibitory effects (<or=25%) were observed with interferon alpha-2a concentrations up to 8000 IU/ml. MMCs expressed progression markers typical of cutaneous metastatic melanoma and showed poor sensitivity in vitro to most anticancer drugs tested, including temozolomide.
The issue of primary cutaneous lymphoma (CL) has been greatly influenced by the increasing knowledge about lymphoid cell biology, the widespread use of sensitive and specific immunological and molecular markers, and the careful correlation among clinical, histological and immunomolecular features. This latter is the key element of the classification of CL proposed by the EORTC Cutaneous Lymphoma Study Group in 1997, which categorizes distinct clinicopathological entities with prognostic and therapeutic relevance. With few exceptions, no reliable diagnosis and subtyping of CL can be made without the aid of immunohistochemistry and/or molecular analysis. On the other hand, the acritical use of immunological and molecular markers can be misleading if not combined properly with a correct clinical and histological evaluation. For this reason, a step-by-step diagnosis and staging protocol is exceedingly important. Finally, great caution should be used in the interpretation of lymphoid cell infiltrates of the skin which show a monoclonal rearrangement in the absence of reliable clinical and/or pathological evidence of neoplasia.
Disturbances of skin barrier function occur in several skin diseases, e.g., atopic dermatitis (AD), irritant/allergic contact dermatitis (ICD, ACD). Skin barrier damage triggers the production of cytokines that stimulate lipogenesis which may also cause inflammatory processes. The aim of this study was to evaluate the efficacy of a topical skin lipid mixture in the treatment of ICD, ACD and AD. 580 consecutive patients suffering from ICD, ACD or AD were treated with a skin lipid mixture containing ceramide-3 and patented nanoparticles. Patients received the lipid mixture alone or in combination with topical corticosteroids until clearance or for 8 weeks. Both treatment groups statistically improved all parameters considered at week 4 and 8 as compared to baseline. Between the 2 treatment groups, there was a statistically significant difference in favour of combined therapy for (ICD, ACD, AD, respectively): erythema, pruritus and overall disease severity; erythema and pruritus; erythema, pruritus, fissuring and overall disease severity. No statistically significant difference was found for (ICD, ACD, AD, respectively): dryness, scaling and fissuring; scaling, fissuring and overall disease severity; dryness and scaling. Between the 2 ACD treatment groups, there was a statistically significant difference in favour of the skin lipid mixture for dryness. In conclusion, the study shows that balanced lipid mixtures are effective in improving barrier properties and the clinical condition of the skin in contact dermatitis.
BACKGROUND: Primary cutaneous follicle centre cell lymphomas (PCFCCL) are the most common type of primary cutaneous B-cell lymphomas. Patients with this disorder develop one or a few clinically indolent tumour nodules, plaques, or papules confined to a circumscribed area. Only limited data have so far been published on the use of immunoglobulin heavy chain variable region (VH) families by these tumours. OBJECTIVES: Because the definition of the repertoire of VH genes could have significant biological and diagnostic implications, we evaluated a group of patients with PCFCCL for VH family use. METHODS: DNA obtained from 15 cases of PCFCCL was amplified by polymerase chain reaction (PCR) using a panel of VH family-specific amplimers. RESULTS: The pattern of VH family usage was similar to that reported in both normal peripheral blood B cells and the most common low grade non-Hodgkin's lymphomas, where VH region utilization is essentially random with frequent usage of the VH3 family. CONCLUSIONS: These findings support the hypothesis that PCFCCL may derive from the mature peripheral lymphoid compartment. Our results may also have implications for the routine analysis of B-lymphoid clonality in PCFCCL.
BACKGROUND: Chemotherapy and immunotherapy are treatments currently employed in advanced melanoma, but responses obtained are poor, and metastatic melanoma patients with visceral localization rarely survive for more than 6 months. Thus, different therapeutic regimens are used in metastatic melanoma and no standardized therapy exists so far. METHODS: We report a retrospective survival study involving 80 patients with metastatic melanoma who were treated either with chemotherapy [dacarbazine (DTIC) alone or DTIC in monotherapeutic or polychemotherapeutic regimen] or immunochemotherapy [interferon (IFN)-alpha at low doses added to chemotherapy]. Survival of patients was statistically evaluated in an actuarial curve taking into account as predictive variables sex, age, marital status, site of primary tumour, histological type, Clark level, sites of metastases, and the different therapeutic regimens (i.e. DTIC alone, DTIC plus IFN-alpha, or others, with or without IFN-alpha). RESULTS: Site of primary melanoma, histological type, Clark level and therapy regimen appeared to exhibit a prognostic significance in survival; when a multivariate analysis was performed to obtain a mutual adjustment of survival values for each variable, only the therapeutic regimen was found to be significant as an independent prognostic variable. Patients treated with immunochemotherapy, i.e. DTIC plus IFN-alpha, showed a probability of dying of 0.41 (95% confidence interval 0.2-0.8) compared with patients treated with DTIC alone. CONCLUSIONS: In our study immunochemotherapy, comprised of DTIC plus IFN-alpha at low doses, was associated with a significantly longer survival of patients, in comparison with chemotherapy comprised of only DTIC.
Explore the source record for details and available documents.
Langerhans cells can originate in vitro from immature precursors stimulated with granulocyte macrophage-colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF)-alpha and stem cell factor (SCF). We asked whether these cytokines also control the differentiation state of Langerhans cells within the epidermis and upon leaving this tissue. We harvested sheets of human epidermis by controlled dispase hydrolysis of keratomes, cultured them in RPMI and 10% fetal calf serum for 48 h and analysed the sheets and the cells migrated spontaneously into the medium, most of which were Langerhans cells containing Birbeck granules. By flow cytometry, the intensity of CD1a expression was reduced quite evenly among Langerhans cells migrated from sheets within 48 h. The cells in the sheets underwent loss of dendrites, with a significant reduction in the cell perimeter that was prevented by GM-CSF and TNF-alpha together. Either of these cytokines induced expression of CD18 by cells in the sheets and those in the medium. Moreover, TNF-alpha induced expression of CD54 by cells in the medium, but not by those retained in the sheets, whereas human SCF induced, dose dependently, expression of CD54 by cells in the sheets, but not from those in the medium. The proliferation of allogeneic lymphocytes was much higher when stimulating Langerhans cells were harvested from cultures with any cytokine, rather than from cultures without cytokines. We conclude the following: (i) GM-CSF and TNF-alpha help to maintain full differentiation of Langerhans cells within the epidermis; (ii) cytokine influence on Langerhans cells adhesiveness is in part context dependent; and (iii) pretreatment with cytokines influences positively the number or accessory activity of Langerhans cells on lymphocytes during subsequent mixed leucocyte reaction.
The immunosuppressant drug cyclosporin A (CsA) is known to cause reduction in number, DNA synthesis and function of Langerhans cells (LC). Since also the differentiation of LC is known to be hampered in conditions of acquired immunodeficiency not due to drugs, we investigated whether this occurs with CsA. Rats were injected subcutaneously with CsA (5, 10 and 50 mgxkg(-1) x d(-1)) for three weeks; the skin was analyzed by Ia immunohistochemistry and by electron microscopy. Epidermal immunolabeled cells were 15+/-3.5 (mean +/- SEM) per 100 basal keratinocytes in untreated controls and 8.75+/-1.3, 4.75+/-1.0 and 1.7+/-1.2 upon increasing doses of CsA (p<0.01). By electron microscopy, monocytoid cells with deep invaginations of the plasma membrane and roundish LC poor in Birbeck granules appeared in the epidermis upon treatment. The results suggest that CsA inhibits the differentiation of LC precursors in the epidermis and that this can in part explain the selective increase in the risk of skin viral disease and cancer in chronically treated patients.
Primary cutaneous B-cell lymphomas (CBCLs) should be clearly separated from non-Hodgkin's B-cell lymphomas with secondary cutaneous involvement and from cutaneous B-cell pseudolymphomas. The majority of CBCLs are characterized by a homogeneous clinical presentation and behavior, with good response to local radiotherapy, low tendency to extracutaneous spread, and excellent prognosis. According to the European Organization for Research on the Treatment of Cancer classification of primary cutaneous lymphomas, CBCLs with an indolent behavior are divided into 2 subgroups: follicular center cell lymphoma and immunocytoma/marginal zone lymphoma, due to putative histologic similarities with their purported nodal counterparts. In addition, a third subgroup with intermediate prognosis (large B-cell lymphoma of the leg) is identified. Conversely, the identification of distinct subgroups is disputable from a strictly histologic, immunophenotypic, and genotypic point of view, and has neither correlation with the clinical course nor the prognosis of the disease. Moreover, the majority of CBCLs show a uniform immunophenotype (CD5-, CD10-) and genotype (lack of bcl-1/bcl-2 and c-myc gene rearrangement) of neoplastic cells. Therefore, we favor the use of the term Skin-Associated Lymphoid Tissue (SALT)-related B-cell lymphomas, due to the close similarities between CBCLs and mucosa-associated lymphoid tissue (MALT) lymphomas, and the evidence for an acquired B-cell arm of SALT.
Explore the source record for details and available documents.