Peripheral blood regulatory T cell measurements correlate with serum vitamin D level in patients with psoriasis.

OBJECTIVE: Vitamin D is the precursor of a hormone (1,25-dihydroxyvitamin D3), which has many biological effects in the skin. The immune modulator properties of vitamin D are mediated in part through effects on regulatory T cells (T-reg). Currently, in psoriasis, the relationship between vitamin D and T-reg has not well elucidated. We assess whether vitamin D status is correlated with circulating T-reg in patients affected by psoriasis and if there is a correlation with the severity of the disease evaluated with Psoriasis Area Severity Index (PASI) score. PATIENTS AND METHODS: For each patient we have analyzed, PASI-score, serum levels vitamin D and regulatory T cell percentages. Spearmen's coefficient was used between serum vitamin D levels and the predictors. Subsequently, the independent predictive factors were assessed by Multiple Regression. RESULTS: A total of 26 patients were included in our analysis. Using no parametric Spearman's Coefficient test between serum levels of vitamin D and the single variables, we found an association with T-reg population (p < 0.001) and with PASI-score (p = 0.04). CONCLUSIONS: While vitamin D treatment induces a cytokine profile known to favor the differentiation of T cells with suppressive activity, at the same time, several studies showed how vitamin D can prime for tolerogenic dendritic cells able to favor the differentiation of Treg from T naïve cells. Low levels of vitamin-D may decrease the number of circulatory T-reg, disrupting the immunological homeostasis in psoriatic patients and encouraging the inflammatory activity.

Is the prognosis and course of acral melanoma related to site-specific clinicopathological features?

OBJECTIVE: Acral melanoma is an uncommon type of melanoma in Caucasian patients. However, acral melanoma is the most common type of melanoma in African and Asian patients. Comparison analyses between hand-acral melanoma and foot-acral melanoma have been rarely reported in the literature. Acral melanoma is an uncommon melanocytic tumor characterized by an intrinsic aggressiveness, with specific histological and clinicopathological features. Acral melanoma involves the palms, soles and sub-ungueal sites. PATIENTS AND METHODS: A total of 244 patients with acral melanoma were included in our analysis. The current study was performed in three different medical centers: Sapienza University of Rome, San Gallicano Institute of Rome and University of Magna Graecia (Italy). The Kaplan-Meier product was used to estimate survival curves for disease-free survival and overall survival. The log-rank test was used to evaluate differences between the survival curves. Assuming that the effects of the predictor variables are constant over time, the independent predictive factors were assessed by Spearman's test and subsequently data were analyzed performing Cox proportional-hazard regression. RESULTS: In both univariate and multivariate analyses Breslow thickness (p < 0.0001) and ulceration (p = 0.003) remained the main predictors. General BRAF mutation was detected in 13.8% of cases. We found that median Breslow value and the percentage of recurrences were similar in hand-acral melanoma and foot-acral melanoma, as well as there were no differences in both short and long-term. CONCLUSIONS: The absence of differences in survival between hand-acral melanoma and foot-acral melanoma shows that the aggressiveness of the disease is related to distinct mutational rate, as well as to anatomical site-specific features, rather than to the visibility of the primary lesion.

Improvement of survival in patients with melanoma and non-melanoma skin cancers compared to patients without double cutaneous malignancies.

OBJECTIVE: The worldwide incidence of cutaneous malignant melanoma (MM) has been rising steadily over the past 30 years. At the same time non-melanoma skin cancers (NMSC) are the most prevalent type of cancer in United States and Europe. Up to date, no paper has explored the influence on the general survival in patients with MM and NMSC. We decided to perform a study with the aim to evaluate the different survival in patients with MM-NMSC compared to control patients (MM-CTRL). PATIENTS AND METHODS: To evaluate prognosis in both groups, we analyzed disease-free survival (DFS) and overall survival (OS).Kaplan-Meier product was performed for the survival analysis. Median DFS was 73 months in group and 72 months in MM-CTRL patients (p = 0.4); while, median OS was 74.2 months in MM-NMSC patients and 63.1 in MM-CTRL (p < 0.001). Also at Odds-Ratio (OR), the statistical significance was maintained (p < 0.007) with a better prognostic value for MM-NMSC. RESULTS: Among group patients, the ones with a basal cell carcinoma showed a batter behavior, than the ones with squamous cell carcinoma (p = 0.01). CONCLUSIONS: Patients with MM-NMSC showed a better survival than MM-CTRL patients (p < 0.001). The causes of this improved survival are still unknown; probably the endogenous immune response can play a pivotal role in this class of patients. However, further studies are necessary to better understand this phenomenon, not yet explored in literature.

Immunohistochemical expression of VDR is associated with reduced integrity of tight junction complex in psoriatic skin.

BACKGROUND: Cell junctions are crucial for the formation and maintenance of the paracellular barrier and for cell polarity in simple epithelia and endothelia. Altered localization and formation of tissue junction proteins in the epidermis have been described in plaque-type psoriasis. Vitamin D receptor (VDR) is a nuclear hormone involved in anti-proliferative and pro-differentiation pathways in keratinocytes. However, still to date, vitamin D/VDR signalling involved in tissue barrier related to psoriasis remains largely unknown. OBJECTIVE: To study the expression of VDR and tight junctions (TJ) proteins (claudin 1, ZO-1 and occludin) in psoriatic skin, and to correlate the expression of VDR with that of the junctional proteins claudin- 1, occludin and ZO- 1. METHODS: A total of 20 psoriatic tissue samples were included in the analysis. Immunohistochemical studies for VDR, claudin-1, occludin and ZO-1 were performed. RESULTS: We observed a reduction of VDR, claudin-1 and ZO-1 expression in psoriatic skin if compared to normal skin, and the statistical analysis showed a significant correlation between a downgrading of VDR expression and that of claudin-1 (P < 0.005) and ZO-1(P < 0.005). CONCLUSIONS: Our results suggest a new role of VDR in the maintenance of the homeostasis skin barrier. Although the exiguity of our cohort, VDR status appears to be associated with the expression level and functions of TJ proteins, suggesting multiple and different cellular functions of the VDR.

Association between autoimmune disease and cutaneous melanoma with regard to melanoma prognosis.

BACKGROUND: An association between autoimmune disease and malignant melanoma (MM) has often been reported in the literature as a positive prognostic factor for MM. Consequently, we evaluated the influence of different autoimmune diseases on the prognosis of MM. AIM: To evaluate the prognosis of patients with MM who also had an autoimmune disorder, whether tumour-associated, paraneoplastic or drug-induced. METHODS: Autoimmune diseases were classified and analysed as tumour-associated, paraneoplastic or drug-induced. Patients were enrolled according to their clinicopathological features and matched with control groups. Kaplan-Meier analysis was used to estimate disease-free survival (DFS) and overall survival (OS), and log-rank test was used to evaluate differences between the survival curves. RESULTS: In total, 49 patients with MM and tumour-associated autoimmune disease were included in our analysis. No case of paraneoplastic autoimmune disease was detected. The survival analyses showed a range of results, from a worsening of DFS and OS to a lack of any difference. In a second analysis, we separately analysed patients who developed autoimmune disorders after starting adjuvant therapy with interferon-α; we did not find significant differences between these patients and the untreated patients. CONCLUSIONS: Autoimmune disease, whether tumour-associated or drug-induced, was not associated with better prognosis in patients with MM. The results suggest that the reported relationship between autoimmunity and MM may be a result of individual variation in sensitivity to the autoimmune disease, the tumour or the treatments.

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.

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.

Costs of therapy with biologics in the treatment of moderate to severe plaque psoriasis in the context of the Italian health-care system.

AIM: Biologics were introduced as innovative and effective therapies for the treatment of moderate-to severe psoriasis. However, in the Italian context there are no comparative cost-effectiveness analyses of all biologics currently approved for psoriasis by the European Medicines Agency (EMA). This study estimates whether the cost of ustekinumab (meant as cost of drug therapies and monitoring) is lower, similar to or higher than that of anti-TNF-α. METHODS: The incremental cost-effectiveness ratio (ICER) and the cost-effectiveness ratio (CER) in terms of cost for patients achieving 75% improvement in PASI (PASI 75) were calculated. The analysis, both during the first 52 weeks, including induction and in maintenance period is based on efficacy data taken from single studies. The costs, based on official source, are calculated in the perspective of National Health Service (SSN). RESULTS: Ustekinumab has the lowest cost for responder, resulting always cost-effective and, in some case, cost saving in the baseline scenario at 52 weeks and in maintenance period. CONCLUSION: Ustekinumab seems to be the most favorable biologic in term of cost per PASI 75 responder for the treatment of psoriasis and it is cost-effective in all scenarios analyzed. Further cost-effectiveness evaluations based on data of use of long-term treatment with biologics in clinical practice, are necessary to support this results.

Male tuberculous mastitis: a rare entity.

A 28-year old male presented to our clinic complaining of a recent onset of a painful right breast lump with redness and nipple discharge. Fine-needle aspiration biopsy revealed caseating granulomas, with a culture positive for Mycobacterium tuberculosis. He was found to have a positive PPD, but no other site of pulmonary or extra-pulmonary tuberculosis was identified. Treatment with anti-tuberculous drugs lead to complete clinical resolution of the breast lesion. The breast is a rare site of extra-pulmonary tuberculosis (TB), comprising only 0.1% of all cases. TB is re-emerging in the Western world with the increasing prevalence of immunosuppressive disorders. Increasing immigration rates and widespread travel are further contributing to TB globalization. With the re-emergence of TB, atypical forms are appearing, with an increase in the proportion of extra-pulmonary disease and a widening of the age range at presentation. Tuberculous mastitis(TM) is found mostly in young, multiparous women. Male TM is extremely rare, and accounts for only 4% of all cases. This strikingly lower incidence in males points towards a significant role of parity, pregnancy and lactation as likely predisposing factors. Although a rare disease, TM is an important differential diagnosis for breast cancer. A high index of suspicion is the cornerstone for diagnosis. Awareness of this condition is important not only for dermatologists, but for surgeons, radiologists and pathologists, as well. Clinicians are encouraged to provide a careful assessment of the breasts, an important organ also in men.

Acute generalized exanthematous pustulosis during antituberculosis therapy.

Acute generalized exanthematous pustulosis (AGEP) is a significant adverse cutaneous reaction most often induced by drugs and by acute infections. Its clinical hallmark is the sudden onset of multiple, disseminated, non-follicular, sterile pustules on an erythematous background usually arising in intertriginous folds, associated with fever, massive neutrophilia and sometimes eosinophilia. Antitubercular therapy is described as an uncommon cause of AGEP. We report the onset of disseminated non-follicular sterile pustules on an erythematous background in a 68-year-old man receiving a combination of isoniazid, pyrazinamide and rifampicin that may have been the etiologic agents. A thorough history, including a medication history, with clinicopathologic correlation is crucial in patients presenting with acute diffuse pustular lesions.

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.

Antibacterial activity of methyl aminolevulinate photodynamic therapy in the treatment of a cutaneous ulcer.

We describe a 79-year-old female with a chronic venous ulceration infected by Staphylococcus aureus and Enterococcus faecalis and not responsive to conventional treatments. The patient was treated with Methyl-Aminolaevulinate Photodynamic Therapy (MAL-PDT). After four weeks the cutaneous swabs become negative and we observed a significant clinical improvement. Therefore we suppose that MALPDT could represent a valid therapeutic option in the treatment of infected chronic ulcers.

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.

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.

[Pyoderma gangrenosum: case series]. / Pioderma gangrenoso: presentazione di alcuni casi clinici.

Pyoderma Gangrenosum (PG) is a rare ulcerative cutaneous condition with distinctive characteristics, and the aetiology is not clear yet. PG is commonly associated with inflammatory bowel disease (Ulcerative Colitis and Crohn's disease). The features of PG are not specific histopathologically and for this reason diagnosis is based on clinical feature. There is no single successful treatment for PG. In fact certain type of lesions respond more readily to some therapies than others. Local treatments (advanced wound care, local corticosteroids, local immunomodulator agents) may be sufficient for some clinical features, while others may be required systemic therapy (corticosteroids, immunosuppressive therapy, intravenous immune globulins, TNF-alpha blocking agents). We present four cases of PG associated with inflammatory bowel diseases treated with different therapeutic approaches.

Psoriasis of the dorsal surface of the tongue.

Psoriasis is primarily an inherited inflammatory skin disease, it is characterized by erythemato-squamous lesions that usually involve elbows, knees and the scalp. Oral manifestations are rare in psoriasis, infact, oral psoriasis involves 2% of psoriatic patients and usually it is observed with the onset of cutaneous lesions and progresses with them. Differential diagnosis should be done for Reiter's syndrome, leukoplakia and geographic tongue. The authors describe a case of tongue psoriasis without cutaneous lesions.