File Name: methotrexate and psoriasis 2009 national psoriasis foundation consensus conference .zip
A systematic review of worldwide epidemiology of psoriasis. J Eur Acad Dermatology Venereol
In the year has been indexed in the Medlinedatabase, and has become a vehicle for expressing the most current Spanish medicine and modern. All articles are subjected to a rigorous process of revision in pairs, and careful editing for literary and scientific style. CiteScore measures average citations received per document published. Read more. SRJ is a prestige metric based on the idea that not all citations are the same.
SJR uses a similar algorithm as the Google page rank; it provides a quantitative and qualitative measure of the journal's impact. SNIP measures contextual citation impact by wighting citations based on the total number of citations in a subject field. Aminopterin was first used empirically for psoriasis and rheumatoid arthritis in by Gubner, an internist, and coworkers, 13 and in this drug was specifically mentioned as a treatment for psoriasis.
Dermatologists promptly began to assess the use of both aminopterin and methotrexate in this disease, testing twice weekly parenteral doses of 50—75 mg, 15 very small daily doses for several consecutive days a month 0. Although minimum and maximum doses have not been universally established, the weekly administration of 7. The toxicity of methotrexate depends on the extracellular concentration of the drug and the period of exposure; toxicity for a given dose will therefore be proportional to the period of exposure to it.
In theory, a toxic event can be anticipated by measuring blood levels of the drug levels higher than 0. Most adverse reactions related to low-dose methotrexate gastrointestinal and mucocutaneous are mild, appear in the first 24—48 h after administration, and do not usually require interruption of the treatment.
In some cases reactions can be attenuated by regulating or dividing the dose, by administering the drug intravenously at night, or by having the patient take folic acid supplements.
However, a similar profile of adverse effects can also be seen with other drugs for which we do not consider test doses. For most dermatologists the test dose was handed down to us as clinical practice when we were residents, and we accepted it uncritically, presumably because it was a matter of prudence in the prescription of medication and out of respect for our superiors; that was the case for me and I believe my experience was typical.
Why then do we not start with test doses of cyclosporin, nonsteroidal anti-inflammatory drugs which, incidentally, cause more frequent adverse effects , tetracyclines, or any other drug we use routinely? Is it perhaps because hypersensitivity reactions to methotrexate, but not to cyclosporin, began to be reported at a certain historical moment?
In my opinion, none of the toxicities associated with methotrexate can be considered hypersensitivity reactions, except for methotrexate-associated pneumonitis, which normally appears several weeks after treatment begins nearly always after the full dose is reached. The test dose can therefore not be used as an excuse for preventing this serious, though unusual, toxic event. From a theoretical standpoint, assessing a test dose is more relevant in cases where methotrexate is being reintroduced, as allergic hypersensitivity could be expected then rather than at the start of treatment.
Interestingly, the general assumption on reintroducing the drug is that the previous experience is sufficient indication of safety and no test dose is needed. However, the literature offers mainly reports of anaphylactoid reactions after high doses in patients who had previously been exposed to methotrexate.
Acute hypersensitivity reactions—though we have no accurate catalog of exactly what to look for, whether anaphylaxis, urticaria, toxic hepatitis, bone marrow aplasia, or toxic epidermal necrolysis—have been sporadically described in the literature almost exclusively in oncology or rheumatology patients who are taking concomitant medications and high doses of parenteral methotrexate; the vast majority of these patients had been previously exposed to the drug.
We do note, however, a report of mild, transient purpura after a test dose of 7. This is not the situation for our patients taking low doses of methotrexate for psoriasis, however. Similarly, leukopenia or pancytopenia are reactions that have been described mainly in patients with underlying conditions especially those with associated renal failure and in hemodialysis or in cases of overdose. What then is the purpose of a test dose?
Solely for the sake of argument, we note that a test dose is indicated for the prevention of a possible non-dose-dependent hypersensitivity reaction, which might be severe and which could be watched for; or we might attenuate a reaction's seriousness by administering a small dose.
Next, my understanding is that we must abandon claiming that the prevention of possible adverse events related to drug accumulation is a criterion for deciding to use a test dose, given that a test occurs at the start of treatment. The only unexpected reaction to methotrexate in psoriasis I have seen was plaque erosion after the first few doses of the drug hypersensitivity?
This reaction is certainly not serious and is only remarkable because of the need to recognize it as what it really is in order to avoid interpreting it as a lack of response to methotrexate and then try raising the dose, thereby leading to acute toxicity due to overdose a practice error, as a higher dose would not be indicated. What constitutes a test dose? That there is also variation in what practitioners consider to be a test dose was also evident in the survey mentioned above, in which respondents chose 2.
Several guidelines suggest a test dose of 5—10 mg, or a lower one of 2. Still, doses of 7. And what if I want to administer a 7. What is, in principle, the dose I eventually want to reach? No studies give guidance on a theoretically optimal dose, and methotrexate is not prescribed according to weight. The precautionary measure of administering low doses would be more valid for patients with underlying risks due to comorbidity, age, or concomitant medication.
A lower initial dose must not be confused with a test dose. The intention in the first instance is to discover the minimum effective dose rather than to prevent toxic reactions: the minimum effective dose and the test dose are not one and the same. The purpose of the test dose is to prevent an immediate acute adverse reaction that could be severe. If the reaction is idiosyncratic or the result of hypersensitivity, I believe it will matter little whether the dose is of 2.
Moreover, any of these doses is far lower than those that had been administered in the reported cases of hypersensitivity reactions. If the intention of a test is to prevent dose-dependent toxicity, then indeed, establishing the minimum effective dose could be considered. How can we be sure that a single dose of 2.
Rather than accepting the test dose as a routine practice, it would be more reasonable to maintain a low dose divided into several weekly intakes and to speak of a test or induction phase rather than a test dose. Personally, I do not prescribe test doses, instead starting patients on an initial dose of 15 mg if they have no comorbidities associated with increased risk when taking this drug. This dose has been suggested on the basis of findings from trials that compared biologic agents to methotrexate, according to Dr Kristian Reich, speaking at the annual congress of the European Academy of Dermatology and Venereology in Gothenburg, Sweden.
In my opinion the main issue in the management of methotrexate therapy is not about dosing regimens; rather, we should be concerned with evaluating patients before starting treatment and following them closely including monitoring laboratory test results , as we have recommended. Any previous relative contraindication experienced by the patient will certainly influence the choice of dose, follow-up, and safety regimens.
Perhaps the reason for ongoing debate lies in the lack of randomized clinical trials. Methotrexate is an old drug that appeared in another era. The lack of appropriate clinical trials was denounced decades ago, 37 yet trials have not been widely or systematically performed for this drug as they have been for cyclosporin and biologic agents, drugs for which a test dose has not been suggested even though their potential to cause very serious adverse events is acknowledged. Methotrexate has been the target of myths and groundless fears high risk of pulmonary and hepatic toxicity, mutagenic potential, etc.
In summary, I believe that when prescribing methotrexate in psoriasis we should consider therapeutic range; patient selection; the so-called attack, or loading, dose as well as the maintenance dose; and follow-up.
A test dose, on the other hand, should not be used for fear of the unknown or figments of our imagination. Methotrexate should receive the same medical, pharmacologic, and pharmacovigilance treatment as any other drug and not be subjected to a verdict of guilty without trial. The author declares that he has no conflicts of interest with regard to this opinion article.
However, he has received fees for speaking at conferences, conducting clinical trials, or otherwise serving as a consultant from the following laboratories: Novartis, Leo-Pharma, MSD, Abbott, Pfizer, and Janssen-Cilag.
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This item has received. Article information. Conflicts of Interest The author declares that he has no conflicts of interest with regard to this opinion article. Rees, J. Beenett, H. Maibach, H. Arch Dermatol, 95 , pp. Roenigk Jr. Maibach, G. Methotrexate therapy for psoriasis. Guideline revisions. Arch Dermatol, , pp. Ann Inter Med, 86 , pp. Auerbach, H. J Am Acad Dermatol, 6 , pp. Roenigk, R. Methotrexate in psoriasis: consensus conference. J Am Acad Dermatol, 38 , pp.
Kalb, B. Strober, G. Weinstein, M. J Am Acad Dermatol, 60 , pp. Paul, A. Gallini, A. Maza, H. Sbidian, S. Aractingi, et al. Evidence-based recommendations on conventional systemic treatments in psoriasis: systematic review and expert opinion of a panel of dermatologists. J Eur Acad DermatolVenereol, 25 , pp. Richard, J. Ann Dermatol Venereol, , pp.
Introduced in , methotrexate MTX is an effective medication that is commonly used in patients with moderate to severe psoriasis 1 , 2. Despite its widespread use in psoriasis treatment, there is little evidence on the safety of MTX in psoriatic patients 3 , 4. Although MTX has had a long history of use, there is insufficient data on cumulative MTX doses that result in early liver toxicity and the duration to develop such adverse events owing to the limited data on MTX safety. In this study, we focused on the common adverse effects caused by MTX and their risk factors in real-world use. Data from psoriasis patients receiving MTX therapy between January and June were retrospectively collected. All patients were administered MTX exclusively for psoriasis management. Only those whose screening laboratory findings were normal commenced treatment with MTX with the exception of 2 patients who had chronic glomerulonephritis.
Advanced Search. Users Online: Weinstein GD. Three decades of folic acid antagonist in dermatology. Arch Dermatol ; Liver injury in long-term methotrexate treatment in psoriasis is relatively infrequent. Aliment Pharmacol Ther ;
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Methotrexate and psoriasis: National Psoriasis. Foundation Consensus Conference. Robert E. Kalb, MD,a Bruce Strober, MD, PhD,b Gerald Weinstein, MD.
Oral systemic therapies are important treatment options for patients with moderate-to-severe psoriasis, either as monotherapy or in therapy-recalcitrant cases as combination therapy with phototherapy, other oral systemics or biologics. Long-term treatment is needed to maintain sufficient disease control in psoriasis, but continuous use of systemic treatments is limited by adverse events AEs and cumulative toxicity risks. The primary aim of this comprehensive literature review was to examine the long-term safety profiles of oral agents commonly used in the treatment of adults with psoriasis. Long-term treatment with acitretin could be associated with skeletal toxicity and hepatotoxicity, although evidence for skeletal toxicity is mixed and hepatotoxicity is rare, particularly at low doses.
И все-таки он пошел в обход. Интересно, о чем он .
Почему. Сьюзан охватила паника. Она быстро проверила отчет программы в поисках команды, которая могла отозвать Следопыта, но ничего не обнаружила. Складывалось впечатление, что он отключился сам по. Сьюзан знала, что такое могло произойти только по одной причине - если бы в Следопыте завелся вирус.
Он был первым афроамериканцем на посту директора Агентства национальной безопасности, но эту его отличительную черту никто никогда даже не упоминал, потому что политическая партия, которую он поддерживал, решительно не принимала этого во внимание, и его коллеги следовали этому примеру. Фонтейн заставил Мидж и Бринкерхоффа стоять, пока сам он молча совершал свой обычный ритуал заваривания кофе сорта Гватемальская ява.
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