Occupational allergic contact dermatitis from methylchloroisothiazolinone and methylisothiazolinone (MCI/MI) in a silicone-emulsion lock lubricant.
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Biomedical subjects
Publications and source records attributed to B Kirby.
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BACKGROUND: Cytokine production is under genetic control, and certain allelic variants of cytokine genes are associated with higher or lower cytokine production in vitro and in vivo. Psoriasis is associated with an overexpression in the involved skin of T-helper cell type 1 (Th1) cytokines, e.g. interferon (IFN) -gamma and tumour necrosis factor (TNF) alpha and relative underexpression of Th2 cytokines, e.g. interleukin (IL) -4 and IL-10. Objective We investigated the hypothesis that allelic variants of genes for a high production of Th1 cytokines or TNF-alpha, or conversely low production of Th2 cytokines might represent a risk factor for developing psoriasis. METHODS: Genotyping for IFN-gamma, IL-10, IL-4 and TNF-alpha was undertaken for 84 patients with psoriasis and compared with control data on file. RESULTS: Genotype frequencies showed no differences between patients and controls for IFN-gamma, TNF-alpha or IL-4. For IL-10, patients with late onset psoriasis (over 40 years) were more likely to be heterozygous at position - 1082 (P = 0.02), corresponding to intermediate production of IL-10 in vitro and in vivo. CONCLUSIONS: Psoriasis is not determined by a genotype consistent with high production of Th1 cytokines or low production of Th2 cytokines. Thus, the Th1 cytokine profile found in psoriatic plaques is most likely a consequence of local factors.
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The aetiology of psoriasis is still unclear but our knowledge of the psoriatic process has grown substantially over the last two decades. The future will undoubtedly bring advances in our understanding of the pathogenesis of psoriasis and, as a consequence, new therapies. Defining the molecular genetics of psoriasis will enhance our understanding of the disease process and hopefully facilitate the development of a representative animal model. This in itself will be a key step in the development and testing of new therapies. Precise identification of the immunological events involved in psoriasis will allow specific T-cell- and cytokine-targeted, and perhaps less toxic. immunotherapies. Anti-angiogenic agents that are in development for use in oncology may also be effective in psoriasis. The adaptation of current topical therapies such as retinoids and vitamin D analogues to produce more effective and better-tolerated formulations will also play a significant role in our future first-line management of patients. The increased recognition and better management of environmental trigger factors such as psychological distress will become an important factor in future psoriasis care. The development of physical therapies including photodynamic therapy and excimer lasers has the potential to expand the remit of psoriasis therapy. There is little doubt that the future for our patients with psoriasis is bright. However, this will only be achievable by a concerted research effort to understand all facets of this enigmatic disease ranging from the molecular to the environmental.
Plaques of psoriasis contain increased levels of cytokines, including tumour necrosis factor-alpha (TNF-alpha), which are thought to be essential to the maintenance of the psoriatic process. We report the successful treatment of severe, recalcitrant psoriasis when infliximab (a monoclonal antibody to TNF-alpha) was used in combination with methotrexate.
The association of lower leg ulcer development and hydroxyurea therapy in patients with myeloproliferative disorders has been reported previously. In most of these cases the ulcers healed with cessation of the hydroxyurea together with meticulous attention to wound care. We report a patient who developed painful vasculitic ulcers secondary to hydroxyurea on both lower legs whilst on long-term hydroxyurea therapy for idiopathic thrombocytosis. The ulcers extended relentlessly despite stopping hydroxyurea, maximizing topical therapies and starting intensive systemic treatment. We discuss the association of hydroxyurea therapy with the development of painful ulceration.
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BACKGROUND: The assessment of psoriasis severity is complex and involves both the physical and psychologic assessment of the individual patient. OBJECTIVE: We compared the Salford Psoriasis Index and several other tools for assessing psoriasis severity for their abilities to assess both the physical and psychologic effects of psoriasis. METHODS: A total of 101 patients (44 women, 57 men) were assessed by means of the Salford Psoriasis Index (SPI), Psoriasis Area and Severity Index (PASI), Self-Administered PASI (SAPASI), Psoriasis Disability Index (PDI), Hospital Anxiety and Depression Scale (HADS), and Illness Perception Questionnaire (IPQ). RESULTS: The "signs" score of SPI (which measures the clinical extent of psoriasis), PASI, and SAPASI correlated well with each other (r = 0.69-0.99; P <.01). They also correlated significantly, but not as strongly, with scores of psoriasis-induced disability, the PDI and SPI "psychosocial disability" score (r = 0.46-0.51; P <.01), but not with general measures of psychologic distress. There was no significant correlation between the historical treatment, "intervention," score in SPI and either the physical or the psychologic score in the SPI. The PDI and "psychosocial disability" score of SPI correlated well with each other (r = 0.69; P <.01) as well as with the depression and anxiety subscale scores of HADS (r = 0.33 and r = 0.37; P <.01, respectively), the total number of symptoms suffered by the patient (r = 0.38; P <.01), and the belief that stress or worry were associated with psoriasis (r = 0.33; P <.01). CONCLUSION: Physical scores of psoriasis severity such as PASI, SAPASI, and the "signs" component of SPI give a partial indication of psychosocial disability caused by psoriasis. In many patients, however, the physical score does not reflect psychosocial disability. Patients should be assessed by a more holistic approach, which takes into account both physical and psychologic measurements, such as used in SPI, when assessing the severity of psoriasis.
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We have developed, tested and validated a new scoring system for psoriasis: the Salford Psoriasis Index (SPI). The SPI incorporates the current clinical extent of psoriasis based on the Psoriasis Area and Severity Index (PASI), a score indicating psychosocial disability, and past severity based on treatment history. The resultant three-figure SPI (signs, psychosocial disability, interventions) is a similar paradigm to the TNM (tumour, nodes, metastasis) classification used for cancer staging. The first figure transforms the PASI into a number from 0 to 10 reflecting extent of psoriasis. The second assesses the psychosocial impact of psoriasis on each patient using a 0-10 visual analogue scale. The third figure reflects historical severity of disease as judged by the need for systemic treatment, admission to hospital and number of episodes of erythroderma. The SPI was prospectively employed in assessing 150 consecutive patients with psoriasis. Furthermore, in a separate cohort of 100 patients we tested the Psychosocial Impact Score against a recognized self-report psoriasis-specific measure, the Psoriasis Disability Index. There was a strong correlation between the two (r = 0.59, P < 0.001). However, the Psychosocial Impact Score correlated poorly with clinical extent scores such as the PASI (r = 0.28, P < 0.05) and the Self-administered PASI in 72 patients tested (r = 0.19, P = 0.1). There was a high correlation between all six observers in 20 patients for both PASI (r = 0.71; 95% confidence interval, CI 0.51-0.86) and the Extent Score (r = 0.70; 95% CI 0. 56-0.89). We believe that the SPI will be more relevant to real-life categorization of psoriasis severity in that it takes an holistic approach based not only on physician assessment but also psychological disability and treatment resistance.
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There is little literature on the use of folic acid supplementation in psoriasis patients being treated with methotrexate. Under the auspices of the British Association of Dermatologists we surveyed, using a questionnaire, the use of folic acid supplementation with methotrexate therapy for psoriasis by dermatologists in the UK. Six-hundred and fifteen questionnaires were sent and 153 responses were received (25%). One-hundred and fourteen of the responders (75%) used folic acid supplementation with methotrexate in psoriasis patients. Thirty (26%) of these used folic acid supplementation in all patients taking methotrexate and 84 (74%) used folic acid only under certain circumstances, the most common of which was an elevated erythrocyte mean corpuscular volume. Forty-six per cent of respondents believed that folic acid supplementation reduced nausea and 60% believed that folic acid did not interfere with the efficacy of methotrexate. A wide variety of dosing regimens were used for folic acid supplementation. In the absence of guidelines and controlled trials, there is great variation in the indication for use, dosing regimens used and beliefs regarding methotrexate supplementation for psoriasis. Randomized controlled trials are necessary to address these questions.
A nine-year-old, neutered female Shetland sheepdog was presented with crusted, ulcerative skin lesions affecting the footpads, commissures of the lips and the lateral canthi of the eyes. Histopathological examination of skin biopsies revealed changes consistent with superficial necrolytic dermatitis and biochemical analysis demonstrated elevated liver enzymes. Abdominal radiography revealed a small liver which, on ultrasonography, appeared diffusely mottled and showed changes suggestive of periportal fibrosis. On exploratory laparotomy, the pancreas appeared normal, but the liver was small and had multiple nodules throughout the parenchyma. This appearance was confirmed as cirrhosis on histopathological examination. The dog was placed on a hepatic support diet and treated with colchicine, essential fatty acid supplementation and raw egg yolks. After four weeks, the skin lesions had resolved and the dog remained free of clinical signs over a 22-month follow-up period.
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