Psoriasis: McHugh N

Kyle S, Chandler D, Griffiths CE, Helliwell P, Lewis J, McInnes I, Oliver S, Symmons D, McHugh N, Anonymous00081. · Royal National Hospital for Rheumatic Diseases, Upper Borough Wells, Bath, BA1 IRL, UK. · Rheumatology (Oxford). · Pubmed #15695305 links to  free full text

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Korendowych E, McHugh N. · Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, BA1 1RL Bath, United Kingdom. · Curr Rheumatol Rep. · Pubmed #16045834 No free full text.

Abstract: The genetic factors that are associated with psoriatic arthritis (PsA) are intricately linked with those that predispose to psoriasis itself. The strongest association is with human leukocyte antigen-Cw*0602, although true susceptibility may lie with one of the neighboring genes along a disease-associated haplotype. There are a number of interesting candidate genes within the major histocompatibility complex (MHC) region with strong functional relevance that have been investigated in PsA. In addition, several areas outside the MHC complex have been highlighted as a result of genetic linkage studies in psoriasis. PsA is a complex, multifactorial disease where multiple genes are likely to influence disease susceptibility, severity, and clinical phenotype. The current evidence for genetic factors in psoriasis and PsA will be reviewed.

Symmons DP, Lunt M, Watkins G, Helliwell P, Jones S, McHugh N, Veale D. · ARC Epidemiology Unit, University of Manchester, United Kingdom. · J Rheumatol. · Pubmed #16463433 No free full text.

Abstract: OBJECTIVE: The study of psoriatic arthritis (PsA) is hampered by the absence of a widely accepted, validated case definition. We investigated whether the physician's opinion can be used as a gold standard when developing classification criteria for peripheral joint PsA. METHODS: UK rheumatologists who had published on PsA and attendees at 3 international meetings on PsA held in the UK were polled by questionnaire. There were 3 phases. The first questionnaire asked whether rheumatologists believed in the construct of PsA. The second survey developed a list of features thought to distinguish patients with PsA from other forms of peripheral arthritis. The final phase was development of a series of 61 "paper" patients with various combinations of the features of PsA. The paper patients were assessed by 15 rheumatologists who were asked whether, in their opinion, the patient had PsA. Latent class analysis was used to identify subgroups of patients and cross-tabulations were used to identify which clinical and laboratory features were associated with each subgroup. RESULTS: Rheumatologists agreed on the construct of PsA and that not all patients with psoriasis and an inflammatory polyarthritis have PsA. Latent class analysis identified 3 classes, corresponding to definite PsA; a middle group that was very likely to be given a diagnosis of PsA by some rheumatologists (high diagnosers), but unlikely to be given the diagnosis by others (low diagnosers); and a third group corresponding to "probably not PsA." CONCLUSION: For the group of patients with "definite PsA" the physician's opinion can be taken as the gold standard when developing classification criteria. However, for patients in the "middle group" there will always be disagreement with the gold standard whether the standard is based on the opinion of the high diagnosers or the low diagnosers.

Korendowych E, Owen P, Ravindran J, Carmichael C, McHugh N. · Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK. · Rheumatology (Oxford). · Pubmed #15901902 links to  free full text

Abstract: OBJECTIVES: Antibodies recognizing a cyclic citrullinated peptide (anti-CCP) are highly specific for rheumatoid arthritis (RA) but their role in psoriatic arthritis (PsA) remains unclear. The aim of this study was therefore to investigate the prevalence of anti-CCP antibodies in PsA and assess their clinical and genetic associations. METHODS: One hundred and twenty-six patients with PsA, 40 patients with seropositive RA and 40 controls were tested for the presence of anti-CCP antibodies, rheumatoid factor (RF) and the HLA-DRB1 shared epitope. Clinical and radiological data were collected prospectively on all patients and compared between anti-CCP-positive and -negative patients. RESULTS: Seven (5.6%) patients with PsA were positive for anti-CCP antibodies compared with 0% of controls and 97% of patients with seropositive RA. The presence of anti-CCP antibodies in PsA was significantly associated with the HLA-DRB1 shared epitope (P<0.005), erosive disease (P<0.05), number of swollen joints (P<0.02) and DMARD use (P<0.05). CONCLUSIONS: Overall, the increased prevalence of anti-CCP antibodies in this PsA population failed to reach statistical significance. However, when present, they were a marker of disease severity and had RA-linked MHC class II associations. Further studies are needed in a larger population of patients with PsA and appropriate controls to confirm any true association that may be present.

Ravindran JS, Owen P, Lagan A, Lewis J, Korendowych E, Welsh K, McHugh N. · Royal National Hospital for Rheumatic Diseases, Bath, UK. · Rheumatology (Oxford). · Pubmed #12890860 links to  free full text

Abstract: OBJECTIVES: To investigate polymorphisms of interleukin (IL) 1alpha, IL-1beta and IL-1 receptor R1 genes in patients with psoriatic arthritis (PsA), their relationship to the age of onset of psoriasis and the pattern of joint involvement. METHODS: One hundred and forty well-characterized patients with PsA were studied. One hundred healthy controls were recruited from primary care. All were genotyped for single-nucleotide polymorphisms in the genes for IL-1alpha (position -889), IL-1beta (position +3953) and IL-1R1 (position +970). The frequencies of the respective variants were compared between patients and controls and in relation to age of onset of psoriasis, to clinical subsets of the disease and to the presence of erosions. RESULTS: All three polymorphisms were in Hardy-Weinberg equilibrium in both patients and controls. The frequency of IL-1alpha -889 CC homozygotes was significantly increased in PsA patients compared with normal controls [58 vs 40%, odds ratio (OR) 2.06, 95%, confidence interval (CI) 1.22-3.47]. The frequency of the IL-1alpha -889 C allele was significantly increased in PsA patients compared with controls (75 vs 65%, OR 1.65, 95% CI 1.11-2.45). In subset analysis there were no other significant differences in allelic frequencies for the IL-1alpha -889 C/T, IL-1beta +3953 C/T and IL-1R1 +970 C/T polymorphisms. CONCLUSIONS: The IL-1 gene complex may play a role in the development of PsA and/or psoriasis or act as a marker for other genes on chromosome 2q12 to 2q13.

Korendowych E, Dixey J, Cox B, Jones S, McHugh N. · Royal National Hospital for Rheumatic Diseases and Bath Institute for Rheumatic Diseases, England. · J Rheumatol. · Pubmed #12508396 No free full text.

Abstract: OBJECTIVE: To investigate the associations of the HLA-DRB1 rheumatoid arthritis shared epitope (SE) with clinical characteristics and radiological outcome in patients with psoriatic arthritis (PsA). METHODS: One hundred fifty-eight patients with well documented PsA and 250 controls were typed for HLA-DRB1 alleles including the SE by polymerase chain reaction. Clinical data collected on the patient group included disease subset, swollen and tender joint counts, the psoriasis area severity index (PASI), and the presence of radiological erosions. Clinical and radiological associations with HLA-DRB1 and SE alleles were determined. RESULTS: There was an increased frequency of HLA-DR7 (41 vs 25%; puncorr = 0.001, OR 2.02, pcorr = 0.01) and a decreased frequency of HLA-DR2 (19 vs 28%; puncorr = 0.03, OR 0.59, pcorr = 0.3) in the patient population compared with controls. There was no significant difference in the frequency of HLA-DR1 and HLA-DR4 between patient and control populations. There was no significant difference in the prevalence of SE alleles between the patient and control populations (48 vs 54%). There was no increase in the prevalence of the SE in the polyarthritis subgroup, but there was a marginal decrease in those who remained in the oligoarthritis subgroup. There were no differences with respect to sex, age of onset of disease, family history, Health Assessment Questionnaire score, joint score, skin score, or nail score between those patients who were SE positive and those who were SE negative. However, significantly more patients who were SE positive developed radiological erosions (60 vs 43%; p = 0.03, OR 2.11). CONCLUSION: Overall, the prevalence of the SE in patients with PsA did not differ from our control population. However, it was overrepresented in those who developed radiological erosions. It is possible that the SE does have a role in the clinical severity of PsA.

Al-Heresh AM, Proctor J, Jones SM, Dixey J, Cox B, Welsh K, McHugh N. · Royal National Hospital for Rheumatic Diseases and Department of Medical Sciences, University of Bath, Bath, UK. · Rheumatology (Oxford). · Pubmed #12011375 links to  free full text

Abstract: OBJECTIVES: To investigate polymorphisms in the genes for tumour necrosis factor alpha (TNFA), interleukin 10 (IL10) and tumour necrosis factor receptor II (TNFRII) in patients with psoriatic arthritis (PsA) and their relationship to the HLA-Cw*0602 allele and to the ages at onset of psoriasis and arthritis and the pattern of joint involvement. METHODS: One hundred and twenty-four well-characterized patients with PsA were studied. Controls were 101 cadaveric organ donors. All were genotyped for single-nucleotide polymorphisms in TNFA (positions -308, -238, +488), IL10 (-1082, -819, -592) and in the 3'-untranslated region of TNFRII (+1663, +1668, +1690). The HLA-Cw*0602 allele was detected by polymerase chain reaction-based techniques. The frequencies of the respective variants were compared between patients and controls and in relation to the ages at onset of psoriasis and arthritis, to clinical subsets of the disease and to the presence of erosions. RESULTS: HLA-Cw*0602 was significantly increased in frequency in PsA (40 vs 26%; P<0.05) and was associated with younger age of onset of psoriasis (P<0.05). There was no significant increase in any of the polymorphisms studied within TNFA, IL10 or TNFRII in the total PsA group. Although the frequency of TNFA allele -238A was not increased in the total PsA group or in patients with a younger age of onset of psoriasis, TNFA allele -238A was absent in the spondyloarthritis group and increased in frequency in patients with peripheral polyarthritis. However, these latter findings could be explained by linkage disequilibrium as all TNFA -238A alleles (23/23) in patients with PsA were HLA-Cw*0602-positive (P<0.0001). CONCLUSIONS: An association between young age of onset of psoriasis and HLA-Cw*0602 is confirmed in patients with PsA. The uncommon TNFA -238A allele is strongly linked to HLA-Cw*0602 and as such is associated with the development of peripheral polyarthritis rather than spondylitis. Further investigation of possible HLA-Cw*0602 linked genes in PsA is warranted.