Evaluation of blood redox-balance, nitric oxide content and CCR6 rs3093024 in the genetic susceptibility during psoriasis.

The aim of our study was to evaluate whether this polymorphism of CCR6 gene and oxidative stress are associated with psoriasis risk in Caucasian population. The association of the CCR6 polymorphism in the genetic susceptibility of psoriasis was performed at the Department of Dermatology and Venereology, Policlinico Umberto I of Rome (Italy). 516 participants were enrolled including 127 patients affected with psoriasis and 389 healthy controls. Cases and controls were genotyped, using a commercially available assay (Life Technologies, Carlsbad, California, USA) for CCR6 rs3093024 polymorphism. To verify the relations between genotypes and psoriasis risk we evaluated genotype frequencies for each individual DNA polymorphism in both case and control series. There were no differences in the genotype frequencies of the polymorphism between psoriasis cases and healthy controls. When patients with arthropathic psoriasis were excluded from the analysis, logistic regression showed that allele A was likely to reduce the risk of developing psoriasis in a dominant model. Logistic regression showed that male patients harboring the heterozygous genotype GA presented a reduced risk of developing psoriasis, compared with the reference GG genotype. None of the clinical features as age at onset, gender, family history of psoriasis, type of psoriasis, severity, BMI, smoking history or alcohol consumption, were associated with the genotype frequencies of the tested CCR6 polymorphism. In blood samples of patients with psoriasis intensive EPR signals of lipoperoxide (LOO.) free radicals were detected. Activity of blood SOD was significantly decreased in psoriatic patients compared to healthy controls. Activity of catalase was significantly increased in psoriatic patients, reflecting a high concentration of peroxide radicals. In blood samples of psoriatic patients decrease of free spin-trapped NO content were detected, that may be explained by biological transformation of NO into other reactive nitrogen species (proxy nitrite or nitrosylated hemoglobin). Thus, the alterations of redox-balance and NO degradation leads to development of skin perfusion impairments, disorder of proliferation and transcription of cell cycle, initiation of T-cell mediated immune responses, formation of chemokine receptor 6 (CCR6) related with intensification of cellular infiltration in the psoriatic plaques. Furthermore, correction of redox-balance is responsible for inhibiting CCR6 formation resulted in suppressed cellular infiltration with concomitant decrease in oxidative stress. The data reviewed suggest the necessity of evaluation of other blood redox-balance and nitric oxide in psoriasis should with additional investigations to targeting CCR6 rs3093024 in the genetic susceptibility of psoriasis.

Safety and prolonged efficacy of Botulin Toxin A in primary hyperhidrosis.

BACKGROUND: Hyperhidrosis is a condition characterized by generalized or localized hyperfunction of the eccrine sweat glands with a deep negative impact on patient's quality of life. OBJECTIVES: To evaluate the efficacy and the safety of Botulin Toxin A (BTX-A) intradermal injection in the treatment of primary axillary and palmar hyperhidrosis, investigating symptoms-free period, and the subjective improving of quality life. MATERIALS AND METHODS: 50 consecutive patients with primary hyperhidrosis were evaluated detecting age, gender, hyperhidrosis onset period, disease duration and years of treatment with BTX-A, Minor's iodine test, Hyperhidrosis Disease Severity Scale (HDSS), Dermatology Life Quality Index (DLQI). RESULTS: The treatment is significantly effective both for axillae and palms: the majority of the patients improved their HDSS and Minor's scores from a value of 4 in the two tests, to values of 1 (HDSS) and 0 (Minor test). Patients reported a duration of symptoms relief from 4 to 12 months, with a mean of 5.68 months; specifically, we have observed that the axillary group experienced a longer symptoms-free period (mean RFS 7.2 months) than the palmar group (mean: RFS 4.27 months). CONCLUSIONS: Authors suggest that BTX-A is a safe, easy, and fast procedure for the treatment of primary axillary and palmar hyperhidrosis.

The role of nitric oxide in the pathogenesis and severity of psoriasis.

The aim of our study was to investigate the possible role of nitrogen reactive species in pathogenesis of psoriasis. A total of 187 individuals were included in this study, out of these 84 were patients suffering from psoriasis and 103 were healthy subjects, served as a control. Patients with psoriasis were graded according to the Psoriasis Area Severity Index (PASI), presenting at the time of blood collection. After obtaining prior consent, about 2 ml of random blood was collected for estimation blood free nitric oxide (NO) content by Electron Paramagnetic Resonance (EPR) Spectroscopic method. For detection of NO in blood the spin-trap (diethilditiocarbamate (DETC) (Sigma) was used. In blood samples of patients with psoriasis nitrosilated hemoglobin (HbNO) complexes and alterations of free spin-trapped NO EPR signal intensity and were detected. Free NO content in blood decreased with the increasing severity of the psoriasis. It may be concluded that under oxidative stress conditions during psoriasis the decrease level of free nitric oxide in the patient's blood may contribute to a violation of the vasomotor activity of subcutaneous capillaries, impairment of skin blood supply, development of hypoxia, exacerbation of oxidative stress, alteration of immune balance, spreading of skin infection and exacerbation of the severity of psoriasis. Use of NO-containing creams will contribute to a partial recovery of disturbed functions and remission of the disease.

Alterations of redox-status during psoriasis.

The skin is constantly exposed to oxidative stress induced by reactive oxygen species (ROS) that are generated both from endogenous neutrophils and external pro-oxidant stimuli. The present study was planned to investigate the possible involvement of free radical oxidation in psoriatic patients. Study was carried out in the Department of Dermatology and Venereology in Tbilisi State Medical University. A total of 60 individuals were included in this study, out of these 40 were patients suffering from psoriasis and 20 were healthy subjects (a control). Psoriasis patients were further graded according to the Psoriasis Area Severity Index (PASI); in patients' blood redox-status superoxide (O2-) and lipoperoxide (LOO.) free radicals, free Mn2+-ions and (ceruloplasmin/Fe3+-transferrin) system antioxidant activity were estimated by Electron Paramagnetic Resonance (EPR) method and activity of catalase (CAT) and superoxide dismutase (SOD) were determined by spectrophotometry. In the blood of patients with psoriasis, the EPR signal intensities of oxidized form ceruloplasmin (Cp) increased and ferrum-transport protein, Fe3+-transferrin (Fe3+-Tr) decreased in comparison to the same parameters of healthy persons. Activity of blood catalase increased and activity of blood SOD decreased with increasing severity of psoriasis. EPR signals of low-molecular Mn2+-containing complexes and lipoperoxide (LOO.) free radicals were detected. The obtained data indicate the alteration of blood redox-balance during psoriasis; the intensity of impairment of redox balance correlates with severity of psoriasis.

Drug cutaneous side effect: focus on skin ulceration.

Skin ulcers are defined as tissue loss interesting the deeper layers of the dermis and hypodermis, with low tendency to spontaneous healing. They cause disability related to pain, risk of infection and amputation, chronic management, requiring working absence with notably economic burden. The major cause is often related to underlying vascular disease, infections, tumors, autoimmunity, trauma, even if literature occasionally reported several cases of drug inducing skin ulceration. Most of drugs involved are chemotherapy agents and more recently molecular target therapies. Evidences supporting these drugs as the major cause of skin ulcers include delay of onset after therapy initiation, improvement after withdrawal of the drug, recurrence after its reintroduction and, sometimes, simultaneous occurrence of other skin lesions that have previously been reported to be associated with these agents. Attention should be reserved to patients undergoing antineoplastic agents, especially if previously affected by predisposing comorbidities, considering such side effect as possible differential diagnosis for skin ulceration in neoplastic patients.

Safety and efficacy of Adalimumab in the treatment of moderate to severe palmo-plantar psoriasis: an open label study.

INTRODUCTION: Psoriasis of the hands and feet is highly debilitating and difficult to treat. Lesions are very painfull, disabilitating and impair quality of life of patients. Most treatment options have limited efficacy, short duration of response and several adverse events. OBJECTIVE: To investigate the safety and efficacy of Adalimumab in the management of palmo-plantar psoriasis. PATIENTS AND METHODS: Adults patients with moderate to severe palmoplantar psoriasis were enrollend in this trial. They received a 6 courses of Adalimumab 40 mg 1 vial every 2 weeks. The study consisted of treatment period of 12 weeks (Weeks 1-12). Safety and efficacy were assessed at weeks 0.6 and 12. PGA (Physician's Global Assesment) and DLQI were used to measure the efficacy. Primary end point of the study was to evaluate patients who achieved a reduction in PGA at week 12. The secondary end point was to evaluate patients who achieved a 50% reduction in PGA at week 12. The tertiary end point evaluated patients who achieved a PGA rating of clear or almost clear. RESULTS: Of 11 patients enrolled 6 showed overall improvement of at least one point of PGA at week 12; 4 of them obtained a PGA of 0 while 5 patient of 11 a ≥ 50% improvement from the beginning of the study. 8 patients showed an increase in quality of life score while receiving the drug at week 12. No serious adverse events were reported during the study. CONCLUSION: Continuous treatment with Adalimumab for 12 weeks was safe and efficacious in this open-label clinical trial of patients with palmoplantar psoriasis.

Efficacy of electrochemotherapy in ulcerated basal cell carcinoma.

Basal cell carcinoma is the most common cutaneous malignant tumor, accounting for up to 80% of non melanoma skin cancers. Surgery, radiotherapy and chemotherapy have been for long time the main options for its treatment. Electrochemotherapy (ECT) is a novel local treatment successfully used in primary skin tumors. We report a case of a man affected by ulcerated basal cell carcinoma treated with ECT. In our case ECT was successful in the management of extensive basal cell carcinoma in clinical conditions whereas other approaches, would have been dangerous and inappropriate. To our knowledge, ECT must be considered as an alternative of traditional techniques when they are contraindicated in relation to the appearance of the lesions or the patient medical history.

Fusariosis and skin T cell lymphoma: concomitant more than a differential diagnosis.

Cytotoxic T cell lymphomas of the skin include a spectrum of a peripheral T cell and natural killer (NK) cell lymphomas with primary and secondary skin manifestation and bad prognosis. Fusarium species have recently emerged as the second most common pathogenic fungi in immunocompromised patients, and they are moderately resistant to most antifungal agents. We report a woman with concomitant cytotoxin T cell lymphomas of the skin and Fusarium spp infection. Patient was treated at the same time with antiblastic and antifungal therapy. First line antifungal therapy was amphotericin B-lipid complex (3 mg/Kg iv/die) and then for clinical failure voriconazole (6 mg/Kg bid, loading dose and 4 mg /Kg bid). Lymphoma was treated with a CHOEP 21 regiment without remission and after with gemcitabine and vinerolbine. Patient presented a partial remission of cutaneous and pulmonary lesions. Our case is intrinsically interesting because Fusarium infection was concomitant to cutaneous lymphoma and did non occur during neutropenic phases of chemotherapy. In a case with multiple ulcerated nodules of the skin is very important to discriminate from disseminated cutaneous Fusarium infection and neoplastic conditions such as cutaneous lymphoma. Early treatment of Fusarium infection in a patient with neoplastic disease could avoid a dissemination during immunosuppressive condition caused by antiblastic therapy.

Folgoration as an Example of Pathergy in a Patient Affected by Pyoderma Gangrenosum and Takayasu's Arteritis.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown aetiology. Clinical manifestations of PG are characterized by destructive, necrotizing, and noninfective ulceration of the skin. 20-30% of cases are initiated and aggravated by minor trauma or surgery, a phenomenon named pathergy. PG is related to several autoimmune diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, and monoclonal gammopathy. The association with Takayasu's arteritis (TA), a chronic inflammatory and stenotic disease of large and medium-sized arteries, is instead less common. We report a case of PG associated with TA that was induced by an accident with folgoration of the skin; in this case the folgoration can be considered as an exemple of Pathergy, that is, a characteristic feature of PG.

A case of infliximab-induced psoriasis.

Anti-tumor necrosis factor (anti-TNF-alpha) are a group of new drugs able to inhibit the action of this cytokine. Although systemic side effects have been well described, cutaneous adverse reactions have not yet been clearly elucidated. The authors report a case of a 29-year-old man affected by Crohn disease and ankylosing spondylitis who developed psoriatic lesions after IV infusion of infliximab 5 mg/Kg. The patient underwent cyclosporine treatment after interruption of biological therapy, and had complete resolution of cutaneous lesions. The reason for this phenomenon is not clear, Obviously more studies are necessary to define more clearly this paradoxical reaction. In addition, dermatologists must be informed about this potential cutaneous adverse event.

Efficacy of Bosentan in treatment of refractory sclerodermic bone prominences skin ulcers.

Scleroderma is an autoimmune disease characterized by skin and internal organs involvement. Cutaneous ulcerations is one of the most important complication. It may cause pain, disability and may lead to infections, scarring and amputation. Sclerodermic skin ulcers management is quite complex and involves non-pharmacologic and pharmacologic modalities both for the treatment and the prevention. In this report, authors describe a case of refractory skin ulcerations in a sclerodermic patient treated with endothelin receptor antagonist Bosentan. Bosentan changed the course of cutaneous lesions leading to their complete healing. This treatment represents an alternative therapeutic approach for sclerodermic skin ulcers and it may be taken into consideration for the ongoing development of a new management of cutaneous wounds.