Journal of Cutaneous Pathology 1977: 4: 233-243
A Topical Treatment Program for Psoriasis with Low Anthralin Concentrations ISSER BRODY' AND ALVAR .lOHANSSON^ Departments of Dermatology' and Photography^ General Hospital, l';skilstuna, Sweden A treattnent program for psoriasis in whieh 0.01-0.05% antliralin was used has been elinically evaluated. In sueh low eoncentrations it is possible to use anthralin if one simultaneously avoids exposing the skin to unneeessary external meehanieal trauma, including the meehanieal removal of the seales from the lesions. Applied in this fashion, anthralin then also becorrres most suitable for use in ambulatory therapy. In these low concentrations it does not irritate either the involved or the non-involved psoriatie skin. No discoloration of the clothes, tire skin, the hair or the nails was observed. (Received for publication April 19, 1977)
In 1916 Galewsky introduced anthralin (= cignolin = dithranol), whieh has been shown to be a very active agent in the topical treatment of psoriasis (Ingram 1953, 1954, Baker & Wilkinson 1972). Its effect is considered to be due to the fact that it slows down enzyme activity and reduces tnitotic rate (Krebs & Sehaltegger 1965, Suurmond 1965, 1966, Wilborn & Montes 1974). Anthralin is commonly used in concentrations of 0.1-0.8% (Baker & Wilkinson 1972). In these concentrations, however, it frequently eauses irritation of the skin and the treatment has to be temporarily discontinued. With the same concentrations the clothes, skin, hair and nails are discolored quite intensely. In a series of macroseopic, light- and electron-microscopic investigations, the absence of effect with topical therapy in cases of recalcitrant psoriasis among ambtilatory patients was attributed to the mechanical element of scraping off of the scales from the lesions (Brody 1975, 1976, 1977a). On the basis of the results of these investigations an ambulatory program for treatment of psoriasis has been developed (Table 1). If the psoriatie skin is exposed to the
least external tnechanical damage, an effect from anthralin is obtained even in such low eoneentrations as 0.01-0.05%. In these eoncentrations neither the involved nor the non-involved skin becotnes irritated nor does diseoloration of the skin, hair, nails or clothes occur (Brody 1976). Material and Methods
24 patients (Table 2) were divided into three groups, A-C. Group A ineluded patients 1-19, who were treated strictly according to the method shown in Table 1. Group B included only one patient (no, 20). Before treatment, this patient had suffered such severe hand (Fig. 6a) and foot damage, including nail involvement, that he had difficulty in walking and in holding things. As he was living alone and was not able to treat himself, he had to be hospitalized. He also had extensive lesions with pustules over large parts of his body (Fig. 5a). Mondays through Fridays the patient received treatment at the outpatient Skin Department. In addition to this, on Saturdays and Sundays help at the inpatient ward with the application of the ointment as shown in Table 1 was provided. Group C comprised patients
234
BRODY AND JOHANSSON Table 1 Treatment program
I. General Instructions The patients are instructed not to pick off the seales and to abstain from scratching and scrubbing the lesions and the skin in its entirety, ineluding the sealp and the nails, if changes are found also on these areas. When the patient washes with soap, only the palnrs of the hands should be used, and the skin should be dried only with a soft towel and without rubbing the skin. The patients may not use their nails or brushes, ineluding nail- and hair-bru.shes, nor may they use sponges, washeloths or coarse towels. Thus, as tar as is praetieally possible, the patients must avoid meehanieal damage to the skin, the scalp and the nails II. Antihistamines are given at least until the indurated, desquanrating lesions are transformed into macular psoriasis III. A. Topical treatment of indurated, desquamating lesions (1) Mondays-l'"ridays treatment onee daily at the outpatient Skin Department (a) 10-15 min bath with liquor earbonis detergens or Mediterranean sea-salt. Mondays and Thursdays eareful lathering with soap and washing of the entire skin, including the lesions, witlr the palms of the hands (b) Ultraviolet light radiation (see under Material and Methods) (e) On the body: thin applieation of 0.01-0.05% anthralin, 10% salicylic acid in white petrolatum. Use of tubular gauze to keep the ointment in plaee and prevent the patients from seratching the skin directly For the nails: thin application of 0.03 % anthralin, 10% salicyelic acid in petrolatum alburn on the nails and on the skin around the nails and on the dorsal surfaee of the entire distal phalanx. Use of eotton gloves and/or stoekings during night For the sealp: 0.03% anthralin, 4% salicyelic acid in lard (= adeps suillus stabilisatus). every other day with washing of the hair every alternate day. Avoid getting ointment in
the eyes (2) Saturdays and Sundays treatment at home once daily with 0.03% anthralin, 10% salieyclic acid in petrolatum album. Use of tubular gauze or thin cotton underwear, and cotton gloves or stoekings. No bath or shower III. B. Treatment of macular psoriasis and scratch marks, of clinically normal skin at the site of earlier lesions and of nail and scalp changes at home (1) The body: Thin applieation of 0.01-0.03% anthralin, 4% salicyhc acid iu petrolatum alburn. Baths, showers and steanr-baths as de.sired. Continued gentle care of the skin as far as this is praetieally possible (a) Macular psoriasis and scratch marks: treatment onee daily (b) Clinically normal skin at the site of earlier lesions: treatment 2-3 times a week (2) The nails: Thin appHeation of 0.03% anthralin, 4% salieyelic acid in white petrolatunr on the nails and on the skin around the nails and on the dorsal surfaee of the entire distal phalanx once daily (3)The scalp: thin applieation of 0.03% anthralin, 4% salieyelie aeid in lard (= adeps suillus stabilisatus) onee a week or onee a fortnight, 8-10 h before washing the hair. No use of hair-brushes
21-24, They were given general instructions as indicated in Table 1 and were also prescribed antihistamines. The patients applied. at home, 0.01-0.03% anthralin and 10% salicylic acid in white petrolatum once daily until all indurated and desquamating lesions had turned into macular psoriasis (Brody 1977b). After this, the patients used 0.010,03% anthralin, 4% salicylic acid in white petrolatum both on macules and on the clinically normal skin at the site of earlier lesions according to III B (Table 1). Those patients who had scalp changes used 0,03%
anthralin in the salve composition indicated under IIL A: lc and III. B: 3 (Table 1). The patients in groups A and B were given tar baths and ultraviolet light radiation at the outpatient Skin Department. A Hanau Original type Hohensonne 2100 lamp, which permits a radiation period of 2-15 sec given at a distance of one tneter from the skin, was used. During the first 3 days, 2 see of ultraviolet light irradiation was given on the front and back of the body, respectively. Thereafter, the exposure was gradually increased by 1 sec every fourth day until 7 see on the
TOPICAL TREATMENT PROGRAM FOR PSORIASIS
235
Table 2 Patient material
Patient no.
Age of patient in years
Sex
A: 1
4
2 3 4 5 6
8 10 18 18 23
7
25
9
8 9
29 37
6 6
Duration of disease
64
9 9
73
9
16 months 3 years 6 years 18 months 17 years 20 years 15 months 14 years 17 years 13 years 21 years 25 years 27 years 26 years 18 months 42 years 50 years 17 months 20 months
B:20
66
d
40 years
C:21
15 15 26 29
9
6 months 18 months 10 years 19 years
10
42
11
44 45 50 52 53 57 63
12 13 14 15 16 17 18 19
22 23 24
front and back of the body, respectively, were maximally given, a period that was not reached until the 21st day of treatment. The patients in group C, who had the same extensive, recalcitrant psoriasis as the patients in group A, were given neither-tar baths nor tzltraviolet light radiation. Nine of the patients were carefully photographed before the treatment, once a week or once a fortnight for the first 3 to 6 weeks, and thereafter once a month or once every third month. From the other patients, who were not photographed, careful frequent notes regarding localization, extent and type of changes were made. The evolution of the lesions was also followed with light and electron microscopy. The effect of the treatment was graded on the basis of a 1-6 scale (see Table 3 and
9 9 6
9 •
6
9
a
6
6 9 c5 d 6
9 9 9
footnote). In view of results obtained earlier (Brody 1975, 1977b) the effect of the treatment was evaluated according to the following criteria: (1) the extent of the lesions in relation to their extent before the commencement of treatment, and (2) the occurrence of a) indurated and/or desquamating lesions, b) macules and c) clinically normal skin at the site of earlier lesions. Results
In the patients of groups A and C a clear effect was observed as early as the 7th day of treatment (Fig. 3), although the scales had not been scrubbed off before the application of the ointment. The lesions at all sites showed a transition to macules within 3-6 weeks after the start of treatment (Table 3, Figs, 1 and 2). In 20 of the patients in groups A and C a transition from macular
236
BRODY AND JOHANSSON
Fig. 1. Case No. 5 before treatment.
TOPICAL TREATMENT PROGRAM FOR PSORIASIS
237
Fig 2. Case No. 5 29 days after initiation of the treattnent progratn aecording to Table 1. Only macules are left. Note the guttate form of the tnacnles on the back in Tig. 2b.
238
BRODY AND JOHANSSON Table 3 l'lffect of treatment
Patient no.
A: 1
Time for transition to maculae after start of treatment in days
Time for transition to clinically normal skin after appearanee of maculae in months
2
30 29
3
22
31/2 _
4 5
23
4
6 7
8 9 10 11 12 13 14 15
16
3
5 2'/2
I4y2
1
40 24
2 3
7 11
1 4
10 "/2
35
2>/2
i4y2
4
8
11 12 6'/2 8
1
29 19 32
_
41
30 32 32 25
1 2 3 4
30 40
2'/2
42 17
4 2
B:20
60
3'/2
C:21
30 20 36 27
3 2V^ V/2
3
6 7
Results*
Time for relapse after start of treatment in months
3 1 2 1 2 5 5
17 18 19
22 23 24
Observation time after start of treatment in months
4'/2 6 5Vi
6
7
5 3
3'/2
1
7'/2 14
6
2 1 1
13
1
6
2 1 1 1
9 12"/2
3'/2
4
14
51/2
3
*Explanation of the numerals under Results 1. Lesions-free: no visible ehanges 2. Almost completely lesions-free: few maeules 3. Considerably improved: slight desquamation on elbows and/or knees, and/or sealp, orseattered maeules on the body 4. Improved: desquamating, indurated lesions but of eonsiderably lesser extent than before the start of treatment 5. Unehanged status: the same appearanee and extent as before the treatment 6. Worsening: same appearanee but with increased extent as compared with status before the treatment
psoriasis to elinically normal skin was observed 1-4 months after the appearance of macules in all areas (Table 3, Fig. 4), At the time of the application of the material, or 4'/2-14!/2 months following the beginning of treatment, 11 of the patients in groups A and C were completely lesions-free, four
patients were almost completely so, while two patients were considerably improved. Six of the patients in group A had a relapse with indurated, desquamating lesions, three of them 7-10y2 months and three of them 3-3/2 months after the start of treatment (Table 3). In those patients in whom clinically
TOPICAL TREATMENT PROGRAM FOR PSORIASIS
239
Fig. 3. Case No. 5. a. Higher magnifieation of the lesions on the lateral surface of the right lower leg in Fig. lc, before treatment, b. The lesions in the same area after 7 days' treatment.
Fig. 4. Case No. 13. a. Before treatment, b. Lesions-free after 2 months' treatment.
240
BRODY AND JOHANSSON
normal skin appeared before the relapse, the relapsed area was eonsiderably less extensive than before the treatment began. In the other patients the relapsed area was of the same extent as before the treatment. While questioning patients in group A it appeared that the degree of effeet, when viewed in a longer perspective, seemed to depend largely on the seriousness with which they took care of their skin according to the instructions given in Table 1. Before the start of treatment patient No. 20 in group B had extensive ehanges with firmly adhering scales and pustules elsewhere on the body (Fig. 5a). On the palms (Fig. 6a) and the soles the skin was greatly thickened and showed seales and large, deep fissures. All the nails on the fingers and toes were greatly thickened and discolored and presented numerous pits. Although the firmly adhering scales were not scrubbed off before the application of the ointment, it was possible to observe improve-ment of the lesions on the body (Fig. 5b), on the hands (Fig. 6b) and on the feet within 16 days after the treatment started. But in the case of this patient, it was still possible, 40 days after the commencement of treatment, to note a fine peeling and a rather intense redness at all the sites of previously indtirated, desquamating changes, exeept on the lower legs. Three-and-a-half-months after the treatment started, the skin was clinically normal at all locations except on the lower legs where rather large, brownish macules were still appearing. Sometimes these were above prominent varices (Fig. 5e) and seemed related to stasis eczema (cf. Ingram 1954). The patient was still lesionsfree exeept for the brownish maeules on the lower legs 13 months after the treatment was eommeneed (Table 3, Fig. 5d). Also the skin of the hands (Fig. 6 a-d) and feet, ineluding the nails, showed progressive improvement. At 13 months after the start of the treatment the skin on the hands and feet was completely lesions-free. The nails showed an almost normal thiekness and color with only a few pits.
Discussion
The present results eonfirm earlier observations (Brody 1977b) indicating that, if the entire patient's skin, including of eourse the lesions, is exposed to the least possible external meehanieal damage (Brody 1975, 1976, 1977a) it is possible to obtain very good results even with sueh low eoncentra tions of anthralin as 0.01-0.05 %. With the criteria chosen to judge the effect of treatment, 12 patients beeame eompletely lesions-free, four patients almost eompletely so, while two patients showed considerable improvement during an observation period of 4'/2-14y2 months. Six patients had a relapse in the form of indurated, desquamating lesions. It seems that the longer the patients were free of the lesions, the less extensive was the relapsed area. Among the parameters considered to evaluate the effect of treatment are ehanges in the degree of desquamation and indtiration. This is possible to ascertain only in lesions -where there is a turn into maeular psoriasis (Brody 1977b). But changes in the degree of desquamation and induration in cases of recalcitrant psoriasis (where there is no transition to macular psoriasis) tell us nothing. Thus in the recalcitrant lesions one found, maeroseopieally and regularly, (Brody 1975) the following sequenee of changes: horny layer with scales that were scratched off-^fresh scratch marks-^old scratches->horny layer with smooth skin surface and without seales-^homy layer with coarse skin surface pattern and without scales^horny layer with scales that were scratched off-*fresh scratches etc. Where the recalcitrant lesions showed a maeroseopieally horny layer without seales or where a reduced induration seemed visible, it would not be logical simply to jump to the conclusion that the redueed desquamation and/or induration was a eonsequenee of the topical therapy. In previous publications, stress was plaeed on the importance of using anthralin in concentrations of 0.1-0.8% and of its being applied only to the lesions themselves
TOPICAL TREATMENT PROGRAM FOR PSORIASIS
241
Fig. 5. Case No. 20. a. Before treatment, b. Improvement after 16 days' treatment, e. After 3% months' treatment elinically normal skin is seen on all sites except for latge brownish maeules on the lower legs. d. After 11 montlis' treatment elearing persists.
Fig, 6, Case No. 20. a. Before treatment, the palm shows indurated, desquamating skin with deep fissures. b. After 16 days' treatment fissures are no longer seen. e. After V/i months' treatment the skin is elinically normal but the naUs are still thickened, d. After 11 months' treatment the skin is clinically normal and the nails show an almost normal thiekness.
TOPICAL TREATMENT PROGRAM FOR PSORIASIS in order, as much as possible, to eliminate the risk of primary irritation. Nevertheless, such skin irritation has been very eommon and led to temporary discontinuation ofthe treatment (Weigand & Everett 1967, Farber & Harris 1970). To facilitate application of the anthralin to the lesions themselves, a paste has also been used as a base (Ingram 1953, 1954, Weigand & Everett 1967, Farber & Harris 1970, Baker & Wilkinson 1972). But the paste sticks firmly to the lesions so that, in order to properly reapply fresh paste, it is first neeessary to remove the paste applied earlier. This involves a certain trauma -with the scraping away of the scales and parts of the horny layer, leading to excoriations. In our program this is avoided by using white petrolatum as a base instead of a paste for the body and lard (= adeps suHlus stabilisatus) to the scalp. Anthralin in the usual coneentrations of 0.1-0.8% implies not only the risk of irritation, but also strong discoloration of the clothes, the skin, the hair and the nails. With the 0.010.05% anthralin, neither the involved nor the non-involved psoriatic skin becomes irritated, thus one does not need to combine anthralin with corticosteroids as proposed by Farber & Harris (1970). Nor are skin, hair, naUs or clothes discolored. Applied in this fashion, anthralin then becomes very suitable for use in ambulatory therapy.
Acknowledgements
This investigation was supported by grants from the Sodermanland County Council and from the Edvard Welander Foundation. References
Baker, H. & Wilkinson, D. S. (1972) Psoriasis. In Textbook of Dertnatology, eds. Rook, A., Wilkinson, D. S. & Ebling, F. J. G. pp. 11921234. Oxford; Blackwell Scientific Publications. Brody, 1. (1975) Do excoriations in psoriasis delay or prevent the effect of topical treatment? Journat of Cutatieous Pathology 2, 163-169.
243
Brody, I. (1976) Elektronermiikroskopisehe Beobaehtung bei Psoriasis vulgaris unter der Behandlung. In Sytttpositittt I. Aktuelle Frgebttisse der Elektrotienmikroskopie. Verhandlungen der Deutschen Dermatologischen Gesellschaft 30. Tagung in Graz, September 1974. Der Hautarzt, Suppl. 1, 207-208. Brody, 1. (1977a) Light and electron microscopy of excoriated psoriatic lesions in patients during topical treatment. Journal of Cutaneous Pathology 4, 68-79. Brody, 1. (1977b) Clinieal and morphological aspects of the topieal treatment of psoriasis. In Proeeeditigs of the Seeond Internatiotial Syttiposiutit on Psoriasis, Stanford, .luly 1976, eds. Farber, E.M., Cox, A.J. & Jaeobs, P.H. pp. 447^49. NewYork: Yorke Medieal Books. Farber, E. M. & Harris. D. R. (1970) Hospital treatment of psoriasis. A modified anthralin program. Archives of Dertnatology 101, 381389. Galewsky (1916) Uber Cignolin, ein Ersatzpraparat des Chrysarobins. Dermatologisehe Wochetischrift 62, 111-115. Ingram, J. T. (1953) The approach to psoriasis. British Medical .lotirtiat 2, 591-594. Ingram, .1. T. (1954) The significance and rnanagemcnt of psoriasis. British Medical Journal 2, 823-828. Krebs, A. & Sehaltegger, H. (1965) Experimentelle Untersuchuiigen iiber den Wirkungsmechanismus von Chrysarobin und Dithranol bei Psoriasis (lndizien fur eine eytostatische Wirkung an der l'^pidermis). Dertnatologiea 131, 1-27. Suurmond, D. (1965) Histologie changes in treated and untreated psoriasis lesions. Dertnatologiea 131, 357-366. Suurmond, D. (1966) Histochemical ehanges in treated and untreated psoriasis. A comparative enzyme histoehemieal study on the effect of topical cortieosteroid and anthralin treatment. Dermatologica 132, 237-247. Weigand, D. A. & Everett, M. A. (1967) Clearing of resistant psoriasis with anthralin. Arehives of Dermatology 96, 554-559. Wilborn, W. H. & Montes, L. F. (1974) Ultrastructural changes in psoriatic epidermis following anthralin treatment. Journal of Cutaneous Pathology 1, 132-150. Address: Isser Brody Depart ttient of Dertnatology General Hospital S-631 88 Eskilstutia Sweden
A Topical Treatment Program for Psoriasis with Low Anthralin Concentrations ISSER BRODY' AND ALVAR .lOHANSSON^ Departments of Dermatology' and Photography^ General Hospital, l';skilstuna, Sweden A treattnent program for psoriasis in whieh 0.01-0.05% antliralin was used has been elinically evaluated. In sueh low eoncentrations it is possible to use anthralin if one simultaneously avoids exposing the skin to unneeessary external meehanieal trauma, including the meehanieal removal of the seales from the lesions. Applied in this fashion, anthralin then also becorrres most suitable for use in ambulatory therapy. In these low concentrations it does not irritate either the involved or the non-involved psoriatie skin. No discoloration of the clothes, tire skin, the hair or the nails was observed. (Received for publication April 19, 1977)
In 1916 Galewsky introduced anthralin (= cignolin = dithranol), whieh has been shown to be a very active agent in the topical treatment of psoriasis (Ingram 1953, 1954, Baker & Wilkinson 1972). Its effect is considered to be due to the fact that it slows down enzyme activity and reduces tnitotic rate (Krebs & Sehaltegger 1965, Suurmond 1965, 1966, Wilborn & Montes 1974). Anthralin is commonly used in concentrations of 0.1-0.8% (Baker & Wilkinson 1972). In these concentrations, however, it frequently eauses irritation of the skin and the treatment has to be temporarily discontinued. With the same concentrations the clothes, skin, hair and nails are discolored quite intensely. In a series of macroseopic, light- and electron-microscopic investigations, the absence of effect with topical therapy in cases of recalcitrant psoriasis among ambtilatory patients was attributed to the mechanical element of scraping off of the scales from the lesions (Brody 1975, 1976, 1977a). On the basis of the results of these investigations an ambulatory program for treatment of psoriasis has been developed (Table 1). If the psoriatie skin is exposed to the
least external tnechanical damage, an effect from anthralin is obtained even in such low eoneentrations as 0.01-0.05%. In these eoncentrations neither the involved nor the non-involved skin becotnes irritated nor does diseoloration of the skin, hair, nails or clothes occur (Brody 1976). Material and Methods
24 patients (Table 2) were divided into three groups, A-C. Group A ineluded patients 1-19, who were treated strictly according to the method shown in Table 1. Group B included only one patient (no, 20). Before treatment, this patient had suffered such severe hand (Fig. 6a) and foot damage, including nail involvement, that he had difficulty in walking and in holding things. As he was living alone and was not able to treat himself, he had to be hospitalized. He also had extensive lesions with pustules over large parts of his body (Fig. 5a). Mondays through Fridays the patient received treatment at the outpatient Skin Department. In addition to this, on Saturdays and Sundays help at the inpatient ward with the application of the ointment as shown in Table 1 was provided. Group C comprised patients
234
BRODY AND JOHANSSON Table 1 Treatment program
I. General Instructions The patients are instructed not to pick off the seales and to abstain from scratching and scrubbing the lesions and the skin in its entirety, ineluding the sealp and the nails, if changes are found also on these areas. When the patient washes with soap, only the palnrs of the hands should be used, and the skin should be dried only with a soft towel and without rubbing the skin. The patients may not use their nails or brushes, ineluding nail- and hair-bru.shes, nor may they use sponges, washeloths or coarse towels. Thus, as tar as is praetieally possible, the patients must avoid meehanieal damage to the skin, the scalp and the nails II. Antihistamines are given at least until the indurated, desquanrating lesions are transformed into macular psoriasis III. A. Topical treatment of indurated, desquamating lesions (1) Mondays-l'"ridays treatment onee daily at the outpatient Skin Department (a) 10-15 min bath with liquor earbonis detergens or Mediterranean sea-salt. Mondays and Thursdays eareful lathering with soap and washing of the entire skin, including the lesions, witlr the palms of the hands (b) Ultraviolet light radiation (see under Material and Methods) (e) On the body: thin applieation of 0.01-0.05% anthralin, 10% salicylic acid in white petrolatum. Use of tubular gauze to keep the ointment in plaee and prevent the patients from seratching the skin directly For the nails: thin application of 0.03 % anthralin, 10% salicyelic acid in petrolatum alburn on the nails and on the skin around the nails and on the dorsal surfaee of the entire distal phalanx. Use of eotton gloves and/or stoekings during night For the sealp: 0.03% anthralin, 4% salicyelic acid in lard (= adeps suillus stabilisatus). every other day with washing of the hair every alternate day. Avoid getting ointment in
the eyes (2) Saturdays and Sundays treatment at home once daily with 0.03% anthralin, 10% salieyclic acid in petrolatum album. Use of tubular gauze or thin cotton underwear, and cotton gloves or stoekings. No bath or shower III. B. Treatment of macular psoriasis and scratch marks, of clinically normal skin at the site of earlier lesions and of nail and scalp changes at home (1) The body: Thin applieation of 0.01-0.03% anthralin, 4% salicyhc acid iu petrolatum alburn. Baths, showers and steanr-baths as de.sired. Continued gentle care of the skin as far as this is praetieally possible (a) Macular psoriasis and scratch marks: treatment onee daily (b) Clinically normal skin at the site of earlier lesions: treatment 2-3 times a week (2) The nails: Thin appHeation of 0.03% anthralin, 4% salieyelic acid in white petrolatunr on the nails and on the skin around the nails and on the dorsal surfaee of the entire distal phalanx once daily (3)The scalp: thin applieation of 0.03% anthralin, 4% salieyelie aeid in lard (= adeps suillus stabilisatus) onee a week or onee a fortnight, 8-10 h before washing the hair. No use of hair-brushes
21-24, They were given general instructions as indicated in Table 1 and were also prescribed antihistamines. The patients applied. at home, 0.01-0.03% anthralin and 10% salicylic acid in white petrolatum once daily until all indurated and desquamating lesions had turned into macular psoriasis (Brody 1977b). After this, the patients used 0.010,03% anthralin, 4% salicylic acid in white petrolatum both on macules and on the clinically normal skin at the site of earlier lesions according to III B (Table 1). Those patients who had scalp changes used 0,03%
anthralin in the salve composition indicated under IIL A: lc and III. B: 3 (Table 1). The patients in groups A and B were given tar baths and ultraviolet light radiation at the outpatient Skin Department. A Hanau Original type Hohensonne 2100 lamp, which permits a radiation period of 2-15 sec given at a distance of one tneter from the skin, was used. During the first 3 days, 2 see of ultraviolet light irradiation was given on the front and back of the body, respectively. Thereafter, the exposure was gradually increased by 1 sec every fourth day until 7 see on the
TOPICAL TREATMENT PROGRAM FOR PSORIASIS
235
Table 2 Patient material
Patient no.
Age of patient in years
Sex
A: 1
4
2 3 4 5 6
8 10 18 18 23
7
25
9
8 9
29 37
6 6
Duration of disease
64
9 9
73
9
16 months 3 years 6 years 18 months 17 years 20 years 15 months 14 years 17 years 13 years 21 years 25 years 27 years 26 years 18 months 42 years 50 years 17 months 20 months
B:20
66
d
40 years
C:21
15 15 26 29
9
6 months 18 months 10 years 19 years
10
42
11
44 45 50 52 53 57 63
12 13 14 15 16 17 18 19
22 23 24
front and back of the body, respectively, were maximally given, a period that was not reached until the 21st day of treatment. The patients in group C, who had the same extensive, recalcitrant psoriasis as the patients in group A, were given neither-tar baths nor tzltraviolet light radiation. Nine of the patients were carefully photographed before the treatment, once a week or once a fortnight for the first 3 to 6 weeks, and thereafter once a month or once every third month. From the other patients, who were not photographed, careful frequent notes regarding localization, extent and type of changes were made. The evolution of the lesions was also followed with light and electron microscopy. The effect of the treatment was graded on the basis of a 1-6 scale (see Table 3 and
9 9 6
9 •
6
9
a
6
6 9 c5 d 6
9 9 9
footnote). In view of results obtained earlier (Brody 1975, 1977b) the effect of the treatment was evaluated according to the following criteria: (1) the extent of the lesions in relation to their extent before the commencement of treatment, and (2) the occurrence of a) indurated and/or desquamating lesions, b) macules and c) clinically normal skin at the site of earlier lesions. Results
In the patients of groups A and C a clear effect was observed as early as the 7th day of treatment (Fig. 3), although the scales had not been scrubbed off before the application of the ointment. The lesions at all sites showed a transition to macules within 3-6 weeks after the start of treatment (Table 3, Figs, 1 and 2). In 20 of the patients in groups A and C a transition from macular
236
BRODY AND JOHANSSON
Fig. 1. Case No. 5 before treatment.
TOPICAL TREATMENT PROGRAM FOR PSORIASIS
237
Fig 2. Case No. 5 29 days after initiation of the treattnent progratn aecording to Table 1. Only macules are left. Note the guttate form of the tnacnles on the back in Tig. 2b.
238
BRODY AND JOHANSSON Table 3 l'lffect of treatment
Patient no.
A: 1
Time for transition to maculae after start of treatment in days
Time for transition to clinically normal skin after appearanee of maculae in months
2
30 29
3
22
31/2 _
4 5
23
4
6 7
8 9 10 11 12 13 14 15
16
3
5 2'/2
I4y2
1
40 24
2 3
7 11
1 4
10 "/2
35
2>/2
i4y2
4
8
11 12 6'/2 8
1
29 19 32
_
41
30 32 32 25
1 2 3 4
30 40
2'/2
42 17
4 2
B:20
60
3'/2
C:21
30 20 36 27
3 2V^ V/2
3
6 7
Results*
Time for relapse after start of treatment in months
3 1 2 1 2 5 5
17 18 19
22 23 24
Observation time after start of treatment in months
4'/2 6 5Vi
6
7
5 3
3'/2
1
7'/2 14
6
2 1 1
13
1
6
2 1 1 1
9 12"/2
3'/2
4
14
51/2
3
*Explanation of the numerals under Results 1. Lesions-free: no visible ehanges 2. Almost completely lesions-free: few maeules 3. Considerably improved: slight desquamation on elbows and/or knees, and/or sealp, orseattered maeules on the body 4. Improved: desquamating, indurated lesions but of eonsiderably lesser extent than before the start of treatment 5. Unehanged status: the same appearanee and extent as before the treatment 6. Worsening: same appearanee but with increased extent as compared with status before the treatment
psoriasis to elinically normal skin was observed 1-4 months after the appearance of macules in all areas (Table 3, Fig. 4), At the time of the application of the material, or 4'/2-14!/2 months following the beginning of treatment, 11 of the patients in groups A and C were completely lesions-free, four
patients were almost completely so, while two patients were considerably improved. Six of the patients in group A had a relapse with indurated, desquamating lesions, three of them 7-10y2 months and three of them 3-3/2 months after the start of treatment (Table 3). In those patients in whom clinically
TOPICAL TREATMENT PROGRAM FOR PSORIASIS
239
Fig. 3. Case No. 5. a. Higher magnifieation of the lesions on the lateral surface of the right lower leg in Fig. lc, before treatment, b. The lesions in the same area after 7 days' treatment.
Fig. 4. Case No. 13. a. Before treatment, b. Lesions-free after 2 months' treatment.
240
BRODY AND JOHANSSON
normal skin appeared before the relapse, the relapsed area was eonsiderably less extensive than before the treatment began. In the other patients the relapsed area was of the same extent as before the treatment. While questioning patients in group A it appeared that the degree of effeet, when viewed in a longer perspective, seemed to depend largely on the seriousness with which they took care of their skin according to the instructions given in Table 1. Before the start of treatment patient No. 20 in group B had extensive ehanges with firmly adhering scales and pustules elsewhere on the body (Fig. 5a). On the palms (Fig. 6a) and the soles the skin was greatly thickened and showed seales and large, deep fissures. All the nails on the fingers and toes were greatly thickened and discolored and presented numerous pits. Although the firmly adhering scales were not scrubbed off before the application of the ointment, it was possible to observe improve-ment of the lesions on the body (Fig. 5b), on the hands (Fig. 6b) and on the feet within 16 days after the treatment started. But in the case of this patient, it was still possible, 40 days after the commencement of treatment, to note a fine peeling and a rather intense redness at all the sites of previously indtirated, desquamating changes, exeept on the lower legs. Three-and-a-half-months after the treatment started, the skin was clinically normal at all locations except on the lower legs where rather large, brownish macules were still appearing. Sometimes these were above prominent varices (Fig. 5e) and seemed related to stasis eczema (cf. Ingram 1954). The patient was still lesionsfree exeept for the brownish maeules on the lower legs 13 months after the treatment was eommeneed (Table 3, Fig. 5d). Also the skin of the hands (Fig. 6 a-d) and feet, ineluding the nails, showed progressive improvement. At 13 months after the start of the treatment the skin on the hands and feet was completely lesions-free. The nails showed an almost normal thiekness and color with only a few pits.
Discussion
The present results eonfirm earlier observations (Brody 1977b) indicating that, if the entire patient's skin, including of eourse the lesions, is exposed to the least possible external meehanieal damage (Brody 1975, 1976, 1977a) it is possible to obtain very good results even with sueh low eoncentra tions of anthralin as 0.01-0.05 %. With the criteria chosen to judge the effect of treatment, 12 patients beeame eompletely lesions-free, four patients almost eompletely so, while two patients showed considerable improvement during an observation period of 4'/2-14y2 months. Six patients had a relapse in the form of indurated, desquamating lesions. It seems that the longer the patients were free of the lesions, the less extensive was the relapsed area. Among the parameters considered to evaluate the effect of treatment are ehanges in the degree of desquamation and indtiration. This is possible to ascertain only in lesions -where there is a turn into maeular psoriasis (Brody 1977b). But changes in the degree of desquamation and induration in cases of recalcitrant psoriasis (where there is no transition to macular psoriasis) tell us nothing. Thus in the recalcitrant lesions one found, maeroseopieally and regularly, (Brody 1975) the following sequenee of changes: horny layer with scales that were scratched off-^fresh scratch marks-^old scratches->horny layer with smooth skin surface and without seales-^homy layer with coarse skin surface pattern and without scales^horny layer with scales that were scratched off-*fresh scratches etc. Where the recalcitrant lesions showed a maeroseopieally horny layer without seales or where a reduced induration seemed visible, it would not be logical simply to jump to the conclusion that the redueed desquamation and/or induration was a eonsequenee of the topical therapy. In previous publications, stress was plaeed on the importance of using anthralin in concentrations of 0.1-0.8% and of its being applied only to the lesions themselves
TOPICAL TREATMENT PROGRAM FOR PSORIASIS
241
Fig. 5. Case No. 20. a. Before treatment, b. Improvement after 16 days' treatment, e. After 3% months' treatment elinically normal skin is seen on all sites except for latge brownish maeules on the lower legs. d. After 11 montlis' treatment elearing persists.
Fig, 6, Case No. 20. a. Before treatment, the palm shows indurated, desquamating skin with deep fissures. b. After 16 days' treatment fissures are no longer seen. e. After V/i months' treatment the skin is elinically normal but the naUs are still thickened, d. After 11 months' treatment the skin is clinically normal and the nails show an almost normal thiekness.
TOPICAL TREATMENT PROGRAM FOR PSORIASIS in order, as much as possible, to eliminate the risk of primary irritation. Nevertheless, such skin irritation has been very eommon and led to temporary discontinuation ofthe treatment (Weigand & Everett 1967, Farber & Harris 1970). To facilitate application of the anthralin to the lesions themselves, a paste has also been used as a base (Ingram 1953, 1954, Weigand & Everett 1967, Farber & Harris 1970, Baker & Wilkinson 1972). But the paste sticks firmly to the lesions so that, in order to properly reapply fresh paste, it is first neeessary to remove the paste applied earlier. This involves a certain trauma -with the scraping away of the scales and parts of the horny layer, leading to excoriations. In our program this is avoided by using white petrolatum as a base instead of a paste for the body and lard (= adeps suHlus stabilisatus) to the scalp. Anthralin in the usual coneentrations of 0.1-0.8% implies not only the risk of irritation, but also strong discoloration of the clothes, the skin, the hair and the nails. With the 0.010.05% anthralin, neither the involved nor the non-involved psoriatic skin becomes irritated, thus one does not need to combine anthralin with corticosteroids as proposed by Farber & Harris (1970). Nor are skin, hair, naUs or clothes discolored. Applied in this fashion, anthralin then becomes very suitable for use in ambulatory therapy.
Acknowledgements
This investigation was supported by grants from the Sodermanland County Council and from the Edvard Welander Foundation. References
Baker, H. & Wilkinson, D. S. (1972) Psoriasis. In Textbook of Dertnatology, eds. Rook, A., Wilkinson, D. S. & Ebling, F. J. G. pp. 11921234. Oxford; Blackwell Scientific Publications. Brody, 1. (1975) Do excoriations in psoriasis delay or prevent the effect of topical treatment? Journat of Cutatieous Pathology 2, 163-169.
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Brody, I. (1976) Elektronermiikroskopisehe Beobaehtung bei Psoriasis vulgaris unter der Behandlung. In Sytttpositittt I. Aktuelle Frgebttisse der Elektrotienmikroskopie. Verhandlungen der Deutschen Dermatologischen Gesellschaft 30. Tagung in Graz, September 1974. Der Hautarzt, Suppl. 1, 207-208. Brody, 1. (1977a) Light and electron microscopy of excoriated psoriatic lesions in patients during topical treatment. Journal of Cutaneous Pathology 4, 68-79. Brody, 1. (1977b) Clinieal and morphological aspects of the topieal treatment of psoriasis. In Proeeeditigs of the Seeond Internatiotial Syttiposiutit on Psoriasis, Stanford, .luly 1976, eds. Farber, E.M., Cox, A.J. & Jaeobs, P.H. pp. 447^49. NewYork: Yorke Medieal Books. Farber, E. M. & Harris. D. R. (1970) Hospital treatment of psoriasis. A modified anthralin program. Archives of Dertnatology 101, 381389. Galewsky (1916) Uber Cignolin, ein Ersatzpraparat des Chrysarobins. Dermatologisehe Wochetischrift 62, 111-115. Ingram, J. T. (1953) The approach to psoriasis. British Medical .lotirtiat 2, 591-594. Ingram, .1. T. (1954) The significance and rnanagemcnt of psoriasis. British Medical Journal 2, 823-828. Krebs, A. & Sehaltegger, H. (1965) Experimentelle Untersuchuiigen iiber den Wirkungsmechanismus von Chrysarobin und Dithranol bei Psoriasis (lndizien fur eine eytostatische Wirkung an der l'^pidermis). Dertnatologiea 131, 1-27. Suurmond, D. (1965) Histologie changes in treated and untreated psoriasis lesions. Dertnatologiea 131, 357-366. Suurmond, D. (1966) Histochemical ehanges in treated and untreated psoriasis. A comparative enzyme histoehemieal study on the effect of topical cortieosteroid and anthralin treatment. Dermatologica 132, 237-247. Weigand, D. A. & Everett, M. A. (1967) Clearing of resistant psoriasis with anthralin. Arehives of Dermatology 96, 554-559. Wilborn, W. H. & Montes, L. F. (1974) Ultrastructural changes in psoriatic epidermis following anthralin treatment. Journal of Cutaneous Pathology 1, 132-150. Address: Isser Brody Depart ttient of Dertnatology General Hospital S-631 88 Eskilstutia Sweden
