Clinical Analysis of Psoriatic Inpatients -A 10-year Retrospective Study

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1 - Clinical Analysis of Psoriatic Inpatients -A 10-year Retrospective Study Ming-Hsiung Yeh 1 Tsen-Fang Tsai 2 Psoriasis is a common chronic inflammatory skin disease that is usually managed in outpatient clinic. There is a trend to reduce hospitalization for psoriasis globally in recent years. To analyze the reasons necessitating hospitalization for psoriasis, especially the causes of acute exacerbation, a retrospective study was carried out in psoriatic inpatients admitted to National Taiwan University Hospital between April 1996 and April Available data were obtained from 120 patients. On average, there was only one psoriasis admission each month. The male to female ratio was 2.9 : 1. The mean age on admission was 45.1 years. The mean duration of hospitalization was 15.3 days. No predominant season of admission was found. Chronic plaque psoriasis was the most common clinical type in psoriatic inpatients. The duration of hospitalization was significantly associated with older age and the clinical type of psoriasis. The reasons of admission were acute exacerbation (73.3%), outpatient treatment failure (15%), uncertain initial diagnosis (10%), and nonpsoriasis-related side effects of psoriatic treatment (1.7%). The most causes of acute exacerbation were unknown (35.2%), followed by infection (29.5%), psoriatic treatment (9.1%), withdrawal of systemic steroid (5.7%), Chinese medicine (4.5%), healthy food (4.5%), topical agents (4.5%), alcohol (3.4%), medication for other concomitant diseases (2.3%), and climate (1.1%). Numerous factors are known to exacerbate psoriasis. In this study, there are some exacerbating factors of psoriasis that have not been reported before. Because this is a retrospective study, there are still a considerable percentage of patients in whom no obvious exacerbating factor is identified. Further systematic prospective researches on the basis of this study will be helpful to understand the causes and pathogenesis of psoriasis. (Dermatol Sinica 25: , 2007) Key words: Psoriasis, Inpatients, Exacerbation From the Department of Dermatology, Cathay General Hospital 1, Department of Dermatology, National Taiwan University Hospital 2, Taipei, Taiwan Accepted for publication: January 31, 2007 Reprint requests: Tsen-Fang Tsai, M.D., Department of Dermatology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan TEL: FAX: Dermatol Sinica, Jun

2 2.9 : (73.3%) (15%) (10%) (1.7%) (35.2%) (29.5%) (9.1%) (5.7%) (4.5%) (4.5%) (4.5%) (3.4%) (2.3%) (1.1%) ( 25: , 2007) INTRODUCTION Psoriasis is a common chronic, immunemediated, genetic skin disease that varies in severity, which has important implication in terms of medical costs and treatment strategies. Numerous factors can exacerbate psoriasis, including infection, endocrine factors, hypocalcemia, medications, psychologic stress, or local trauma. 1 Psoriasis can considerably impair patients quality of life, and the therapeutic options should be based on objective assessment as well as the patients subjective morbidity. Although most psoriasis patients respond well to the various forms of outpatient therapy, a small percentage of patients can progress to one of the more severe forms of psoriasis and require hospitalization or more intensive treatment. The identification of exacerbating factors of psoriasis, especially the unnoticed ones, is helpful to give the patients a thorough instruction to prevent the aggravation of disease. To analyze the reasons necessitating hospitalization for psoriasis and find out the causes of acute exacerbation, a retrospective study was carried out in 120 psoriatic inpatients admitted to National Taiwan University Hospital between April 1996 and April MATERIALS AND METHODS Patients and clinical data The patients discharged from National Taiwan University Hospital with a main diagnosis of psoriasis between April 1996 and April 2006 were enrolled in this study. After searching the database, we found the patients were all admitted to dermatology ward. Because the attending physicians in charge of the care of psoriatic patients have not changed in recent 10 years, the criteria of admission and discharge are supposed to keep the same. The following clinical data were collected and analyzed: the gender, the age at onset and on admission, the year and season of admission, the clinical type of psoriasis, the reason of admission, the cause of acute exacerbation, the treatment, and the duration of hospitalization. The reasons of admission were classified into acute exacerbation, outpatient treatment failure, uncertain initial diagnosis, and nonpsoriasis-related side effects of psoriatic treatment. Acute exacerbation was defined as sudden worsening of the disease which was previously under control. The patients who had not achieved acceptable relief of the disease in the outpatient clinic were classified into outpatient treatment failure. The patients admitted under other tentative diagnosis and later definitely diagnosed as psoriasis were classified into uncertain initial diagnosis. Nonpsoriasis-related side effects were defined as the side effects other than worsening of psoriasis. The causes of acute exacerbation were inferred from the significant events prior to the occurrence of exacerbation. 104 Dermatol Sinica, Jun 2007

3 Fig. 1 Distribution of the age on admission for men and women. Fig. 2 Distribution of the duration of hospitalization for men and women. STATISTICS Categorical variables were described as frequencies and percentages. Continuous data were described as mean standard deviation. Unpaired two-tailed Student s t-test was used to compare continuous variables between two groups. One-way analysis of variance (ANO- VA) was used to compare continuous variables among three or more groups. The chi-square test was used to compare categorical variables. A 0.05 significance level was stabilized for all analyses. The tables, figures and analyses were done by Microsoft Excel RESULTS There were 120 psoriatic inpatients (89 men, 31 women; man : woman = 2.9 :1) in our hospital during this period. The mean age on admission was years (man, years; woman, years; p=0.894). The frequency distribution of the age on admission, considered at 10-year intervals, is shown in Fig. 1. The mean age at onset, exclusive of those admitted for uncertain initial diagnosis, was years (man, years; woman, years; p=0.719). There were 29 patients admitted in spring, 29 in summer, 29 in fall, and 33 in winter (p=0.940). Chronic plaque psoriasis was the most common clinical type among the inpatients (41.7%) (Table 1). Seventeen patients (14.2%) were concomitantly diagnosed as psoriatic arthropathy. The mean duration of hospitalization was days (man, days; woman, days; p=0.417). The frequency distribution of the duration of hospitalization, considered at 5-days intervals, is shown in Fig. 2. The duration of hospitalization was significantly associated with the age on admission (age 45 years, days; age<45 years, days; p=0.016) and the clinical type of psoriasis (nonpustular psoriasis, days; pustular psoriasis, days; p=0.034), but not associated with the reason of admission (acute exacerbation, 15.5 Fig. 3 Comparison of the reasons of admission by year. AE: acute exacerbation (p=1.000); OTF: outpatient treatment failure (p=0.996); UID: uncertain initial diagnosis (p=1.000); SE: nonpsoriasis-related side effects of psoriatic treatment (p=0.699). Dermatol Sinica, Jun

4 Table 1. Distribution of Psoriasis Subtype (n=120) Table 2. Comparison of the Duration of Hospitalization Table 3. Reasons of Admission (n=120) 106 Dermatol Sinica, Jun 2007

5 Table 4. Causes of acute exacerbation of psoriasis (n=88) Table 5. The Treatments of Psoriatic Inpatients (n=120) Dermatol Sinica, Jun

6 10.7 days; outpatient treatment failure, days; uncertain initial diagnosis, days; nonpsoriasis-related side effects of psoriatic treatment, days; p=0.840) and the year of admission (April 1996 to April 2001, days; April 2001 to April 2006, days; p=0.854). Comparison of the duration of hospitalization among different groups is shown in Table 2. The reasons of admission were acute exacerbation (73.3%), outpatient treatment failure (15%), uncertain initial diagnosis (10%), and nonpsoriasis-related side effects of psoriatic treatment (1.7%) (Table 3). The reasons of admission did not differ significantly by the year of admission (Fig. 3).The most causes of acute exacerbation were unknown (35.2%), followed by infection (29.5%), psoriatic treatment (9.1%), withdrawal of systemic steroid (5.7%), Chinese medicine (4.5%), healthy food (4.5%), topical agents (4.5%), alcohol (3.4%), medication for other concomitant diseases (2.3%), and climate (1.1%) (Table 4). Of the infection-exacerbated psoriasis, upper respiration infection was the leading cause (18 of 26). Of the psoriatic treatment-exacerbated psoriasis, efalizumab was the leading cause (6 of 8). There was one patient each exacerbated by oral Ganoderma lucidum ( ), oral Corbicula fluminea ( ), topical Euphorbia resinifera ( ), topical pesticide, topical propolis and oral terbinafine. The treatments of the psoriatic inpatients are listed in Table 5. Ten patients (8.3%) received single therapy, among which topical corticosteroids were the most commonly prescribed treatment modality (5 of 10). The most commonly prescribed systemic medication in combination therapy was oral retinoids (63 of 110), and the most commonly prescribed topical medication in combination therapy was corticosteroids (87 of 110). Phototherapy of ultraviolet B (UVB) was used more commonly than psoralen with ultraviolet A (PUVA) in combination therapy (56 versus 17 of 110). Goeckerman regimen, treatment with UVB phototherapy after applying coal tar for 4 to 6 hours, was used in 11 patients. Oral retinoids with topical corticosteroids were the most common regimen used in combination therapy (12 of 110). DISCUSSION Most psoriatic patients present with mild to moderate degree of disease and usually are not hospitalized for their skin condition. A small part of patients, however, may suffer from severe forms of psoriasis that have devastating consequences on every aspect of their lives. Life quality of these patients can be greatly improved after appropriate inpatient therapy. 2 Psoriasis was the most common diagnosis on admission at some medical centers in the United Kingdom and the United States. 3 Inpatient therapy can considerably shorten the mean length of treatment compared with outpatient therapy. 4 Our study provides the basic clinical data of psoriatic inpatients in Taiwan in recent 10 years, which can be a reference for establishing Diagnosis-Related Group (DRG) of psoriasis. The mean age on admission was 45.1 years, which is lower compared to the report in the United Kingdom. 4 The mean duration of hospitalization was 15.3 days, which is longer than the report in the United Kingdom 4 but shorter than the report in the United States 5 during the similar period. The inpatients in our study had a higher mean age both at presentation and at onset than the outpatients in the study of Chen et al., 6 whose mean age at presentation and at onset was 43.6 and 33.8 years, respectively. There was an interval of approximately 10.2 years between onset and presentation for both the inpatients and the outpatients. The male to female ratio of the inpatients was higher than that of the outpatients, which was 2.1 : 1. Plaque-form psoriasis was the most prevalent clinical type in the inpatients as in the outpatients. Although winter was found to be an exacerbating factor of psoriasis in half the outpatients, 6 the degree of exacerbation was probably mild so that no predominant season of admission was noted in the inpatients. The gender, the year of admission and the reason of admission did not have a significant impact on 108 Dermatol Sinica, Jun 2007

7 the duration of hospitalization. Patients older than 45 years and those presented with nonpustular psoriasis tended to have longer duration of hospitalization. Acute exacerbation was the most common reason of admission. Among the identifiable causes of acute exacerbation, infection was the most common one. Upper respiratory infection accounted for most infection-exacerbated psoriasis in our study. There have been numerous associations between group A beta hemolytic streptococci and guttate psoriasis. T lymphocytes specific for group A streptococcal antigens have been consistently isolated from guttate psoriasis lesions, 7 and altered responses of mononuclear cells to streptococcal antigen in psoriatic patients have been reported. 8, 9 There is an extensive sequence homology between streptococcal M6 protein and human K14 keratin to which immune system mediators can crossreact and produce psoriatic lesions. 10, 11 Besides, there were studies indicating that superantigens likely represent the important strategy by which bacteria and viruses altered T-cell responses and 12, 13 activate the immune system. In our study, there were 6 psoriatic patients admitted due to acute exacerbation during or after treatment with efalizumab. The 6 patients had a shorter duration of hospitalization, which was 9.5 days on average. Efalizumab is a humanized monoclonal antibody that binds to the alpha subunit of leukocyte function-associated antigen-1 (CD11a) on the surface of T cells, thereby preventing several T-cell processes important in the pathogenesis of psoriasis. 14 Psoriasis adverse events was reported to occur in 3.2% of patients treated with efalizumab during the first 12-week treatment period of phase III placebo-controlled studies. 15 The rate of rebound during the 12-week follow-up period after efalizumab discontinuation was 14%. Both psoriasis adverse events and rebound were more commonly observed in those patients with poorer response to therapy. Five patients were admitted due to acute exacerbation of psoriasis after withdrawal of treatment with systemic steroids: one patient presented with generalized pustular psoriasis, two with plaque-type psoriasis, and two with erythrodermic psoriasis. Oral steroids and particularly their withdrawal are well known etiological factors in acute generalized pustular psoriasis Extensive use of potent topical steroids was also reported to be associated with 19, 20 induction of generalized pustular psoriasis. Chinese herbal medicine was found to be responsible for acute exacerbation of 4 psoriatic patients in our study. There have been some clinical trials showing that several Chinese herbal medicine, including Panax ginseng ( ), Astragalus membranaceus ( ), Glycyrrhiza glabra ( ) and Echinacea purpurea ( ), have immune-stimulating 21, 22 activity. It is plausible that some Chinese herbal medicine may exacerbate psoriasis via their effect on immune cells activation. Some studies suggested a relative risk factor of 8.01 between alcohol use and plaque-type psoriasis, particularly in men. 23 However, the studies did not document an increased risk for plaque-type psoriasis in women who drank alcohol. In our study, all the three psoriatic patients exacerbated by alcohol drinking were males, of whom two presented with erythrodermic psoriasis and one with plaque-type psoriasis. Noteworthily, there was one patient each exacerbated by oral Ganoderma lucidum ( ), oral Corbicula fluminea ( ), topical Euphorbia resinifera ( ), topical pesticide, topical propolis and oral terbinafine. It is unclear whether these factors contributed directly to acute exacerbation of psoriasis or these observations were incidental. Available evidences support that Ganoderma lucidum and terbinafine may exacerbate psoriasis. Polysaccharide purified from Ganoderma lucidum has been shown to promote the activation and maturation of immature dendritic cells and T helper 1 immune response, 24 which could make Ganoderma lucidum an exacerbating factor of psoriasis. More than 24 cases of flare-up of previous psoriasis or psoriasis de novo after 25, 26 oral terbinafine have been reported. The latency period between start of terbinafine ther- Dermatol Sinica, Jun

8 apy and development of psoriasis was less than 4 weeks. 27 The patient exacerbated by terbinafine in our study had been taking terbinafine for 4 weeks before the onset of generalized pustular psoriasis. 28 In comparison with psoriatic outpatients, 6 there was a higher percentage of psoriatic inpatients receiving combination therapy. This could be explained by that psoriatic inpatients had more severe degree of disease involvement or were more refractory to treatment. In the regimens of combination therapy, oral retinoids and topical corticosteroids were the most commonly prescribed systemic and topical medication, respectively. Phototherapy, mainly UVB, was prescribed for more than 50% of the inpatients. However, only 9.2% of the inpatients received Goeckerman regimen. The phototherapy in conventional Goeckerman regimen is broad-band UVB. The equipment of UVB phototherapy in our hospital is narrow-band in recent 10 years, which may hamper the attending physicians to prescribe Goeckerman regimen. CONCLUSION This is a retrospective epidemiologic study of psoriatic inpatients in Taiwan. The results of this study, especially the commonly prescribed treatments and the duration of hospitalization, can serve to establish Diagnosis-Related Group (DRG) of psoriasis. The identification of the causes of acute exacerbation can help the patients avoid exacerbating factors. The major limitation of our study is that there was a lack of systematic inquiry about the exacerbating factors in the records, which could account for the high percentage of unknown exacerbating factor. Prospective systematic researches on the basis of this study are anticipated to reveal a more detailed list of exacerbating factors, to explore the pathogenesis of psoriasis and to improve the life quality of psoriatic patients. REFERENCES 1. De Jong EM: The course of psoriasis. Clin Dermatol 15: , Finlay AY, Kelly SE: Psoriasis: an index of disability. Clin Exp Dermatol 12: 8-11, Ayyalaraju RS, MRCP, Finlay AY, et al.: Hospitalization for severe skin disease improves quality of life in the United Kingdom and the United States: a comparative study. J Am Acad Dermatol 49: , Cockayne SE, Cork MJ, Gawkrodger DJ: Treatment of psoriasis: day care vs. inpatient therapy. Br J Dermatol 140: , Stern RS: Inpatient hospital care for psoriasis: a vanishing practice in the United States. J Am Acad Dermatol 49: , Chen HH, Tseng MP, Tsai TF: An epidemiologic study of Taiwanese psoriatic patients in a single clinic. Dermatol Sinica 21: , Baker BS, Bokth S, Powles A, et al.: Group A streptococcal antigen-specific T lymphocytes in guttate psoriatic lesions. Br J Dermatol 128: , Aiba S, Tagami H: Proliferative responses of peripheral blood mononuclear cells from psoriatic patients to T lymphocyte-stimulating cytokines (IL-2, IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor) and OK-432. Arch Dermatol Res 281: , Baker BS, Powles AV, Malkani AK, et al.: Altered cell-mediated immunity to group A hemolytic streptococcal antigens in chronic plaque psoriasis. Br J Dermatol 125: 38-42, McFadden J, Valdimarsson H, Fry L: Cross-reactivity between streptococcal M surface antigen and human skin. Br J Dermatol 125: , Valdimarsson H, Baker BS, Jonsdottir I, et al.: Psoriasis: a T-cell-mediated autoimmune disease induced by streptococcal superantigens? Immunol Today 16: , Yarwood JM, Leung DY, Schlievert PM: Evidence for the involvement of bacterial superantigens in psoriasis, atopic dermatitis, and Kawasaki syndrome. FEMS Microbiol Lett 192: 1-7, Lafon M: [Viral superantigens].[french] Rev Med Interne 21: , Gottlieb A, Krueger JG, Bright R, et al.: Effects of administration of a single dose of a humanized monoclonal antibody to CD11a on the immunobiology and clinical activity of psoriasis. J Am Acad Dermatol 42: , Raptiva [efalizumab] [package insert]. South San Francisco, CA: Genentech Inc, Ryan T, Baker H: Systemic corticosteroids and folic acid antagonists in the treatment of generalized pustular psoriasis. Evaluation and prognosis based on the study of 104 cases. Br J Dermatol 81: , Dermatol Sinica, Jun 2007

9 17.Ryan T, Baker H: The prognosis of generalized pustular psoriasis. Br J Dermatol 85: , Mengesha Y, Bennett M: Pustular skin disorders: diagnosis and treatment. Am J Clin Dermatol 3: , Hellgren L: Induction of generalized pustular psoriasis by topical use of betamethasone-dipropionate ointment in psoriasis. Ann Clin Res 8: , Telfer NR, Dawer RP: Generalized pustular psoriasis associated with withdrawal of topical clobetasol-17-propionate. J Am Acad Dermatol 17: , Brush J, Mendenhall E, Guggenhem A, et al.: The effects of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra on CD69 expression and immune cell activation in humans. Phytother Res [Epub ahead of print], Block KI, Mead MN: Immune system effects of Echinacea, ginseng, and astragalus: a review. Integr Cancer Ther 2: , Behnam SM, Behnam SE, Koo JY: Alcohol as a risk factor for plaque-type psoriasis. Cutis 76: , Lin YL, Lee SS, Hou SM, et al.: Polysaccharide purified from Ganoderma lucidum induces gene expression changes in human dendritic cells and promotes T helper 1 immune responses in BALB/c mice. Mol Pharmacol 70: , Le Guyadec T, Saint-Blancard P, Bosonnet S, et al.: [Oral terbinafine-induced plantar pustular psoriasis].[french] Ann Dermatol Venereol 127: , Szepietowski JC: Terbinafine exacerbates psoriasis: case report with a literature review. Acta Dermatovenerol Croat 11: 17-21, Gupta AK, Sibbald RG, Knowles SR, et al.: Terbinafine therapy may be associated with the development of psoriasis de novo or its exacerbation: four case reports and a review of druginduced psoriasis. J Am Acad Dermatol 36: , Tjiu JW, Tsai TF, Chu CY: Severe generalized pustular psoriasis provoked by oral terbinafine. Dermatol Sinica 22: , Dermatol Sinica, Jun