Sex-related differences of clinical features in hidradenitis suppurativa: analysis of an Italian-based cohort.

The clinical characteristics associated with hidradenitis suppurativa (HS) severity are poorly understood. In this study, 124 patients with HS from 6 Italian dermatology centres participated in this study. Disease severity was assessed using the Hidradenitis Suppurativa Physician's Global Assessment score (HS-PGA) and Hurley score. The impact of clinical characteristics on disease severity was assessed by logistic regression. Clinical characteristics were similar between men (n = 53) and women (n = 71). Disease severity was also similar; 75% of the patients had Hurley stage II or III disease, and > 60% had moderate, severe or very severe HS as judged by HS-PGA. Lesions were more frequent in the gluteal region in men (32.3% in men vs. 8.7% in women, P < 0.001) and more frequent on the breast in women (16.3% in women vs. 4.6% in men, P = 0.02). Obesity was associated with increased disease severity as measured by HS-PGA (OR: 3.28, 95% CI 1.55-6.95, P < 0.01) and Hurley classification (OR: 3.22, 95% CI 1.34-7.31, P < 0.01). Although severity of HS is similar between the sexes, the localization of lesions is different.

T helper (Th)1, Th17 and Th2 imbalance in mesenchymal stem cells of adult patients with atopic dermatitis: at the origin of the problem.

BACKGROUND: Atopic dermatitis (AD) is a chronic and inflammatory disease characterized by a marked imbalance of T helper (Th)2 vs. Th1/Th17 cells in the early phase of AD, whereas a mixed Th1/Th2 pattern of inflammation is usually found at the chronic stage. These features have not been extensively evaluated in undifferentiated skin cells of patients affected by AD. OBJECTIVES: To evaluate the relative expression of 22 genes encoding Th1, Th2 and Th17 cytokines and the secretion of the corresponding proteins in cutaneous mesenchymal stem cells (MSCs) isolated from skin of patients with AD (AD-MSCs) and their role in AD onset. METHODS: AD-MSCs were isolated, characterized and profiled by polymerase chain reaction array and enzyme-linked immunosorbent assay for the relative expression and secretion of cytokines involved in the Th1, Th2 and Th17 pathways. MSCs isolated from the skin of healthy people were used as controls (C-MSCs). RESULTS: AD-MSCs showed an upregulation of many Th1/Th17 cytokines [interleukin (IL)-6, IL-8, IL-12, IL-13, IL-17A, IL-17F, transforming growth factor-ß, interferon-γ], while Th2 chemokines (IL-2, IL-4, IL-5, IL-23A) were downregulated in AD-MSCs. Finally, some genes/proteins (CCL1, IL-17C, tumour necrosis factor-α) did not show variations between C-MSCs and AD-MSCs. CONCLUSIONS: The profile of MSCs obtained from patients with chronic AD retraces the Th1/Th17 cell environment observed in differentiated cells of chronic AD. This evidence could open a new scenario in the pathogenesis of AD, according to which the inflammatory process may involve MSCs early on.

Ingenol mebutate in actinic keratosis: a clinical, videodermoscopic and immunohistochemical study.

BACKGROUND: Actinic keratosis (AK) is a cutaneous intraepithelial neoplasm that typically develops on sun-damaged skin. The incidence of AK is increasing worldwide, and it is accepted as the most frequent pre-malignant lesion in humans. OBJECTIVES: To demonstrate that ingenol mebutate gel is effective in the treatment of actinic keratoses because of its clinical, dermoscopic, capillaroscopic, histopathological and immunohistochemical treatment outcomes. METHODS: Sixty individuals with multiple non-hypertrophic AKs were enrolled into this non-randomized, open-label, prospective, trial. Acquisition of clinical, dermoscopic and capillaroscopic images at baseline (T0), immediately after treatment on 3rd (trunk and/or extremities) or 4th (scalp and/or face) day (T1), 14 days after the end of the treatment (T2) and at 60 days (T3). A subgroup of 20 patients received a cutaneous biopsy both at baseline and at T3 for histological and immunohistochemical evaluation. RESULTS: Clinical improvement was observed in 100% of cases: total clearance in 41 patients (68.3%); partial clearance in 19 patients (32.7%). After treatment, dermoscopic improvement of all non-pigmented and pigmented AK lesions was observed. Most of the dermoscopic features disappeared with treatment. Total disappearance of specific vascular structures or significant reduction in the number and calibre of new blood vessels was capillaroscopically observed in all patients analysed (P ≤ 0.001). The immunohistochemical expression of p63 (P = 0.002), Ki-67 (P = 0.015) and VEGF (P = 0.016) significantly decreased. CONCLUSIONS: The clinical efficacy of ingenol mebutate on AKs is confirmed by its effect on angiogenesis, stem cell activity and cell proliferation in vivo.

Homocysteine plasma levels in psoriasis patients: our experience and review of the literature.

BACKGROUND: People with psoriasis are at higher cardiovascular risk. Plasma levels of homocysteine over the normal range have been recognized as marker of cardiovascular risk. Psoriasis patients express higher levels of plasma homocysteine than healthy people. OBJECTIVE: Our study aims to investigate the correlation between homocysteinaemia, severity and duration of psoriasis and psoriasis arthritis, and to evaluate the effect of a 12-week administration of a target therapy for psoriasis on homocysteinaemia. METHODS: Fifty-two psoriasis patients (study group) submitted to different kind of therapy for psoriasis (biological, systemic not biological and topical) and 24 healthy Italian subject (control group) were evaluated for their plasmatic homocysteine levels, both at baseline (T0) and 12 weeks after they a specific therapy for psoriasis. RESULTS: A significant difference between the homocysteinaemia of psoriasis patients (mean 19.71 ± 11.16) and control group (13.90 ± 11.18), P < 0.05 (Fig. 1), was found at baseline (T0). The mean plasma levels of homocysteine were directly correlated with disease severity (P = 0.0401), but not with disease duration (P = 0.6018) or presence of arthritis (P = 0.6221) at baseline. None among the treatments administered to psoriasis patients caused a significant reduction in homocysteinaemia after 12 weeks of treatment. CONCLUSION: Our results confirm that psoriasis patients with more severe disease, can have hyperhomocysteinaemia, without regard to disease duration or joint involvement. Hyperhomocysteinaemia is not influenced by a target therapy for psoriasis and it is as greater as psoriasis severity. However, limitation of our study is the relatively small number of cases. Homocysteine plasmatic levels should be advisable as a further independent risk factor for cardiovascular disease in psoriasis patients.

Onabotulinumtoxin type A (Botox(®)) versus Incobotulinumtoxin type A (Xeomin(®)) in the treatment of focal idiopathic palmar hyperhidrosis: results of a comparative double-blind clinical trial.

Focal hyperhidrosis often has a substantial psychological and social impact on quality of life, since it interferes with daily activities. To date, for the treatment of focal hyperhidrosis, the botulinum toxin type A is an effective second line tool. The purpose of this study was to compare Onabotulinumtoxin A (Botox(®)) and Incobotulinumtoxin A (Xeomin(®)) administration in the treatment of palmar hyperhidrosis. In a double-blind clinical trial, 25 patients with moderate or severe palmar hyperhidrosis received in the same session intradermal injections of Onabotulinumtoxin A on one hand and Incobotulinumtoxin A on the other. Several measures of efficacy and safety were evaluated: disease severity improvement, sweat reduction, hand-grip strength decrease, pain/discomfort during the treatment, and patient's global satisfaction. All patients were responsive to the treatments (HDSS at T4 vs HDDs at T0; p < 0.0001), and no significant difference between Onabotulinumtoxin A and Incobotulinumtoxin A in terms of anhidrotic effect (Minor's test at T4; p = 0.51), long-term efficacy (Minor's test at T12; p = 0.76), (Minor's test at T24; p = 0.58), subjective pain related to the injections (p = 0.88), muscle strength reduction after treatment (p = 0.56), and global satisfaction with the treatment (p = 0.26). Onabotulinum toxin A and Incobotulinumtoxin A seem to be comparable in terms of anhidrotic effect (short-term results), duration of benefits (long-term efficacy), muscle strength reduction (safety), pain related to injections (tolerability), and treatment satisfaction expressed by patients.

Electrochemotherapy: an effective local treatment of cutaneous and subcutaneous melanoma metastases.

Treatment of multiple cutaneous and subcutaneous melanoma metastases is still represents a therapeutic challenge for both dermatologists and oncologists. Electrochemotherapy (ECT) is a promising therapeutic procedure, owing to its ability to improve the penetration of cytotoxic drugs into cancer cells by application of current electric pulses. The aim of our study is to evaluate efficacy, tolerability and long-term efficacy of ECT in the treatment of advanced metastatic melanoma. Thirty patients affected by a total of 654 cutaneous and subcutaneous melanoma metastatic nodules were recruited. All patients were treated after they had undergone to a mild general anesthesia. Intravenous Bleomicina solution was administered 8 minutes before the application of electric pulses, generated by a Cliniporator (TM) (the device validated for ECT). The objective response rate of 100% (67.28% complete response and 32.72% partial response) was observed. A total of 214 metastatic lesions from 24 patients received a second ECT session, among them 141 showed a further complete response. Twenty-four months later, the local tumor control rate was 72%. The results of this study seem to demonstrate that ECT is an effective and valid therapeutic tool for the treatment of cutaneous metastases from melanoma. ECT can be considered a first-line palliative treatment since it is able to alleviate pain and reduce the tumor's spontaneous bleeding with a significant improve of patients' quality of life.

Microvessel density and VEGF, HIF-1α expression in primary oral melanoma: correlation with prognosis.

OBJECTIVE: To understand the role of angiogenesis and hypoxia in cancer progression of primary oral melanoma (POM). MATERIALS AND METHODS: Sixteen malignant primary melanomas were immunostained with markers CD34, VEGF and HIF-1α. Stained cells were counted in the invasive front and inside the tumour, and the differences were compared and correlated with histological parameters and disease-specific survival of the patients. RESULTS: Tumour invasive front showed increased MVD and increased vessel VEGF and HIF-1α expression compared with the intratumoural compartment. No such differences were seen in tumoural melanocytes of the two compartments. Positive correlations were observed between CD34 and VEGF, CD34 and HIF-1α and VEGF and HIF-1α expression in invasive front vessels. CD34 expression was statistically correlated with the level of infiltration. A significant trend to worse disease-free survival was also determined with increased invasive front vessel expression of CD34, VEGF and HIF-1α. CONCLUSIONS: Our data highlight the importance of the invasive margin in POM biology. The high angiogenic activity and endothelial VEGF and HIF-1α expression in invasive front vessels have a significant impact on patient survival and future agents targeted against VEGF pathway may represent a novel and effective therapeutic opportunity. Larger studies are needed to further address our findings.

Serum and tissue CTACK/CCL27 chemokine levels in early mycosis fungoides may be correlated with disease-free survival following treatment with interferon alfa and psoralen plus ultraviolet A therapy.

BACKGROUND: Neoplastic T-cell recruitment into the skin is a critical step in the pathogenesis of mycosis fungoides (MF), and the cutaneous T-cell attracting chemokine, CTACK/CCL27, might be involved. OBJECTIVES: To investigate the clinical and prognostic significance of CTACK/CCL27 levels in patients with early-stage MF. METHODS: Serum samples and skin biopsy specimens were collected from 15 patients at the time of diagnosis and after the end of treatment with psoralen plus ultraviolet A/interferon alfa-2b combination therapy. Serum samples were also collected from 20 healthy donors as controls. CTACK/CCL27 serum levels were analysed by enzyme-linked immunosorbent assays. CTACK/CCL27 tissue expression was determined by immunohistochemistry on skin biopsy specimens taken at diagnosis and after therapy. Event-free survival was taken as the primary clinical outcome. RESULTS: In patients with MF at diagnosis, CTACK/CCL27 serum levels were not significantly different from healthy controls, whereas CTACK/CCL27 expression in the skin was increased in 87% of cases compared with normal controls. After therapy, all patients obtained a clinical complete remission, serum levels did not change significantly and tissue expression remained abnormal in 80% of patients, even if complete histological remission was recorded. Serum levels were not significantly different in cases with different intensity of cutaneous immunostaining. Eight patients experienced a relapse: the combination of high CTACK/CCL27 levels both in sera and skin increased the probability of experiencing an event at 51 months from 36% to 83%. CONCLUSIONS: Our data seem to indicate that CTACK/CCL27 levels in skin and sera after therapy might be correlated with risk of recurrence.

In vitro activity and in vivo efficacy of tigecycline alone and in combination with daptomycin and rifampin against Gram-positive cocci isolated from surgical wound infection.

The aim of this work was to determine the in vitro activity of tigecycline and its bactericidal effect for a large number of Gram-positive cocci, as well as to investigate its in vitro interaction with six clinically used antibiotics. In vivo, a wound model was established through the panniculus carnosus of BALB/c mice, and then inoculated with 5 × 10(7) colony-forming units (CFU) of Staphylococcus aureus or Enterococcus faecalis. For each bacterial strain, the study included an infected or non-infected group that did not receive any treatment, three groups singly treated with tigecycline, rifampin, and daptomycin, and two groups that received tigecycline treatment plus rifampin or daptomycin. In the in vitro studies, tigecycline, daptomycin, and teicoplanin were active against all of the 48 Gram-positive isolates. The combination of tigecycline with rifampicin and daptomycin was synergistic against S. aureus and Enterococcus spp. In the in vivo studies, all groups treated with single drugs showed statistically significant results compared to the control group. The two groups treated with a combination of drugs showed the highest antimicrobial efficacy. In conclusion, our results suggested a strong activity of tigecycline alone and in combination with other antimicrobial agents against multi-resistant Gram-positive organisms isolated from wound infections.

Doxycycline-isoniazid: a new therapeutic association for recalcitrant acne agminata.

Acne agminata is a rare asymptomatic, inflammatory dermatosis, which affects adolescence and young adults, whose etiopathogenesis is already controversial. Clinically, acne agminata is characterized by red-yellow-brown papular-pustular eruption involving the central face, in particular cheeks, chin, forehead, and eyelids. The authors report a case of a 25-year-old Caucasian man affected by acne agminata treated with doxycycline and isoniazid.

Videocapillaroscopic pattern of alopecia areata before and after diphenylciclopropenone treatment.

Alopecia areata (AA) is an inflammatory skin disease the most effective therapy for which is diphenylcyclopropenone (DPCP). Videodermatoscopy and intra-vital capillaroscopy (IVCP) are two non-invasive techniques that help in the differential diagnosis of alopecias. It is known that, after DPCP therapy, there is a histologically proven significant increase of VEGF in hair follicle keratinocytes and a consequent increase in capillary vessels in the dermis of the same follicles. The aim of our study is to emphasize any clinical and videodermatoscopic-videocapillaroscopic changes after DPCP treatment in 20 patients affected by alopecia areata. Videodermatoscopic images and an intravital videocapillaroscopic analysis were performed at T0, T12 and T24 to emphasize clinical modifications and microscopic changes in vascular pattern before and after DPCP treatment. At T0, videodermatoscopy showed the presence of exclamation point hairs, hair follicles filled with hyperkeratotic plugs (yellow dots), hair follicles containing cadaverized hairs (black dots) and broken hairs. IVCP highlighted a pale scalp, and vessels were not visible. At 24 weeks (T24), videodermatoscopy revealed the disappearance or a statistically significant reduction of AA hallmarks and an increase of number of vellus hairs. Videocapillaroscopy showed a statistically significant increase of new vessels and, where neoangiogenesis were more marked, a major hair regrowth was evident. Our study emphasizes that, after DPCP therapy, neoangiogenesis is detectable by videocapillaroscopy and these new capillaries could be considered an initial positive attempt to compensate capillary loss of T0 alopecia areata images.

Reciprocal altered expression of E-cadherin and P-cadherin in mucous membrane pemphigoid.

E- and P- cadherins are involved in the selective adhesion of epidermal cells. To gain insight into the role of cadherins on the acantholysis of keratinocytes and further investigate the pathogenesis of Mucous Membrane Pemphigoid, we examined the expression of P-cadherin and E-cadherin, in normal human oral mucosa, lesional and peri-lesional mucosa in MMP. Twenty-nine samples from paraffin-embedded specimens of MMP were used for the study. Five specimens of healthy oral mucosa were evaluated as control group. To evaluate the E- and P-Cadherin expression, a mean percentage of positive cells was determined from the percentage of positive cells derived from the analysis of 100 cells in ten random areas at x400 magnification. It was observed that E-cadherin was weakly and discontinuously expressed on the epithelial layers of pemphigoid mucosa, while it was intensively expressed on all keratinocytes in normal human skin. In contrast, P-cadherin was strongly expressed throughout the entire epidermal layer in MMP samples, although its expression is restricted to the basal cell layer in normal human skin. Statistical analyses showed that the percentage of E-cadherin positive cells in the epithelium of pemphigoid cases was significantly decreased compared with that in normal human mucosa. There was a significant increase in the percentage of P-cadherin positive cells in the epithelial layers of MMP compared with normal human mucosa. The present study showed that there is downregulation of E-cadherin expression and upregulation of P-cadherin expression in MMP mucosa, which may be involved in the pathogenesis of MMP.

Treatment of focal idiopathic hyperhidrosis with Botulinum Toxin Type A: clinical predictive factors of relapse-free survival.

BACKGROUND: No material about the identification of predictive clinical factors of therapeutic response to Botulinum Toxin Type A (BTX-A) in focal idiopathic hyperhidrosis has been found. OBJECTIVE: To evaluate if age, sex, extension rate of hyperhidrotic area, localization, disease-related impairment of life quality, number of previous local, non-invasive treatments different from BTX-A, and duration of disease, may affect the relapse-free survival (RFS) after a BTX-A treatment in palmar and axillary focal idiopathic hyperhidrosis. METHODS: Forty-one patients suffering from palmar hyperhidrosis, and 38 patients suffering from axillary hyperhidrosis received intradermal injections of BTX-A. All patients were clinically screened before and after treatment; they were followed for 15 months after it, according to Hyperhidrosis Disease Severity Scale (HDSS), Minor's test, and DLQI test, to state disease severity, and disease-related impairment of quality of life. RESULTS: The duration of therapeutic effect of BTX-A is not significantly influenced by age (P = 0.783), sex (P = 0.762), extension of hyperhidrotic area (P = 0.770), site of involvement (P = 0.402), disease-induced impairment of life quality (P = 0.745), number of previous therapies (P = 0.730), or site of involvement (P = 0.402). In palmar idiopathic hyperhidrosis, patients with a longer disease history show a shorter duration of RFS after a treatment with BTX-A (P = 0.01). CONCLUSIONS: Patients suffering from palmar hyperhidrosis have a longer lasting disease, and a length of disease more than 20 years in these patients influences the RFS after BTX-A treatment.

In vitro activity of the lipopeptide derivative (Pal-Lys-Lys-NH), alone and in combination with antifungal agents, against clinical isolates of dermatophytes.

BACKGROUND: An increasing number of antimycotics have become available for the treatment of dermatophytoses; however, there are reports suggesting recalcitrance to therapy or resistance of a dermatophyte against conventional treatment. Lipopeptides represent novel therapeutic drugs with a new mode of action. OBJECTIVES: The aim of this study was to investigate the in vitro effects of the lipopeptide Pal-Lys-Lys-NH(2) (PAL) alone and in combination with standard antifungal agents, such as fluconazole (FLU), itraconazole (ITRA) and terbinafine (TER) against 24 clinical isolates of dermatophytes belonging to four species. METHODS: A broth microdilution method following the Clinical and Laboratory Standards Institute recommendations (M38-A) was used for testing drugs alone and in combination. RESULTS: PAL minimum inhibitory concentrations (MICs) ranged from < or = 0.25 to > 16 microg mL(-1) and they were similar to those of FLU and higher than those of either ITRA or TER. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or = 0.50, was observed in 67%, 52% and 15% of PAL/ITRA, PAL/TER and PAL/FLU interactions, respectively. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. CONCLUSIONS: Our study demonstrates that PAL has potential activity against dermatophytes. In addition, the in vitro activity of PAL can be enhanced upon combination with standard drugs. This lipopeptide applied in the form of lacquer, spray or ointment, could represent an interesting new therapy, particularly when combined with conventional treatment in recalcitrant or resistant dermatophyte infections.

Angiogenesis in psoriatic skin and its modifications after administration of etanercept: videocapillaroscopic, histological and immunohistochemical evaluation.

Several studies suggest that microangiopathy plays a crucial role in the pathogenesis of psoriasis. TNFalpha up-regulates the genetic transcription of VEGF, a pro-angiogenetic cytokine over-expressed in psoriatic skin, which promotes micrangiopathic modifications in psoriatic plaque. Etanercept is a chimeric protein used in the treatment of psoriasis and other immunomediated disorders, which blocks inflammatory response by interfering in the binding of TNF-alpha to its receptors. Starting from this data, we retain that etanercept can improve microangiopathy in psoriatic skin by reducing the synthesis of pro-angiogenetic chemokine VEGF. The aims of the study are: to verify the effect of etanercept on cutaneous en plaque capillaries in vivo using intra-vital videocapillaroscopy analysis, to evaluate the relation between the en plaque videocapillaroscopic pattern and the immunohistochemical cutaneous expression of VEGF in psoriasis, and finally to correlate all these in data with clinical disease activity. Eighteen patients (10 male and 8 female, mean age 51, range 21-60) suffering from stable, en plaque type psoriasis, involving at least 10 percent of body surface area (BSA), and not responsive to conventional therapy were included in the study. All the enrolled patients received etanercept 50mg/twice/week, subcutaneously, for 12 weeks, and were carefully followed up for clinical response with PASI score and DLQI index both before (T0) and after 12 weeks (T12) of treatment with etanercept. A well demarcated psoriatic plaque of the extensor surface of upper extremities was chosen to perform an intra-vital videocapillaroscopy analysis (IVCP), and a skin biopsy for immunohistochemical study both at T0 and T12 in all the included patients, in order to evaluate the presence of microangiopathy and its modification after therapy. All the patients experienced a clinical improvement of cutaneous disease with a significant decrease of PASI score (p<0.0001) and DLQI level (p<0.0001), throughout the twelve weeks of treatment. On IVCP analysis, microangiopathy dramatically decreased (p<0.0001), this modification being significantly related with PASI and DLQI decrease at T12. Immunohistochemical expression of VEGF decreased significantly from T0 to T12 (p<0.0001), and was related with a reduction of psoriatic microangiopathy at T12. The results of our videocapillaroscopic and immunohistochemical investigation confirm that the therapeutic potentiality of etanercept is based also on its capability to promote the regression of psoriatic microangiopathy. Moreover, according to these considerations, videocapillaroscopic evaluation of psoriatic plaque, both before and after treatment with etancercept, may be a useful tool to objectively demonstrate its effect on microcirculation.