Health-related quality-of-life improvements during 98 weeks of infliximab therapy in patients with plaque-type psoriasis in real-world practice.

PURPOSE: We evaluated the effect of plaque-type psoriasis on health-related quality of life (HRQoL) of patients who received infliximab (IFX) in real-world clinical settings. METHODS: REALITY was a prospective, observational, open-label study of the efficacy and safety of up to 98 weeks of IFX (5 mg/kg infused at weeks 0, 2, 6, and every 8 weeks thereafter) in patients with moderate-to-severe plaque-type psoriasis. Patients with ≥25 % Psoriasis Area Severity Index (PASI) improvement (PASI 25) at week 50 were eligible for the Extended Treatment Phase (treatment to week 98). Inclusion criteria were diagnosis of plaque-type psoriasis, age ≥18 years, decision to start IFX, and patient consent. Key secondary efficacy outcomes included the Dermatologic Life Quality Index (DLQI; mean DLQI scores, attainment of DLQI 0/1), which was analyzed over 98 weeks. Post hoc analyses examined improvement in DLQI and the relationship between PASI and DLQI. RESULTS: In the Treatment Phase, patients (n = 516, 66.0 % men, mean age 46.4 years) had a mean baseline PASI of 18.1. Mean DLQI improved from 12.7 at baseline to 4.7 [mean change (95 % CI); -8.0 (-8.9, -7.1)] at week 50; 64.0 % (229/358) of patients improved by ≥5 DLQI points. At week 50 (n = 362), 37.6 % (95 % CI; 32.7, 42.7) achieved a DLQI of 0. In the Extended Treatment Phase, patients (n = 167, 68.3 % men, mean age 46.6 years) had a mean baseline PASI of 20.4. Mean DLQI improved from 12.3 at baseline to 2.8 at week 98 [mean change (95 % CI); -9.4 (-10.8, -8.0)]; 68.6 % (96/140) of patients improved by ≥5 DLQI points. At week 98 (n = 141), 47.5 % (95 % CI; 39.4, 55.7) achieved a DLQI of 0. CONCLUSIONS: Patients with plaque-type psoriasis who received treatment with IFX for 50 weeks or up to 98 weeks reported substantial HRQoL improvement.

Idiopathic guttate hypomelanosis: an electron microscopy study.

BACKGROUND: Few published data, concerning the electron microscopy findings of idiopathic guttate hypomelanosis have been published so far. OBJECTIVES: To reveal the electron microscopic findings of idiopathic guttate hypomelanosis and their aetiopathogenetic associations. METHODS: Punch biopsy specimens from four patients with idiopathic guttate hypomelanosis, after being properly processed, were observed under the electron microscope. RESULTS: In the epidermis, melanocytes and melanosomes were normal in structure. In some areas, there was a reduced uptake of melanosomes by the keratinocytes. In the dermis, fibroblasts were structurally normal. Also, most elastic and collagen fibres were normal, but there were focal elastotic changes. CONCLUSIONS: No significant structural abnormality of the melanocytes was observed, but rather a functional defect in the transfer of melanosomes from the melanocytes to the keratinocytes.

Reactive arthritis.

Reactive arthritis (ReA) is an immune-mediated seronegative arthritis that belongs to the group of spondyloarthropathies and develops after a gastrointestinal or genitourinary system infection. The condition is considered to be characterized by a triad of symptoms (conjunctivitis, arthritis and urethritis) although a constellation of other manifestations may also be present. ReA is characterized by psoriasiform dermatological manifestations that may resemble those of pustular psoriasis and, similar to guttate psoriasis, is a post-infectious entity. Also, the articular manifestations of the disorder are similar to those of psoriatic arthritis and both conditions show a correlation with HLA-B27. These facts have led several authors to suggest that there is a connection between ReA and psoriasis, listing ReA among the disorders related to psoriasis. However, the pathogenetic mechanism behind the condition is complex and poorly understood. Bacterial antigenicity, the type of host response (i.e. Th1/Th2 imbalance) and various genetic factors (i.e. HLA-B27 etc.) play an important role in the development of the disorder. It is unknown whether all the aforementioned factors are part of a mechanism that could be similar to, or share basic aspects with known psoriasis pathogenesis mechanisms.

Long-term efficacy and safety of infliximab maintenance therapy in patients with plaque-type psoriasis in real-world practice.

BACKGROUND: Tumour necrosis factor-α inhibitors, including infliximab (IFX), can improve disease control of plaque-type psoriasis. OBJECTIVES: The Real-World Assessment of Long-Term Infliximab Therapy for Psoriasis (REALITY) study evaluated the efficacy and safety of maintenance IFX therapy in typical clinical settings. METHODS: In this prospective, observational, open-label, multicentre study in patients with plaque-type psoriasis, IFX 5 mg kg was infused at weeks 0, 2 and 6, and every 8 weeks thereafter during a 50-week treatment phase. The primary outcome was ≥ 75% Psoriasis Area and Severity Index (PASI) improvement from baseline to week 50. Patients with ≥ 25% PASI improvement from baseline to the end of the treatment phase were potentially eligible to enter a 48-week extended treatment phase. Response maintenance and other efficacy measures were evaluated. Adverse events (AEs) were collected. RESULTS: In total 660 patients enrolled. Of 521 efficacy-evaluable treatment phase patients (66% male, mean age 46·5 years, mean PASI 18·1), 56·8% achieved PASI 75 at the end of the treatment phase. Response was maintained at week 50 by 64·7% (205/317) of patients who achieved PASI 75 at week 14. During extended treatment, 66·3% (112/169) of patients attained PASI 75 at week 98; response was maintained at week 98 by 71·6% (101/141) of those who achieved PASI 75 at week 50. IFX was generally well tolerated. During treatment, 7·6% (50/659) of patients had serious AEs. During extended treatment, 4·1% (eight of 193) of patients had serious AEs. CONCLUSIONS: PASI 75 response was achieved by 56·8% and 66·3% of patients at weeks 50 and 98, respectively. The AE pattern was consistent with previous reports.

Correlation of antibodies against desmogleins 1 and 3 with indirect immunofluorescence and disease status in a Greek population with pemphigus vulgaris.

BACKGROUND: The use of ELISA testing of antibodies to desmogleins 1 and 3 (anti-Dsg1 and anti-Dsg3) and indirect immunofluorescence (IIF) has been strongly supported for the serologic diagnosis of pemphigus. The purpose of this study was to correlate anti-Dsg1 and anti-Dsg3 with IIF values, disease localization, treatment and clinical course in Greek patients with pemphigus vulgaris (PV). METHODS: A total of 54 patients with PV had ELISA serum testing for the presence and titers of anti-Dsg1, anti-Dsg3 and IIF. Anti-Dsg1, anti-Dsg3 and IIF were correlated with treatment and disease localization. For 40 patients, titers of anti-Dsg1 and anti-Dsg3 were assessed in relation to treatment and clinical course after 12 months. RESULTS: Anti-Dsg3 and anti-Dsg1 positivity in patients with negative IIF was 70.6% and 58.8%, respectively. Anti-Dsg1 and anti-Dsg3 were positive in 89.3% and 100% of patients with mucocutaneous disease, respectively, 88.9% and 66.7% of patients with skin limited disease, respectively and 52.9% and 76.5% of patients with mucosal limited disease, respectively. Both antibody titers showed significant correlation with IIF and treatment status. Improvement of clinical status was associated with significant decrease of both anti-Dsg1 and anti-Dsg3 after 12 months. CONCLUSIONS: Serum testing of anti-Dsg1 and anti-Dsg3 in PV patients not only provides significant correlations with IIF, treatment and disease type, but may serve as a monitoring tool for clinical course and treatment guidance.

Advances in Merkel cell carcinoma pathogenesis and management: a recently discovered virus, a new international consensus staging system and new diagnostic codes.

Merkel cell carcinoma is a rare but aggressive neuroendocrine carcinoma of the skin with a rising incidence and a high mortality rate. It occurs primarily in sun-exposed skin of older individuals. It is characterized by a high rate of local recurrence, regional lymph node metastases and distant metastases, occurring even after prompt treatment. Many controversies exist regarding its pathogenesis and optimal management. The discovery of Merkel cell polyomavirus has been a major breakthrough in understanding the aetiology of the disease. A recently adopted new international consensus staging system in combination with new international diagnostic codes are expected to facilitate future clinical trials and improve the management of patients. According to recent (2010) guidelines, most patients should be managed with a combination of surgery and radiotherapy.

Association of thyroid autoimmunity with acne in adult women.

BACKGROUND: During the last decades an increase has been observed regarding acne in adults and especially women. OBJECTIVE: To evaluate the association between thyroid disorder and the presence of post-adolescent acne in adult women, comparing with healthy controls. METHODS: 107 adult women with post-adolescent acne and 60 healthy controls were included. Complete blood count and standard biochemical profile of C-Reactive Protein (CRP) and levels of thyroid hormones and antibodies [triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), free T3 (FT3), free T4 (FT4), antithyroglobulin antibodies (anti-TG) and anti-thyroid peroxidase antibodies (anti-TPO)] were determined in all subjects of both the acne and control groups. A thyroid ultrasound was also performed. RESULTS: There was a statistically significant difference (P=0.008) in the prevalence of positive anti-TG antibodies, with 25.2% of the acne group and 8.3% of the control group having elevated (>40 U/mL) anti-TG levels, respectively. Adult women with acne had a statistically significant increased relative risk to have high levels of anti-TG in comparison with healthy controls (odds ratio 3.89, P=0.011). This association was independent of age. Values for TSH, FT4, FT3, T4 and anti-TPO did not significantly differ between the two groups. No significant difference was found regarding the thyroid ultrasound findings. Although there was no significant difference between cases and controls regarding CRP levels, it is interesting that we observed a significant elevation in CRP in those acne patients who had positive antithyroglobulin antibodies. CONCLUSIONS: It is likely that thyroid autoimmunity might be more frequent in the adult acne patients and this should be kept in mind when screening women with post-adolescent acne.

Effectiveness of topical calcineurin inhibitors as monotherapy or in combination with hydroxychloroquine in cutaneous lupus erythematosus.

BACKGROUND: Calcineurin inhibitors show potent anti-inflammatory effects and favorable safety profile when used in the treatment of cutaneous lupus erythematosus (CLE). OBJECTIVE: The present study investigates the change in clinical parameters of erythema, desquamation and edema, when calcineurin inhibitors are used as monotherapy or in combination with hydroxychloroquine in CLE for a period of 60 days. METHODS: 18 patients were treated with topical tacrolimus and 20 patients with topical pimecrolimus, as monotherapy or in combination with hydroxychloroquine. Clinical parameters of erythema, desquamation and edema were assessed on a scale from 0 to 3 for erythema and edema and 0 to 2 for desquamation. RESULTS: Statistically significant improvement in erythema, desquamation and edema was observed in patients on monotherapy with calcineurin inhibitor and combination treatment with hydroxychloroquine, regardless of disease type. Combination treatment resulted in improvement of edema in 100% of patients, while monotherapy did so in 75% of patients. CONCLUSIONS: Topical calcineurin inhibitors enhance the therapeutic effect of systemic agents in cutaneous lupus erythematosus, and result in improvement of the clinical parameters studied.

The role of inflammatory markers in assessing disease severity and response to treatment in patients with psoriasis treated with etanercept.

BACKGROUND: Psoriasis is a chronic, systemic, inflammatory disease. Inflammatory markers are used in clinical practice to detect acute inflammation, and as markers of treatment response. Etanercept blocks tumour necrosis factor (TNF)-α, which plays a central role in the psoriatic inflammation process. AIM: To reveal any possible association between disease severity [measured by Psoriasis Area and Severity Index (PASI)] and the inflammatory burden (measured by a group of inflammatory markers), before and after etanercept treatment. METHODS: In total, 41 patients with psoriasis vulgaris, eligible for biological treatment with etanercept, were enrolled in the study. A set of inflammatory markers was measured, including levels of white blood cells and neutrophils, fibrinogen, ferritin, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), haptoglobin, ceruloplasmin and α1-antitrypsin, before and after 12 weeks of etanercept 50 mg twice weekly. RESULTS: All markers were reduced after treatment (P < 0.001). PASI correlated with fibrinogen and hs-CRP. Of the 41 patients, 19 (46.3%) achieved reduction of 75% in PASI (PASI75). An increase in hs-CRP and ESR difference (values before minus values after treatment) was related to higher likelihood of achieving PASI75. CONCLUSIONS: Inflammatory markers, particularly hs-CRP and to a lesser extent, fibrinogen and ESR, can be used to assist in assessing disease severity and response to treatment in patients with psoriasis. A combination of selected inflammatory factors (which we term the Index of Psoriasis Inflammation) in combination with PASI might reflect inflammatory status in psoriasis more accurately than each one separately.

Psoriasis: is it the tip of the iceberg for the quality of life of patients and their families?

OBJECTIVE: To evaluate the impact of psoriasis on patients' and their relatives' quality of life (QoL). METHODS: Eighty patients with their accompanying family members were included in the study. For measuring health related QoL (HRQoL) of patients with psoriasis, two questionnaires were used: Short Form 36 Health Survey (SF-36) and EuroQol (EQ-5D). Disease-specific HRQoL was assessed by the Dermatology Life Quality Index. For measuring the quality of life of patients' relatives, a specific questionnaire for dermatological diseases was used (Family Dermatology Life Quality Index, FDLQI). RESULTS: Of our patients, 88.3% reported that their disease affects in many and different ways their QoL whereas only 11.2% reported that psoriasis does not influence at all their life. Regarding FDLQI, 90% of the participating family members, responded that their relative's psoriasis affected their own QoL. CONCLUSIONS: Psoriasis is a chronic disease that affects in a cumulative way the quality of life of both patients and their close relatives.

Psoriasis in children: a retrospective analysis.

BACKGROUND: Few epidemiological studies are available on childhood psoriasis. METHODS: Between 2005 and 2008, information was collected about all children diagnosed with psoriasis in the Pediatric Dermatology Unit of Andreas Sygros Skin Hospital, in Athens, Greece. RESULTS: A total of 125 children with psoriasis were examined, the male to female ratio was 1.4:1 and the peak age of onset was in the 9- to 10-year-old age group. Only 16% of the patients had a positive family history. Plaque type psoriasis was the most prevalent type at presentation with 56.8% of the children affected, followed by scalp involvement (33.6%). The limbs were the most prevalent site of involvement (70 children, 56%), followed by the body (59 children, 47.2%) and scalp (60 children, 48%) equally affected. Most of the children had <5% of their skin affected by psoriasis (53.2%). Age of onset had no influence on the severity of the disease (P=0.107), whereas a positive correlation was found with sex and severity of the disease, with male patients being more severely affected (P=0.008). Family history did not influence the age at presentation (P=0.68). Topical steroids were used in most commonly followed by keratolytics, calcipotriol, topical tacrolimus and topical pimecrolimus. CONCLUSION: Our study reflects the patterns of presentation of childhood psoriasis in sunny countries like Greece.

Acne-associated syndromes: models for better understanding of acne pathogenesis.

Acne, one of the most common skin disorders, is also a cardinal component of many systemic diseases or syndromes. Their association illustrates the nature of these diseases and is indicative of the pathogenesis of acne. Congenital adrenal hyperplasia (CAH) and seborrhoea-acne-hirsutism-androgenetic alopecia (SAHA) syndrome highlight the role of androgen steroids, while polycystic ovary (PCO) and hyperandrogenism-insulin resistance-acanthosis nigricans (HAIR-AN) syndromes indicate insulin resistance in acne. Apert syndrome with increased fibroblast growth factor receptor 2 (FGFR2) signalling results in follicular hyperkeratinization and sebaceous gland hypertrophy in acne. Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) and pyogenic arthritis-pyoderma gangrenosum-acne (PAPA) syndromes highlight the attributes of inflammation to acne formation. Advances in the understanding of the manifestation and molecular mechanisms of these syndromes will help to clarify acne pathogenesis and develop novel therapeutic modalities.

Infliximab for the treatment of psoriasis in Greece: 4 years of clinical experience at a single centre.

BACKGROUND: Infliximab, a chimeric monoclonal antibody, has been shown to be effective for moderate to severe psoriasis. Clinical experience with long-term infliximab therapy for psoriasis is accumulating, and it is therefore important to share our experience with its use in real-life clinical practice. OBJECTIVES: To report our experience with infliximab (Remicade; Schering Plough, Kenilworth, NJ, U.S.A.) for the treatment of moderate to severe plaque psoriasis (and/or arthritis) from a single clinic in Greece. PATIENTS AND METHODS: Between August 2004 and March 2008, 62 patients presenting to our clinic with moderate to severe psoriasis were treated with infliximab. Disease phenotype, clinical course, disease severity and adverse events were assessed throughout the treatment period. RESULTS: Infliximab resulted in a reduction of median Psoriasis Area and Severity Index (PASI) of 70% at week 6 and 84.4% at week 14. Nineteen patients who have completed 1 year on infliximab treatment experienced sustained efficacy with a median PASI improvement of 92.16% and a Physician's Global Assessment (PGA) of 'clear' or 'almost clear', while nine patients have reached approximately 20 months of continuous therapy. All patients with psoriatic arthritis showed marked improvement in their clinical symptoms following the first infusion. Eight patients (12.9%) experienced adverse events that required discontinuation of treatment. There were no statistically significant differences in PASI and Dermatology Life Quality Index (DLQI) scores between patients with arthritis and those with only skin lesions, or between those who received methotrexate, either from the beginning or during infliximab therapy, and those who did not receive methotrexate at all. Selected patients of interest are discussed. CONCLUSIONS: The above data confirm previous reports that treatment with infliximab is an efficacious and safe option for patients with moderate to severe plaque psoriasis (and/or arthritis). Long-term follow-up, continued pharmacovigilance, and controlled comparative studies will be required to fully evaluate its use in the treatment of psoriasis.

Pimecrolimus cream 1% for the treatment of papulopustular eruption related to epidermal growth factor receptor inhibitors: a case series and a literature review of therapeutic approaches.

BACKGROUND: Cutaneous side effects of epidermal growth factor receptor inhibitors (EGFRIs) are very frequent and well known. The aim of our study was to investigate the efficacy and safety of pimecrolimus 1% cream in the treatment of papulopustular eruption caused by EGFRIs and to review the relevant literature on therapeutic approaches. METHODS: Twenty cancer patients being treated with EGFRIs were included in the study. Nine of the patients showed grade 1 and 11 showed grade 2 papulopustular eruption. All patients were treated with pimecrolimus 1% cream, which was applied twice daily. Patients with grade 2 eruption also received systemic minocycline 100 mg/day. RESULTS: All patients with grade 1 eruption responded to treatment, with 4/9 experiencing complete resolution of the lesions 2 weeks after the initiation of treatment. Five out of 11 patients with grade 2 eruption had more than 50% improvement in erythema and pustules, and 1 had complete resolution of the skin lesions. Two patients did not respond to treatment but were significantly improved after substitution of pimecrolimus 1% cream with metronidazole 1% cream. No side effects were recorded. CONCLUSIONS: Our case series shows that pimecrolimus cream may be an effective and safe approach in the management of papulopustular eruption related to EGFRIs.