microRNA-214 contributes to melanoma tumour progression through suppression of TFAP2C.

Malignant melanoma is fatal in its metastatic stage. It is therefore essential to unravel the molecular mechanisms that govern disease progression to metastasis. MicroRNAs (miRs) are endogenous non-coding RNAs involved in tumourigenesis. Using a melanoma progression model, we identified a novel pathway controlled by miR-214 that coordinates metastatic capability. Pathway components include TFAP2C, homologue of a well-established melanoma tumour suppressor, the adhesion receptor ITGA3 and multiple surface molecules. Modulation of miR-214 influences in vitro tumour cell movement and survival to anoikis as well as extravasation from blood vessels and lung metastasis formation in vivo. Considering that miR-214 is known to be highly expressed in human melanomas, our data suggest a critical role for this miRNA in disease progression and the establishment of distant metastases.

Clinical experience with ipilimumab 3 mg/kg: real-world efficacy and safety data from an expanded access programme cohort.

BACKGROUND: Ipilimumab improves survival in patients with advanced melanoma. The activity and safety of ipilimumab outside of a clinical trial was assessed in an expanded access programme (EAP). METHODS: Ipilimumab was available upon physician request for patients aged 16 or over with pretreated stage III (unresectable)/IV melanoma, for whom no other therapeutic option was available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Patients with stable disease or an objective response to ipilimumab were eligible for retreatment upon disease progression. Tumour assessments were conducted at baseline and week 12. Patients were monitored for adverse events (AEs) within 3 to 4 days of each scheduled visit. RESULTS: Of 855 patients participating in the EAP in Italy, 833 were evaluable for response. Of these, 13% had an objective immune response, and the immune-related disease control rate was 34%. Median progression-free survival and overall survival were 3.7 and 7.2 months, respectively. Efficacy was independent of BRAF and NRAS mutational status. Overall, 33% of patients reported an immune-related AE (irAE). The frequency of irAEs was not associated with response to ipilimumab. CONCLUSIONS: Outside of a clinical trial setting, ipilimumab is a feasible treatment option in patients with pretreated metastatic melanoma, regardless of BRAF and NRAS mutational status. Data from this large cohort of patients support clinical trial evidence that ipilimumab can induce durable disease control and long-term survival in patients who have failed to respond to prior treatment.

Sequential treatment with ipilimumab and BRAF inhibitors in patients with metastatic melanoma: data from the Italian cohort of the ipilimumab expanded access program.

Of 93 patients with pretreated, BRAF(V600) mutation-positive advanced melanoma who received vemurafenib or dabrafenib before (n = 45) or after (n = 48) treatment with ipilimumab 3 mg/kg, median overall survival (mOS) from first treatment was 9.9 and 14.5 months, respectively. Among patients treated with a BRAF inhibitor first, mOS from the end of BRAF inhibition was 1.2 months for those who did not complete ipilimumab treatment as per protocol, compared with 12.7 months for those who did (p < .001). Prospective, randomized studies are required to determine the optimal sequencing of ipilimumab and BRAF inhibitors in patients with BRAF-mutated metastatic melanoma.

A retrospective analysis of the costs and management of genital warts in Italy.

BACKGROUND: In Italy the prevalence of genital warts in women (15-64 years) is approximately 0.6% with an incidence of 0.4% per year. Treatments for GW are usually long, with moderate success and high costs. The aim of the study was to evaluate the diagnostic-therapeutic pathway, duration and setting of treatment, costs of episodes of condyloma in a population attending a regional STI clinic in Piedmont. METHODS: This was a retrospective observational study conducted using medical records of outpatients who first visited the STI Clinic of San Lazzaro Dermatological Hospital in 2008. The patients' medical histories were analysed for episodes that occurred and were cleared in 18 months following the initial visit. Data on screening methods for STIs, type of diagnosis for condyloma, treatment type, treatment setting, and anatomic lesion site were obtained from medical records. The costs were calculated for each episode. RESULTS: A total of 450 episodes were analysed (297 men,153 women). The most frequently affected anatomic site was the genital area (74%) in both genders. With regard to treatment setting, 78.44% of patients received outpatient treatment at the STI clinic, 4% were treated at home, and 0.22% were hospitalised; 11.11% were treated in multiple settings. The mean number of treatments per episode was 2.03; although many patients received only 1 treatment (n = 207, 46%), exspecially cryotherapy or diathermy coagulation (64.73% versus 28.02% of episodes, respectively). The mean episode duration was 80.74 days. The mean cost (in 2011 euros) for an episode was €158.46 ± 257.77; the mean costs were €79.13 ± 57.40 for diagnosis and €79.33 ± 233.60 for treatment. The mean cost for treatment in a STI-Clinic setting was €111.39 ± 76.72, that for home treatment was €160.88 ± 95.69, and that for hospital care was €2825.94. CONCLUSIONS: The treatment of and associated costs for genital warts are significant. Several factors affect the cost, and internal STI clinic protocols, such as the 6 month window used to consider a recurrence or new diagnosis, create bias. Nonetheless, our findings how costs similar to those reported in the international literature and should be considered when deciding on which HPV vaccination programs should be provided by the public health system.

Diagnostic and therapeutic approaches in Italian hospitals: adjuvant and metastatic therapy in melanoma.

Melanoma incidence and mortality rates are rising in Italy, indicating that more effective treatments are required both in the adjuvant and metastatic settings. We analyzed clinical practices in the adjuvant and metastatic settings by conducting a nationwide survey of clinicians responsible for managing melanoma treatment and follow-up in a representative sample of Italian hospitals. 95% of participating hospitals completed the panel of questions on adjuvant and metastatic treatment, making it likely that these results give a realistic picture of treatment and follow-up of melanoma patients in Italy. In low-volume hospitals (<25 new melanoma diagnoses yearly) adjuvant therapy was significantly more used than in large-volume hospitals for patients in stage III and IV (82 versus 66% and 56 versus 30%, respectively), and only 11% of patients were enrolled in clinical trials. In the metastatic setting dacarbazine was the preferred first-line treatment (32%) followed by polychemotherapy (23%); 12% of patients were enrolled in clinical trials and less than 10% received interleukin-2, usually subcutaneously. The information provided by this study was used by the Italian Melanoma Intergroup to improve the quality of care and to redirect financial resources.

Time course, clinical pathways, and long-term hazards risk trends of disease progression in patients with classic mycosis fungoides: a multicenter, retrospective follow-up study from the Italian Group of Cutaneous Lymphomas.

BACKGROUND: Mycosis fungoides (MF) is an indolent primary cutaneous T-cell lymphoma. To the authors' knowledge, no data currently are available regarding the evolution over time of the risk of developing specific pathways of disease progression. METHODS: This retrospective study analyzed 1422 patients with MF who were diagnosed and followed from 1975 through 2010 in 27 Italian Study Group for Cutaneous Lymphoma centers. The primary objectives were to ascertain the time course, pathways, and hazards risk trends of cutaneous/extracutaneous disease progression; to evaluate whether different tumor-lymph node-metastasis-blood (TNMB) stages have different pathways of disease progression; and to analyze differences between tumor-stage and erythrodermic MF with regard to clinical onset, disease evolution, and prognosis. The secondary objective was to provide a further validation for the revised International Society for Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (ISCL/EORTC) classification. RESULTS: The median follow-up was 14.5 years; stage progression occurred in 29.7% of patients and blood involvement was the most frequent extracutaneous site of disease progression. Patients with stage IA to stage IB disease demonstrated a steady low annual incidence of disease progression to tumor-stage (1%-2%); patients with stage IIA disease had a higher risk within the first years (up to 9.4%). Erythroderma evolved with a significantly higher frequency from patches/plaques (13.9%/28.2%) than tumors (P = .028 and P = .013, respectively). Hazards rates of extracutaneous involvement were low (< 1%). The T-score was found to be associated with extracutaneous involvement site, tumor-stage disease with lymph node/visceral lesions, and erythroderma with blood involvement. TNMB classification and stage progression resulted as independent prognostic variables being detected on multivariate analysis; the type of extracutaneous involvement was found to affect survival . CONCLUSIONS: The data from the current study support the need for a stage-tailored follow-up, suggest that the classification of tumor-stage disease at a stage below erythroderma could be modified, and offer a further validation for the revised TNMB classification.

Electrochemotherapy in the treatment of Kaposi sarcoma cutaneous lesions: a two-center prospective phase II trial.

BACKGROUND: Electrochemotherapy (ECT) is an emerging treatment for cutaneous lesions of different tumor types. The combination of chemotherapy and electroporation enhances drug uptake into tumoral cells. However, its role in the treatment of Kaposi sarcoma (KS) has not yet been well defined, and to date, literature reports are scarce. We prospectively evaluated clinical activity and safety of ECT in KS patients. METHODS: Twenty-three patients with histologically confirmed unresectable KS, not treatable by radiotherapy or intralesional vincristine therapy, were enrolled onto the study according to the European Standard Operating Procedures of Electrochemotherapy (ESOPE) guidelines and treated with a pulse generator. RESULTS: A response to the first ECT session was obtained in all patients, with a complete response (CR) in 14 (60.9%) of 23 patients. A second ECT was performed in 5 (21.7%) and a third in 2, with a median interval between two sessions of 5.1 (range 2.5-25.5) months. Overall, a total of 15 patients (65%) experienced a CR. After a median follow-up of 1.5 years (range 2 months to 4.2 years), 16 patients maintained the response, 4 after repeated courses. Sustained local control of treated lesions was present in 20 of 23 patients. The overall survival rate was 74.4% at 2 years. CONCLUSIONS: ECT represents an additional therapeutic tool for the management of KS cutaneous lesions, characterized by a definite clinical activity and long-lasting remissions. The absence of systemic side effects and the low impact on the immune system also make this treatment suitable for elderly people, even with repeated courses.

Thymopentin down-regulates both activity and expression of iNOS in blood cells of Sézary syndrome patients.

While thymopentin has been used for many years in the experimental treatment of Sézary syndrome (SS), a rare and very aggressive lymphoma, its mechanism of action is still not known. Herein we show that this peptide acts as an inhibitor of isolated iNOS and nNOS isoforms, and reduces iNOS protein/mRNA levels and iNOS activity in blood cells obtained from both healthy donors and SS patients. Similar results were obtained with TPN-2, the N(ω)-nitro analogue of the Arg-Lys motif present in thymopentin. Additional investigations are necessary to confirm the role and the relative importance of the two mechanisms of iNOS down-regulation in the therapeutic action of these peptides against SS.

Intralesional cidofovir for the treatment of multiple and recalcitrant cutaneous viral warts.

Cidofovir is a nucleoside analog of deoxycytidine with a strong activity against a broad spectrum of DNA viruses, including human papillomavirus. The first objective was to evaluate efficacy of cidofovir for the treatment of cutaneous viral warts, recalcitrant after conventional therapies or where the surgery approach is difficult for their location or extension. Second, the present authors propose to point out possible local and systemic side effects consequent to treatment. Two-hundred eighty patients affected by recalcitrant cutaneous viral warts, were treated with intralesional cidofovir 15 mg/mL once a month. The present authors stated that candidates were those who had made before at least two other treatments reported in the guideline for management of cutaneous viral warts. In 276 cases, warts completely cleared: 158 of those have a follow-up period longer than 12 months and 118 have a follow-up of 6 months. On the average, 3,2 injections were enough to solve the problem. Local side effects consisted of pain and burning sensation during the injections; itching, erythema, and post-inflammatory hyperpigmentation were observed. No cases of systemic side effects were noted. The treatment was well tolerated, and the warts were completely cleared without relapses. Intralesional cidofovir is emerging as an effective therapeutic alternative for warts that are unresponsive to conventional treatments.

Functional and phenotypical impairment of polymorphonuclear cells in atopic dermatitis: an additional cause for the known susceptibility to infections?.

BACKGROUND: Atopic dermatitis (AD) patients present an high susceptibility to infections. The phagocytic activity of polymorphonuclear granulocytes (PMNs) is mediated by the interactions between Toll-like receptors (TLRs) and pathogen-associated molecular patterns. OBJECTIVE: To investigate functional activity and phenotype of PMNs in AD patients. METHODS: In vitro PMN phagocytosis and intracellular killing towards Klebsiella pneumoniae were evaluated in 24 AD patients; flow cytometry was applied to analyze PMN phenotype. RESULTS: PMNs from AD patients displayed both reduced phagocytic activity and intracellular killing against K. pneumoniae than healthy subjects (HS). CD11b, CD66b, TLR2, TLR4 and TLR5 median fluorescence intensity (MFI) on PMN membrane were significantly higher in AD patients than in HS. CONCLUSION: PMN functional impairment in AD patients could represent an additional cause of skin infections, coupled with other known defects in the innate immune system. The increased MFI of adhesion molecules and TLRs is rather a consequence of the increased skin barrier permeability to bacterial molecules capable of stimulating immunological reactions.

Skin cancers and other cutaneous diseases in renal transplant recipients: a single Italian center observational study.

Kidney transplant recipients frequently suffer from skin infections and malignancies, due to the effects of long-term immunosuppressive therapy. Herein, a dermatological screening was performed to evaluate the relationship between risk factors, cutaneous tumours and other skin diseases in a group of 282 kidney transplant patients. Infectious diseases (16.7%) were the most frequent dermatological disorders, whereas cutaneous inflammatory and autoimmune diseases were relatively rare, probably due to an indirect therapeutic role of immunosuppressive regimens. Thirty patients experienced cutaneous side effects from immunosuppressants, mainly when receiving corticosteroids (p = 0.0372). We identified 99 patients (35.1%) who developed cutaneous tumours after transplantation. Cumulative tumour incidence was observed during long-term immunosuppressive therapy; no relationships were identified between skin cancer risk and single class of drug or combination regimens. When we evaluated the eventual relevance of other risk factors for skin cancers, we demonstrated a statistical significance in univariate analysis for male gender, more advanced age at transplantation, long duration of immunosuppressive regimens, no sunscreen usage, outdoor job, absence of cherry angiomas and presence of actinic keratoses (AKs). Age at transplantation (p = 0.0174), presence of AKs (p = 0.0005) and duration of immunosuppression (p = 0.0011) also confirmed their significance in multivariate analysis.

Functional and phenotypical alterations of polymorphonuclear cells in Sézary syndrome patients.

Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL), has a poor prognosis and infections represent the most frequent cause of death. Polymorphonucleate granulocytes (PMNs) constitute an essential part of the innate immune system: their phagocytic and killing activity against pathogens is mediated by the interactions between Toll-like receptors (TLRs) and the Pathogen-associated molecular patterns (PAMPs). The aim of this study was to investigate PMN functional activity and phenotype in SS patients and their correlation with the onset of infectious complications. This prospective study enrolled 18 consecutive SS patients; PMN functional activity was evaluated by phagocytosis and intracellular killing tests towards Klebsiella pneumoniae. Flow-cytometry was applied to analyze PMN phenotype. PMNs from SS patients displayed a reduced phagocytic activity and intracellular killing against K. pneumoniae at 30 min and 60 min, more pronounced in SS patients with recurrent infections. CD11b and CD66b median fluorescence intensity (MFI) was significantly higher in SS than in healthy subjects, whereas CD62L MFI was decreased. No significant differences in TLR2, 4, 8 and 9 percentage expression or MFI were found. An increased TLR5 percentage expression was documented. The impairment in PMN functional activities in SS could favour the immune-suppression and raise infection risk.

Therapeutic hotline. A rare vandetanib-induced photo-allergic drug eruption.

Vandetanib is an inhibitor of the vascular endothelial growth factor receptor 2 tyrosine kinase and the epidermal growth factor receptor tyrosine kinase, recently used in the treatment of different tumors. We describe a case of a photo-allergic reaction to vandetanib in an 80-year-old Caucasian woman affected by metastatic non-small cell lung cancer. Phototoxic reactions to vandetanib have been rarely reported in the literature. Dermatologists should be aware of this cutaneous side effect of vandetanib treatment and affected patients should be counseled to use adequate sun protection.

High-dose immunoglobulines and extracorporeal photochemotherapy in the treatment of febrile ulceronecrotic Mucha-Habermann disease.

Febrile ulcero-necrotic Mucha-Habermann disease (FUMHD) is a rare subtype of pityriasis lichenoides et varioliformis acuta (only 41 cases described to date), characterized by an acute onset of ulcero-necrotic papules accompanied by high fever and severe constitutional symptoms. We report a case of a 23-year-old man with a steroid-resistant FUMHD treated by intravenous immunoglobulins (IVIG) combined with methotrexate. Only one case of FUMHD treated by IVIG has been reported to date in literature. Also in our case, IVIG proved to be effective in inducing a dramatic improvement of ulceration and in arresting the appearance of new lesions. Moreover, in our experience we decided to perform a maintenance treatment with extracorporeal photochemotherapy (ECP), to the best of our knowledge not previously used in the treatment of pityriasis lichenoides et varioliformis acuta. ECP, which involves extracorporeal exposure of peripheral blood mononuclear cells to photo-activated 8-methoxypsoralen, induces an immunological reaction against auto-reactive T cell clones, without immune-depression and thus could potentially be useful particularly in FUMHD avoiding the risk of an infective reactivation.

Long-term evolution of an untreated primary cutaneous follicle center lymphoma of the scalp.

Among primary cutaneous B-cell lymphomas, follicle center lymphomas represent, according to the World Health Organization-European Organisation For Research and Treatment of Cancer classification, a subgroup with a favorable prognosis. We describe the case of a 45-year-old man who presented with large infiltrated tumors and nodules coalescing into a wide ulcerated plaque of the scalp, extending from the frontal to the occipital region. At the vertex, 2 large ulcerations were present, reaching the subcutaneous tissues and the underlying bone structures with osseus infiltration and erosion and consequent meningeal exposure. A left retroauricular lymphadenopathy was also present. Histology and immunohystochemistry diagnosed a relapse of primary cutaneous follicle center lymphoma with multilobated histomorphology and lymph node involvement. The histological picture was unchanged from the first sample of 1989. Due to a refusal to treatment, the lesion progressively grew until now. After 6 courses of chemotherapy (cyclophosphamide, vincristine, liposomal doxorubicin, prednisone-Rituximab), the tumor displayed an impressive complete regression with the persistence of a 4-cm occipital ulceration and underlying bone erosion. The adenopathy disappeared as well. This case gave us the opportunity to observe the natural development of the disease, leading to local mutilating and destroying lesions but with low tendency to systemic spread and an impressive response to chemotherapy.

Zosteriform cutaneous metastases: a literature meta-analysis and a clinical report of three melanoma cases.

BACKGROUND: Despite frequent skin involvement with solid tumors, zosteriform metastases are a rare, not well-defined entity, with only few cases published in literature. The unifying characteristic is merely topographic: cutaneous lesions were distributed along dermatomes, despite the variety of clinical features, including vesicobullous, papular, and nodular lesions. Several theories have been proposed to explain the pathogenetic mechanism of zosteriform dissemination, even if none was adequately proved. OBJECTIVE: In this article, we report three new cases of patients with melanoma with skin zosteriform metastases and present a meta-analysis of literature data. METHODS AND MATERIALS: We collected all Entrez-PubMed articles about zosteriform skin metastasis since 1970 and reviewed 56 cases, including our own taken from a 4,774-patient series. RESULTS: The histotypes mainly implicated were melanoma (18%); lymphoma (14%); breast cancer (12%); squamous cell carcinoma (12%); and digestive (10.7%), respiratory (10.7%), and urinary tumors (7%), with other histotypes accounting for 14%. In only one case in our series did we describe a typical herpetiform pattern, whereas in the others we found papulonodular lesions with a dermatomeric distribution. CONCLUSION: Cutaneous metastases with zosteriform pattern are rare and show a wide clinicopathologic spectrum that could affect the disease course. The authors have indicated no significant interest with commercial supporters.

Variants of parvovirus B19: bioinformatical evaluation of nested PCR assays.

Variants of parvovirus B19 are currently grouped into three genotypes: 1 (reference B19 strains), 2 and 3. It has been evidenced that isolate K71 of genotype 2 is more prevalent in skin than the conventional B19 genotype 1. In this study we investigated the detection of parvovirus B19 genotypes by using two nested PCRs and evaluating the suitability of these assays by BLAST search of parvovirus isolates. Subsequently, we analyze the present genotypes in skin biopsies. The two nested PCRs employed in this study allow to amplify 41 isolates as confirmed by bioinformatical validation. The molecular epidemiological characterization of our casistics confirmed the presence of isolate K71 in human skin.

Low-dose intermittent alemtuzumab in the treatment of Sézary syndrome: clinical and immunologic findings in 14 patients.

BACKGROUND AND OBJECTIVES: Alemtuzumab may be effective in Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma, but is associated with severe hematologic toxicity and infections. This study investigated whether low-dose subcutaneous alemtuzumab can induce hematologic, immunologic, and clinical responses similar to those obtained with the standard regimen, but with less toxicity. DESIGN AND METHODS: Fourteen SS patients were enrolled: 11 had relapsed/refractory disease and three had untreated SS with high counts of circulating Sézary cells (SC). Four received 3 mg alemtuzumab on day 1, 10 mg on day 3, then 15 mg on alternating days; circulating SC were evaluated after the fourth 15 mg dose and treatment was interrupted in the presence of counts <1,000/mm (3). A reduced dosage (3 mg on day 1, then 10 mg on alternating days) was administered to the remaining patients, with SC counted before every injection, until a reduction to values of <1,000/mm (3). RESULTS: The median SC count decreased by 95.5%. Overall, 12/14 patients (85.7%) achieved a clinical response, with three complete responses (21.4%). After a median follow-up of 16 months, the median time-to-treatment failure is 12 months. Infectious complications occurred in 28.6% of patients, all included in the group treated with 15 mg. No patient in the group treated with 10 mg developed hematologic toxicity or infections. An early recovery of circulating NK, B and CD3+CD8+ cells occurred after the first cycle. INTERPRETATION AND CONCLUSIONS: Subcutaneous alemtuzumab at very low doses (10 mg maximum per administration), given for a short period based on SC levels, has a good toxicity profile, high response rate and causes durable remissions in SS patients with high tumor burden in the peripheral blood.

Prognostic relevance of baseline and sequential peripheral blood tyrosinase expression in 200 consecutive advanced metastatic melanoma patients.

The relationship between the disease course and the prognostic relevance of sequential tyrosinase reverse transcription-PCR assay in the peripheral blood of advanced metastatic melanoma patients was ascertained. The clinical usefulness of tyrosinase in stage IV melanoma patients is still debated, owing to the wide range of variability (positive expression from 30 up to 100% of patients) and the possibility of a transient shedding of melanoma cells into the bloodstream. A total of 200 consecutive stage IV metastatic patients treated at our department were included, 149 with active metastatic disease undergoing systemic therapies (group A), and 51 disease free after surgery (group B). For each patient, a baseline sample was obtained within 3 weeks of either the clinical/radiological demonstration of metastatic disease or the surgical treatment; thereafter, tyrosinase determinations were performed at day 1 of each therapy course before chemotherapy administration or at each follow-up visit. Tyrosinase expression was determined using standard reverse transcription-PCR nested techniques. A baseline positive determination was obtained in 72.5% of the patients with active metastatic disease (group A) but not in any of the patients who were disease free after surgery (group B). Therapy administration induced an early clearance of circulating melanoma cells, from 72.5 to 44.9% at the second down to 29.5% at the third determination. Tyrosinase expression before the third cycle was significantly associated with the clinical response: 56/81 (69.1%) patients with a negative tyrosinase determination obtained a response or a stable disease, whereas 29/34 (85.3%) patients with a positive test developed a progressive disease (P<0.001). A clinical response was observed in all the patients who had a negative tyrosinase at the first three determinations, although all patients whose first three determinations were positive developed a progressive disease. Multivariate analysis showed that baseline tyrosinase status carries an independent prognostic value on both overall survival and time to progression; moreover, tyrosinase results during follow-up were entered as time-dependent covariates in a multivariate analysis and were shown to be the most significant prognostic parameter associated to both overall survival and time to progression. In particular, the presence of a constant positive expression during follow-up was associated with the development of new metastatic sites in 95.6% of patients with active metastatic disease. Our results demonstrate that the discrepancies in the positive tyrosinase rates reported in the literature are related to the disease status at the time of sampling and to chemotherapy administration. Tyrosinase expression in the peripheral blood both at baseline and during follow-up can be considered a reliable prognostic parameter associated with the response to treatment, development of new metastatic sites, time to progression and survival.

Serum levels of the Th1 promoter IL-12 and the Th2 chemokine TARC are elevated in erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis and correlate with soluble Fas ligand expression. An immunoenzymatic study from the Italian Group of Immunopathology.

BACKGROUND: No data exist as to Th2 chemokines in erythema multiforme (EM) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). OBJECTIVE: To evaluate thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and regulated upon activation, normal T-lymphocyte-expressed and secreted chemokine (RANTES) expression in EM and SJS/TEN and to correlate with the serum levels of the Th1 promoter interleukin (IL)-12 and soluble Fas ligand (sFasL). MATERIALS AND METHODS: IL-12, sFasL, TARC, MDC and RANTES expression were analyzed by ELISA techniques in 31 untreated EM (n = 24) or SJS/TEN (n = 7) patients and in 28 healthy donors (HD). RESULTS: EM and SJS/TEN exhibited significantly higher levels of TARC, IL-12 and sFasL with respect to HD. TARC upregulation paralleled both the IL-12 (p = 0.0225) and sFasL increase (p = 0.0194). CONCLUSIONS: Our results support a role of TARC in the pathophysiology of EM/SJS/TEN and confirm the coexistence of a Th2 response in addition to the predominant Th1 profile.