Children with psoriasis and COVID-19: factors associated with an unfavourable COVID-19 course, and the impact of infection on disease progression (Chi-PsoCov registry).

BACKGROUND: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. OBJECTIVES: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments. METHODS: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms. RESULTS: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01). DISCUSSION: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.

A real-world, non-interventional, prospective study of the effectiveness and safety of apremilast in bio-naïve adults with moderate plaque psoriasis treated in the routine care in Greece - the 'APRAISAL' study.

BACKGROUND: Real-world data in patients with moderate psoriasis treated with apremilast is limited. OBJECTIVES: To evaluate the effectiveness and safety of apremilast in bio-naïve patients with moderate psoriasis in real-world clinical settings. METHODS: This was a 52-week multicenter, observational, prospective study of adult outpatients with moderate psoriasis {[10% < body surface area < 20% or 10 < psoriasis area severity index (PASI) < 20] and 10 < dermatology quality of life index (DLQI) < 20} initiated on apremilast ≤7 days before enrollment. Missing data were imputed using the last observation carried forward method. RESULTS: A total of 287 eligible patients (median age: 54.2 years; median psoriasis duration: 9.8 years) were consecutively enrolled. At baseline, the median DLQI and PASI scores were 12.0 and 11.8, respectively. The 52-week DLQI ≤ 5 and PASI75 response rates were 68.3% and 61.0%. At 52 weeks, 70.8% and 72.7% of the patients shifted from moderate/severe/very severe to clear/minimal scalp and palmoplantar psoriasis involvement, respectively; the pruritus severity state improved in 67.2%. The 52-week Kaplan-Meier estimated drug continuation rate was 85.3%. The adverse drug reaction rate was 19.9%. CONCLUSIONS: Apremilast is a safe and effective treatment for bio-naïve patients with moderate psoriasis and specific psoriasis manifestations.

FCGR3A-V158F polymorphism is a disease-specific pharmacogenetic marker for the treatment of psoriasis with Fc-containing TNFα inhibitors.

Psoriasis is a multifactorial skin disease affecting ~2% of world's population, causing a dramatic decrease in patients' quality of life and a significant increase in health-care expenses. Biological agents such as the anti-TNFα ones had an enormous impact in patients' therapy; however, a significant proportion of them do not respond well, an outcome attributed mainly to genetic factors. Recently, in a large European cohort of rheumatoid arthritis patients we have shown association with variation in the receptors that correspond to the Fc portion of the biological agents. As both diseases share common immunological fingerprints, we examined the hypothesis that they share common pharmacogenetic markers. Analysis of FCGR2A-H131R and FCGR3A-V158F polymorphisms in 100 psoriasis patients showed association only with respect to FCGR3A-V158F and response to etanercept (P=0.018). Interestingly, no association was found between FCGR2A-H131R and response to anti-TNFα therapy (P=0.882). This study suggests a role for FCGR3A-V158F polymorphism unique for psoriasis.

A pharmacogenetic study of ABCB1 polymorphisms and cyclosporine treatment response in patients with psoriasis in the Greek population.

Psoriasis affects 2-3% of the population, causing significant morbidity and financial burden. Immunosuppressive drugs such as cyclosporine are first line systemic therapies for moderate-to-severe forms. However, patients exhibit heterogeneity in their response to therapy, possibly due to genetic factors. The aim of the present study was to assess the ABCB1 T-129C, G1199A, C1236T, G2677T and C3435T single-nucleotide polymorphisms (SNPs) as candidate predictive markers of response to cyclosporine treatment in 84 psoriasis patients. 62% of the patients were defined as responders and 38% as nonresponders. All SNPs complied with Hardy-Weinberg equilibrium. SNP and haplotype analyses were performed to access responsiveness to treatment. Association analysis revealed statistically significant association of SNP 3435 T with negative response (P=0.0075), a result that was further validated in haplotype analysis. This study is the first in the field of the pharmacogenetics of cyclosporine in psoriasis whose results merit further exploitation in larger independent cohorts.

Identification of human papillomavirus DNA in melanoma biopsy specimens of Greek population.

The aim of this retrospective study was to evaluate melanoma biopsy specimens from the Greek population living in the prefecture of Larissa for the presence of human papillomavirus (HPV) DNA and to determine the possible relationship between HPV and clinical outcome in these patients. Twenty-eight melanoma biopsy specimens, 20 from primary cutaneous melanoma and eight from melanoma metastasis were obtained from 28 patients. The biopsy samples were formalin-fixed and paraffin wax-embedded. The control group consisted of three junctional melanocytic nevi, histologically confirmed, and three punch biopsies from normal skin that were obtained from six healthy individuals. The presence and types of HPV DNA were assessed by the amplification of a fragment of the LI region by consensus primer polymerase chain reaction (PCR) combined with restriction fragment length polymorphism analysis (RFLPA). In each biopsy specimen that was evaluated, HPV 6, HPV 11, HPV 16 and HPV 18 positive controls from genital HPV lesions were included. Five of 28 (17.85%) biopsy melanoma specimens were positive for HPV DNA. Conversely, HPV was not detected in any of the biopsy specimens of the control group (0/6). HPV viral type 16 was found in two samples and HPV 6 DNA in three. Our results regarding the possible relationship between melanoma and HPV DNA were not statistically significant (p > 0.05). These findings suggest that ultraviolet sun exposure remains the main cause of melanoma in our region. The role of cutaneous HPV infection in the pathogenesis of melanoma remains elusive.

Early T cell activation in the skin from patients with systemic sclerosis.

OBJECTIVES: To determine if T cells in skin lesions in systemic sclerosis (SSc) express the early activation antigen CD69 that participates in cell-cell interactions. METHODS: Skin biopsy specimens from 17 patients with SSc were analysed by immunohistochemistry using the indirect peroxidase method and monoclonal antibodies for CD3 (T cell marker), CD69 (early T cell activation marker), and CD68 (macrophage marker). RESULTS: Mononuclear cells, containing mostly T cells and macrophages, were increased in SSc skin lesions and were present in perivascular areas. CD69 was expressed in these mononuclear cells. There was no correlation between the number of CD3+, CD69+, or CD68+ cells and the Rodnan skin score or disease duration. CONCLUSIONS: The expression of early T cell activation antigen CD69 in skin lesions suggests that T cells may actively participate in cell-cell contact with fibroblasts to promote fibrosis.

Evaluation of cytokine serum levels in patients with plaque-type psoriasis.

Psoriasis is a chronic debilitating cutaneous disorder that affects both sexes and appears clinically as inflamed, edematous skin lesions covered with a silvery white scale. Strong evidence suggests that immune mechanisms are implicated in its pathogenesis, such as persistent activation of T-lymphocytes, excessive proliferation of keratinocytes and reactivation of proto-oncogenes and other elements. Additionally, several recent studies have demonstrated that cytokines play a significant role in the pathogenesis of the disease, as they can be found in the affected skin of psoriatic patients. In this study we evaluated levels of circulating cytokines in the serum of 45 Greek psoriatic patients before initiation of treatment and compared the results with those in 45 healthy volunteers. According to our findings interleukin (IL)-2, IL-10, IL-12 and tumor necrosis factor-alpha (TNF-alpha) levels were statistically significantly elevated in the serum of psoriatic patients before therapy compared with those of controls. IL-6 serum levels did not differ between psoriatic patients and healthy volunteers. Conversely, interferon-gammaserum levels of psoriatic patients were statistically significantly lower than those of healthy volunteers.

Calcipotriol monotherapy versus calcipotriol plus UVA1 versus calcipotriol plus narrow-band UVB in the treatment of psoriasis.

The purpose of this study was to evaluate the efficacy of calcipotriol ointment as monotherapy versus calcipotriol in combination with narrow-band ultraviolet (UV)-B or UVA1 phototherapy and to determine whether calcipotriol in combination with UVA1 is an alternative to calcipotriol with narrow-band UVB phototherapy. Forty-five patients with plaque psoriasis were divided into three treatment groups with no significant differences in Psoriasis Area and Severity Index (PASI) scores, mean age, sex or skin type. The total duration of the treatment was 3 months. Regarding PASI score, psoriasis regression was statistically significant between the groups. The response to UVA1 and narrow band UVB with calcipotriol was superior to calcipotriol monotherapy. UVA1 phototherapy with calcipotriol could be an alternative to narrow-band UVB phototherapy with calcipotriol.

Increasing incidence of melanoma in central Greece: a retrospective epidemiological study.

The increasing incidence of melanoma in the general population during the last few decades has provoked a great deal of research, aiming to identify the possible relationship between old and new etiological factors involved in the pathogenesis of this tumor. The aim of the study was to evaluate the incidence of melanoma in central Greece, especially in the prefecture of Larissa from January 1988 to December 1998. Data were collected from the General Hospital of Larissa. Seventy-one cases of melanoma were studied (41 females, 30 males). The incidence increased from 1.36/100,000 patients during the first year of the study (1988) to 5.2/100,000 patients in the last year of the study (1998). The patients'skin types were: type 12.8%, type II 52.1%, type III 45.1%. The median age of patients was 61.9 years, 61.4 years in female and 62.5 years in male patients. Concerning their occupation, farmers accounted for 56.3%. Melanomas were most frequently located on head and neck (36.6%), extremities (30.98%) and trunk (11.3%). Superficial spreading melanomas were observed in 44% of the patients and nodular melanomas in 20%. In conclusion. there was a rapid increase in the incidence of melanoma in our region especially during the last 3 years.

Objective biophysical findings in patients with sensitive skin.

The term sensitive skin has been used to describe a clinical phenomenon of hyperreactivity of the human skin, which develops exaggerated reactions when exposed to external factors. The aim of this study was to determine objective biophysical findings in patients with sensitive skin compared to those individuals with nonsensitive skin. Thirty-two patients with sensitive skin and 30 healthy volunteers with nonsensitive skin were studied. The testing methods included in vivo and in vitro tests: epicutaneous testing (Patch tests); measurement of sebum and hydration of the skin; alkali resistance test; stinging test with lactic acid; reaction to aqueous solution of methyl nicotinate 0.5%, 1.4% and acetyl-b-methylcholine chloride 1:1000; pH measurement; dermographism; and measurement of total and specific IgE. Significant results were observed in the measurement of sebum (p < 0.01) and hydration (p < 0.05) of the skin, in the alkali resistance test (p < 0.05), in the vascular reaction to methyl nicotinate (p < 0.01) and to acetyl-b-methylcholine chloride (p < 0.01) and in the skin response to allergens of the European standard (p < 0.01) and cosmetic series (p < 0.05). In addition, the subjective findings of stinging test produced significant results (p < 0.001) as was anticipated. Patients with sensitive skin possess very dry skin with low fatness, which leads to a disturbance of the protective skin barrier function. They also present a hyperreaction of the skin blood vessels, increased transcutaneous penetration of water-soluble chemicals, enhanced immune responsiveness, significant decrease of alkali resistance and a heightened neurosensory stimulation.

Psychiatric factors in patients with sensitive skin.

The term sensitive skin has been used to describe a clinical phenomenon of skin hyperreactivity induced after exposure to different external factors. The diagnosis is mainly based on patient's self-assessment because of the lack of objective clinical signs of the disease. The aim of this study was to investigate psychiatric factors in patients with sensitive skin and to estimate the possible need for psychological intervention to these patients. Thirty-seven patients with sensitive skin and 38 individuals with nonsensitive skin were studied. The psychometric instruments used were the Symptom Checklist-90 (SCL-90) and the Delusions-Symptoms-States Inventory/states of Anxiety and Depression (DSSI/sAD). Statistically significant differences in subjects with sensitive skin compared to those with nonsensitive skin were observed in the SCL-90 subscales of somatization, phobic anxiety, hostility, interpersonal sensitivity and the DSSI/sAD subscale of anxiety. Our findings suggest that somatization, anxiety, phobic anxiety, hostility and interpersonal sensitivity symptoms may be associated with hypersensitivity of human skin. Psychological factors should be taken into consideration in the treatment of patients with sensitive skin.

Comparison of isepamicin with amikacin for the empirical treatment of febrile neutropenic children with malignancies.

The efficacy and safety of isepamicin at 7.5 mg/kg i.v. q 12 h was prospectively compared with that of amikacin at the same dose for the treatment of febrile neutropenic children with malignancies. Thirty-nine patients were enrolled in the study; 25 received isepamicin and 14 amikacin. Clinical and bacteriological response rates were 100% for both groups. No adverse events occurred. Median peak serum levels were 19.7 mg/l for isepamicin and 19.20 mg/l for amikacin. Median trough serum levels were 0.72 mg/l for isepamicin and 0.68 mg/l for amikacin. It was concluded that isepamicin was as effective and safe as amikacin for the treatment of febrile neutropenic children with malignancies, and might be used in areas where resistance to other aminoglycosides is a problem.