Long-term clinical efficacy and safety of ixekizumab for psoriatic patients: a single-center experience.

OBJECTIVE: While clinical trials provide invaluable evidence, real-world data can offer further insight on the efficacy and safety of biologic drugs. This report aims to analyze the long-term efficacy and safety of ixekizumab in real-world clinical practice in our facility. PATIENTS AND METHODS: Patients with a diagnosis of psoriasis and who started treatment with ixekizumab were included in this retrospective study and followed for 156 weeks. The severity of cutaneous manifestations was evaluated using the PASI score at several time points and clinical efficacy was evaluated using PASI 75, -90 and -100 responses. RESULTS: Not only PASI 75, but also PASI 90 and 100 responses showed a favorable outcome after treatment with ixekizumab. Responses at week 12 were sustained through the following three years in the majority of patients. No statistically significant difference was found between bio-naive and bio-switch patients and weight and disease duration had no impact on the efficacy of the drug. Ixekizumab had a favorable safety profile, as we observed no major adverse events. Two cases of eczema were observed and led to drug discontinuation. CONCLUSIONS: This study confirms the efficacy and safety of ixekizumab in real-world clinical practice.

Psoriasis patients' characteristics associated with high PASI response to tildrakizumab: an international dual center study.

OBJECTIVE: Heterogeneous real-world evidence can complement the more strictly regulated clinical trial data. A benefit of this is the wide range of backgrounds, comorbidities and characteristics that can give additional insights into treatments. Observational, retrospective studies can help to fill in the mosaic that makes up a treatments landscape. Tildrakizumab, an interleukin 23p19 inhibitor, is approved for the treatment of plaque psoriasis and has been shown to be a safe and efficacious therapy in clinical trials and emerging real-world evidence. We aimed at confirming the efficacy of tildrakizumab in patients with plaque psoriasis in a dual center setting and identifying patients' characteristics leading to better treatment response. PATIENTS AND METHODS: Patients with moderate to severe plaque psoriasis, eligible for systemic biological treatment, and treated with tildrakizumab were included in the study and the routine clinical parameters - Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and safety - were retrospectively analyzed. RESULTS: The combined cohorts included 89 patients, of which 64% were naïve to biologic therapies. At the time of analysis efficacy assessment was available for 39 patients after 12 months of treatment, 73 patients after 36 weeks, 79 patients after 16 weeks and 82 patients after 4 weeks. PASI and DLQI decreased significantly over time, with 52/73 (71.2%) patients achieving PASI 100 after 36 weeks. No severe side-effects were recorded in association with tildrakizumab. CONCLUSIONS: We confirmed the safety and efficacy of tildrakizumab in a real-world clinical setting. A higher proportion of patients naïve to biologics achieved a greater PASI response than patients who had previously been treated with biologics. The same was true for older patients and patients with a shorter history of disease.

Dermoscopy of papulopustular rosacea and comparison of dermoscopic features in patients with or without concomitant Demodex folliculorum.

BACKGROUND: The dermoscopic findings of papulopustular rosacea include tiny papules and pustules, follicular plugs and follicular dilatation. Demodex tails and Demodex follicular openings are dermoscopic indicators that are mainly found in primary demodicosis and, less frequently, in rosacea. AIM: To describe the dermoscopic features of papulopustular rosacea and to investigate the differential dermoscopic features between patients with and without concomitant Demodex infestation. METHODS: We conducted a prospective study of patients with almost-clear, mild or moderate papulopustular rosacea. For each patient, dermoscopic images were taken and a standardized skin surface biopsy was performed. RESULTS: In this group of 60 patients, the most frequent dermoscopic findings were yellow dots, vascular polygons and follicular scales. Patients with moderate rosacea had more Demodex follicular openings compared with patients with mild rosacea (P = 0.02), while patients with mild rosacea had a higher frequency of follicular scales than did patients with almost-clear rosacea (P = 0.01). Patients with moderate rosacea had higher rates of Demodex follicular openings (P = 0.02), follicular scales (P < 0.001), follicular annular pigmentation (P = 0.001) and follicular pustules (P < 0.001) compared with patients with almost-clear rosacea. No significant dermoscopic differences were observed between patients with and without concomitant Demodex infestation. CONCLUSIONS: Papulopustular rosacea has specific dermoscopic findings. In our opinion, dermoscopy is not sufficient by itself for the diagnosis of Demodex proliferation in rosacea.

Sun-safe behaviours, personal risk, level of concern, and knowledge about cutaneous melanoma in italy: time for social marketing?

INTRODUCTION: The incidence of cutaneous melanoma is increasing, although 80-95% of all deaths caused by melanoma can be avoided through protective behaviours. There is evidence that social marketing as an approach in public health can improve health-related behaviours and encourage sun-safe behaviours. METHODS: A multicentre survey was conducted to collect and compare data about cutaneous melanoma risk, knowledge, concern, and protective behaviours across Northern, Central, and Southern Italy, and explore how these data could potentially inform a social marketing intervention to improve sun-safe behaviours. Data were analysed using descriptive and inferential statistics. RESULTS: A total of 1,028 questionnaires were collected. Apart from 'Personal Risk' no statistically significant differences were found between the three regions. About 30% (n = 344) of the total sample had high levels of personal risk, and low levels of concern and protective behaviour, and over 70% (n = 711) gave priority to sun tanning. The worst scores were related to knowledge about melanoma (30% wrong answers, and over 40% 'don't know'). Protective behaviour was moderately correlated with age (p = 0.03). Personal risk was significantly higher in women (10.84 vs 10.05), and lower in individuals with a degree (9.46 vs 11.38; p < 0.001). CONCLUSIONS: Over 70% of our sample gave priority to sun tanning, which combined with low levels of concern and knowledge about melanoma, and high levels of personal risk, confirm that much still needs to be done in terms of melanoma prevention, but all these are aspects that could be effectively addressed through social marketing interventions.

Autoantibody profile and clinical patterns in 619 Italian patients with cutaneous lupus erythematosus.

BACKGROUND: Anti-nuclear antibodies (ANA), anti-extractable nuclear antigens (ENA) and anti-dsDNA antibodies are often associated with cutaneous lupus erythematosus (CLE), with variable frequency depending on skin subtype. However, specific data based on large case-series on the pathogenetic, diagnostic and prognostic meaning of such autoantibodies are still lacking. OBJECTIVE: To characterize the correlations between CLE subtypes as well as LE-non-specific skin lesions and their autoantibody pattern. METHODS: Epidemiological, clinical and immunopathological data of 619 Italian patients with CLE and LE-non-specific skin lesions were analysed. Differences in age, sex, clinical features and autoantibody profile were evaluated in each LE subgroup. RESULTS: Anti-nuclear antibodies (P < 0.0001), anti-dsDNA (P < 0.0001), ENA (P = 0.001), anti-Sm (P = 0.001), anti-RNP (P = 0.004) and anti-histone (P = 0.005) antibodies were associated with SLE. A strong association between ANA (P < 0.0001) and anti-dsDNA (P < 0.0001) and female gender was also found: positive ANA and positive anti-dsDNA had a higher prevalence among females. Chronic CLE resulted to be negatively associated with ENA (OR = 0.51, P < 0.0001), anti-Ro/SSA (OR = 0.49, P < 0.0001) and anti-dsDNA (OR = 0.37, P < 0.0001). Intermittent CLE resulted to be negatively associated with ENA (OR = 0.50, P = 0.007) and ANA (OR = 0.61, P = 0.025). Subacute CLE resulted to be associated with ENA (OR = 5.19, P < 0.0001), anti-Ro/SSA (OR = 3.83, P < 0.0001), anti-Smith (OR = 2.95, P = 0.004) and anti-RNP (OR = 3.18, P = 0.007). Acute CLE resulted to be strongly associated with anti-dsDNA (OR = 6.0, P < 0.0001) and ANA (OR = 18.1, P < 0.0001). LE-non-specific skin lesions resulted to be significantly associated with systemic involvement. Livedo reticularis was significantly associated with ENA (P = 0.007) and anti-Ro/SSA (P = 0.036). Palpable purpura and periungual telangiectasia were significantly associated with ANA. CONCLUSION: According to our findings, some well-known associations between CLE subtypes and autoantibody profile were confirmed; moreover, specific association between autoantibodies and LE-non-specific skin lesions was highlighted. A strict association between anti-ENA and anti-Ro/SSA antibodies and livedo reticularis, ANA and palpable purpura, and ANA and periungual telangiectasia was evidenced.

Serological diagnostics in the detection of IgG autoantibodies against human collagen VII in epidermolysis bullosa acquisita: a multicentre analysis.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a rare, potentially devastating autoimmune disease of the skin. IgG autoantibodies directed against type VII collagen (Col7), the major component of anchoring fibrils, induce skin fragility leading to cutaneous and mucocutaneous blister formation, which is mostly of a scarring phenotype. Thus, powerful and reproducible diagnostic assays are critical to establish the diagnosis of EBA early to avoid irreversible sequelae. OBJECTIVES: The present international, retrospective multicentre study included a large cohort of patients with EBA and evaluated the diagnostic power of four different diagnostic assays for the detection of anti-Col7 IgG autoantibodies. METHODS: Overall, 95 EBA sera and 200 control sera consisting of 100 bullous pemphigoid sera, 50 pemphigus vulgaris sera and 50 sera of healthy controls were tested for anti-Col7 IgG autoantibodies using indirect immunofluorescence (IIF), two commercial enzyme-linked immunosorbent assay (ELISA) systems and Western blot (WB) analysis. EBA sera were taken from patients with positive direct immunofluorescence and IgG reactivity in at least one of the immunoserological assays (IIF, ELISA, WB). RESULTS: A Col7-NC1/NC2 ELISA (MBL, Nagoya, Japan) showed the highest sensitivity (97·9%), followed by a Col7-NC1 ELISA (Euroimmun, Lübeck, Germany) (89·5%), WB with Col7-NC1 (85·3%), and IIF on saline-split human skin (74·7%). The specificities of both ELISA systems were comparable (NC1 98·7%, NC1/NC2 99·3%). Furthermore, WB was more sensitive than IIF, which was more specific. CONCLUSIONS: The two commercially available ELISA systems allow for a highly sensitive and specific diagnosis of EBA. The sensitivity of the Col7-NC1/NC2 ELISA is significantly higher compared with the ELISA based on the Col7-NC1 domain only.

Generalized annular granuloma associated with crowned dens syndrome, which resolved with colchicine treatment.

Granuloma annulare (GA) is a chronic, benign, and usually self-limiting cutaneous inflammatory disease, typically characterized by small, localized, skin-coloured papules that are usually asymptomatic or mildly pruriginous. Its aetiopathogenesis is still unknown and treatments are rarely effective. Generally, 50-70% of localized GA cases are self-limiting and show spontaneous resolution after 1-2 years, whereas disseminated GA is less likely to disappear without treatment. Treatment of generalized GA is usually based on single case reports, and only a few studies involving large case series have been published. We present the case of a patient affected by generalized GA, which resolved after colchicine treatment used for concomitant crowned dens syndrome due to calcium pyrophosphate deposition disease (CPPD). Colchicine may have worked by a direct action on GA or, alternatively, by controlling CPPD, as a possible trigger. As the low-dosage colchicine treatment was well tolerated by our patient, this could be easily used in the management of GA. However, further studies are needed to confirm the action of colchicine on GA.

Changes in neurosyphilis presentation: a survey on 286 patients.

Although neurosyphilis (NS) keeps plaguing worldwide, often with oligosymptomatic and atypical manifestations, the most recent reports fail to provide useful information, like details of the clinical history and even of the previous early therapy. We conducted a survey of the literature of the last 5 years on the clinical presentation of NS, recording the aforementioned inaccuracies. One hundred and thirty-seven articles were collected, reporting on 286 patients. General paresis was the commonest form (49%), often manifesting with cognitive impairment and psychiatric symptoms. Syphilitic meningitis was found in 63 patients (22%), mainly with ocular or auditory involvement. Meningovascular and tabetic form were both found in 12% of cases. Gummatous and epileptic manifestations were rare. Perusal of the literature confirms that NS prevalence is increasing, often with manifestations that are atypical for timing and type of lesions. Unfortunately, many articles are lacking of critical information, like an accurate clinical history and timing of the therapy making difficult to assess the effectiveness of penicillin in preventing NS.

The high incidence of anti-Ro/SSA and anti-p200 antibodies in female patients with connective tissue diseases confirms the importance of screening for congenital heart block-associated autoantibodies during pregnancy.

It is known that anti-Ro/SSA positivity leads to higher risk of miscarriage and fetal cardiac malformations. Particularly, anti-p200 antibodies against a finer specificity of the Ro/SSA antigen, have been associated with congenital heart block. The aim of the study was to assess the frequency of anti-p200 among female patients with different connective tissue diseases and, among these, the relevance of anti-p200 values in patients with cutaneous diseases compared to systemic diseases. Anti-p200 were investigated in 110 anti-Ro/SSA positive female sera, sent to our laboratory between 2008 and 2014 with suspect of connective disease, by using ELISA testing. Positivity was found in 40.9 % samples, 34 of them showed a strong positivity (values ≥ 1.0, cut off = 0.7). Patients with systemic diseases were anti-p200 positive in the 45.9 % of cases while patients with cutaneous diseases were positive in the 24.0 % of cases. Positivity for anti-p200 antibodies was revealed in 24.0 % of patients with discoid lupus erythematosus; 100 % of patients with dermatomyositis; 40.0 % of patients with mixed connective tissue disease; 25.0 % of patients with rheumatoid arthritis; 100 % of patients with Sjögren's syndrome; 33.3 % of patients with subacute cutaneous lupus erythematosus; 42.9 % of patients with systemic lupus erythematosus; 80.0 % of patients with systemic sclerosis. No significant difference in anti-p200 prevalence was found between systemic and cutaneous involvement, nevertheless, considering only positive sera, the antibody titer was higher in systemic diseases rather than in cutaneous diseases (2.6 ± 1.7 and 1.7 ± 1.9; p = 0.041). The authors think screenings for anti-Ro/SSA and anti-p200 antibodies should be included in the laboratory checklist for pregnancy.

Bilateral Warthin tumor in psoriatic patients in therapy with multiple immunosuppressive therapy.

Anti-TNFα drugs have strongly changed the way in which we deal with moderate and severe psoriasis. However, it is debatable whether biological drugs could increase the risk of developing cancer. The correlation between anti-TNFα drugs and lymphomas is well-known and is reported in all the technical details of biologic drugs. However, the association between anti-TNFα agents and solid tumors is still controversial. The authors report a case of bilateral salivary gland tumor in a psoriatic patient treated with several immunosuppressive therapies including anti-TNFα inhibitors.

Vasculitis associated with connective tissue diseases.

Vasculitis in connective tissue disease (CTD) is quite rare, it is reported in approximately 10% of patients with CTD; systemic lupus erythematosus (SLE) shows the highest association rate. Vessels of any size may be involved, but mainly small vessels vasculitis is reported. At present the classification of these vasculitis is unsatisfactory. According to the 2012 revised International Chapel Hill Consensus Conference, vasculitides secondary to CTD are a well identified entity and are classified under the category of "vasculitis associated with systemic disease". However only lupus vasculitis and rheumatoid vasculitis are explicitly listed, while the remaining are generically included under the heading "others". Petechiae, purpura, gangrene and ulcers are the most frequent cutaneous manifestations that should investigated in order to rule out potentially dangerous systemic involvement, especially if cryoglobulinemic or necrotizing vasculitis are suspected. This review will focus on the cutaneous involvement in CTD associated vasculitis.

Dermatological consultations in an observation unit of an emergency department in Italy.

BACKGROUND: Dermatological emergencies exist and should not be underestimated. On the other hand, many accesses to the emergency department (ED) of patients with dermatological conditions are unjustified. OBJECTIVE: Our main objective is to describe dermatological conditions seen in an ED observation unit (EDOU). Secondly, our aim is to identify alarm symptoms and signs of 'true emergencies'. METHODS: We conducted a prospective study, including dermatological patients admitted to EDOU of the University Hospital of San Martino, Genoa, Italy, in 3 years. RESULTS: Overall 372 patients were studied. The most common condition seen was infection (41.67%) (mainly bacterial), followed by atypical exanthem (13.98%) and vasculitis (11.29%). The highest rate of cases peaked in May (13%); infectious diseases showed two peaks (spring and autumn). CONCLUSION: Given constraints involved in health care today, it is crucial to understand which dermatological presentations are 'true emergencies'. In such a scenario knowing the epidemiology of dermatological emergencies and the alarming skin signs and symptoms might be useful.