Psoriasis Subjects Research Articles

Risks of developing psychiatric disorders in pediatric patients with psoriasis

Symptoms of psoriasis can be embarrassing and distressing, and may increase risk of developing psychiatric disorders in young people. We sought to compare incidences of psychiatric disorders between pediatric patients with psoriasis and psoriasis-free control subjects. Patients (<18 years) with continuous health plan enrollment 6 months before and after first psoriasis diagnosis (index date) were selected (Thomson Reuters MarketScan database, 2000-2006 [Thomson Reuters, New York, NY]). Patients with psoriasis (N = 7404) were matched 1:5 on age and sex to psoriasis-free control subjects (N = 37,020). Patients were followed from index date to first diagnosis of a psychiatric disorder (ie, alcohol/drug abuse, depression, anxiety disorder, bipolar disorder, suicidal ideation, eating disorder), end of data availability, or disenrollment. Patients with psychiatric diagnoses or psychotropic medication use before the index date were excluded. Cox proportional hazard models controlling for age, sex, and comorbidities were used to estimate the effect of psoriasis on risks of developing psychiatric disorders. Patients with psoriasis were significantly more at risk of developing psychiatric disorders versus control subjects (5.13% vs 4.07%; P = .0001; hazard ratio = 1.25; P = .0001), especially depression (3.01% vs 2.42%; P = .0036; hazard ratio = 1.25; P = .0053) and anxiety (1.81% vs 1.35%; P = .0048; hazard ratio = 1.32; P = .0045). Retrospective, observational studies of medical claims data are typically limited by overall quality and completeness of data and accuracy of coding for diagnoses and procedures. Pediatric patients with psoriasis had an increased risk of developing psychiatric disorders, including depression and anxiety, compared with psoriasis-free control subjects.

A nonimmunosuppressant approach on Asia psoriasis subjects: 5-year followup and 11-year data analysis.

Mono- or combine immunosuppressants are commonly used for psoriasis; however the side effect caused by potent systemic immunosuppressants frequently incurred; moreover the inflammation flares up shortly after immunosuppressants are discontinued. An alternative nonimmunosuppressive therapy was introduced to psoriasis subjects. A retrospective observational study consisted of 1583 psoriasis patients who were treated with Herose Psoria capsule 1440 mg three times daily at two clinical centres, one in China, the other in Singapore, from 1 January 2000 to 1 January 2011. Psoriasis lesion evolution was photographed at monthly visit, and efficacy and safety were assessed using psoriasis area severity index PASI score grading, renal and liver function testing, and adverse event reporting and supplemented by information obtained during targeted telephone interviews. The effectiveness of Herose on psoriasis was inversely associated to prior immunosuppressants exposure (r = 0.9154), significant improvements occurred in non-immunosuppressants subjects, and complete clearance was achieved in 8 months (87.5%, 14 of 16); the wavelike evolution of psoriatic lesion appeared in prior immunosuppressants subjects.

Ultrasonographic Assessment of the Local Cutaneous Changes Induced by Phototherapy in Psoriasis Patients

High-frequency ultrasonography can be used for the detection of cutaneous changes associated with phototherapy. The aim of the study was to assess the changes of ultrasonographic (US) parameters in psoriasis patients, exposed to UV-rays. The study was performed on 20 psoriasis subjects, that underwent a variable number of phototherapy sessions. The cutaneous changes were assessed with a 20-MHz ultrasound scanner (Dermascan C, Denmark). US images were acquired from dorsal forearm (DF) and zygomatic level (ZL), before and after phototherapy. The following parameters were measured: thickness of epidermis and dermis and the number of low, medium and high echogenic pixels. After phototherapy we noticed a decrease of the epidermal thickness at DF (0.173 ± 0.038 mm vs 0.183 ± 0.024, p = 0.03) and ZL (0.148 ± 0.028 mm vs 0.157 ± 0.032, p = 0.025); an increase of the dermis thickness on the DF (1.093 ± 0.389 mm vs 0.095 ± 0.269, p = 0.03) and ZL (1.599 ± 0.263 vs 1.399 ± 0.332, p = 0.02); an increase of low (DF: 9631.88 ± 3771.24 vs 1066.33 ± 2739.28, ZL: 1999.1 ± 5254.33 vs 17801.86 ± 532.45) and medium echogenic pixels (DF: 1937.77 ± 1445.31 vs 1654 ± 763,76, ZA: 1089.71 ± 1057.95 vs 987.11 ± 951,52 vs) on both examined sites and a significant decrease of hyperechogenic pixels on the DF (1169.55 ± 1067.53 vs 673.77 ± 580.36, p = 0.006). High frequency ultrasonography is a modern, noninvasive method that offers specific and objective markers that quantify local cutaneous changes induced by phototherapy.

Chronic plaque psoriasis and plaque-induced chronic periodontitis; is there any association: a cross-sectional study

Abstract Background and aims. Psoriasis and periodontitis are characterized by an exaggerated host immune response to epithelial cell surface microbiota. Thus, mediators produced as part of host response orchestrate the inflammatory cascade and cause tissue destruction. The aim this study was to investigate the prevalence of periodontitis in psoriasis patients, and to find whether any correlation exists between them. Materials and methods. This hospital-based cross-sectional study included 100 age- and gender-matched subjects divided into two groups: group 1: psoriasis (test) and group 2: chronic periodontitis (CP) (control). Both groups were evaluated for periodontal clinical parameters (gingival index (GI), plaque index (PI), probing depth (PD), periodontal attachment level (PAL) and tooth loss (1-3 or ≥4). Furthermore, subgingival microbial analysis of dental plaque was carried out to estimate the levels of periodontopathic organisms, using polymerase chain reaction (PCR). ANOVA, independent sample t-test and chi-squared test were used for statistical analysis. Results. Psoriasis patients showed significantly higher GI, PI, PD, PAL and tooth loss (≥4) compared to controls. Further-more, their microbiological analysis showed significantly greater number of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis positive samples. However, no difference was found in Tannerella forsythia positive samples. Conclusions. The prevalence of periodontitis is higher in psoriasis subjects as compared to age- and gender-matched peri-odontitis controls. We hypothesized that this assumption is valid as periodontitis shares several important common pathways with psoriasis. Further studies with larger sample sizes are warranted to substantiate this association.

Prolactin level is significantly elevated in lesional skin of patients with psoriasis

Accumulating data point to a potential role of prolactin in the pathogenesis of psoriasis. We initiated a study including psoriasis patients (n = 15) and healthy volunteers (n = 15) as controls. Psoriasis area and severity index (PASI) score was evaluated, and prolactin levels in serum and blister fluid were assessed by enzyme-linked immunosorbent assay (ELISA). Prolactin levels were significantly (P < 0.01) elevated in blister fluid of psoriatic lesional skin. Correlations between PASI score and different serum prolactin levels in lesional and non-lesional skin were insignificant. Significant positive correlations of prolactin level were observed between lesional and non-lesional skin in psoriasis (P < 0.05) and between serum and clinically normal skin in both psoriasis and control subjects (P < 0.05). Locally produced prolactin may be involved in the pathogenesis of psoriatic lesions.

Treatment Decision Needs of Psoriasis Patients: Cross-sectional Survey

Informed shared decision making is a mutual process engaging both doctor and patient and informed by best medical evidence and patient values and preferences. Our aim was to identify the needs of psoriasis patients in decisions on selecting treatment. Psoriasis subjects participated in an online survey on decisional role, postdecisional conflict, and treatment awareness. Of 2,622 people invited to participate, 248 completed surveys. Their most recent treatment decision was either made by subjects alone (42%) or physicians alone (28%) or was shared (29%). Subjects perceived that their doctors lacked time to stay abreast of treatments, to provide counseling, and to access appropriate treatments. Deficiencies most frequently identified were information on options, clarification of values, access to physicians, and decision-making skills. Those with a body surface area (BSA) ≥ 3% more frequently indicated that having the skill or ability to make treatment decisions was important. The limitations of this study include sampling, recall, and reporting bias. Percent BSA was not verified. The multiple deficiencies in support of psoriasis patients in treatment decisions may preclude informed shared decision making.

419 V600EB-RAF cooperates in Epithelial to Mesenquimal Transition regulating E-Cadherin and ILK-1 expression through the MEK/ERK-MAPK pathway

Eczema vaccinatum (EV), a disseminated viral skin infection, is a life-threatening complication of vaccinia virus (VV) inoculation in patients with atopic dermatitis (AD) and is thought to be associated with a defective innate immune response. However, the precise mechanism or mechanisms and key factor or factors of EV are unknown.Given that patients with psoriasis, another inflammatory skin disorder, are not susceptible to EV, we compared the global transcriptional response of skin to VV in healthy subjects, patients with psoriasis, and patients with AD, focusing on AD-specific genes. We hypothesized that differences in the transcriptional response to VV between patients with AD and patients with psoriasis or healthy subjects would identify a defective pathway or pathways that might be associated with the development of EV.Gene expression profiling of sham-treated and VV-treated unaffected skin explants from patients with AD (n = 12), patients with psoriasis (n = 12), or healthy subjects (n = 13) were generated with U133_Plus2 (54,613 probe sets) GeneChips and analyzed with the GCOS_1.4/SAM_2.1/MAPPFinder_2.0 pipeline.Sixty-seven genes were significantly affected by VV in AD skin but not in psoriatic and healthy skin. Genes associated with defense response, response to wounding, and immune response were the most affected by VV in AD skin. All genes in these ontologies were downregulated, including the innate immunity genes leukotriene B4 receptor (LTB4R), orosomucoid 1 (ORM1), coagulation factor II (thrombin) receptor (F2R), complement component 9 (C9), and LPS-binding protein (LBP). These findings were confirmed by means of real-time PCR and validated by means of PubMatrix analysis. ORM1, Toll-like receptor 4 (TLR4), and NLR family pyrin domain containing 1 (NLRP1) genes were also linked to AD severity.This study identified groups of innate immunity genes that are associated with the aberrant response of AD skin to VV and represent potential targets for EV pathogenesis.

Heterotopic pruritic conditioning and itch – Analogous to DNIC in pain?

Pain can be endogenously modulated by heterotopic noxious conditioning stimulation (HNCS) through a mechanism which is known as diffuse noxious inhibitory control (DNIC). Since DNIC can be impaired in patients suffering from chronic pain, a comparable impaired itch inhibition may exist in patients suffering from chronic itch. The aim of the present study was to investigate whether heterotopic pruritic conditioning stimulation (HPCS) would display an impaired modulation of itch in patients suffering from chronic itch compared with healthy subjects. To this end, electrical stimuli were applied before and after histamine application (HPCS) to female patients with psoriasis and healthy female control subjects. Subjects reported the intensity of electrically evoked itch before and after HPCS. In order to replicate earlier findings for DNIC, electrically evoked pain was additionally investigated before and after cold stimulation (HNCS). As expected, the intensity of itch evoked by the electrical stimulus was significantly less after than before HPCS in healthy subjects, and the same was found for the intensity of electrically evoked pain after compared to before HNCS. Contrarily, in the patients levels of electrically evoked itch were significantly higher after than before HPCS, and no significant difference in pain intensity before and after HNCS was observed. In line with pain modulation, results suggest that there is a DNIC analogous mechanism for itch, i.e., diffuse pruritic inhibitory control (DPIC), which is impaired in patients with chronic itch, possibly due to a dysregulation of descending itch modulatory systems.

CD16 (FcRγIII) as a potential marker of osteoclast precursors in psoriatic arthritis

IntroductionPsoriatic arthritis (PsA) is a chronic inflammatory arthritis characterized by bone erosion mediated by osteoclasts (OC). Our previous studies showed an elevated frequency of OC precursors (OCP) in PsA patients. Here, we examined if OC arise from CD16-positive monocytes in PsA.MethodsPeripheral blood mononuclear cells (PBMC) or monocytes were isolated from human peripheral blood and sorted based on CD16 expression. Sorted cells were cultured alone or with bone wafers in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Enumeration and bone erosion activity of OC were examined after culture. The effects of tumor necrosis factor-alpha (TNFα), OC-promoting (M-CSF plus RANKL), and dendritic cell (DC)-promoting (GM-CSF plus interleukin (IL)-4) cytokines on CD16 surface expression were examined by flow cytometry.ResultsPsA and psoriasis (Ps) subjects had a higher percentage of circulating inflammatory CD14+CD16+ cells than healthy controls (HC). Exposure of cells to OC-promoting, but not DC-promoting media, was associated with CD16 up-regulation. PBMC of Ps and PsA had a higher frequency of cells expressing intermediate levels of CD16. OC were mainly derived from CD16+ cells in PsA. Increased CD16 expression was associated with a higher bone erosion activity in PsA.ConclusionsAn increased frequency of circulating CD14+CD16+ cells was noted in PsA compared to controls, and intermediate levels of CD16 may suggest a transitional state of OCP during osteoclastogenesis. Intriguingly, TNFα blocked CD16 expression on a subset of CD14+ monocytes. Collectively, our data suggest that CD16 has the potential to serve as an OCP marker in inflammatory arthritis.

Vaccinia virus–specific molecular signature in atopic dermatitis skin

Eczema vaccinatum (EV), a disseminated viral skin infection, is a life-threatening complication of vaccinia virus (VV) inoculation in patients with atopic dermatitis (AD) and is thought to be associated with a defective innate immune response. However, the precise mechanism or mechanisms and key factor or factors of EV are unknown. Given that patients with psoriasis, another inflammatory skin disorder, are not susceptible to EV, we compared the global transcriptional response of skin to VV in healthy subjects, patients with psoriasis, and patients with AD, focusing on AD-specific genes. We hypothesized that differences in the transcriptional response to VV between patients with AD and patients with psoriasis or healthy subjects would identify a defective pathway or pathways that might be associated with the development of EV. Gene expression profiling of sham-treated and VV-treated unaffected skin explants from patients with AD (n = 12), patients with psoriasis (n = 12), or healthy subjects (n = 13) were generated with U133_Plus2 (54,613 probe sets) GeneChips and analyzed with the GCOS_1.4/SAM_2.1/MAPPFinder_2.0 pipeline. Sixty-seven genes were significantly affected by VV in AD skin but not in psoriatic and healthy skin. Genes associated with defense response, response to wounding, and immune response were the most affected by VV in AD skin. All genes in these ontologies were downregulated, including the innate immunity genes leukotriene B(4) receptor (LTB4R), orosomucoid 1 (ORM1), coagulation factor II (thrombin) receptor (F2R), complement component 9 (C9), and LPS-binding protein (LBP). These findings were confirmed by means of real-time PCR and validated by means of PubMatrix analysis. ORM1, Toll-like receptor 4 (TLR4), and NLR family pyrin domain containing 1 (NLRP1) genes were also linked to AD severity. This study identified groups of innate immunity genes that are associated with the aberrant response of AD skin to VV and represent potential targets for EV pathogenesis.

Mean platelet volume in psoriasis and psoriatic arthritis

Mean platelet volume (MPV), an indicator of platelet activation, is a newly emerging risk factor for atherothrombosis. There is evidence of platelet activation in psoriasis and psoriatic arthritis (PsA). The association between psoriasis, PsA, and atherosclerosis is well documented, yet, the underlying mechanisms remain unclear. The aim of this study was to investigate the differences of MPV values in patients with psoriasis, PsA, and healthy subjects and the correlation between MPV and the clinical disease activity. A total of 106 patients with psoriasis were included in this study. The study population grouped as 48 patients with PsA (group 1) and 58 patients without PsA (group 2) and 95 healthy controls (group 3). MPV was measured in psoriasis and PsA patients. MPV values were collected from standard complete blood count samples. Clinical features and PASI scores in group 1 and 2 were also recorded. MPV in patients with psoriasis 8.7 +/- 0.9 fL was significantly higher than that of control subjects 7.3 +/- 0.8 fL (p < 0.001). There was also statistical difference between MPV levels of patients with (9.5 +/- 0.8) and without (8.0 +/- 0.7) arthritis (p < 0.001). MPV levels were positively correlated with psoriasis area and severity index score (p = 0.000, r = +0.735). MPV levels showed positive correlation with disease duration (p = 0.01, r = 0.518). MPV levels are increased in patients with psoriasis and PsA. MPV may be a marker for the severity of psoriasis. This study may confirm previous observation indicating increased platelet activation in psoriasis. Increased platelet activity could contribute to increasing the atherosclerotic risk in patients with psoriasis and PsA.

Incidence and clinical predictors of psoriatic arthritis in patients with psoriasis: A population‐based study

To determine the incidence and disease-specific predictors of clinically recognized psoriatic arthritis (PsA) in patients with psoriasis. We identified an incidence cohort of psoriasis subjects age >/=18 years diagnosed between January 1, 1970 and December 31, 1999 in a population-based setting. Psoriasis diagnoses were validated by confirmatory diagnosis in the medical record. Incident and clinically recognized PsA subjects were classified according to the Classification of Psoriatic Arthritis (CASPAR) criteria. Cox proportional hazards models were used to identify predictors of PsA within the psoriasis cohort. The psoriasis incidence cohort comprised 1,633 subjects. Of these, 40 were diagnosed with PsA concurrently with psoriasis and were excluded from analysis. The remaining 1,593 psoriasis subjects had a mean age of 43 years and 50% were men. Over 20,936 person-years of followup, 57 subjects were clinically recognized with new-onset PsA, with a cumulative incidence of 1.7% (95% confidence interval [95% CI] 1.0-2.3%), 3.1% (95% CI 2.2-4.1%), and 5.1% (95% CI 3.7-6.6%) at 5, 10, and 20 years following psoriasis incidence, respectively. Psoriasis features associated with higher risk of PsA were scalp lesions (hazard ratio [HR] 3.89, 95% CI 2.18-6.94), nail dystrophy (HR 2.93, 95% CI 1.68-5.12), and intergluteal/perianal lesions (HR 2.35, 95% CI 1.32-4.19). Calendar year was not associated with risk of PsA (P = 0.15), indicating that the likelihood of PsA in psoriasis subjects did not change over time. In this population-based study, <10% of patients with psoriasis developed clinically recognized PsA during a 30-year period. Psoriasis features associated with a higher likelihood of PsA were nail dystrophy, scalp lesions, and intergluteal/perianal psoriasis.

Elevated plasma osteopontin level is associated with occurrence of psoriasis and is an unfavorable cardiovascular risk factor in patients with psoriasis

The association between psoriasis and cardiovascular diseases is well documented yet the underlying mechanisms remain elusive. We sought to study the role of circulating osteopontin (OPN) in the pathogenesis of cardiovascular diseases in patients with psoriasis. Plasma samples from 40 patients with psoriasis and 37 control subjects were collected for enzyme-linked immunosorbent assays. The clinical significance of OPN levels in patients with psoriasis versus control subjects was analyzed using the Mann-Whitney U test and logistic regression. DNA samples from 268 patients with psoriasis and 146 control subjects were collected for genotyping of the OPN gene. Higher body mass index values (P = .047) and hypertension (odds ratio [OR] 2.68, P = .05) were observed in patients with psoriasis. Increased plasma OPN levels (>or=62.95 ng/mL) were significantly associated with psoriasis (OR 6.24, P = .001), hypertension (OR 3.05, P = .03), and diabetes mellitus (OR 3.13, P = .05). Occurrence of psoriasis (OR 5.12, P = .003) appeared to be the single independent risk factor for high plasma OPN values after multivariate logistic regression. Among patients with psoriasis, increased plasma OPN values were associated with the presence of hypertension (OR 4.69, P = .05). However, no significantly different allelic distributions of single nucleotide polymorphisms of the OPN gene were found between psoriasis and control groups. The number of patients evaluated was relatively small. High plasma OPN levels are an unfavorable factor for development of cardiovascular disease in patients with psoriasis.

Cutaneous T-cell lymphoma and Staphylococcus aureus colonization

Bacterial infections are a common complication of cutaneous T-cell lymphoma (CTCL). The most common pathogen of cutaneous infections in CTCL patients is Staphylococcus aureus. The purpose of this study was to assess S aureus colonization rates among CTCL subjects compared to control subjects. Fifty subjects with CTCL, 25 psoriasis control subjects, and 25 healthy control subjects were included in this study. Culture swabs were obtained from nares and lesional skin or normal skin in the healthy controls. S aureus colonization rates were 44% in CTCL subjects, 48% in psoriasis subjects, and 28% in healthy control subjects (P = .29). The sample size was small, and the exclusion criteria resulted in an underestimation of the colonization rate. There was a trend for higher methicillin-sensitive S aureus colonization in the CTCL group compared with healthy control subjects. S aureus colonization may be directly related to body surface area of CTCL.

The angiotensin‐converting enzyme insertion/deletion and the endothelin ‐134 3A/4A gene polymorphisms in patients with chronic plaque psoriasis

Psoriasis is a common chronic inflammatory skin disease. Vasoactive peptides such as endothelin-1 (ET-1) and bradykinin have previously been implicated in the pathogenesis of chronic plaque psoriasis. The angiotensin-converting enzyme (ACE) gene carries a 287-base pair insertion/deletion (I/D) gene polymorphism, which is associated with plasma concentrations of bradykinin-degrading ACE. A functional polymorphism (EDN1 -134 3A/4A) in the gene encoding ET-1 has been shown to affect ET-1 expression. The purpose of the present study was thus to investigate a hypothesized association between these gene polymorphisms and the presence of chronic plaque psoriasis. The present case-control study comprised 207 patients with chronic plaque psoriasis (136 with early onset and 71 with late onset disease) and 182 control subjects. Genotypes of EDN1 and ACE were determined by a 5' exonuclease assay (Taqman). The prevalence of the homozygous ACE II genotype was significantly higher in patients with early-onset psoriasis than among control subjects (30.9% vs 19.2%, P = 0.016), yielding an odds ratio of 1.88 [95% confidence interval (CI): 1.12-3.15] for early-onset disease. For late-onset psoriasis, presence of the ACE II genotype was associated with a non-significant odds ratio 1.54 (95% CI: 0.81-2.92). As for the EDN1 -134 3A/4A gene polymorphism, no significant differences in genotype distributions were found between patients with either early- or late-onset psoriasis and control subjects (EDN1 -134 4A/4A: 9.6% in early-onset and 5.6% late-onset psoriasis vs 7.7% in controls; P > 0.05). Our data suggest that homozygosity for the ACE I allele may affect susceptibility to early-onset psoriasis.

Bathing Practices and Emollient Use among Psoriasis Patients

The following submission is a brief report of a recently conducted survey on the bathing practices of people with psoriasis. The scope of the survey was to discover what practices psoriasis patients have adopted in caring for their skin as compared to controls. An Institutional Review Board (IRB)-approved survey was conducted in conjunction with the National Psoriasis Foundation National Conference, which took place Aug. 5–7, 2005, in Boston, Mass. Subjects reported their frequency of bathing, the amount of pain they experienced when bathing and showering, and whether or not they applied moisturizer on a daily basis. Psoriasis subjects were also asked to rate the severity of their psoriasis. Significant differences were found in people reporting pain with showering in the psoriasis group as compared with controls, and psoriasis respondents preferred cooler water temperatures when bathing. Both of these findings correlated with disease severity. Further, psoriasis subjects were found to use moisturizers more frequently and avoid the use of harsher products such as exfoliators when compared to controls. The findings of this survey suggest that the bathing practices of psoriasis patients are affected by their skin condition. In addition, daily pain associated with showering may negatively impact a patient's quality of life. The results of this research suggest that increased efforts should be made to evaluate pain severity and other affected aspects of caring for skin in this patient population.

Circulating levels of brain‐derived neurotrophic factor correlate with disease severity in the intrinsic type of atopic dermatitis

Recent studies have shed light on the complex regulation of genetic, environmental, immunologic and pharmacologic factors, which contribute to the development of atopic dermatitis (AD). However, it is still unclear to which extent neuroimmune mediators have a role in AD. To assess peripheral neurotrophin levels and their correlation with scoring atopic dermatitis (SCORAD) scores in both the intrinsic and extrinsic types of AD compared with patients with psoriasis and nonatopic healthy subjects. Levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were assessed in peripheral blood with enzyme-linked immunosorbent assay. Based on IgE-mediated sensitization, AD was divided into the extrinsic and intrinsic type. Severity of AD was assessed with SCORAD score and with psoriasis area and severity index (PASI) in patients with psoriasis. Brain-derived neurotrophic factor and NGF were detectable in all the subjects studied. However, the levels of both neurotrophins were significantly higher in patients with extrinsic and intrinsic types of AD compared with patients with psoriasis and nonatopic healthy subjects (NGF: P < 0.001, BDNF: P < 0.001). NGF and BDNF levels were similar in the intrinsic and extrinsic type of AD. There was a significant correlation between BDNF and SCORAD score only in patients with the intrinsic type of AD (r = 0.57, P < 0.05). This study shows for the first time that NGF and BDNF are increased in both, the extrinsic type and the intrinsic type of AD. This finding points to a similar pathophysiologic background implicating a neuroimmune network in both variants of this chronic inflammatory skin disease. Future studies are needed to show the direct mechanisms of neurotrophin action in chronic inflammatory skin.

Expression of Neutrophil Chemoattractants and their Receptors in Subjects with Atopic Dermatitis and Psoriasis

RATIONALE: Despite colonization with microbes, the skin of atopic dermatitis (AD) subjects is characterized by the lack of neutrophils in contrast to psoriasis.METHODS: Peripheral blood neutrophils and biopsies were obtained from 4 AD, 4 psoriasis subjects and 4 controls. The expression of neutrophil chemoattractans (IL-8, GRO-alpha and MIP-1alpha) was assessed by Real-time PCR. Neutrophils were analyzed by dual-color flow cytometry (CD16) for expression of receptors relevant for cell migration: CCR1, CXCR1, CXCR2, C3a receptor®, C5aR, C3bR, FMLPR, PAFR and CRTH2(DP2).RESULTS: IL-8, GRO-alpha and MIP-1alpha mRNA was highly expressed in the skin of AD (71-fold, 40-fold and 10-fold; respectively) and psoriasis subjects (96-fold, 42-fold and 5-fold; respectively) compared to controls. No difference between groups was observed for any of the receptors except CRTH2 and PAFR. CRTH2 - thought to identify Th2-lymphocytes was detected on neutrophils of controls and psoriasis (netMFI 24±;7 and 46±;11; respectively) in contrast to AD subjects who expressed little to no CRTH2 (netMFI 1±;0.4, p<0.05). PAFR showed a tendency toward higher expression in psoriatics (netMFI 27±;7) compared to controls (netMFI 8±;1) and AD subjects (netMFI 11±;1).CONCLUSIONS: Despite the lack of neutrophils in AD, IL-8, GRO-alpha and MIP-1alpha were markedly increased in AD skin. Their receptors were equally expressed across subject groups. Unexpectedly, CRTH2 was expressed on neutrophils from controls and psoriasis but not AD subjects. The relevance of this finding and that of PAFR will be the focus of future experiments. This preliminary work suggests that the lack of neutrophils in AD is due at least in part to the lack of priming. RATIONALE: Despite colonization with microbes, the skin of atopic dermatitis (AD) subjects is characterized by the lack of neutrophils in contrast to psoriasis. METHODS: Peripheral blood neutrophils and biopsies were obtained from 4 AD, 4 psoriasis subjects and 4 controls. The expression of neutrophil chemoattractans (IL-8, GRO-alpha and MIP-1alpha) was assessed by Real-time PCR. Neutrophils were analyzed by dual-color flow cytometry (CD16) for expression of receptors relevant for cell migration: CCR1, CXCR1, CXCR2, C3a receptor®, C5aR, C3bR, FMLPR, PAFR and CRTH2(DP2). RESULTS: IL-8, GRO-alpha and MIP-1alpha mRNA was highly expressed in the skin of AD (71-fold, 40-fold and 10-fold; respectively) and psoriasis subjects (96-fold, 42-fold and 5-fold; respectively) compared to controls. No difference between groups was observed for any of the receptors except CRTH2 and PAFR. CRTH2 - thought to identify Th2-lymphocytes was detected on neutrophils of controls and psoriasis (netMFI 24±;7 and 46±;11; respectively) in contrast to AD subjects who expressed little to no CRTH2 (netMFI 1±;0.4, p<0.05). PAFR showed a tendency toward higher expression in psoriatics (netMFI 27±;7) compared to controls (netMFI 8±;1) and AD subjects (netMFI 11±;1). CONCLUSIONS: Despite the lack of neutrophils in AD, IL-8, GRO-alpha and MIP-1alpha were markedly increased in AD skin. Their receptors were equally expressed across subject groups. Unexpectedly, CRTH2 was expressed on neutrophils from controls and psoriasis but not AD subjects. The relevance of this finding and that of PAFR will be the focus of future experiments. This preliminary work suggests that the lack of neutrophils in AD is due at least in part to the lack of priming.

Population Pharmacokinetics of Efalizumab (Humanized Monoclonal Anti‐CD11a Antibody) Following Long‐Term Subcutaneous Weekly Dosing in Psoriasis Subjects

The population pharmacokinetics of efalizumab was characterized in patients with moderate to severe plaque psoriasis. The study included 1088 subjects who received 1 or 2 mg/kg/wk subcutaneous efalizumab for 12 weeks from a phase I (64 subjects) and 3 phase III studies with day 42 and/or day 84 trough levels (1024 patients). Due to the limitation of the data, a 1-compartment model with first-order absorption and elimination was used to fit the data. The population means for V/F, Ka, and CL/F were 9.13 L, 0.191 day(-1), and 1.29 L/d, respectively, for a typical subject receiving a 1-mg/kg dose. Interindividual variability in CL/F was 48.2%. Body weight has the largest influence on CL/F. Other covariates (obesity, baseline lymphocyte counts, Psoriasis Area and Severity Index score, and age) had only modest effects. Subjects in the 2-mg/kg dose group had a 24.0% lower CL/F, consistent with nonlinear pharmacokinetics of efalizumab. The results of this analysis support the current body weight-adjusted dosing strategy.

CARD15: a Pleiotropic Autoimmune Gene That Confers Susceptibility to Psoriatic Arthritis

A recent genomewide scan in psoriatic arthritis (PsA) revealed a susceptibility locus at 16q. This region overlaps CARD15, a susceptibility gene in Crohn disease. The possibility of a common susceptibility gene between PsA and Crohn disease is further supported by epidemiological studies that note an increased incidence of psoriasis in subjects with Crohn. We screened 187 patients with PsA and 136 healthy controls, all from Newfoundland, for the three common, independent sequence variants of CARD15 (R702W, leu1007fsinsC, and G908R), which were detected by polymerase chain reaction by use of allele-specific primers and visualized through gel electrophoresis. In total, 53/187 (28.3%) probands with PsA had at least one variant of the CARD15 gene, compared with 16/136 (11.8%) controls (odds ratio 2.97; 95% confidence interval 1.61-5.47; P=.0005). Allele frequencies of R702W, leu1007fsinsC, and G908R were 10.43%, 3.21%, and 1.61%, respectively, in patients with PsA, compared with 3.31%, 2.57%, and 0.37%, respectively, in the control patients. CARD15 conferred susceptibility to PsA independent of HLA-Cw*0602. Thus, CARD15 represents a pleiotropic autoimmune gene and is the first non-MHC gene to be associated with PsA.