Clinical and Experimenlology Dermalology 1992; 17: 159-162.
Topical fish oil in psoriasis^a controlled and blind study S.O.ESCOBAR, R.ACHENBACH, R.IANNANTUONO AND V.TOREM Department of Pharmacology and 1st Chair of Dermatology, Faculty of Medicine, University of Buenos Aires, Argentina Accepted for publication 19 July 1991
Summary
reducrion in LT levels is followed by improvement in Omcga-3 polvunsaturated fatty acids compete with ara- psoriatie plaques.^' The omega-3 pol\unsaturated fatty aeids («-3 PUIvAs) cbidonic acid as substrates tor lipoperoxidases, whicb present in marine Hsb oil (FO) could reduce LT derived transform rbem into leukorrienes with low biological from \ A, generate LTs with lower biological activity,'- or acrivity. As tbis process,, in skin, may benefit psoriatic otber putative anti-infiammatory metabolites.'-^^ltbougb patients, a randomized eontrolled single blind-studv was systemic VO bas been employed in several studies, some carried out on a sample of 25 patients. In tbe study fish oil under double-blind conditions, irs therapeutic value bas (FO) was compared witb liquid paratfin (LP); both were nor been clearh established.'"* '* ropicalh applied and administered dailv for 6 b under an Taking inro aeeounr rhe higb liposolubiliry of H-3 oeelusive dressing over a 4-vvcek period. E\ aluarions were PL F,As, we decided to carry out a clinical trial comparing performed w'eekly assessing eryrbema, scabng, plaque ropical VO uirb liquid paraffin (LP). botb administered rbickness (induration) and irehing. under oeelusive dressings. Afterwards, LP was applied to I'be results showed statisticalh significant iniproveone plaque, FO to tbe other according to tbe randomizamenl in eryrbema and scaling- for both rreatments compared ro basal values; significant differences between tion code. Then borb plaques were covered vvirh a rreatments were acbieved in scaling but not in erytbema, polyethylene film. Patients were instructed to keep tbe (Compared to ba-seline, l''O significanrly improved plaque oeelusive dressing in place for ar least 6 b overnigbr and to thickness wbile LP did nor. After 4 weeks, FO proved to repeat tbe procedure for 7 days until rhe next visit. be significanrh better rban LP. All patients accepted tbe Finally, tbev were told ro vvasb both plaques vvirh a treatment despite its unpleasant smell. Irritation and a glycerine .soap tbe morning before eacb examination to burning sensation were reported in tbe FO treated plaque ensure observer blindness. I".valuations were performed before treatment and rhen of one patient. This adverse eflect reverted after eomplerrepeated every week for 1 nionrb, always by tbe same ing tbe rrearmenr. Tbese findings demonstrate tbat observer and under standard lighr conditions. Tbe ropical FO sbovvs a betrer perfbrmanee than LP under an variables—erytbema, scaling, and plaque rhickness— oeelusive dressing. w ere evaluated b} means of an inereasing deterioration scale ranging from 0 to 4, being 0--absent, l^mild, 2 =^moderate, 3^moderately-severe and 4 = severe. ItcbAt present, an important role bas been suggested tor ing was assessed using a 10 cm long, visual analogue scale several ditlerenr eicosanoids in tbe patbogenesis of (VAS). psoriasis. Pbospholipase A2 acrivity is increased in Weekly evolution was statistically evaluated by means unaffected skin of psoriaric patients.''' Higber levels of of tbe Friedman Test for eacb group and with tbe araebidonic acid (AA), leukotriene B (LTB4) and 12Wilcoxon Ranked Test for comparisons between treatIIETE can be detected in psoriatic skin compared vvirh ments. A TADPOLE i n program tor IBM PC was used. normal.' ^ LTB4, possesses powerful ebemoattraerant properties for polymorphonuclear leueoeyres (PMNL)''" and, wben Methods topically applied to normal skin, it leads to PMNL aeeumulation in tbe upper epidermis similar to that Sample observed in psoriasis (Munro's niicroabscesses).^ On tbe The study was carried out between autumn and winter in otber band, this LT bas proved to stimulate keratinoeyre 1988 and 1989: a total of 25 patients (U women and 14 replication in vitro and in rnY;.'*-'" Furtbermore, a men) witb the clinical and histopatbological diagnosis of 159
160
S.O.KSCOBAR ct al. Medication VO was supplied by Smith & Zoon Laboratories, and analysed in Farmerit Laboratories, Buenos Aires, by means of Gas-Liquid C.hromatography. It was determined that this oil contained F,PA 15-8%, DHA 10-1**,, and other fatty acids 74-l'^^(>, its chromatogram and composition is shown in Figure 1.
Sturt
Fat'y ocid 40 -
Design
Miristsc Polmitic Polfnitoleic
CI4 ,0 CI6:0 CI6 ; I Steonc CIS :0 CIS :! Oleir, CIB :2 Linoleic CIB ;4 OcSaTetroenoic C20:i Eicosaenoic C20:4 Arachidonic Eicosopenlaenoic C20^5 Docusotetfoenoic C22:4 Doi;osopentaenoic C22 '5 DocoMhexaenoic C22 :6
EPA
70
75 ,64 9,7 2,5 3,? 2 6 2,8 I5B
Results
O'hers mo concentrotion lower thon 1%
DHA
The study was prospective, randomized and blind for the observer, each patient being his own control. Two symmetrical and distant plaques were chosen from each patient, 48*\, of them were located on the trunk and 52^>o on the limbs {n% upper limbs and 20"o lower limbs).
90
I'tjjure 1, Fish oil composition and its correspondinti chromatogram.
psoriasis were included. Mean age was 40-3 ± 14-1 (range 18-66) years. Patients who had received systemic cytostatic or corticosteroid treatment during the previous year were excluded, as well as those with renal,, hepatic or haematological disease and who reecived any treatment that could interfere with the evolution of psoriasis: NSAIO's,, Beta adrenergic receptor blockers or antimalarial drugs. One patient also had Hanscn's disease treated with the World Health Organization multibacillary protocol.
In Table 1, mean values and s.e. of all the variables studied, can be seen. Main significant results arc shown in Figure 2. Both treatments significantly reduced scaling compared with basal values but differences between treatments reached statistical significance at 4 weeks, with FO appearing superior to LP. In the assessment of plaque thickness, LP w as no better than at basal values, while FO significantly reduced values. Additionally, FO proved to be statistically better than LP, In the assessment of erythema, although both trcatmenis significanrly improved lesions; there were no differences between them. Itching did not show a significant improvement with any treatment. How ever, it is interesting to note that after a marked decrease during the first 2 weeks, values tended to recover their pre-trcatment levels by the end of the study. Marked irritation and a burning sensation were
Table 1. -Mean values ;md s,c, variances for A\\ parameters throughdut the study Ihsal
Week 1
Week 2
Week 3
2'')l + ()-21 2-81+l)-3!
0-9()±0-33 1-63 + 0-22
!-H)±0-21 ]-8l±0-32
0-'>l±0-,i2 1-41 ± 0 - 3 4
Induration
F O 2-21 ± 0 - 2 1 I.P 2 - 4 0 ± 0 - 1 8
(l-82±i)-21 I-,S2 + O-3O
1-10 + 0 - 1 2 J-61 ±(1-2!
0-'M±0-14 l^i^lO-Ul
r.rvthema
1 () \ .P
2-7i±0-i7 2-61±()'21
! -62 + 0- 20 1-88±()- 18
1-49 t 0-16 1-2210-12 O'')O + 0-21f 1-.W±O-!1 1-7 2 ±0-20 l-10±O-25t
Ild-inji
\ •{) f .P
6-22±l-()5 7-2(11 M 5
6 -01+0- 75 3-40±0-Sl 4-3 5 ±0-73 5-7-S±0-75 NS 5-61 tO' 55 3-21 K)-62 4-7 5 + 0-62 5-15 + 0-65 -NS
}•() LP
nt vs. basal values /'
Topical fish oil in psoriasis^a controlled and blind study S.O.ESCOBAR, R.ACHENBACH, R.IANNANTUONO AND V.TOREM Department of Pharmacology and 1st Chair of Dermatology, Faculty of Medicine, University of Buenos Aires, Argentina Accepted for publication 19 July 1991
Summary
reducrion in LT levels is followed by improvement in Omcga-3 polvunsaturated fatty acids compete with ara- psoriatie plaques.^' The omega-3 pol\unsaturated fatty aeids («-3 PUIvAs) cbidonic acid as substrates tor lipoperoxidases, whicb present in marine Hsb oil (FO) could reduce LT derived transform rbem into leukorrienes with low biological from \ A, generate LTs with lower biological activity,'- or acrivity. As tbis process,, in skin, may benefit psoriatic otber putative anti-infiammatory metabolites.'-^^ltbougb patients, a randomized eontrolled single blind-studv was systemic VO bas been employed in several studies, some carried out on a sample of 25 patients. In tbe study fish oil under double-blind conditions, irs therapeutic value bas (FO) was compared witb liquid paratfin (LP); both were nor been clearh established.'"* '* ropicalh applied and administered dailv for 6 b under an Taking inro aeeounr rhe higb liposolubiliry of H-3 oeelusive dressing over a 4-vvcek period. E\ aluarions were PL F,As, we decided to carry out a clinical trial comparing performed w'eekly assessing eryrbema, scabng, plaque ropical VO uirb liquid paraffin (LP). botb administered rbickness (induration) and irehing. under oeelusive dressings. Afterwards, LP was applied to I'be results showed statisticalh significant iniproveone plaque, FO to tbe other according to tbe randomizamenl in eryrbema and scaling- for both rreatments compared ro basal values; significant differences between tion code. Then borb plaques were covered vvirh a rreatments were acbieved in scaling but not in erytbema, polyethylene film. Patients were instructed to keep tbe (Compared to ba-seline, l''O significanrly improved plaque oeelusive dressing in place for ar least 6 b overnigbr and to thickness wbile LP did nor. After 4 weeks, FO proved to repeat tbe procedure for 7 days until rhe next visit. be significanrh better rban LP. All patients accepted tbe Finally, tbev were told ro vvasb both plaques vvirh a treatment despite its unpleasant smell. Irritation and a glycerine .soap tbe morning before eacb examination to burning sensation were reported in tbe FO treated plaque ensure observer blindness. I".valuations were performed before treatment and rhen of one patient. This adverse eflect reverted after eomplerrepeated every week for 1 nionrb, always by tbe same ing tbe rrearmenr. Tbese findings demonstrate tbat observer and under standard lighr conditions. Tbe ropical FO sbovvs a betrer perfbrmanee than LP under an variables—erytbema, scaling, and plaque rhickness— oeelusive dressing. w ere evaluated b} means of an inereasing deterioration scale ranging from 0 to 4, being 0--absent, l^mild, 2 =^moderate, 3^moderately-severe and 4 = severe. ItcbAt present, an important role bas been suggested tor ing was assessed using a 10 cm long, visual analogue scale several ditlerenr eicosanoids in tbe patbogenesis of (VAS). psoriasis. Pbospholipase A2 acrivity is increased in Weekly evolution was statistically evaluated by means unaffected skin of psoriaric patients.''' Higber levels of of tbe Friedman Test for eacb group and with tbe araebidonic acid (AA), leukotriene B (LTB4) and 12Wilcoxon Ranked Test for comparisons between treatIIETE can be detected in psoriatic skin compared vvirh ments. A TADPOLE i n program tor IBM PC was used. normal.' ^ LTB4, possesses powerful ebemoattraerant properties for polymorphonuclear leueoeyres (PMNL)''" and, wben Methods topically applied to normal skin, it leads to PMNL aeeumulation in tbe upper epidermis similar to that Sample observed in psoriasis (Munro's niicroabscesses).^ On tbe The study was carried out between autumn and winter in otber band, this LT bas proved to stimulate keratinoeyre 1988 and 1989: a total of 25 patients (U women and 14 replication in vitro and in rnY;.'*-'" Furtbermore, a men) witb the clinical and histopatbological diagnosis of 159
160
S.O.KSCOBAR ct al. Medication VO was supplied by Smith & Zoon Laboratories, and analysed in Farmerit Laboratories, Buenos Aires, by means of Gas-Liquid C.hromatography. It was determined that this oil contained F,PA 15-8%, DHA 10-1**,, and other fatty acids 74-l'^^(>, its chromatogram and composition is shown in Figure 1.
Sturt
Fat'y ocid 40 -
Design
Miristsc Polmitic Polfnitoleic
CI4 ,0 CI6:0 CI6 ; I Steonc CIS :0 CIS :! Oleir, CIB :2 Linoleic CIB ;4 OcSaTetroenoic C20:i Eicosaenoic C20:4 Arachidonic Eicosopenlaenoic C20^5 Docusotetfoenoic C22:4 Doi;osopentaenoic C22 '5 DocoMhexaenoic C22 :6
EPA
70
75 ,64 9,7 2,5 3,? 2 6 2,8 I5B
Results
O'hers mo concentrotion lower thon 1%
DHA
The study was prospective, randomized and blind for the observer, each patient being his own control. Two symmetrical and distant plaques were chosen from each patient, 48*\, of them were located on the trunk and 52^>o on the limbs {n% upper limbs and 20"o lower limbs).
90
I'tjjure 1, Fish oil composition and its correspondinti chromatogram.
psoriasis were included. Mean age was 40-3 ± 14-1 (range 18-66) years. Patients who had received systemic cytostatic or corticosteroid treatment during the previous year were excluded, as well as those with renal,, hepatic or haematological disease and who reecived any treatment that could interfere with the evolution of psoriasis: NSAIO's,, Beta adrenergic receptor blockers or antimalarial drugs. One patient also had Hanscn's disease treated with the World Health Organization multibacillary protocol.
In Table 1, mean values and s.e. of all the variables studied, can be seen. Main significant results arc shown in Figure 2. Both treatments significantly reduced scaling compared with basal values but differences between treatments reached statistical significance at 4 weeks, with FO appearing superior to LP. In the assessment of plaque thickness, LP w as no better than at basal values, while FO significantly reduced values. Additionally, FO proved to be statistically better than LP, In the assessment of erythema, although both trcatmenis significanrly improved lesions; there were no differences between them. Itching did not show a significant improvement with any treatment. How ever, it is interesting to note that after a marked decrease during the first 2 weeks, values tended to recover their pre-trcatment levels by the end of the study. Marked irritation and a burning sensation were
Table 1. -Mean values ;md s,c, variances for A\\ parameters throughdut the study Ihsal
Week 1
Week 2
Week 3
2'')l + ()-21 2-81+l)-3!
0-9()±0-33 1-63 + 0-22
!-H)±0-21 ]-8l±0-32
0-'>l±0-,i2 1-41 ± 0 - 3 4
Induration
F O 2-21 ± 0 - 2 1 I.P 2 - 4 0 ± 0 - 1 8
(l-82±i)-21 I-,S2 + O-3O
1-10 + 0 - 1 2 J-61 ±(1-2!
0-'M±0-14 l^i^lO-Ul
r.rvthema
1 () \ .P
2-7i±0-i7 2-61±()'21
! -62 + 0- 20 1-88±()- 18
1-49 t 0-16 1-2210-12 O'')O + 0-21f 1-.W±O-!1 1-7 2 ±0-20 l-10±O-25t
Ild-inji
\ •{) f .P
6-22±l-()5 7-2(11 M 5
6 -01+0- 75 3-40±0-Sl 4-3 5 ±0-73 5-7-S±0-75 NS 5-61 tO' 55 3-21 K)-62 4-7 5 + 0-62 5-15 + 0-65 -NS
}•() LP
nt vs. basal values /'
