Interventions for guttate psoriasis (Review) Chalmers R, O’Sullivan T, Owen CM, Griffiths CEM This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2013, Issue 10 http://www.thecochranelibrary.com Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 n-3 fatty acid infusion vs n-6 fatty acid infusion, Outcome 1 Change in semi-quantitative psoriasis severity score. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.2. Comparison 1 n-3 fatty acid infusion vs n-6 fatty acid infusion, Outcome 2 Change in patient-scored subjective severity score. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1 1 2 2 2 3 4 4 5 5 6 6 8 8 9 9 10 10 10 10 11 11 i [Intervention Review] Interventions for guttate psoriasis Robert Chalmers1 , Teresa O’Sullivan2 , Caroline M Owen3 , Christopher EM Griffiths1 1 The Dermatology Centre, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester, UK. 2 Department of Behavioural Medicine, Salford Royal NHS Foundation Trust, Manchester, UK. 3 Royal Blackburn Hospital, Blackburn, UK Contact address: Robert Chalmers, The Dermatology Centre, The University of Manchester, Salford Royal NHS Foundation Trust, Stott Lane, Salford, Manchester, M6 8HD, UK. [email protected]. Editorial group: Cochrane Skin Group. Publication status and date: Edited (no change to conclusions), published in Issue 10, 2013. Review content assessed as up-to-date: 3 January 2000. Citation: Chalmers R, O’Sullivan T, Owen CM, Griffiths CEM. Interventions for guttate psoriasis. Cochrane Database of Systematic Reviews 2000, Issue 2. Art. No.: CD001213. DOI: 10.1002/14651858.CD001213. Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT Background Guttate psoriasis is a distinctive acute form of psoriasis which characteristically occurs in children and young adults. Very little specific evidence-based guidance is available in standard texts to help make rational decisions about treatment options. Objectives To assess the effectiveness of treatments for guttate psoriasis. Search methods We searched the Cochrane Clinical Trials Register (Cochrane Library, Issue 3, 1999), Medline (1966- September 1999), Embase (1988-September 1999), Salford Database of Psoriasis Trials (to November 1999) and European Dermato-Epidemiology Network (EDEN) Psoriasis Trials Database (to November 1999) for terms GUTTATE and PSORIASIS. We also searched 100 unselected RCTs of psoriasis therapy and all 112 RCTs of phototherapy for psoriasis in the Salford Database of Psoriasis Trials for separate stratification for guttate psoriasis. Selection criteria Randomised trials in which patients with acute guttate psoriasis were randomised to different treatments, except those trials examining antistreptococcal interventions which are addressed in a separate Cochrane review. Data collection and analysis Two reviewers independently assessed trial eligibility and quality. Main results No published report could be found to support or to challenge current commonly used methods of management. Only one trial which met the selection criteria was identified. In this small study of 21 hospitalised patients with guttate psoriasis, intravenous infusion of an n-3 fatty acid rich lipid emulsion was compared with placebo emulsion containing n-6 fatty acids. The n-3 preparation appeared to be of some benefit for patients with guttate psoriasis. Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1 Authors’ conclusions There is currently no firm evidence on which to base treatment of acute guttate psoriasis. Studies comparing standard treatment modalities, including phototherapy and topical regimens, are required to enable informed decisions on treatment choices to be made. PLAIN LANGUAGE SUMMARY Treatments for guttate psoriasis Psoriasis is a skin disease that causes scaly pink patches. Guttate psoriasis is a particular form of the disease that usually affects children and young adults. It can happen on its own, or as a complication of ordinary (chronic plaque) psoriasis. Often, it follows a bacterial throat infection or tonsillitis. Antibiotics and tonsillectomy as treatments for guttate psoriasis are covered by another review. This review could find no evidence, from trials, about the effects of any other commonly used treatments for guttate psoriasis. BACKGROUND Description of the condition Guttate psoriasis is a distinctive form of psoriasis which characteristically occurs in children and young adults. It may arise on its own (acute guttate psoriasis) or may complicate existing, often quite limited, chronic plaque psoriasis (guttate flare of chronic psoriasis). It is strongly associated with preceding or concurrent streptococcal infection, evidence of which can be found in a majority of affected patients (Telfer 1992). Typically, showers of tiny red papules (likened to rain-drops or guttate) erupt over large areas of the skin surface one to two weeks after an episode of acute tonsillitis. In the early stages before the typical scale has had a chance to develop, guttate psoriasis can be mistaken for a drug eruption especially in people given an antibiotic for the associated streptococcal infection. The true diagnosis, which is a clinical one, soon becomes apparent as characteristic psoriatic scaling develops on the surface of the papules. Guttate psoriasis may be itchy and may have a profound effect on self-esteem, especially in the psychologically vulnerable age group in which it most commonly occurs. If left untreated, guttate psoriasis may clear spontaneously or may develop into chronic plaque psoriasis. Either form may recur although the risk is not well defined (Martin 1996). nol) and topical corticosteroids may also be used (with or without UVB phototherapy). Other forms of phototherapy used include narrow-band UVB, psoralen plus ultraviolet A (PUVA) and psoralen bath PUVA (all with or without the oral retinoid, acitretin or, formerly, etretinate). More recently vitamin D analogues (calcipotriol, tacalcitol) have been introduced for treating psoriasis and are used by some dermatologists for guttate psoriasis. How the intervention might work In view of the associated streptococcal infection some dermatologists advocate the use of antibiotic therapy or tonsillectomy. The optimal method for achieving clearance of guttate psoriasis is not known. Furthermore it is not clear whether any interventions can effectively prolong the duration of remission or prevent progression to chronic plaque psoriasis. Why it is important to do this review There is remarkably little guidance in standard texts as to how this distinctive form of psoriasis should be treated and whether it should be managed differently from chronic plaque psoriasis (Camp 1998). Interventions aimed at treating or preventing the associated streptococcal infection are addressed in a separate Cochrane review (Owen 2000). Description of the intervention There is no consensus on the best treatment for guttate psoriasis. Commonly, various forms of tar are applied topically in conjunction with ultraviolet B (UVB) phototherapy. Anthralin (dithra- OBJECTIVES Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 2 Primary objectives To assess the effectiveness of any treatment aimed at clearing psoriasis from the skin of patients with acute guttate psoriasis or an acute guttate flare of chronic psoriasis. To establish whether there is any evidence to support the use of commonly used treatments of guttate psoriasis such as topical tars, anthralin or vitamin D analogues with or without UVB or other phototherapy. Secondary objectives To define, so far as is possible, the optimal regimen for treating guttate psoriasis based not only on objective measures of disease improvement but also on patient-perceived benefits to health and quality of life set against the acceptability or inconvenience of each treatment method. To examine the implications for dermatological practice of any recommendations made, including the associated healthcare costs of each treatment method. To examine whether treatment method affected subsequent clinical course (by either prolonging remission or preventing progression to chronic plaque psoriasis) To determine what further study is required to enable dermatologists to make informed choices between existing treatments. Types of outcome measures Primary outcomes There is no information as to what percentage reduction in psoriasis severity score is perceived by people with psoriasis as being “worthwhile”. It may be possible to achieve a modest reduction in objective psoriasis severity score which, whilst achieving statistical significance, does not have a significant impact on either the patient’s or the physician’s perception of overall disease severity. There is enormous variation between patients in their perceptions of what constitutes a satisfactory response to treatment. Guttate psoriasis is a condition where near complete clearance of disease may be expected in a majority of treated patients. Therefore, where scores were given, a relative treatment difference of at least 50% for comparison between active treatment versus placebo, or at least 20% between two or more active treatments was accepted as being the minimum clinically meaningful change. (These figures were derived by discussion within the Cochrane Skin Group.) The nominated primary outcome measures agreed in consultation with the Group were thus: 1. Improvement or clearance of psoriasis as measured by reduction in the Psoriasis Area Severity Index (PASI) score or other objective semi-quantitative measure of disease severity 2. Reduction in patients’ self-assessed (or parent/guardianassessed) psoriasis severity scores over the time course of the intervention. 3. Improvement in patient satisfaction measures and quality of life assessment measures over the time course of the intervention. METHODS Secondary outcomes Criteria for considering studies for this review Types of studies Randomised trials which examine interventions other than those aimed specifically at eradicating streptococcal infection which are addressed in a separate review (Owen 2000). 1. Proportion of patients developing chronic plaque psoriasis within one year of acute guttate psoriasis. 2. Proportion of patients with no further episodes of guttate psoriasis within a series of defined periods (one year, five years, ten years). 3. Implications for healthcare costs of different treatments which are shown to be effective. Search methods for identification of studies Types of participants Children and adults with a clinical diagnosis of acute guttate psoriasis or guttate exacerbation of chronic psoriasis. Types of interventions Any intervention other than those aimed at eradicating streptococcal infection. Electronic searches We searched the Cochrane Clinical Trials Register (Cochrane Library, Issue 3, 1999), Medline (1966- September 1999), Embase (1988-September 1999), Salford Database of Psoriasis Trials (to November 1999) and European Dermato-Epidemiology Network (EDEN) Psoriasis Trials Database (to November 1999) for the terms GUTTATE and PSORIASIS using the Cochrane Skin Group search strategy. Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 3 A validation check was undertaken by cross-checking with the Salford Database of Psoriasis Trials for trials containing the keywords GUTTATE PSORIASIS. The Salford Database is derived from searches of Medline (from 1966-1999) and Embase (from 19801999) using the terms STUDY or TRIAL* or RANDOM* in the text, COMPAR* in the title or CLINICAL-TRIAL in the subject heading; the Cochrane Controlled Trials Register; and the EDEN Psoriasis Trials Database. All retrieved studies had been screened and coded by disease type including GUTTATE PSORIASIS. Searching other resources In addition the full text of 100 unselected RCTs of psoriasis therapy and all trials of phototherapy for psoriasis from the Salford Database were scrutinised for evidence of separate stratification for guttate psoriasis in order to examine whether such studies might contain sub-groups which were not declared in the title or abstract and had not been detected in the keyword coding process. References in retrieved articles were scrutinised for evidence of studies which may have been missed by these procedures. The authors of relevant trials, members of the Cochrane Skin Group and dermatologists interested in psoriasis were approached informally and asked whether they were aware of any other relevant data. We also asked Professor Chris Silagy to conduct a search for guttate psoriasis in his database of trials conducted in primary care. Data collection and analysis We considered whether studies of guttate psoriasis treatment may have been hidden within RCTs for psoriasis but were unable to find any evidence for this from scrutiny of 100 unselected RCTs of psoriasis therapy. The only trial which we were able to find involved treatment of people with guttate psoriasis by hospitalisation for 10 days, during which they received twice daily intravenous infusions of lipid emulsions rich in either n-3 (“active”) or n-6 (placebo) fatty acids (Grimminger 1993). Please see Characteristics of included studies. One trial (Melski 1977) was excluded, please see Characteristics of excluded studies. Risk of bias in included studies The single trial was of satisfactory quality with adequate concealment of allocation. Effects of interventions No trials of standard therapies for guttate psoriasis were available for consideration. Intravenous n-3 fatty acid supplementation produced a rapid beneficial effect (improvement in severity scores of between 45% and 76% over ten days) in patients with acute guttate psoriasis. This degree of improvement was not seen in patients receiving placebo (n-6) supplementation (16% to 25% over ten days)(Grimminger 1993). Please see Analysis 1.1 and Analysis 1.2. Selection of studies All identified studies were scrutinised to ensure that diagnostic criteria, randomisation methods and outcome measurements enabled a satisfactory comparison of interventions. All relevant studies were evaluated using guidelines set out in the Cochrane Collaboration Handbook and were assessed independently by two members of the Group before being accepted into the review. Subgroup analysis of patients with and without preexisting chronic plaque psoriasis (“guttate flares” vs “acute guttate psoriasis” ) would be performed if available data allowed. Where these details were not clear from the publication, authors were asked to provide further clarification. RESULTS Description of studies No trials of topical therapy or phototherapy were identified. DISCUSSION Summary of main results The single study which was found (Grimminger 1993) was not designed to compare established methods of treating guttate psoriasis but was intended to test the hypothesis that fish oil-derived n-3 fatty acids might be beneficial for acute guttate psoriasis. Furthermore, only adults (mean age 39.7 years) were recruited and it was thus not representative of acute guttate psoriasis, a disease seen mainly in children and young adults. It is of theoretical interest that this trial appeared to show benefit from treatment with intravenous n-3 fatty acids but, when costs of hospitalisation and inconvenience to the patient are considered, it is clear that this cannot be recommended in the routine management of guttate psoriasis. It is known that fish oil exerts a mild beneficial effect in chronic plaque psoriasis (Bittiner 1988,Gupta 1989) and it is certainly possible that the effects may be more pronounced in acutely flaring psoriasis. It might be appropriate to look at the effects of oral n-3 fatty acids in patients with acute guttate psoriasis. Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 4 Overall completeness and applicability of evidence Despite the fact that the appearance and clinical course of guttate psoriasis is known to differ from that of chronic plaque psoriasis, many studies treat patients with these diseases as one group. Although there are studies that include patients with guttate psoriasis, they are seldom stratified separately to different treatment groups. To give an example, a study examining various forms of phototherapy and systemic retinoids (Green 1992) recruited 45 patients with chronic plaque or guttate psoriasis and allocated each to one of three treatment groups. From the report it was impossible to determine how many patients had guttate psoriasis or into which group they had been allocated. We looked very carefully for studies in which patients with guttate psoriasis were randomised to receive different treatments but were unable to identify any study in which treatments in common use for acute guttate psoriasis were compared. It is possible that some RCTs of treatments for psoriasis may have contained subgroups in which patients with acute guttate psoriasis were independently randomised and evaluated, but scrutiny of 100 unselected psoriasis trials failed to uncover any such study. Furthermore we were unable to detect any such study in an extensive departmental database of psoriasis trials which had been methodically tagged by keywords including “guttate psoriasis”. As an additional check, we read all 112 trials of phototherapy for psoriasis (UVB or Psoralen plus UVA) in our database, since these were the studies where one might have expected patients with guttate psoriasis to be represented. One large study of 1308 patients receiving PUVA therapy (Melski 1977) did include over 120 patients with guttate psoriasis but, although response to treatment in the guttate group was evaluated separately, the allocation of these patients to different treatment groups was not stratified. It is surprising that there appears to have been virtually no research into the treatment of a relatively common and well-defined entity. There is no firm evidence to guide physicians treating patients with acute guttate psoriasis. dressed. How do standard topical therapies (e.g. tar, topical corticosteroids, anthralin) compare with vehicle alone or newer therapies (e.g. vitamin D analogues)? What is the role of phototherapy in acute guttate psoriasis? Which modality should be used? Should it be broad-band or narrowband UVB? Is there a place for photochemotherapy (oral or bath psoralens with ultraviolet light A)? Should topical therapy be administered in conjunction with phototherapy and, if so, what is the optimal regimen? Is there a role for systemic retinoid therapy? Can any intervention prolong the duration of remission from guttate psoriasis or prevent progression to chronic plaque psoriasis? We suggest that the most pressing priorities are as follows: 1. Comparison of tar alone, topical corticosteroid alone, calcipotriol alone and vehicle alone 2. Comparison of the two most effective of the treatments from above study with UVB thus: best treatment alone, best treatment + UVB, next best treatment + UVB, vehicle + UVB In view of the apparent benefit of intravenous n-3 fatty acids in acute guttate psoriasis and the known mild beneficial effects of oral fish oil in chronic plaque psoriasis, it would also be worth performing a study comparing oral fish oil against placebo oil in acute guttate psoriasis. It is also important to examine the place of antibiotic therapy in patients with guttate psoriasis and tonsillectomy for those with recurrent attacks. This is addressed in a separate Cochrane review (Owen 2000). AUTHORS’ CONCLUSIONS ACKNOWLEDGEMENTS Implications for practice To Boots Healthcare for funding Teresa O’Sullivan as part-time research assistant to the Cochrane Skin Group. There is no firm evidence on which to make any recommendations for the routine treatment of guttate psoriasis. To Ms Christine Clark for assisting in data retrieval. Implications for research To Professor Luigi Naldi for providing access to the EDEN psoriasis trials database. There is a requirement for the most basic of questions to be ad- To colleagues for useful suggestions and support. Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 5 REFERENCES References to studies included in this review Grimminger 1993 {published data only} Grimminger F, Mayser P, Papavassilis C, Schlotzer E, Heuer KU, Fuhrer D, et al.A double-blind, randomised, placebocontrolled trial of n-3 fatty acid based lipid infusion in acute, extended guttate psoriasis. Rapid improvement of clinical manifestations and changes in neutrophil leukotriene profile. Clin Invest (Germany) 1993;71:634–43. References to studies excluded from this review Melski 1977 {published data only} Melski JW, Tanenbaum L, Parrish JA, Fitzpatrick TB, Bleich HL. Oral methoxypsoralen photochemotherapy for the treatment of psoriasis: a cooperative clinical trial. Journal of Investigative Dermatology 1977;68:328–35. Additional references Bittiner 1988 Bittiner SB, Tucker WFG, Cartwright I, Bleehen SS. A double-blind, randomised, placebo-controlled of fish oil in psoriasis. Lancet 1988;1:378–80. Camp 1998 Camp RDR. Psoriasis. In: Champion RH, Burton JL, Burns DA, Breathnach SM editor(s). Textbook of Dermatology. 6th Edition. Oxford: Blackwell Science, 1998:1589–649. Green 1992 Green C, Lakshmipathi T, Johnson BE, Ferguson J. A compaarison of the efficacy and relapse rates of narrowband UVB (TL-01) monotherapy vs. etretinate(re-TL-01) vs. etretinate-PUVA (re-PUVA) in the treatment of psoriasis patients. British Journal of Dermatology 1992;127:5–9. Gupta 1989 Gupta AK, Ellis CN, Tellner DC, Anderson TF, Voorhees JJ. Double-blind, placebo-controlled study to evaluate the efficacy of fish oil and low-dose UVB in the treatment of psoriasis. British Journal of Dermatology 1989;120:801–7. Martin 1996 Martin BA, Chalmers RJG, Telfer NR. How great is the risk of further psoriasis following a single episode of acute guttate psoriasis?. Archives of Dermatology 1996;132:717. Owen 2000 Owen CM, Chalmers RJG, O’Sullivan T, Griffiths CEM. Owen CM, Chalmers RJG, O’Sullivan T, Griffiths CEM. Cochrane Database of Systematic Reviews 2000, Issue 2. Telfer 1992 Telfer NR, Chalmers RJG, Whale K, Colman G. The role of streptococcal infection in the initiation of guttate psoriasis. Archives of Dermatology 1992;128:39–42. ∗ Indicates the major publication for the study Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 6 CHARACTERISTICS OF STUDIES Characteristics of included studies [ordered by study ID] Grimminger 1993 Methods Random allocation, (random list) Participants 21 patients hospitalised for acute guttate psoriasis with at least 10% body surface area involved (mean 25.7±20.4%, range 10-90%). Mean age 39.7 years (range 21-65). 1 dropout on day 1; 20 patients evaluated Interventions “Active” intervention: ten day course of twice daily intravenous infusions of n-3 fatty acidbased lipid emulsion (Omegavenös, Fresenius) providing 2.1g of eicosapentaenoic acid and 2.1g of docosahexaenoic acid. Placebo: identical regimen using n-6 fatty acid-based lipid emulsion (Lipovenös, Fresenius) consisting mainly of palmitic and oleic acids (<0.3% eicosapentaenoic acid and arachidonic acid) Outcomes Reduction in disease severity scores over 10 days Notes Patients receiving systemic drug therapy of any kind excluded. Topical corticosteroid therapy stopped at least 5 days before entering study. Additional topical therapy limited to 0. 03% anthralin ointment Risk of bias Bias Authors’ judgement Support for judgement Allocation concealment (selection bias) Low risk A - Adequate Characteristics of excluded studies [ordered by study ID] Study Reason for exclusion Melski 1977 This study of 1308 patients receiving PUVA therapy included over 120 patients with guttate psoriasis. Although response to treatment in the guttate group was evaluated separately, the allocation of these patients to different treatment groups was not stratified. A good response to therapy was observed in all groups, but guttate psoriasis patients required fewer treatments to achieve clearance than those with chronic plaque disease or erythroderma Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 7 DATA AND ANALYSES Comparison 1. n-3 fatty acid infusion vs n-6 fatty acid infusion No. of studies Outcome or subgroup title 1 Change in semi-quantitative psoriasis severity score 1.1 Change in erythema 1.2 Change in infiltration 1.3 Change in desquamation 1 1 1 1 2 Change in patient-scored subjective severity score 1 No. of participants Statistical method Effect size Mean Difference (IV, Fixed, 95% CI) Subtotals only 20 20 20 Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI) 20 Mean Difference (IV, Fixed, 95% CI) -25.0 [-41.26, -8.74] -36.0 [-62.87, -9.13] -23.4 [-57.28, 10. 48] -57.6 [-106.73, -8. 47] Analysis 1.1. Comparison 1 n-3 fatty acid infusion vs n-6 fatty acid infusion, Outcome 1 Change in semiquantitative psoriasis severity score. Review: Interventions for guttate psoriasis Comparison: 1 n-3 fatty acid infusion vs n-6 fatty acid infusion Outcome: 1 Change in semi-quantitative psoriasis severity score Study or subgroup n-3 fatty acid Mean Difference n-6 fatty acid N Mean(SD) N Mean(SD) Grimminger 1993 9 -50 (18.9) 11 -25 (17.9) Subtotal (95% CI) 9 Weight IV,Fixed,95% CI Mean Difference IV,Fixed,95% CI 1 Change in erythema 100.0 % 11 -25.00 [ -41.26, -8.74 ] 100.0 % -25.00 [ -41.26, -8.74 ] Heterogeneity: not applicable Test for overall effect: Z = 3.01 (P = 0.0026) 2 Change in infiltration Grimminger 1993 9 Subtotal (95% CI) 9 -50.4 (37.8) 11 -14.4 (17.9) 100.0 % 11 -36.00 [ -62.87, -9.13 ] 100.0 % -36.00 [ -62.87, -9.13 ] Heterogeneity: not applicable Test for overall effect: Z = 2.63 (P = 0.0086) 3 Change in desquamation Grimminger 1993 9 Subtotal (95% CI) 9 -45 (32.4) 100.0 % 11 -21.6 (44.77) 11 -23.40 [ -57.28, 10.48 ] 100.0 % -23.40 [ -57.28, 10.48 ] -100 -50 n-3 FA (active) 0 50 100 n-6 FA (placebo) (Continued . . . ) Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 8 (. . . Study or subgroup n-3 fatty acid Mean Difference n-6 fatty acid N Mean(SD) N Mean(SD) Weight IV,Fixed,95% CI Continued) Mean Difference IV,Fixed,95% CI Heterogeneity: not applicable Test for overall effect: Z = 1.35 (P = 0.18) Test for subgroup differences: Chi2 = 0.53, df = 2 (P = 0.77), I2 =0.0% -100 -50 0 n-3 FA (active) 50 100 n-6 FA (placebo) Analysis 1.2. Comparison 1 n-3 fatty acid infusion vs n-6 fatty acid infusion, Outcome 2 Change in patientscored subjective severity score. Review: Interventions for guttate psoriasis Comparison: 1 n-3 fatty acid infusion vs n-6 fatty acid infusion Outcome: 2 Change in patient-scored subjective severity score Study or subgroup n-3 fatty acid Mean Difference n-6 fatty acid N Mean(SD) N Mean(SD) Grimminger 1993 9 -79.2 (70.2) 11 -21.6 (29.8) Total (95% CI) 9 Weight IV,Fixed,95% CI Mean Difference IV,Fixed,95% CI 100.0 % 11 -57.60 [ -106.73, -8.47 ] 100.0 % -57.60 [ -106.73, -8.47 ] Heterogeneity: not applicable Test for overall effect: Z = 2.30 (P = 0.022) Test for subgroup differences: Not applicable -100 -50 n-3 FA (active) Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 0 50 100 n-6 FA (placebo) 9 WHAT’S NEW Last assessed as up-to-date: 3 January 2000. Date Event Description 3 October 2013 Amended This review is going to be updated. We have written a published note to say that because the updating team is completely new and the original review is very old, a new protocol and then a new review will be written HISTORY Protocol first published: Issue 3, 1998 Review first published: Issue 2, 2000 Date Event Description 17 October 2008 Amended Converted to new review format. 27 November 2003 New search has been performed Minor update. 3 January 2000 New citation required and conclusions have changed Substantive amendment 1 October 1999 Amended Reformatted. CONTRIBUTIONS OF AUTHORS Teresa O’Sullivan performed the initial searches and draft of the review under the supervision of Robert Chalmers. The searches were rechecked by Caroline Owen. The final review was synthesised by Caroline Owen and Robert Chalmers. Christopher Griffiths provided comments and criticism. DECLARATIONS OF INTEREST Support from Boots Healthcare did not result in any conflict of interest. Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 10 SOURCES OF SUPPORT Internal sources • Section of Dermatology, University of Manchester, UK. External sources • Boots Healthcare, UK. NOTES This review is being updated by way of a new protocol and then a review because the updating team is completely new, and the original review is very old. INDEX TERMS Medical Subject Headings (MeSH) Psoriasis [∗ therapy] MeSH check words Humans Interventions for guttate psoriasis (Review) Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 11
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