Search

Background: Psoriasis involves skin inflammation that often worsens with stress, but the mechanism of this effect remains obscure. We have shown that corticotropin-releasing hormone (CRH) is increased in the serum of patients with psoriasis. A peptide, neurotensin (NT), can trigger skin histamine release and augment the ability of CRH to increase skin vascular permeability., Objectives: To investigate the serum level of NT, and the expression of genes for NT and NT receptor-1 (NTR-1) in lesional and nonlesional skin of patients with psoriasis, compared with normal controls. Also, to study the effect of NT on human mast cell release of vascular endothelial growth factor (VEGF), which is increased in psoriatic skin., Methods: Serum was obtained from patients with psoriasis (n = 56) and controls (n = 33); NT levels were measured with the Milliplex microbead assay. Biopsies were obtained from the lesional and nonlesional skin of patients with chronic plaque psoriasis (n = 40), who had not received any treatment for at least 15 days and were free of any systemic inflammatory diseases. Control skin samples were obtained from healthy subjects (n = 30). Expression of genes for NT and NTR-1 in the skin was evaluated by quantitative reverse transcriptase-polymerase chain reaction. LAD2 human mast cells were stimulated by NT (1 μmol L(-1)) for 24 h and VEGF was measured by enzyme-linked immunosorbent assay., Results: Serum NT was increased in patients with psoriasis, while expression of genes for NT and NTR-1 in lesional skin was decreased compared with controls. NT induced VEGF release from mast cells and was augmented by interleukin-33., Conclusion: NT may play a role in psoriasis pathogenesis and its worsening by stress, at least in part through activation of skin mast cells., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists 2012.)

Background: Psoriasis is a chronic, systemic, inflammatory disease. Inflammatory markers are used in clinical practice to detect acute inflammation, and as markers of treatment response. Etanercept blocks tumour necrosis factor (TNF)-α, which plays a central role in the psoriatic inflammation process., Aim: To reveal any possible association between disease severity [measured by Psoriasis Area and Severity Index (PASI)] and the inflammatory burden (measured by a group of inflammatory markers), before and after etanercept treatment., Methods: In total, 41 patients with psoriasis vulgaris, eligible for biological treatment with etanercept, were enrolled in the study. A set of inflammatory markers was measured, including levels of white blood cells and neutrophils, fibrinogen, ferritin, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), haptoglobin, ceruloplasmin and α1-antitrypsin, before and after 12 weeks of etanercept 50 mg twice weekly., Results: All markers were reduced after treatment (P < 0.001). PASI correlated with fibrinogen and hs-CRP. Of the 41 patients, 19 (46.3%) achieved reduction of 75% in PASI (PASI75). An increase in hs-CRP and ESR difference (values before minus values after treatment) was related to higher likelihood of achieving PASI75., Conclusions: Inflammatory markers, particularly hs-CRP and to a lesser extent, fibrinogen and ESR, can be used to assist in assessing disease severity and response to treatment in patients with psoriasis. A combination of selected inflammatory factors (which we term the Index of Psoriasis Inflammation) in combination with PASI might reflect inflammatory status in psoriasis more accurately than each one separately., (© The Author(s). CED © 2011 British Association of Dermatologists.)

Background: Solar lentigines are common, benign, cosmetically disfiguring lesions. Available physical treatments are effective, but they are costly and carry risks of side-effects., Objective: To evaluate the efficacy and safety of a preparation containing undecylenoyl phenylalanine 2% in the topical treatment of solar lentigines., Methods: In total, 36 patients with solar lentigines of the hands were randomly assigned to apply the active preparation on one side and the vehicle alone on the other side, twice daily for 12 weeks. Patients were evaluated monthly for efficacy and safety., Results: In all, 30 patients (28 women and 2 men; age range 47-75 years) completed the study. The duration of lesions ranged from 8 months to > 10 years. All patients responded partially on the side of the active treatment. Of the partial responders, 19 (63.3%) had moderate improvement and 11 (36.6%) had marked improvement. Improvement was evident from the first follow-up visit. On the side of the vehicle, 26 remained stable (86.6%) and 4 (13.3%) had partial improvement. There was a significant difference (P < 0.01) in efficacy of the active preparation vs. the vehicle. Using patient assessment ratings, 80% were 'much more satisfied/more satisfied' with the result. The reported side-effects were minor and included erythema and itching or burning on the side of active treatment., Conclusions: Undecylenoyl phenylalanine 2% is a novel depigmenting agent, which possibly acts as an alpha-melanocyte-stimulating hormone antagonist, thus inhibiting melaninogenesis. It achieved a significant lightening of the lesions with minimal side-effects. Most patients were satisfied with the improvement. Undecylenoyl phenylalanine 2% may represent a safe, effective and inexpensive therapeutic alternative for solar lentigines.

We report a case of leukaemia cutis presenting as stasis dermatitis-like eruption in a patient with myelodysplastic syndrome progressing to acute myelogenic leukaemia.

Objective: To evaluate the safety and efficacy of etanercept for the management of hidradenitis suppurativa., Methods: In a prospective open-label phase II study, etanercept was administered subcutaneously in a dose of 50 mg once weekly for 12 weeks in 10 patients. They were followed up to 24 weeks and their disease activity and Sartorius score were assessed, with also a self-evaluation by visual analogue scale (VAS). Disease activity was an assessment of the extent of the disease by the attending physicians who were unaware of the protocol., Results: A >50% score improvement was found in six patients at week 12 and in seven patients at week 24. The VAS was decreased compared with baseline in seven patients at week 12 and in six patients at week 24. All changes were statistically significant. All patients reported a decrease of local pain at the site of lesions after week 4. Drainage of pus from the affected areas recurred in eight patients within 4-8 weeks after the end of administration of etanercept. The treatment was well-tolerated., Conclusions: Etanercept is a safe and effective therapy for hidradenitis suppurativa and decreases the extent of the disease and improves the quality of life. A double-blind, placebo-controlled trial is required to elucidate fully the role of etanercept for hidradenitis suppurativa.

Background: The clinical improvement of hidradenitis suppurativa reported in a small number of patients with antitumour necrosis factor (anti-TNF)-alpha therapies supports the hypothesis for an altered immune response in these patients., Objectives: To evaluate the state of the innate and adaptive immune responses in patients with hidradenitis suppurativa., Methods: Fifty-three patients and six healthy controls were studied. Blood was sampled and subpopulations of lymphocytes were analysed by flow cytometry; monocytes were isolated and their function was evaluated from the concentrations of TNF-alpha and interleukin (IL)-6 in supernatants of cell cultures after triggering with endotoxins (lipopolysaccharides). TNF-alpha and IL-6 were estimated by an enzyme immunoassay., Results: CD3/CD8 lymphocytes were lower in patients with involvement of the perineum than in controls; patients with involvement of the breast had higher levels of natural killer (NK) cells than controls. A negative correlation was found between years lapsing since initial presentation of lesions of hidradenitis and the percentage of NK cells. Monocytes isolated from healthy volunteers were more active for the secretion of TNF-alpha and IL-6 than those of patients with hidradenitis suppurativa., Conclusions: A reduction in the percentage of NK cells over time and a lower monocyte response to triggering by bacterial components is observed in patients with hidradenitis suppurativa. Further research is needed to clarify if these changes are connected to an autoimmune mechanism in the pathogenesis of hidradenitis suppurativa.

Background: Tipranavir, a novel protease inhibitor, has demonstrated antiviral activity against protease inhibitor-resistant human immunodeficiency virus type 1 (HIV-1) isolates. The Randomized Evaluation of Strategic Intervention in multi-drug reSistant patients with Tipranavir (RESIST-2) trial is an ongoing, open-label, phase III trial comparing ritonavir-boosted tipranavir (TPV/r) plus an optimized background regimen with an individually optimized, ritonavir-boosted protease inhibitor in treatment-experienced, HIV-1-infected patients., Methods: Patients at 171 sites in Europe and Latin America who had received > or = 2 previous protease inhibitor regimens, had triple-antiretroviral class experience, had an HIV-1 RNA level > or = 1000 copies/mL, and had genotypically demonstrated primary protease inhibitor resistance were eligible. After genotypic resistance tests were performed, a protease inhibitor and optimized background regimen were selected before randomization. Patients were randomized to receive either TPV/r or comparator protease inhibitor-ritonavir (CPI/r) and were stratified on the basis of preselected protease inhibitor and enfuvirtide use. Treatment response was defined as a confirmed HIV-1 load reduction > or = 1 log10 less than the baseline value without a treatment change at week 24., Results: A total of 863 patients were randomized and treated. At baseline, the mean HIV-1 load was 4.73 log10 copies/mL, and the mean CD4+ cell count was 218 cells/mm3. The preplanned 24-week efficacy analyses of 539 patients demonstrated treatment response rates of 41% in the TPV/r arm and 14.9% in the CPI/r arm (intent-to-treat analysis; P<.0001). The mean CD4+ cell count increased by 51 cells/mm3 in the TPV/r arm and by 18 cells/mm3 in the CPI/r arm. The most common adverse events were mild-to-moderate diarrhea, nausea, and headache. Grade 3 or greater elevations in serum transaminase, cholesterol, and triglyceride levels were more frequent in the TPV/r arm., Conclusions: TPV/r had superior antiviral activity and increased immunologic benefits, compared with CPI/r, at week 24 among treatment-experienced patients infected with multidrug-resistant HIV-1.

Background: There is evidence that a T-helper (Th) 2 cytokine pattern dominates in the peripheral blood as well as in tissue of patients with Sézary syndrome (SS), and that the malignant clone is of Th2 phenotype. However, there are conflicting studies on the cytokine pattern in the peripheral blood in different stages of cutaneous T-cell lymphoma (CTCL)., Objectives: To examine, by means of flow cytometry (FC), the Th1/Th2 cytokine profile [cytoplasmic interferon (IFN)-gamma/interleukin (IL)-4] in peripheral blood T cells from patients with mycosis fungoides (MF) and SS, the most common forms of CTCL, and to correlate their expression with clinical stage, clonality and T-cell immunophenotype changes in order to evaluate their relevance in CTCL progression., Methods: We investigated by FC the percentage of CD3+ T cells expressing cytoplasmic IFN-gamma and IL-4 after stimulation in blood specimens of 43 CTCL patients (32 stage I-II and 11 stage III-IV), eight of whom were erythrodermic. Next, we compared cytoplasmic IFN-gamma and IL-4 expression between patients of different stages and controls, and correlated our findings to T-cell receptor (TCR)-gamma gene rearrangement, used as a marker of clonality, and changes in T-cell immunophenotype (CD4+, CD8+, CD4+/CD7-, CD4+/CD25+) and natural killer cells. Polymerase chain reaction amplification of the TCR-gamma gene was performed in 41 blood and 26 skin specimens. We also examined the cytokine expression pattern in patients with erythrodermic MF and SS., Results: A significantly higher frequency of CD3+/IL-4+ T cells was found in late (III-IV) compared with early (I-II) CTCL patients (P = 0.002) or controls (P < 0.001). There were significant positive correlations between the percentages of CD3+/IL-4+ and the percentages of CD3+/CD4+ T cells (r = 0.385, P = 0.05), CD4+/CD7- T cells (r = 0.335, P < 0.05) and CD4+/CD25+ T cells (r = 0.433, P = 0.01); there was a negative correlation between the percentages of CD3+/IL-4+ and CD3+/CD8+ T cells (r = -0.463, P = 0.005) and a positive correlation between the percentages of CD3+/IFN-gamma+ and CD3+/CD8+ T cells (r = 0.368, P = 0.02). Increased percentages of CD3+/IL-4+, CD3+/CD4+ and CD4+/CD7- T lymphocytes were associated with the presence of clonality (P = 0.025, P < 0.001 and P = 0.0031, respectively). All independent variables showed a statistically significant difference between SS and erythrodermic MF patients, or controls, apart from cytoplasmic IL-4, which was high both in erythrodermic MF and SS patients compared with controls (P = 0.003 and P = 0.008, respectively). In multiple regression logistic analysis, the probability of belonging to advanced CTCL stages was associated only with increased cytoplasmic IL-4 (P = 0.007, odds ratio 1.13, 95% confidence interval 1.033-1.229)., Conclusions: Increased T-cell cytoplasmic IL-4 is more frequent in late CTCL stages, correlates with T-cell immunophenotype changes found in advanced disease and is associated with clonality. Increased cytoplasmic IL-4 is frequent both in erythrodermic MF and SS patients, in contrast to other variables found increased only in SS, suggesting that IL-4 may be an early indicator of disease progression. Moreover, our results show that increased cytoplasmic IL-4 is the sole predictor of advanced CTCL disease and confirm the relevance of FC determination of IL-4 in the routine evaluation of CTCL cases.

Background: Poikiloderma of the face and neck (Civatte) is a rather common, indolent, chronic dermatosis, most often affecting menopausal females. Cumulative excessive sun exposure, a phototoxic or a photoallergic reaction, hormonal changes of menopause and genetic factors have all been incriminated in its obscure aetiopathogenesis., Objective: To evaluate the role of contact sensitization and photosensitivity in the pathogenesis of poikiloderma of Civatte (PC)., Methods: Thirty-two patients (24 females and eight males, age range 38-74 years) with PC were patch tested with the European standard series and the fragrance series, and were photopatch tested with the photoallergens series. Additionally, photo-testing with a monochromator was performed., Results: Thirteen of 32 patients (40.62%) had one or more positive reactions to allergens of the standard series. Eight patients (25%) had positive reactions to fragrance mix and/or Balsam of Peru, which are included in the standard series, or to allergens of the fragrance series. Nickel sulphate was the single most common cause of contact sensitization (18.75%) among our patients. Ninety-seven subjects, who were patch tested with the standard series for suspected allergic contact dermatitis of the face and/or neck, served as age, sex and site controls. Of these, nine (9.27%) had one or more positive reactions to fragrance compounds. Statistical analysis showed a statistically significant difference in the frequency of positive reactions to fragrances between the PC group and the control group (chi2 value = 3.91, P < 0.05). In contrast, none of the PC patients had a positive photopatch test for the allergens included in the photoallergens series. The estimated minimal erythemal dose for the PC group was in all cases within normal limits for all wavelengths of ultraviolet (UV) radiation examined., Conclusions: Contact sensitization, mostly to perfume ingredients, may develop in PC, possibly playing a pathogenetic part, at least in a subset of patients. Despite negative results of photopatch testing, an allergic photo-contact reaction cannot be definitely excluded. PC seems not to be a photosensitivity disorder of the type of chronic actinic dermatitis. UV radiation-induced dermal connective tissue changes are the predominant histological feature of PC, leading to telangiectasia due to loss of vascular support. Reticular pigmentation may result from a delayed hypersensitivity reaction to perfume and/or cosmetic ingredients. Patch testing with the standard series and avoidance of documented allergens may be of value in patients with PC.

Poikiloderma of Civatte (PC) is a rather common, benign skin condition of obscure etiopathogenesis: cumulative exposure to UV radiation, hormonal changes associated with the menopause, and photo-allergic mechanisms have been implicated. We present seven cases of PC among the members of two unrelated Greek families, who have not shared common extrinsic influences. Literature review revealed no other reported familial cases. Familial tendencies, as well as the not unusual occurrence of PC in individuals with minimal sun exposure, and who are not using perfumes or cosmetics, provide support for the hypothesis that a genetic predisposition to the disease may exist; this predisposition is possibly transmitted as an autosomal dominant trait.