Treatment for Psoriasis with Modified Goeckerman Regimen -One Year Experience in Southern Taiwan-

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1 Treatment for Psoriasis with Modified Goeckerman Regimen -One Year Experience in Southern Taiwan- Chih-Sheng Lai Po-Han Huang Ji-Chen Ho Despite the recent advances in treatment for psoriasis, it is still challenging in treating patients with moderate to severe psoriasis. The Goeckerman regimen, which was introduced by Goeckerman in 1925, is still considered to be one of the most effective and relatively safe therapies for patients. We started the modified Goeckerman regimen for treating moderate to severe psoriatic patients in Taiwan in March, patients had been treated from March 2002 to May Among them thirty-two patients with more than 5% body surface area psoriatic lesions, who had neither systemic therapy in the past 6 months nor concurrent oral antipsoriatics during this treatment, were collected. The mean psoriasis area and severity index (PASI) scores declined from to during therapy, and the mean duration of remission was months. There was no severe side effect though mild local burn and itching were fairly common. Herein we present the preliminary data and comparison to other therapies in the literature.(dermatol Sinica 23: , 2005) Key words: Psoriasis, Goeckerman regimen, Tar, Ultraviolet, Phototherapy ( 23: , 2005) From the Department of Dermatology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan Accepted for publication: March 10, 2005 Reprint requests: Po-Han Huang, M.D., Department of Dermatology, Chang Gung Memorial Hospital,123, Ta-Pei Road, Kaohsiung, Taiwan, R.O.C. TEL: ext FAX: ext Dermatol Sinica, Sep 2005

2 INTRODUCTION Psoriasis is a distressing, chronic disease that affects skin and joints with estimated prevalence varies from 0.1 to 2.8% in the general population in published reports. 1, 2 The prevalence in the Mongoloid race was estimated about 1% in spite of the climate geographic difference. 3 The therapies for this disease had much advances in the past decades but it is still challanging in treating moderate to severe patients. We introduced the modified Goeckerman regimen in March 2002 and established our psoriasis day care center at the same time. Herein we present our preliminary data of the past 1 year. This report is not intended to be a well controlled study but to share our experience in treating psoriasis with the modified Goeckerman regimen. MATERIALS AND METHODS PATIENTS Patients with moderate to severe chronic plaque type psoriasis (body surface area >5%) who had poor response to previous therapy and could follow the treatment schedule of our psoriasis center were enrolled in the day care program. Those who were allergic to tar preparation or could not tolerate the odor of tar were excluded. Patients who took other systemic medications for psoriasis during or within 6 months before enrollment were excluded in this preliminary report. 32 patients were collected between March 2002 to May 2003 (Fig. 1). DAY CARE PROGRAM Tar preparation at different concentrations was applied to the whole body surface except the face and genitalia, and occluded with clothes or plastic tapes for at least 5 hours. After that, the patients took a shower to wash off tar and received phototherapy with broad band ultraviolet B (UVB) thereafter. TAR PREPARATION Polytar emollient (tar 7.5%, coal tar 2.5%, cadeoil 7.5%, Arachis oil extract of crude coal tar 7.5%, Stiefel) or coal tar and salicylic acid (1g contains strong coal tar solution 0.1ml, salicylic acid 20mg, Otsuka-Taiwan) were used. The concentration of tar preparation e.g. polytar emollient was diluted to 2% for most patients and 1% for patients with marked erythema. If there was no obvious irritation or discomfort after 3 consecutive treatments, the concentration was increased to 5%. After another 3 treatments the concentration was added to 10% and then kept till the end of treatment. Genital area was spared of tar and treated with mid-potent topical steroid if lesions present (few of our patients had genital lesions). Fig.1 Flow chart of patient selection. Dermatol Sinica, September

3 PHOTOTHERAPY Broad band UVB (NBC HOUVA II, PHILIPS UVB TL100W/12) was used with initial dose around mj/cm 2 according to the skin type and degree of erythema. The dose was then increased 10-15% each time till mild erythema but no obvious burn was noted. The patients received 5 times of therapy per week. CONCURRENT THERAPY Topical calcipotriol ointment or scalp lotion (0.005%) was routinely used in all patients after phototherapy. Tazarotene gel (0.1%) was used in thick plaques of 16 patients. Mid to low potency topical steroids were prescribed only to relieve irritations from tar preparations or mild burn following phototherapy. Otherwise, topical steroids were prohibited. MAINTENANCE THERAPY Patients who completed the course of modified Goeckerman s regimen were suggested to keep phototherapy 1-3 times per week and the frequency was decreased gradually if condition was stable. Topical calcipotriol and tazarotene were used as needed. Topical steroids were still prohibited except relief of burn following phototherapy. If relapse occurred, systemic medications were prescribed or modified Goeckerman regimen was done again. RELAPSE OF DISEASE Since there was no consensus on the definition of relapse and the criteria varies greatly, we defined relapse as more than 5% body surface area involvement or more than 30% of ini- tial lesions, which was near the median value of previous literatures. Because our patients were followed at different hospitals in Taiwan, some of the data were got by telephone contact with the patients. PATIENT OVERALL SATISFACTION At the end of follow up the patient s overall satisfaction about this therapy was assessed with visual analogue scale (0-10) which was obtained by telephone contact. RESULTS There were 20 males and 12 females included in this report. The average duration of treatment was weeks (range 2-14 Fig. 3 Percentage of patients achieved 50% improvement in PASI score (PASI 50) and 75% improvement of PASI score (PASI 75) in all patients and in whom initial PASI score >10. Fig. 4 Percentage of patients achieved PASI50 and PASI75 stratified by initial PASI score. A: initial PASI<10; B: initial PASI 10-20; C: initial PASI>20 Fig. 2 The PASI score during therapy. Fig. 5 Two of the patients before and after treatment. 115 Dermatol Sinica, September 2005

4 weeks) and the final dose of UVB in average was mj/cm 2. Their demographic data had shown in Table 1. PSORIASIS AREA AND SEVERITY INDEX (PASI) SCORES DURING THERAPY The mean PASI score at the initial and the end of the therapy was and The mean PASI score at initial was for the more severe subgroup (BSA>10%). The changes of PASI in each week were shown in Fig. 2. The percentage of patients who achieved 50% improvement (PASI 50) and 75% improvement (PASI 75) were shown in Fig. 3, and the percentage of patients achieved PASI 50 and PASI 75 subclassified according to the initial PASI scores were shown in Fig. 4. Two of the patients photographs before and after treatment were shown in Fig. 5. SIDE EFFECTS DURING THERAPY Because of aggressive phototherapy, localized burn was frequently seen (23 in 32 patients, 72%). However, more generalized first degree burn was seen in only one patient (3%). Itching was also common. In 32 patients, there were 18 (56%) patients experienced moderate to severe itching during therapy, especially at night. Besides, irritation due to tar preparation, marked lichenification, and obvious new lentigines lesions (>5 new lesions) were occasionally seen. The side effects and their frequency were listed in Table 2. FOLLOW-UP DATA 28 of 32 patients were contacted and traced their condition after therapy at clinics or by telephone. The mean follow-up time was months (range 5-18). The average duration to relapse was months. If the patients were subclassified according to the initial PASI score to PASI <10 (n=9), PASI (n=10), and PASI >20 (n=9), the mean duration to relapse were , , and (Table 3). There were 15 patients still in the remission status at the end of the follow up. The most common site to relapse was the scalp (n=13). the overall satisfaction evaluated with visual analogue score (0-10) was The follow-up data was summarized in Table 3. DISCUSSION Psoriasis is a chronic immune-mediated disease that bothers the patients very much. Despite the advances of psoriasis treatment in the past decades, it is still challenging. Many patients, and even some dermatologists who treat them, are frustrated because of unsatisfied result with most treatment modalities. According to the past literature, the Goeckerman treatment, which firstly described by Goeckerman in 1925, or its modifications (Table 4), is one of the most effective and safest treatments for psoriasis patients with severe or disabling disease. 4 Therefore we have introduced the modified Goeckerman regimen since March Because we would like to provide Table 1. Basic data of the patients. Mean SD Range Male : Female 20:12 Age Age of onset Duration of psoriasis (year) Family history 2 in 29 Duration of treatment (week) Final dose of Whole body(n=32) UVB(mJ/cm2) Legs(n=14) Table 2. Side effects during therapy. Case number(n=32) Percentage(%) Burn (localized) Burn (generalized) 1 3 Itching Irritation 3 9 Marked lichenification 2 6 Lentigines 5 16 Dermatol Sinica, September

5 a day care program and make the best use of the photosensitivity of tar preparation, a one-day 5- hour tar occlusion with following light therapy was designed. However, there was no controlled trial to compare different modifications of the Goeckerman regimen. While selecting our patients, severity was obviously an important factor. However, there was no standard criteria for the definition of severity in psoriasis. 5 Most authors or clinical trials defined severity by body surface area involvement or the PASI scores, but others thought that quality of life and subjective perception should be important issues. 5 We selected our patients by both body surface area involvement and patients' need which could be categorized as moderate or severe. The criteria we used (>5% BSA) was similar to the definition of the National Psoriasis Foundation in which 2%-10% BSA was categorized as moderate and more than 10% BSA was severe. 6 The milder subgroup of our patients were either with lesions over the critical areas (face, hands, etc.) or with poor response to previous therapies. Therefore they were enrolled in the treatment with modified Goeckerman regimen. Spuls et al. reviewed the systemic treatments for severe psoriasis in 1997 and found that PUVA was most effective with clearance rate (95-100% improvement) 70% and good response rate (75-100% improvement) 83%, followed by UVB, cyclosporine, and retinoids (etretinate/acitretin) with good response rate of 68%, 64%, and 56%. 7 MTX was not included in their review because most literatures were with concomitant antipsoriatic therapy, outdated dosage, or inadequate documentation. Another randomized controlled study of MTX versus cyclosporine in moderate-to-severe chronic plaque psoriasis in 2003 revealed that roughly 60% and 40% of patients treated with MTX and 71% and 33% of patients treated with cyclosporine achieved partial (more than 75% reduction in PASI score) and complete (more than 90% reduction in PASI score) remission. 8 Comparing our data to these systemic therapies, it seems that our regimen is not superior since only 66% of patients reach PASI 75. However, an interesting finding is that if the patients are subclassified with initial PASI score to <10, 10-20, and >20, it seems that the more severe initial condition, the better response during thera- Table 3. Follow-up data. Mean SD Range Duration of follow up (months)(n=28) Duration to Total (n=28) relapse Severe group Initial PASI > (months) (months)(n=19) Subclassified Initial PASI < by PASI (months)(n=9) Initial PASI (months)(n=10) Initial PASI > (months)(n=9) First site to recur (n=28)* Scalp: 13; legs: 6; trunk: 3; arm: 1; face: 1; nonspecific: 1 URI or stressful event before relapse (n=28)* 2 Patient satisfaction (VAS 0-10) *including patients with focal recurred lesions but not fulfill the definition of relapse 117 Dermatol Sinica, September 2005

6 py is noted (PASI 75 are 33%, 58%, and 91% in each group), though the duration of remission is much shorter in the most severe group (see discussion below). Menter et al. claimed greater than 90% improvement was achieved in all their 300 patients. 9 However, most enrolled patients are 20% or more of BSA according to the suggested guidelines at most psoriasis centers. 10 Therefore, the response rate of the more severe group is quite similar. As to the less severe groups ( less than 20% of BSA), we highly suspect if the relatively poor response is due to inadequate treatment in some patients, especially the less severe groups (several patients terminated before all lesions cleared because of job or better looking). Definitely, the majority of our patients were more satisfied with the modified Goeckerman regimen than previous other systemic therapy. There are several different modifications of the Goeckerman regimen in the world. In the Mayo Clinic, they applied 2% crude coal tar in petrolatum three times a day and then removed excess ointment before phototherapy in the next morning. After phototherapy a cleansing soap tub bath was given before new ointment was applied. 4 In Mount Sinai Medical Center, 5% tar preparation was applied at bedtime followed by an early morning soap and water bath. After that, phototherapy was done. 11 Another different regimen used in the University of California, San Francisco (UCSF) and the Baylor University Medical Center, Dallas (BUMC) was initial UVB treatment followed by a tar shampoo, and 2-5% crude coal tar application. The tar application was repeated twice during the day. Prior leaving the center, patients bathed or showered off the residual tar. 9 The duration of remission were 1.7 years in male and 1.8 years in female in the Mayo Clinic, 125 days (remained clear) in the Mount Sinai Medical Center, and longer than 1 year in 73% patients in the UCSF and BUMC. Our regimen was most similar to the Mount Sinai Medical Center because we both applied tar and then wash off before phototherapy. This method s advantage might be that no remaining tar on the skin would promote UVB penetration and irradiated at the most photosensitive period after tar application. The average remission time of our patients was a little shorter than these centers but possibly due to shorter follow-up period. Table 4. Original Goeckerman regimen and some of its modifications. Centers Regimen Original Goeckerman Application of CCT UV radiation (hot quartz) regimen 21 removal tar with olive oil oatmeal and soda bath Mayo Clinic 4 2% CCT in petrolatum applied 3 times a day remove excess oint with gauze pad saturated with vegetable oil in the next morning UV radiation (hot quartz) cleansing soap tub bath Mt Sinai Medical Center 11 Application of CCT or polytar at bedtime early morning soap and water bath UV radiation emollients as needed UCSF/BUMC 9 UVB tar shampoo CCT to the general body with occlusion twice daily 6-7 hr later wash off tar emollients KCGMH Tar preparation with occlusion 5 hr later wash off the tar UVB radiation emollients as needed CCT: crude coal tar; UCSF: University of California, San Francisco; BUMC: Baylor University Medical center; KCGMH: Chang Gung Memorial Hospital, Kaohsiung Dermatol Sinica, September

7 There was also at home Goeckerman regimen which could reduce hospital stay but with shorter remission time (5.1 months). 12 One of the most important factors that patients care is the duration of remission of a specific therapy. Since psoriasis is a chronic disease, the duration of remission means the period that patients may get off from hospital and medication and live a more normal life. According to previous literature, topical corticosteroids, calcipotriol, or tazarotene maintained remission for about only months. 13 Other systemic medications did not do better: etretinate may maintain remission before any sign of psoriasis or the appearance of any new lesions for about 8 weeks; cyclosporine treatment associated with relapse with PASI returned to 50% of the baseline in only 6 weeks; and methotrexate had remission time from about 10 weeks to 6 months. 13 The biologics, which mark the new era of psoriasis treatment, though relatively safe and convenient, have an average remission time of 7 months or shorter Phototherapy alone also has average remission time of only 4 to 5 months. 13 In the review of Koo and Lebwohl, the therapies that had longest remission time were phototherapeutic modalities, especially Goeckerman and PUVA therapy. 13 It s difficult to compare all studies because the definition of remission or relapse varied greatly. However, it is universally recognized that the Goeckerman regimen, or its modifications, may maintain remission much longer than other systemic therapy except PUVA. Some author claimed that the remission time after Goeckerman therapy was as long as years. 4 Our data was not so good but 15 of 32 patients still in remission status at the end of follow up. Therefore the mean remission time may be longer if we keep following these patients. Another interesting finding in our data was that it seemed no obvious difference in the duration of remission between two groups with PASI <10 and PASI (11.5 versus 13.2 months). However, for the most severe group (PASI >20), the mean duration of remission was much shorter (5.6 months) in spite of the high percentage (91%) reached PASI 75 at the end of therapy. We wondered if this could correlate to the findings reported by Peng Y et al. that these patients belonged to the most severe and refractory group (type 6). 18 Because of the chronic nature of psoriasis, not only effectiveness but also safety is an important consideration while treating these patients. Although systemic agents such as methotrexate, cyclosporine, or acitretin may have good therapeutic effects, possible side effects to liver, kidney, hematopoietic system, or fetus may limit use. 19 The modified Goeckerman regimen, however, has few side effects both in the previous literature and in our experience. Common acute side effects including light sensitivity (5%), tar sensitivity (1%), and folliculitis were reported. 12, 20 We found other immediate complications including itching, localized burn, marked lichenification, and obvious new lentiginous lesions. Concerns about long term complication such as increased skin cancer incidence have not been observed even after 25 years follow up. 4 There are still some advantages with the mode of day care center. First, patient-patient and patient-physician interaction was more frequent and some kind of unofficial supporting group might develop in such environment. Actually, many patients have had better mood during therapy not only due to improvement in skin lesions but also due to empathy and supports of other patients. Second, since patients will stay for hours each day at hospital, therapeutic group sessions, relaxation and exercise classes or other activities may be conducted in the day care center, as at the UCSF and BUMC. 9 Although very effective and safe, however, the modified Goeckerman regimen has some disadvantages which makes it lesser been used today. First, it is very time-consuming. Each patient has to stay at hospital for 6-7 hours per day, 5-6 days per week, and lasting for about 5 weeks. Some of our patients that could not reach 75% improvement of PASI score were due to limitation in time available to stay at our 119 Dermatol Sinica, September 2005

8 hospital. Second, it is too messy for many patients to accept this therapy. Other disadvantages might be encountered including accelerated photoaging which should be concerned during such therapy. CONCLUSION Herein we reported this preliminary data about our experience of treating psoriasis patients with the modified Goeckerman regimen in Taiwan. Our experience confirmed that the modified Goeckerman regimen is still a good alternative choice if proper space and equipments are available. REFERENCES 1. Farber EM, Nall L: Epidemiology: Natural History and Genetics. In: Roegnigk HH, Maibach HI, eds. Psoriasis. 3rd ed. New York:Marcel Dekker, , Christophers E, Mrowietz U: Psoriasis. In: Freedberg IM, Eisen AZ, Wolff K, et al., eds. Fitzpatrick s Dermatology in General Medicine. 6th ed. New York:McGraw-Hill, , Yip SY: The prevalence of psoriasis in the Mongoloid race. J Am Acad Dermatol. 10: , Muller SA, Perry HO: The Goeckerman treatment in psoriasis: six decades of experience at the Mayo Clinic. Cutis 34: , Krueger GG, Feldman SR, Camisa C, et al.: Two considerations for patients with psoriasis and their clinicians: What defines mild, moderate, and severe psoriasis? What constitutes a clinically significant improvement when treating psoriasis? J Am Acad Dermatol 43: , Lebwohl MG, Feldman SR, Koo JYM, et al.: Psoriasis: Treatment options and patient management. National Psoriasis Foundation, 1-5, Spuls PI, Witkamp L, Bossuyt PMM, et al.: A systematic review of five systemic treatments for severe psoriasis. Br J Dermatol 137: , Heydendael VMR, Spuls PI, Opmeer BC, et al.: Methotrexate versus cyclosporine in moderate-tosevere chronic plaque psoriasis. N Engl J Med 349: , Menter A, Cram DL: The Goeckerman regimen in two psoriasis day care centers. J Am Acad Dermatol 9: 59-65, Camisa C: Handbook of psoriasis. 1st ed. Blackwell Science, , Cort DH, Schleider NR, Moskowitz RS, et al.: Retrospective analysis of a modified Goeckerman regimen for the treatment of psoriasis. Cutis 25: , DesGroseilliers JP, Cullen AE, Rouleau GA: Ambulatory Goeckerman treatment of psoriasis: experience with 200 patients. CMAJ 124: , Koo J, Lebwohl M: Duration of remission of psoriasis therapies. J Am Acad Dermatol 41: 51-59, Krueger GG, Callis KP: Development and use of alefacept to treat psoriasis. J Am Acad Dermatol 49: S87-S97, Leonardi CL: Efalizumab: an overview. J Am Acad Dermatol 49: S98-S104, Goffe B, Cather JC: Etanercept: an overview. J Am Acad Dermatol 49: S105-S111, Gottlieb AB: Infliximab for psoriasis. J Am Acad Dermatol 49: S112-S117, ,,, et al.: : , Yamauchi PS, Rizk D, Kormeili T, et al.: Current systemic therapies for psoriasis: Where are we now? J Am Acad Dermatol 49: S66-S77, Perry HO, Soderstrom CW, Schulze RW, et al.: The Goeckerman treatment of psoriasis. Arch Dermatol 98: , LeVine MJ: Does tar belong in the Goeckerman regimen? Int J Dermatol 21: , Dermatol Sinica, September