Effectiveness of guselkumab in patients with facial and/or genital psoriasis: Interim analysis results at Week 12 from the GULLIVER study.

BACKGROUND: Facial (FP) and genital psoriasis (GP) significantly affect patients' quality of life. Despite the advances in treatments, limited data on efficacy and safety are available on these difficult-to-treat areas. Guselkumab is an interleukin (IL)-23 inhibitor which has been proven effective in treating patients with moderate-to-severe plaque psoriasis. OBJECTIVES: The aim of this interim analysis was to report the efficacy and safety of guselkumab in the treatment of patients with FP and/or GP. MATERIALS AND METHODS: GULLIVER is a 52-week Italian observational study to evaluate the effectiveness and safety of guselkumab in a real-life setting in patients with FP and/or GP. Adult patients with facial and/or genital moderate-to-severe psoriasis (sPGA score ≥ 3) were included. The primary endpoint of this analysis was the percentage of patients achieving a facial or genital sPGA score of 0 (clear) or 1 (almost clear), at Week 12. The change in the score of the facial or genital sPGA components in patients with a score ≥3 for each sPGA component was assessed. PASI score in patients with a baseline PASI above or below 10 was evaluated. RESULTS: Overall, 351 patients were included in the study; 83.3% of FP and 76.5% of GP patients achieved the primary endpoint. Similar response rates were observed for the facial or genital sPGA components in patients with a baseline facial or genital sPGA score ≥3 in each component. Among patients with a baseline PASI score >10, mean PASI score improved from 19.0 (SD 8.3) to 2.2 (SD 4.8). Forty-four AEs were observed in 32 patients; two mild and transient AEs (fatigue and nausea) were considered treatment related. No SAEs were observed. CONCLUSIONS: Guselkumab, showing to be effective and safe in treating FP and GP, may be a valid therapeutic option for patients with psoriasis localized in these difficult-to-treat areas.

Dermoscopic spectrum of mycosis fungoides: a retrospective observational study by the International Dermoscopy Society.

BACKGROUND: The dermoscopic features of classic patch stage mycosis fungoides (MF) have been described, but data on plaque and tumoral stage as well as rarer MF subtypes is limited. OBJECTIVE: To evaluate dermoscopic morphology and dermoscopic-pathological correlations of classic MF stages and investigate dermoscopic features of MF variants. METHODS: Patients with histopathologically confirmed lesions of classic MF (patch, plaque and tumoral stage) or folliculotropic, erythrodermic and poikilodermatous MF were included. Standardized evaluation of dermoscopic pictures of the included MF variants and comparative analysis and dermoscopic-pathological correlation assessment of different stages of classic MF were performed. RESULTS: A total of 118 instances were included (75 classic MF, 26 folliculotropic MF, 9 erythrodermic MF and 8 poikilodermatous MF). Linear/linear-curved vessels and white scales in the skin furrows were significantly associated with patch-stage MF, while clustered dotted vessels were related to plaque-stage MF and peripheral linear vessels with branches, ulceration and red globules separated by white lines to tumour-stage MF. Moreover, patchy white scales were significantly more common in patches and plaques compared to tumours, whereas focal bright white structureless areas were related to plaque and tumoral stage. Vessels histopathologically corresponded to dilated vascular structures in the dermis, orange structureless areas to either dermal hemosiderin (patch/plaque stage) or dense cellular infiltration (tumours), bright white lines/structureless areas to dermal fibrosis and ulceration to loss of epidermis. The main dermoscopic findings of folliculotropic MF were lack of hairs, dilated follicles and follicular plugs, while erythrodermic MF was mainly characterized by linear/dotted vessels, patchy white scales and focal orange structureless areas and poikilodermatous MF by focal white and brown structureless areas, white patchy scales and brown reticular lines. CONCLUSION: Dermoscopy may allow a more precise characterization of classic MF and reveal clues suggestive of the main MF variants.

Dupilumab therapy of atopic dermatitis of the elderly: a multicentre, real-life study.

BACKGROUND: Treatment of moderate-to-severe atopic dermatitis (AD) in the elderly may be challenging, due to side-effects of traditional anti-inflammatory drugs and to comorbidities often found in this age group. Furthermore, efficacy and safety of innovative drugs such as dupilumab are not yet well known. OBJECTIVES: A multicentre retrospective, observational, real-life study on the efficacy and safety of dupilumab was conducted in a group of patients aged ≥65 years and affected by severe AD. Their main clinical features were also examined. METHODS: Data of elderly patients with severe (EASI ≥24) AD treated with dupilumab at label dosage for 16 weeks were retrospectively collected. Treatment outcome was assessed by comparing objective (EASI) and subjective (P-NRS, S-NRS and DLQI) scores at baseline and after 16 weeks of treatment. RESULTS: Two hundred and seventy-six patients were enrolled in the study. They represented 11.37% of all patients with severe AD. Flexural eczema was the most frequent clinical phenotype, followed by prurigo nodularis. The coexistence of more than one phenotype was found in 63/276 (22.82%) subjects. Data on the 16-week treatment with dupilumab were available for 253 (91.67%) patients. Efficacy of dupilumab was demonstrated by a significant reduction of all the scores. No statistically significant difference regarding efficacy was found in elderly patients when compared to the group of our AD patients aged 18-64 years, treated with dupilumab over the same period. Furthermore, only 18 (6.52%) patients discontinued the drug due to inefficacy. Sixty-one (22.51%) patients reported adverse events, conjunctivitis and flushing being the most frequent. One (0.36%) patient only discontinued dupilumab due to an adverse event. CONCLUSIONS: Therapy with dupilumab led to a significant improvement of AD over a 16-week treatment period, with a good safety profile. Therefore, dupilumab could be considered as an efficacious and safe treatment for AD also in the elderly.

Standardization of dermoscopic terminology and basic dermoscopic parameters to evaluate in general dermatology (non-neoplastic dermatoses): an expert consensus on behalf of the International Dermoscopy Society.

BACKGROUND: Over the last few years, several articles on dermoscopy of non-neoplastic dermatoses have been published, yet there is poor consistency in the terminology among different studies. OBJECTIVES: We aimed to standardize the dermoscopic terminology and identify basic parameters to evaluate in non-neoplastic dermatoses through an expert consensus. METHODS: The modified Delphi method was followed, with two phases: (i) identification of a list of possible items based on a systematic literature review and (ii) selection of parameters by a panel of experts through a three-step iterative procedure (blinded e-mail interaction in rounds 1 and 3 and a face-to-face meeting in round 2). Initial panellists were recruited via e-mail from all over the world based on their expertise on dermoscopy of non-neoplastic dermatoses. RESULTS: Twenty-four international experts took part in all rounds of the consensus and 13 further international participants were also involved in round 2. Five standardized basic parameters were identified: (i) vessels (including morphology and distribution); (ii) scales (including colour and distribution); (iii) follicular findings; (iv) 'other structures' (including colour and morphology); and (v) 'specific clues'. For each of them, possible variables were selected, with a total of 31 different subitems reaching agreement at the end of the consensus (all of the 29 proposed initially plus two more added in the course of the consensus procedure). CONCLUSIONS: This expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This tool, if adopted by clinicians and researchers in this field, is likely to enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology. What's already known about this topic? Over the last few years, several papers have been published attempting to describe the dermoscopic features of non-neoplastic dermatoses, yet there is poor consistency in the terminology among different studies. What does this study add? The present expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This consensus should enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology.

Dermoscopy of genital diseases: a review.

The male and female external genital regions are anatomical areas in which various types of skin disorders may occur. Although most of these conditions can be diagnosed by means of clinical examination and an accurate medical history, in most cases further investigations with time-consuming and/or invasive procedures are needed in order to reach the correct diagnosis. Dermoscopy, as a modern non-invasive tool, is able to better diagnose pigmented and non-pigmented skin tumours along with various inflammatory and infectious skin and appendage disorders. The aim of this paper was to provide a review of the use of dermoscopy in genital disorders based on published data and to include personal experience gained from real life, focusing on any possible gender difference and whether disease mucosal/semimucosal dermoscopy features may differ from those observed on the skin. In conclusion, genital dermoscopy should always be considered during clinical inspection in order to enhance the diagnosis or to rule out those conditions that may look similar but that show a different dermoscopy pattern, thus narrowing down the differential diagnoses and avoiding unnecessary invasive investigations.

Dermoscopy in the differential diagnosis between malar rash of systemic lupus erythematosus and erythematotelangiectatic rosacea: an observational study.

BACKGROUND: Malar rash is one of the three cutaneous diagnostic criteria of systemic lupus erythematosus (SLE). Although its clinical recognition is often straightforward, the differential diagnosis with erythematotelangiectatic rosacea may sometimes be challenging. OBJECTIVE: To describe dermoscopic features of SLE malar rash and investigate the accuracy of dermoscopy for the differential diagnosis with erythematotelangiectatic rosacea. METHODS: A representative dermoscopic image of target areas was evaluated for the presence of specific features. Fisher's test was used to compare their prevalence between the two cohorts, and accuracy parameters (specificity, sensitivity, and positive and negative predictive values) were evaluated. RESULTS: Twenty-eight patients were included in the analysis, of which 13 had SLE malar rash and 15 erythematotelangiectatic rosacea. The main dermoscopic features of malar rash were reddish/salmon-coloured follicular dots surrounded by white halos ('inverse strawberry' pattern), being present in 53.9% of the cases, while network-like vessels (vascular polygons) turned out to be the main feature of erythematotelangiectatic rosacea, with a prevalence of 93.3%. The comparative analysis showed that the 'inverse strawberry' pattern was significantly more common in SLE malar rash, with a specificity of 86.7%, while vascular polygons were significantly more frequent in rosacea, with a specificity of 92.3%. CONCLUSION: Dermoscopy may be a useful support to distinguish SLE malar rash and erythematotelangiectatic rosacea by showing peculiar features.

Accuracy of dermoscopy in distinguishing erythroplasia of Queyrat from common forms of chronic balanitis: results from a multicentric observational study.

BACKGROUND: Clinical differentiation of erythroplasia of Queyrat (EQ) and chronic forms of balanitis may be challenging, especially in early phases or in overlapping cases. Dermoscopy has been shown to be a useful supportive tool in facilitating the distinction between tumoral and inflammatory skin conditions; yet, data on EQ and balanitis are scarce or sparse. OBJECTIVES: To systematically assess the dermoscopic features of both EQ and common forms of chronic balanitis and to investigate the accuracy of dermoscopy in distinguishing these conditions. METHODS: Subjects with EQ or chronic balanitis confirmed histologically or microbiologically (for infectious forms) were recruited. A representative dermoscopic image of a target lesion was retrospectively assessed for the presence of specific morphological findings. A correlation matrix was created using Spearman's rho. Proportions of dermoscopic variables scoring among different conditions were compared with the non-parametric Pearson's chi-square test. RESULTS: A total of 81 lesions (14 EQ, 23 psoriasis, 31 Zoon plasma cell balanitis and 13 candidal balanitis) from 81 patients were included in the study. Glomerular vessels (both clustered and diffusely distributed) were highly predictive for the diagnosis of EQ, while diffuse dotted vessels were strongly associated with psoriatic balanitis. Finally, Zoon plasma cell balanitis was characterized by orange structureless areas (focal or diffuse) and focused linear curved vessels, whereas cottage cheese-like structures (sparse white coating corresponding to Candida yeast colonies growth) showed a strong correlation with candidal balanitis. CONCLUSIONS: Erythroplasia of Queyrat and balanitis may display different dermoscopic patterns, thereby bearing the usefulness of dermoscopy as a supportive non-invasive tool for the recognition and differential diagnosis of such conditions.

Dermoscopic features of mammary Paget's disease: a retrospective case-control study by the International Dermoscopy Society.

BACKGROUND: Mammary Paget's disease (MPD) is a rare intraepidermal adenocarcinoma of the nipple-areola complex, associated with an underlying breast cancer in approximately 90% of cases. Delayed diagnosis of MPD is common. Its dermoscopic features have been ill defined in the literature. OBJECTIVES: To determine the clinical and dermoscopic features of MPD versus other dermatologic entities that involve nipple and areola. METHODS: Members of the IDS were invited to submit any case of histologically confirmed MPD, as well as other benign and malignant dermatoses that involve the nipple and areola complex. A standardized evaluation of the dermoscopic images was performed and the results were statistically analyzed. RESULTS: Sixty-five lesions were included in the study, 22 (33.8%) of them MPD and 43 (66.2%) controls. The most frequent dermoscopic criteria of MPD were white scales (86.4%) and pink structureless areas (81.8%), followed by dotted vessels (72.7%), erosion/ulceration (68.2%) and white shiny lines (63.6%). The multivariate analysis showed that white scales and pink structureless areas were significant predictors of MPD, posing a 68-fold and a 31-fold probability of MPD, respectively. Split of the population into pigmented and non-pigmented lesions showed that in pigmented MPD, pink structureless areas, white lines and grey granules and dots are positive predictors of the disease. Among non-pigmented lesions, pink structureless areas, white lines, erosion/ulceration and white scales served as predictors of MPD. CONCLUSIONS: The most frequent profile of an individual with MPD is an elderly female with unilateral, asymptomatic, erythematous plaque of the nipple, dermoscopically displaying pink structureless areas, fine white scales, dotted and a few short linear vessels. In case of pigmentation we may also observe brown structureless areas and pigmented granules. LIMITATIONS: Small sample size, retrospective design.

Differentiation of pityriasis lichenoides chronica from guttate psoriasis by dermoscopy.

Clinical differentiation between pityriasis lichenoides chronica (PLC) and guttate psoriasis (GP) may sometimes be a difficult task, which often requires histological analysis to reach a definitive diagnosis. In this study, PLC and GP lesions were examined using dermoscopy, and the significance of specific dermoscopic findings was investigated in order to facilitate their differentiation and decrease the number of cases requiring biopsy. We found that the incidence of orange-yellowish structureless areas, focal dotted vessels and nondotted vessels was statistically significant in PLC, while the incidence of diffuse dotted vessels was statistically significant in GP.

Melanoma detection in Italian pigmented lesion clinics.

AIM: Accuracy in melanoma detection is important to recognize early curable melanomas and to minimize the unnecessary excision of benign lesions. The aim of this paper was to evaluate melanoma screening accuracy of Italian pigmented lesion clinics in terms of number needed to excise (NNE), melanoma thickness, and number of melanomas diagnosed during patient follow-up. METHODS: Information on all skin tumors excised in 2011 were extracted from the databases of the participating centers. Information whether the lesion was excised at the baseline examination or during patient follow-up was recorded, as well as the overall number of patients examined in each center in 2011. RESULTS: After e-mail solicitation, 22 of 40 centers agreed to participate. A total of 8229 excised lesions were collected. The overall number of examined patients was 86.564, thus 9.5% of screened patients had a lesion removed. Of the excised lesions, 866 were diagnosed as melanoma (1% of examined patients) and 5311 (88.9%) were melanocytic nevi. Three NNE were calculated giving values of 7.9 excised lesions to find 1 melanoma, 7.1 melanocytic lesions to find 1 melanoma, and 3.7 lesions to find 1 skin malignancy. The median melanoma thickness was 0.6 mm, with only 15.1% of melanomas ≥ 1 mm of thickness. Melanomas detected over time were 96 (11.1%; mean thickness, 0.3 mm), with 15.6% of lesions excised after short-term follow-up and 84.4% after long-term follow-up. CONCLUSION: The NNE values comparable to those achieved in specialized clinical settings and the high number of early melanomas diagnosed at the baseline examination or during patient follow-up indicate a high level of accuracy in melanoma screening achieved by Italian pigmented lesion clinics.

Videocapillaroscopic findings in the microcirculation of the psoriatic plaque during etanercept therapy.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a pivotal cytokine in the pathogenesis of psoriasis, and upregulation of VEGF by tumour necrosis factor (TNF)-α and inflammatory factors causes marked alterations in the cutaneous microcirculation. Etanercept is a fully soluble TNF receptor fusion protein that primarily binds soluble TNF-α, thus blocking its pro-angiogenic function. AIM: To assess the modifications in the superficial capillary bed in psoriatic plaques during treatment with etanercept. METHODS: The study enrolled 22 patients (13 men, 9 women; age range 31-74 years) with plaque psoriasis resistant to conventional therapy. The patients were stated on etanercept 50 mg/week, which was continued for 24 weeks. At the beginning of the study (baseline), and at weeks 6, 12, 18 and 24, in vivo videocapillaroscopy analysis of a selected plaque was performed. Levels of erythema, scaling and infiltration were assessed using a four-point plaque severity score, with an overall score obtained by the sum of these three scores. The Psoriasis Activity and Severity Index (PASI) was also determined. RESULTS: Etanercept produced a significant reduction in PASI, plaque severity score and diameter of the basket-weave area at every time point. Four patients had complete remission, although none of the patients regained a normal capillaroscopic pattern. CONCLUSIONS: Similar to other conventional therapies, etanercept is able to improve PASI, plaque severity score and basket-weave area diameter, but it is unable to induce normalization of the microcirculation in psoriatic plaques.

Psoriasis vulgaris does not adversely influence the quality of sleep.

AIM: Sleep could be severely affected in psoriasis because of skin symptoms and psychological repercussions of the disease. The aim of this study was to investigate the influence of psoriasis on sleep. METHODS: A total of 202 patients with psoriasis and 202 healthy volunteers have completed a self-rated questionnaire, the Pittsburgh Sleep Quality Index, which assesses sleep quality and disturbances over a 1-month time interval. The severity of the dermatoses has been evaluated utilizing the PASI score. RESULTS: In psoriatic patients the Pittsburgh Sleep Quality Index resulted between 0 and 17 (5.56±3.93), in the controls between 0 and 18 (5.13±4.16). No statistically significant correlation was observed between the score of Pittsburgh Sleep Quality Index and PASI. The anti-psoriatic therapy, while causing a marked improvement of lesions and itching, does not affect the quality of sleep. CONCLUSION: Although literature indicated that psoriasis negatively affects the quality of sleep, in this study this correlation was not observed.

Detection of DNA of Chlamydophila psittaci in subjects with psoriasis: a casual or a causal link?

BACKGROUND: Recent evidence indicates that subclinical infection by Chlamydophila psittaci occurs in a significant percentage of patients with chronic inflammatory polyarthritis, including psoriatic arthritis. OBJECTIVE: To assess the prevalence of Chlamydiae infection in a large cohort of well-characterized patients with psoriasis. METHODS: The presence of a subclinical C. psittaci infection was investigated in 64 patients with psoriasis, including 12 patients with psoriatic arthritis. Two hundred and twenty-five healthy controls were also investigated. The presence of infection was assessed in peripheral blood mononuclear cells using several polymerase chain reaction protocols, targeting different regions of the bacterial genome. The DNA of other species (Chlamydophila pneumoniae and Chlamydia trachomatis) was also investigated. RESULTS: Chlamydophila psittaci infection was observed in a significantly higher percentage of patients with psoriasis (11/64, 17%) compared with healthy controls (1/225, 0.4%) (odds ratio 46.49, 95% confidence interval 5.87-368.03; P < 0.0001). No differences in age, sex or disease duration were noticed between positive and negative patients, but the majority of the positive patients were on immunomodulatory treatments. CONCLUSION: Chlamydophila psittaci may be an infectious trigger possibly involved in the pathogenesis of psoriasis.

Effectiveness of cyclosporine A in patients with moderate to severe plaque psoriasis in a real-life clinical setting in Italy: the TRANSITION study.

BACKGROUND: Cyclosporine A (CsA) is one of the systemic therapeutic options for moderate-to-severe psoriasis, based on its efficacy and rapidity of action. The current study investigated the response to CsA in patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: TRANSITION was an observational, cross-sectional, multicentre study which evaluated the proportion of partial- and suboptimal-responders among patients with moderate-to-severe plaque psoriasis treated with continuous CsA for ≥12 weeks. Patients demonstrating a Psoriasis Area and Severity Index (PASI) response of ≥90, ≥75 and <90, ≥50 and <75 and <50 were defined as responders, suboptimal-responders, partial-responders, and non-responders, respectively. RESULTS: A total of 196 patients (mean age, 46.6 years; 62.8% males) from 14 sites in Italy were evaluated. At the study visit, the mean (SD) PASI score was 4.2(5.5) compared with 15.3(7.1) prior to the last CsA cycle. For response categories, 39.8%, 22.4%, 16.8%, and 20.9% of patients were responders, suboptimal-responders, partial-responders, and non-responders to CsA treatment. Overall, 28.6% of patients permanently discontinued treatment with CsA (lack of efficacy [10.2%], poor tolerability and voluntary discontinuation [3.6% each], and other [11.7%]). CONCLUSION: Patients were only partially satisfied with CsA treatment, reporting measurable impact on quality of life. Only 40% patients showed a satisfactory response to CsA.

Absence of clinical and dermoscopic differences between congenital and noncongenital melanocytic naevi in a cohort of 2-year-old children.

BACKGROUND: Congenital melanocytic naevi (CMN) are present at birth. Some naevi, tardive congenital naevi (TCN), become clinically apparent only after birth, during the first years of life. The number of naevi continues to increase due to the appearance of acquired melanocytic naevi (AMN). When AMN begin to appear has not been well defined. OBJECTIVES: To investigate the clinical and dermoscopic features of the melanocytic naevi present in 2-year-old children and to search for and highlight any differences between CMN present at birth (BPN) and naevi appearing after birth during the first 2 years of life (FLN). METHODS: A nonrandomized observational study was performed. A total of 133 melanocytic naevi in 103 children aged 21-26 months were analysed by clinical and dermoscopic examination. RESULTS: Of the subjects, 76% of children had one naevus, 20% had two naevi, 3% had three naevi and 1% had four naevi. Of the naevi, 76 were BPN and 57 were FLN. The naevi with the largest diameters were significantly associated with BPN (P = 0·025). Polycyclic edges (P = 0·0378) were observed with a higher frequency in BPN than in FLN. The predominant dermoscopic patterns were globular (BPN 51%; FLN 58%) and reticular (BPN 28%; FLN 14%). CONCLUSIONS: The number of naevi present in the first 2 years of life is small, and over half have already appeared at birth. They are distributed widely over the skin. BPN are larger than FLN, but most naevi are small. There was no significant difference in the dermoscopic features between the 133 BPN and FLN. The predominant patterns were globular and reticular. We could not identify defined criteria that allowed us to diagnose CMN with certainty and distinguish them from TCN and AMN.