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Biomedical subjects

Christopher E M Griffiths

Publications and source records attributed to Christopher E M Griffiths.

At least 19 recordsLinked to original sources
PubMed2006

Impaired Langerhans cell migration in psoriasis.

We have examined whether psoriasis is associated with systemic effects on epidermal Langerhans cell (LC) function and, specifically, the migration of LCs from the skin. Compared with normal skin, the frequency and morphology of epidermal LCs in uninvolved skin from patients with psoriasis was normal. However, mobilization of these cells in response to stimuli that normally induce migration (chemical allergen, tumor necrosis factor alpha [TNF-alpha], and interleukin-1beta [IL-1beta]) was largely absent, despite the fact that treatment with TNF-alpha and IL-1beta was associated with comparable inflammatory reactions in patients and controls. The failure of LC migration from uninvolved skin was not attributable to altered expression of receptors for IL-1beta or TNF-alpha that are required for mobilization, nor was there an association with induced cutaneous cytokine expression. Although a role for altered dynamics of LC migration/turnover has not been formally excluded, these data reveal a very consistent decrement of LC function in psoriasis that may play a decisive role in disease pathogenesis.

Adolescent↗
PubMed2006

Interaction between genetic control of vascular endothelial growth factor production and retinoid responsiveness in psoriasis.

Vascular endothelial growth factor (VEGF) promotes angiogenesis, and elevated levels are found in plaques of psoriasis. Two VEGF polymorphisms, +405 and -460, are associated with early-onset psoriasis and are close to the functional activator protein-1 site (+419) through which retinoids, an established systemic therapy for psoriasis, can block production of VEGF. We report that peripheral blood mononuclear cells (PBMCs) and epidermal keratinocytes (KC) from patients with psoriasis demonstrate differential, genotype-dependent, regulation of VEGF. For PBMCs, VEGF genotype distinguishes two groups of patients with psoriasis - "high and low VEGF producers" (P < 0.001). In contrast, KC production of VEGF is not genotype dependent. However, the effects of all-trans retinoic acid (RA) on cellular expression of VEGF are determined by both cell type and genotype. RA inhibits KC production of VEGF in a genotype-dependent manner (P < 0.005) whereas RA stimulates PBMCs production irrespective of VEGF genotype (P < 0.001). We also report that the -460 VEGF polymorphism appears to have a clinical pharmacogenetic role in predicting response or non-response of psoriasis to acitretin (P = 0.01). In future, determination of VEGF gene polymorphisms and thus individual patient VEGF "signatures" may be used as a prognostic factor for psoriasis susceptibility/severity and as a means for optimizing treatment response.

Acitretin↗
PubMed2006

A randomized, investigator-masked clinical evaluation of the efficacy and safety of clobetasol propionate 0.05% shampoo and tar blend 1% shampoo in the treatment of moderate to severe scalp psoriasis.

The clinical benefit of currently available tar blend shampoos for the treatment of scalp psoriasis is restricted due to their limited efficacy, low cosmetic appeal and potential for carcinogenicity. This 4-week multicentre, randomized, parallel-group, investigator-masked study included 162 subjects and aimed to compare the efficacy, safety and cosmetic acceptability of clobetasol propionate 0.05% shampoo versus a currently marketed tar blend 1% shampoo in subjects with moderate to severe scalp psoriasis. Clobetasol propionate shampoo was superior to tar blend shampoo with respect to all efficacy variables tested (p<0.001): Total and Global Severity Score; erythema; plaque thickening; desquamation; pruritus; total scalp area involved; and the subject's global assessment of clinical improvement. Both treatments were safe and well-tolerated. Furthermore, more subjects indicated that clobetasol propionate shampoo was more cosmetically acceptable than tar blend shampoo. Clobetasol propionate 0.05% shampoo is a good alternative to tar blend shampoo in the treatment of moderate to severe scalp psoriasis.

Administration, Cutaneous↗
PubMed2006

The CX3CL1-CX3CR1 system and psoriasis.

CX3CL1 is a chemoattractant and adhesion molecule that induces the redistribution of CX3CR1-positive inflammatory leucocytes to sites of inflammation. As a consequence of their increased expression in plaques of psoriasis, and location within genomic regions previously linked to this disease, CX3CL1, and its receptor CX3CR1, represent attractive positional and functional 'psoriasis susceptibility genes'. To investigate the CX3CL1-CX3CR1 system in psoriasis, eight single nucleotide polymorphisms (SNPs) in CX3CL1 and two SNPs in CX3CR1 were genotyped in 281 psoriasis patients and 184 unrelated controls. Allele, genotype and estimated haplotype frequencies were then compared between experimental groups. Allele frequency differences between healthy volunteers and psoriasis patients revealed associations with two CX3CR1 SNPs (hCV11578468, P = 0.03 and c_5687_1, P = 0.04). No associations were observed between CX3CL1 SNPs and psoriasis. These results support a role for the CX3CL1-CX3CR1 system in the pathogenesis of psoriasis and identify SNPs within the chemokine receptors that are associated with the disease.

Adult↗
PubMed2006

Infliximab for the treatment of psoriasis.

Psoriasis is a common immune-mediated skin disease producing significant morbidity. Tumour necrosis factor (TNF)-alpha, a pro-inflammatory cytokine, plays a key role in the cutaneous inflammation characteristic of psoriasis. Infliximab is a chimeric monoclonal antibody that specifically binds to TNF-alpha, thereby blocking its biological activity. Data from Phase II and III studies indicate that infliximab is a highly effective, rapidly acting systemic therapy for patients with moderate-to-severe psoriasis. Regular 8-weekly infusions of infliximab maintain significant clinical improvement in the majority of patients for at least 1 year. Infliximab is generally well tolerated, but patients may be susceptible to infection and malignancy.

Adult↗
PubMed2005

Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene.

OBJECTIVE: The protein tyrosine phosphatase N22 (PTPN22) gene exhibits regulatory activities for both T cells and B cells. A missense single-nucleotide polymorphism (SNP) within this gene (rs2476601) has recently been associated with 4 autoimmune diseases: rheumatoid arthritis (RA), systemic lupus erythematosus, autoimmune thyroid disease, and type 1 diabetes mellitus, all of which are T cell-mediated and associated with the elaboration of autoantibody. The aim of this study was to investigate associations of the missense SNP of PTPN22 in a number of autoimmune diseases in the UK population, including RA, juvenile idiopathic arthritis (JIA), psoriasis, psoriatic arthritis (PsA), and multiple sclerosis (MS), some of which have not been examined previously. METHODS: The PTPN22 missense SNP was genotyped in 886 RA, 661 JIA, 279 psoriasis, 455 PsA, and 379 MS patients and in 595 healthy controls. Association with the PTPN22 SNP was analyzed by chi-square test as implemented in Stata software. RESULTS: There was a significant association between the PTPN22 SNP and RA (P = 1.8 x 10(-8)) and JIA (P = 0.0005). In contrast, no association with psoriasis, PsA, or MS was detected. CONCLUSION: We replicated the findings of a previous association with RA and identified a novel association with JIA. Together with previous data showing associations with other autoimmune diseases, our findings provide further evidence that the PTPN22 gene plays a role in the pathogenesis of a subgroup of autoimmune diseases.

Adult↗
PubMed2005

Evidence for common genetic control in pathways of inflammation for Crohn's disease and psoriatic arthritis.

OBJECTIVE: Clinical, pharmacologic, and epidemiologic evidence supports the hypothesis that common genetic pathways may underlie inflammatory diseases. In a previous study, a Crohn's disease gene, CARD15, was demonstrated to be associated with psoriatic arthritis (PsA). Recently, a functional haplotype of 2 single-nucleotide polymorphisms (SNPs) mapping to the organic cation transporter (OCTN) genes, SLC22A4 and SLC22A5, was identified as a second Crohn's disease susceptibility locus. The SLC22A4 gene has also been associated with rheumatoid arthritis. This study was undertaken to further elucidate associations of PsA with Crohn's disease susceptibility genes. METHODS: Association with CARD15 and OCTN was investigated in UK Caucasian patients with PsA (n = 472) and population controls (n = 594), using 5' allelic discrimination assays (TaqMan). Two SNPs in OCTN, forming a haplotype previously associated with Crohn's disease, were also tested in patients with psoriasis (n = 218) and patients with early undifferentiated inflammatory arthritis (n = 386). Allele and estimated haplotype frequencies were compared between patients and controls. RESULTS: No association of PsA with CARD15 was detected. In contrast, a functional SNP mapping to the promoter region of SLC22A5 (rs2631367) was associated with PsA (for CC versus GG, odds ratio 1.65, 95% confidence interval 1.13-2.41, uncorrected P = 0.005). In addition, the haplotype associated with Crohn's disease was also associated with PsA (P = 0.001). No association was detected in the cohort with psoriasis alone or in the cohort with undifferentiated inflammatory arthritis. CONCLUSION: The OCTN haplotype previously associated with Crohn's disease is also associated with PsA, suggesting that these 2 diseases may share some common genetic control in pathways of inflammation.

Adolescent↗
PubMed2005

Psychologic factors in psoriasis: consequences, mechanisms, and interventions.

The article examines the English-language research literature concerning psychologic aspects of psoriasis published since 1995. The literature is concerned with (1) the consequences of psoriasis in terms of quality of life, disability, depression, anxiety, and stigmatization and factors that may predict such outcomes; (2) potential mechanisms of the interaction between psychologic factors, stress, and the pathophysiology of psoriasis; and (3) examination of the clinical utility of psychologic interventions on extent of psoriasis and psychologic distress. The implications of the findings are discussed with reference to future directions for research and practice.

Humans↗
PubMed2005

Associations between ultraviolet radiation, basal cell carcinoma site and histology, host characteristics, and rate of development of further tumors.

BACKGROUND: Patients with basal cell carcinoma (BCC) frequently develop further tumors during follow-up. OBJECTIVE: We sought to elucidate the relative effects of pattern of ultraviolet radiation exposure, and site and histologic type of the first tumor, on the rate of increase in BCC numbers. METHODS: We used negative binomial regression analysis to study the association of selected variables on the rate of increase in BCC numbers in 266 Caucasian patients who first presented with a tumor on the head/neck or trunk with nodular or superficial histology. RESULTS: Patients with an initial truncal BCC with superficial histology demonstrated significantly faster increases in BCC numbers than did patients with other site and histology combinations. CONCLUSIONS: These data indicate that site and histology define subsets of patients with BCC.

Aged↗
PubMed2005

Alexithymia in patients with psoriasis: clinical correlates and psychometric properties of the Toronto Alexithymia Scale-20.

OBJECTIVE: The objective of this study was to examine the psychometric properties and clinical correlates of the 20-item Toronto Alexithymia Scale (TAS-20) in patients with psoriasis. METHODS: Three hundred patients with psoriasis completed the TAS-20 and had the severity of their psoriasis clinically assessed. Test-retest reliability was assessed over 10 weeks in a subset of 71 patients receiving standard medical treatment for their psoriasis. Examination of the factor structure employed both exploratory (EFA) and confirmatory (CFA) factor analysis techniques. RESULTS: The overall prevalence of alexithymia in this population of psoriasis patients, as indicated by the TAS-20, was 33%. The TAS-20 total score was not related to clinical severity, age, age at onset or duration of psoriasis. The 10-week test-retest reliability on a sample of 71 psoriasis patients, pre- and posttreatment with photochemotherapy, was found to be acceptable (r=.69; P<.001). EFA produced no stable solutions. The three-factor structure of the TAS-20 using CFA was also not replicable in this sample. CONCLUSIONS: The findings of this study support the contention that alexithymia is not significantly influenced by either disease severity or chronicity in patients with psoriasis. It is recommended that when employing the TAS-20 in patients with psoriasis, caution is exercised in the interpretation of the scale scores and that further psychometric evaluation of the scale is undertaken as appropriate.

Adolescent↗
PubMed2005

Optimal management of severe plaque form of psoriasis.

Psoriasis is a chronic, inflammatory, hyperproliferative skin disease that affects 1-2% of the general population in the UK and US. Plaque psoriasis is the most common form, accounting for approximately 90% of cases. The disease is usually chronic and persistent, although up to 50% of patients may enter spontaneous remission for varying periods of time. There is no cure for psoriasis; therefore, the aim of treatment is to minimize the extent and severity of the disease to the point at which it no longer substantially disrupts the patient's quality of life. First-line therapy of psoriasis usually consists of topical agents, such as emollients, tar, dithranol, and vitamin D3 analogs. In cases of severe, extensive psoriasis, where topical therapy is either impractical or not sufficiently effective, systemic treatment may be warranted at the outset. In these circumstances, the therapeutic options include: (i) intensive inpatient or day center topical therapy; (ii) phototherapy; and/or (iii) systemic agents. There are now a number of systemic agents available for the treatment of severe psoriasis, but all have potential adverse effects. We review the current treatment options, which include the use of phototherapy and systemic agents, and provide recommendations on their use in clinical practice. Importantly, treatment should be tailored to each individual patient depending on concurrent medical problems (which might preclude certain agents), patient choice and acceptance of the risk of adverse effects.

Administration, Oral↗
PubMed2004

Associations between UVR exposure and basal cell carcinoma site and histology.

While sunlight is critical in basal cell carcinoma (BCC) pathogenesis the relationship between exposure and tumor site and histology is unclear. We determined if tumor site (trunk or head/neck) or histology (nodular or superficial) is determined by exposure pattern. In 66 cases with truncal and 362 patients with head/neck BCC at first presentation, average hours exposure/year, intermittency score, childhood sunburning and skin type were not significantly associated with tumor site or histology. However, often sunbathing was associated with a five-fold increased risk of truncal BCC. Average sunbathing score was significantly greater in 22 cases with truncal compared with 325 cases with head/neck nodular tumors and also in 44 cases with superficial truncal compared with superficial head/neck BCC. Thus, sunbathing determined tumor site but not histology.

Abdomen↗
PubMed2004

Psoriasis: future research needs and goals for the twenty-first century.

Psoriasis research is entering a new era. Progress in delineating immunogenetics and pathomechanisms of disease brings with it a need to understand fully the clinical spectrum of disease and integrate phenotype with genomics and proteomics. Involvement of patient groups and an understanding of the psychosocial aspects of psoriasis, particularly its significant impairment of quality of life, are keys to progress. The biologic revolution in therapy of inflammatory disease has embraced psoriasis bringing with it an urgent need for evidence-base, consensus on outcome measures, and long-term real-life studies.A concerted effort between academia, industry, and patients will take forward the understanding of, and therapy for, psoriasis.

Combined Modality Therapy↗
PubMed2004

Retinoic acid receptor alpha expression and cutaneous ageing.

Intrinsic ageing of human skin is a subtle and gradual process that demonstrates few clinical or histological features until old age (>70 years). Initial work indicates that aged skin is "retinoid sensitive" but there is little data on the role of retinoic acid receptors (RARs) or retinoid X receptors (RXRs) in skin ageing. As nuclear retinoid receptors have been implicated in ageing in rodents, we studied the distribution of these receptors in intrinsically aged as compared to young, photoprotected human skin. We found that intrinsic ageing of skin in vivo is accompanied by significant increases of RAR alpha mRNA and protein whereas other isoforms show no alteration with age. In vitro transfection of COS-1 cells with the RAR alpha gene induces expression of matrix metalloproteinase-1 (MMP-1), an enzyme known to play an active role in remodelling of the dermis in intrinsically aged and photoaged skin. Furthermore, addition of all-trans retinoic acid (RA) to cultures of RAR alpha-transfected COS-1 cells diminishes RAR alpha and returns levels of MMP-1 to those approaching baseline. These results demonstrate that intrinsic ageing of human skin is accompanied by significant elevation in the content of RAR alpha and that over-expression of RAR alpha influences expression of MMP-1, an important mediator of skin ageing.

Adult↗
PubMed2004

The impact of psychological and clinical factors on quality of life in individuals with atopic dermatitis.

OBJECTIVE: The aim of the study was to assess the influence of general and dermatitis-specific psychological and clinical factors on quality of life in adults with atopic dermatitis (AD). METHOD: A total of 125 adults recruited through the National Eczema Society of U.K. (NES) completed a number of psychological and dermatological questionnaires, including the Dermatology Life Quality Index (DLQI), the Stigmatisation and Eczema Questionnaire (SEQ), the Hospital Anxiety and Depression Scale (HADS), the Fear of Negative Evaluation Scale (FNE) and the Rosenberg Self-Esteem Scale (RSE). RESULTS: Pearson's correlational analyses suggested that perceptions of stigma were significantly associated with psychological factors as well as quality of life (Ps<.01). An association was also found between perceived stigma and disease severity (-.28, P<.01). Almost 46% of participants were identified as having probable mood disorder. Regression analysis indicated that perceptions of stigma and depression accounted for 44.5% of the variance in quality of life in this sample [F(3,121)=34.18, P<.001], when disease severity was controlled for. CONCLUSION: Psychological factors and disease severity were strong predictors of quality of life in adults with AD. AD-related perceptions of stigma were of particular importance in predicting AD-related quality of life over and above more general psychological factors, such as depression. These findings have important implications for the psychological and clinical management of AD.

Adult↗