- Email: [email protected]
Psoriasis improvement after bariatric surgery
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Surgery for Obesity and Related Diseases ] (2014) 00–00
Original article
Psoriasis improvement after bariatric surgery Héctor Romero-Talamás, M.D.a, Ali Aminian, M.D.a, Ricard Corcelles, M.D.a, Anthony P. Fernandez, M.D., Ph.D.b, Philip R. Schauer, M.D.a, Stacy Brethauer, M.D.a,* b
a Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio Departments of Dermatology and Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio Received December 14, 2013; accepted March 31, 2014
Abstract
Background: Psoriasis is a chronic inflammatory skin disease known to be associated with obesity and metabolic syndrome. Single case reports and small series suggest remission or improvement after bariatric surgery, hypothetically through a GLP-1 mediated mechanism. The objective of this study was to investigate on the effect of bariatric surgery on the clinical behavior of psoriasis in obese patients. Methods: A total of 33 morbidly obese individuals with psoriasis who were on active medical treatment were identified. Demographic characteristics and follow-up data were extracted from our database. Medication usage and percentage of affected body surface area (%ABSA) were recorded preoperatively and at least 6 months after bariatric surgery. Results: Nine (27.2%) patients were on systemic therapy at baseline. At a mean follow-up time of 26.2 ⫾ 20.3 months, a mean excess weight loss (EWL) of 48.7 ⫾2 6.6% was achieved. This was associated with improvement of psoriasis based on downgrade of medication and %ABSA in 30.3% and 26.1% of patients, respectively. In total, 13 of 33 patients (39.4%) had improvement based on either criteria. Eight (24.2%) patients were not on any psoriasis medication at the latest follow-up (P ¼ .001). Older age at the time of surgery (54.8 ⫾ 8.1 versus 48.1 ⫾ 10.4 years, P ¼ .047), Roux-en-Y gastric bypass versus nonbypass procedures (52.4% versus 16.7%, P ¼ .043), and greater EWL (64.2 ⫾ 26.0% versus 43.4 ⫾23.6%, P ¼ .036) predicted improvement. Only 1 (3%) patient experienced worsening after surgery. Conclusion: Almost 40% of our cohort showed improvement of psoriasis several months after bariatric surgery. Improvement is directly related to the degree of postoperative weight loss and is associated with the Roux-en-Y configuration. (Surg Obes Relat Dis 2014;]:00–00.) r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Bariatric surgery; Psoriasis; GLP-1; Metabolic syndrome; Gastric bypass
Psoriasis is a chronic inflammatory skin disease that affects 1–4% of the world’s population [1]. Patients with psoriasis are affected by chronic skin lesions that may involve any part of their body and usually require long-term treatment that negatively affects their quality of life [2]. It is well known that obesity is a risk factor for psoriasis and increased body *
Correspondence: Dr. Stacy Brethauer, Cleveland Clinic, Bariatric and Metabolic Institute, 9500 Euclid Avenue, M61, Cleveland, OH 44194. E-mail: [email protected]
mass index (BMI) is associated not only with greater extent of the disease, but also more refractory disease [3,4]. The association between psoriasis and obesity has been postulated as a complex interplay between the immune system, adiposity and metabolic dysregulation [5]. Although the exact mechanism of this relationship is unknown, investigators hypothesize that an increase in proinflammatory cytokines such as (tumor necrosis factor α), interleukin (IL)-1, IL-6, IL-8, and leptin) synthesized by adipose tissue in obese individuals plays a central role. Obesity is linked with low-grade
http://dx.doi.org/10.1016/j.soard.2014.03.025 1550-7289/r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.
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systemic inflammation that in theory may precipitate and/or exacerbate psoriatic lesions in overweight and obese individuals [1]. The obesity epidemic continues to grow worldwide and surgery remains the only effective and durable therapy for many individuals [6]. Bariatric surgery has been shown to induce weight loss, improve quality of life, and reduce co-morbidities [7]. Currently, the effect of bariatric surgery on psoriasis has not been well studied. Case reports suggest that Roux-en-Y gastric bypass (RYGB) in patients with psoriasis could result in complete resolution of the disease [8]. Further small series support the benefits of weight loss surgery on the behavior of psoriasis. The aim of this study is to further clarify these findings and identify predictive factors of psoriasis resolution after bariatric surgery. Methods This was an Investigative Research Board approved retrospective chart review of all morbidly obese individuals with psoriasis who underwent bariatric surgery at our center between January 2004 and December 2012. We identified morbidly obese patients with psoriasis who were on active medical treatment at the time of surgery. Demographic characteristics (age, sex, and related co-morbidities) and follow-up data were extracted and analyzed to assess preoperative and postoperative parameters and outcomes. Psoriasis medication types and status and the percentage of affected body surface area (%ABSA) were recorded before surgery and at least 6 months after the intervention. The %ABSA was calculated based on the dermatologist’s assessment, according to the National Psoriasis Foundation’s palm method (the surface area of the hand corresponds to 1%) [9]. Improvement of psoriasis was defined as a decrease in %ABSA and/or a downgrade in 1 or 2 of the 3 treatment classes (no treatment, local and systemic therapy). The presence of a Koebner lesion (development of isomorphic pathologic psoriatic lesions at the operative site scar) was recorded, if present during follow-up [10]. Remission of type 2 diabetes mellitus (T2DM) was defined as glycated hemoglobin (HbA1 c) o 6.5% and fasting blood glucose (FBG) o 126 mg/dL without diabetic medications. Clinical improvement of T2DM was defined as significant reduction in HbA1 c (by 4 1%), FBG (by 4 25 mg/dL), or diabetes medication requirement [11]. Treatment goals of co-morbidities were defined based on the American Diabetes Association criteria for control of diabetes (HbA1 c o 7%), blood pressure (o 130/80 mm Hg), and cholesterol (LDL o 100 mg/dL). Data were analyzed using SPSS version for Windows (SPSS, Inc., Chicago, IL, USA). Results were expressed in mean ⫾ SD, and frequency (%). Statistical significance of means and proportions was tested with T test and Z-test, respectively. Categorical variables were analyzed with Χ2
or Fisher’s exact tests. Statistical significance was considered at P o .05. Results A total of 33 patients with psoriasis were identified. Most patients were female (60.6%). Mean age of the studied population was 50.8 ⫾ 10.0 years and the mean duration of psoriasis before bariatric surgery was 24.0 ⫾ 9.0 months. Psoriatic arthropathy and family history of psoriasis were present in 24.2% and 9.1%, respectively. Presurgical treatment of psoriasis included local therapies in 24 (72.7%) patients and systemic medication in 9 patients (27.2%). Systemic agents included Methotrexate, oral corticosteroids, and biologics (tumor necrosis factor α blockers). Metabolic co-morbidities included T2DM (63.6%), hypertension (69.7%), and dyslipidemia (75.7%). Bariatric procedures included RYGB (n ¼ 21), sleeve gastrectomy (SG) (n ¼ 8), and laparoscopic adjustable gastric banding (n ¼ 4). There were no conversions to open surgery in our cohort, and no major postoperative complications occurred. Mean BMI at the time of surgery was 50.2 ⫾ 10.1 kg/m2, and BMI decreased to 38.5 ⫾ 9.8 at a mean follow-up period of 26.2 ⫾ 20.3 months (range, 6–77), which corresponded to mean percent excess weight loss (EWL) of 48.7 ⫾ 26.6%. Table 1 summarizes the metabolic profile of patients at baseline and follow-up. A total of 13 patients (39.4%) reported improvement in psoriasis after the surgical intervention based on downgrade in medication category (30.3%) and %ABSA (26.1%). Eight patients (24.2%) were not on any medication at the latest follow-up point (P ¼ .001). Six (75%) of them underwent RYGB, 1 (12.5%) had a SG, and 1 (12.5%) a laparoscopic adjustable gastric banding. Only 1 patient (3%), who underwent a SG, experienced worsening of psoriasis after bariatric surgery. Five (15.1%) patients were on a systemic medication at follow-up. A significant reduction in %ABSA was observed after bariatric surgery Table 1 Metabolic profile of patients with psoriasis after bariatric surgery (n¼33) Metabolic parameters*
Baseline
BMI (kg/m ) 50.2 ⫾ 10.1 A1C (%) 7.9 ⫾ 1.3 FBG (mg/dL) 138.3 ⫾ 58.9 LDL cholesterol (mg/dL) 111.2 ⫾ 29.2 HDL cholesterol (mg/dL) 55.5 ⫾ 23.7 Triglycerides (mg/dL) 140.9 ⫾ 86.4 American Diabetes Association goals A1C o 7% (%) 23.1 BP o 130/80 mmHg (%) 19.4 LDL o 100 mg/dL (%) 35.7 2
Follow-up
P value
38.5 ⫾ 9.8 6.4 ⫾ 1.2 101.3 ⫾ 27 81.5 ⫾ 29.2 66 ⫾ 20.1 116.9 ⫾ 116
o.001 .007 .005 .001 .002 .236
61.5 51.6 78.6
.038 .005 .014
BMI ¼ body mass index; BP ¼ blood pressure; FBG ¼ fasting blood glucose; HbA1c ¼ glycated hemoglobin A1c; HDL ¼ high density lipoprotein; LDL ¼ low density lipoprotein * Values are mean ⫾ SD.
125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 T1150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179
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(5.7 ⫾ 4.1% versus 1.7 ⫾ 2.1%, P ¼ .04). No patient developed Koebner phenomenon within surgical scars during the follow-up period. Predictors of psoriasis improvement were older age at the time of surgery (54.8 ⫾ 8.1 versus 48.1 ⫾ 10.4 years, P ¼ .047), RYGB versus nonbypass procedures (52.4% versus 16.7%, P ¼ .043) and greater %EWL (64.2 ⫾ 26.0 versus 43.4 ⫾ 23.6, P ¼ .036). Discussion Psoriasis is an immune-mediated disease characterized by increased epithelial turnover. Patients with psoriasis present with erythematous scaly patches and plaques that can involve any part of their anatomy. The negative effect of psoriasis on patient’s quality of life is significant, similar to that of T2DM [12]. Psoriasis is also associated with metabolic syndrome that may lead to hypertension, T2DM, and myocardial infarction [13]. The association between psoriasis and obesity has been well established in several epidemiologic studies. A systematic review and meta-analysis of 16 observational studies including 4200,000 psoriasis patients has shown that individuals with psoriasis have a higher incidence and prevalence of obesity compared to the general population (OR 1.66, CI95% CI 1.46–1.89) [14]. The same meta-analysis demonstrated that patients with severe psoriasis have a higher risk of being obese (OR 2.23, CI95% 1.63–3.05) than patients with a mild form of the disease (OR 1.46, CI95% 1.17–1.82). A recent cohort study by Love et al. [15] involving 75,395 individuals with psoriasis reports an increased risk of psoriatic arthritis with increased BMI (relative risk of 1.48 in patients with a BMI Z 35 kg/m2). Currently, the role of weight loss as a treatment modality for psoriasis in obese patients is under investigation. There are a few randomized trials that investigate the clinical effects of weight loss on the severity of this skin disease [16,17]. Gisondi et al. [16] observed that weight loss induced by a low-calorie diet improved the response to low-dose cyclosporine therapy in patients with psoriasis. A prospective randomized controlled trial conducted by Jensen et al. [17] also recently addressed the effect of weight loss reduction in overweight psoriasis patients. In this study, the intervention group, which received a low energy diet (800–1000 kcal/d) for 8 weeks, experienced a significant improvement in clinical response and quality of life over the control group. Given this scenario, it seems reasonable to surmise that weight loss surgery could be a treatment option in obese patients with psoriasis. The literature regarding bariatric surgery and psoriasis is limited to a few case reports and small case series describing improvement of the skin lesions after surgery [18–21]. Conversely, 1 case report showed psoriasis worsening after surgery, although the type of procedure was not specified [22]. Herein, we report the
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outcomes of 33 consecutive morbidly obese patients after weight loss surgery. Forty percent of patients showed improvement in psoriasis after surgical intervention based on %ABSA affected and medication downgrade. The clinical improvement observed in our study was inferior to that published by other authors; however, there are several points that must be taken into consideration. Farias et al. [19] reported a 70% psoriasis resolution rate at 6 months follow-up and this is currently the highest rate ever published. However, the study included only 10 patients and there is no mention of how improvement was measured. In addition, 4 of the 7 patients who had initially achieved remission relapsed at mid-term follow-up (0.5–2.5 yr), bringing the resolution rate to a 30%. Hossler et al. [23] observed improvement of the skin lesions in 62% (n ¼ 34) of patients undergoing bariatric surgery (88% had RYGB). Data was collected retrospectively using a telephone survey and no follow-up parameters were described. Differences in type of bariatric procedures, follow-up time, and the lack of documentation of medication status after surgery make the comparison between studies difficult. Our study presents the longest reported follow-up to date on this topic (26.2 ⫾ 20.3 mo). The differences in methods used to determine psoriasis improvement after surgery might also explain different results among the published series. In our study, we demonstrated psoriasis improvement in 40% based on % ABSA and medication class reduction. We used the simple and reproducible palm method to calculate the extent of disease based on the dermatologist description. The palm method scores 1% for each palm (100% of BSA corresponds to 100 palms) but fails to evaluate local severity. In our cohort who were on active pharmacotherapy at the time of surgery, 8 patients (24.2%) were not on any psoriasis medication at the latest follow-up visit (P ¼ .001), while 19 patients were being treated by topical medications only, compared with the 24 individuals at baseline. It is also important to mention that only 1 patient worsened after surgery (3%). This was a 60-year-old man who developed more widespread psoriasis 1-year after SG, despite EWL of 50% and significant improvement of T2DM. Our analysis identified greater EWL (P ¼ .036), RYGB (P ¼ .043), and advanced age at time of surgery (P ¼ .047) as predictors of psoriasis improvement. It has been reported that surgical and medical weight loss has a clear beneficial effect over the activity of the disease. This hypothesis was supported by our analysis, which showed a significant correlation between degree of EWL and psoriasis improvement after surgery. RYGB was also associated with significant improvement in our analysis. The 12 patients who did not undergo RYGB (8 sleeve gastrectomy, 4 gastric banding) had inferior outcomes in terms of improvement compared with the RYGB group, a finding that is supported by results observed by other authors [19]. Interestingly, the only patient that had worsening of the
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disease had a laparoscopic sleeve gastrectomy as his bariatric procedure. On this note, several studies have shown that the gastrointestinal rearrangement after RYGB (duodenal exclusion with rapid food transit to the distal ileum) is associated with T2DM and lipid profile improvement by endocrine-mediated mechanisms [24]. Because an increase in GLP-1 seen after RYGB and sleeve has been associated with resolution of some metabolic conditions, some researchers have hypothesized that GLP-1 could play a role in psoriasis improvement after RYGB through an anti-inflammatory effect [25]. There are recently published reports of significant and rapid improvement of psoriasis in patients treated with a GLP-1 receptor agonist (exenatide, liraglutide) [26,27], probably due to a direct antiinflammatory effect on invariant natural killer T-cells [28]. Furthermore, the presence of GLP-1 receptors has been identified in biopsies of psoriasis plaques demonstrating the possibility of direct interaction between the lesion and the peptide [29]. Further studies are required to explore the relationship between psoriasis resolution and GLP-1. In conjunction with obesity, metabolic syndrome contributes to the development of a chronic systemic inflammatory state and has been associated with psoriasis [22]. Significant improvement in proinflammatory profiles (CRP, IL-6, leptin) and insulin sensitivity has recently been reported after RYGB and this could certainly play an important role in the improvement of psoriasis [30]. The improved metabolic profiles in our cohort support this concept. Surprisingly, advanced age at the time of surgery was also identified as a predictor of psoriasis improvement after surgery. We expected advanced age to negatively affect outcomes secondary to the chronicity of wellestablished disease; however, we found the exact opposite. The positive effect of advanced age on outcomes has been reported by Hossler et al. [23], but a possible mechanism remains to be clarified. There are some limitations in our retrospective study. First, the estimation of %ABSA by relying on clinical records was not ideal and does not account for other important clinical aspects of disease, including plaque thickness and amount of scale. Second, the sample size is relatively small but sufficient to determine significant improvement and predictors of it. Third, we were unable to assess whether other indirect factors may have also contributed to psoriasis improvement, including increased physical activity, dietary changes, or decreases/discontinuation in nonpsoriatic medications. Also, a psoriasis-related quality of life assessment could have enhanced this report and should be included in future studies examining this obesity-related co-morbidity. Conclusion Nearly 40% of our cohort showed improvement of psoriasis several months after bariatric surgery, confirming
the beneficial effect that these procedures have on psoriasis. Improvement appears to be directly related to the degree of postoperative weight loss of the individual as well as to the choice of procedure. Psoriasis should be added to the list of medical conditions that improve after bariatric surgery. Further prospective research is warranted to evaluate the mechanism by which these outcomes are achieved. Disclosures xx References [1] Schon MP, Boehncke WH. Psoriasis N Engl J Med 2005;352: 1899–912. [2] Johnson MA, Armstrong AW. Clinical and histologic diagnostic guidelines for psoriasis: a critical review. Clin Rev Allergy Immunol 2013;44:166–72. [3] Naldi L, Chatenoud L, Linder D, et al. Cigarette smoking, body mass index, and stressful life events as risk factors for psoriasis: results from an Italian case-control study. J Invest Dermatol 2005;125:61–7. [4] Setty AR, Curhan G, Choi HK. Obesity, waist circumference, weight change, and the risk of psoriasis in women: Nurses' Health Study II. Arch Intern Med 2007;167:1670–5. [5] Hamminga EA, van der Lely AJ, Neumann HA, Thio HB. Chronic inflammation in psoriasis and obesity: implications for therapy. Med Hypotheses 2006;67:768–73. [6] Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010. JAMA 2012;307:483–90. [7] Buchwald H, Estok R, Fahrbach K, Banel D, Sledge I. Trends in mortality in bariatric surgery: a systematic review and meta-analysis. Surgery 2007;142:621–32. [8] Halawi A, Abiad F, Abbas O. Bariatric surgery and its effects on the skin and skin diseases. Obes Surg 2013;23:408–13. [9] Bremmer S, Van Voorhees AS, Hsu S, et al. Obesity and psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol 2010;63:1058–69. [10] Mendez-Fernandez MA. Koebner phenomenon: what you don't know may hurt you. Ann Plast Surg 2000;44:644–5. [11] Brethauer SA, Aminian A, Romero-Talamas H, et al. Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg 2013;258: 628–36. [12] Grozdev I, Kast D, Cao L, et al. Physical and mental impact of psoriasis severity as measured by the compact Short Form-12 Health Survey (SF-12) quality of life tool. J Invest Dermatol 2012;132: 1111–6. [13] Yeung H, Takeshita J, Mehta NN, et al. Psoriasis severity and the prevalence of major medical comorbidity: a population-based study. JAMA Dermatol 2013;149:1173–9. [14] Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and obesity: a systematic review and metaanalysis of observational studies. Nutr Diabetes 2012;2:e54. [15] Love TJ, Zhu Y, Zhang Y, et al. Obesity and the risk of psoriatic arthritis: a population-based study. Ann Rheum Dis 2012;71:1273–7. [16] Gisondi P, Del Giglio M, Di Francesco V, Zamboni M, Girolomoni G. Weight loss improves the response of obese patients with moderate-to-severe chronic plaque psoriasis to low-dose cyclosporine therapy: a randomized, controlled, investigator-blinded clinical trial. Am J Clin Nutr 2008;88:1242–7.
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Psoriasis after Bariatric Surgery / Surgery for Obesity and Related Diseases ] (2014) 00–00 [17] Jensen P, Zachariae C, Christensen R, et al. Effect of weight loss on the severity of psoriasis: a randomized clinical study. JAMA Dermatol 2013;149:795–801. [18] de Menezes Ettinger JE, Azaro E, de Souza CA, et al. Remission of psoriasis after open gastric bypass. Obes Surg 2006;16:94–7. [19] Farias MM, Achurra P, Boza C, Vega A, de la Cruz C. Psoriasis following bariatric surgery: clinical evolution and impact on quality of life on 10 patients. Obes Surg 2012;22:877–80. [20] Higa-Sansone G, Szomstein S, Soto F, et al. Psoriasis remission after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Obes Surg 2004;14:1132–4. [21] Hossler EW, Maroon MS, Mowad CM. Gastric bypass surgery improves psoriasis. J Am Acad Dermatol 2011;65:198–200. [22] Perez-Perez L, Allegue F, Caeiro JL, Zulaica JM. Severe psoriasis, morbid obesity and bariatric surgery. Clin Exp Dermatol 2009;34: e421–2. [23] Hossler EW, Wood GC, Still CD, Mowad CM, Maroon MS. The effect of weight loss surgery on the severity of psoriasis. Br J Dermatol 2013;168:660–1. [24] Patel RT, Shukla AP, Ahn SM, Moreira M, Rubino F. Surgical control of obesity and diabetes: The role of intestinal vs. gastric
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[28]
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[30]
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mechanisms in the regulation of body weight and glucose homeostasis. Obesity (Silver Spring) 2014;22:159–69. Faurschou A, Zachariae C, Skov L, Vilsboll T, Knop FK. Gastric bypass surgery: improving psoriasis through a GLP-1-dependent mechanism? Med Hypotheses 2011;77:1098–101. Buysschaert M, Tennstedt D, Preumont V. Improvement of psoriasis during exenatide treatment in a patient with diabetes Diabetes Metab 2012;38:86–8. Faurschou A, Knop FK, Thyssen JP, et al. Improvement in psoriasis after treatment with the glucagon-like peptide-1 receptor agonist liraglutide. Acta Diabetol 2014;51:147–50. Hogan AE, Tobin AM, Ahern T, et al. Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis. Diabetologia 2011;54: 2745–54. Faurschou A, Pedersen J, Gyldenlove M, et al. Increased expression of glucagon-like peptide-1 receptors in psoriasis plaques. Exp Dermatol 2013;22:150–2. Brethauer SA, Heneghan HM, Eldar S, et al. Early effects of gastric bypass on endothelial function, inflammation, and cardiovascular risk in obese patients. Surg Endosc 2011;25:2650–9.
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Surgery for Obesity and Related Diseases ] (2014) 00–00
Original article
Psoriasis improvement after bariatric surgery Héctor Romero-Talamás, M.D.a, Ali Aminian, M.D.a, Ricard Corcelles, M.D.a, Anthony P. Fernandez, M.D., Ph.D.b, Philip R. Schauer, M.D.a, Stacy Brethauer, M.D.a,* b
a Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio Departments of Dermatology and Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio Received December 14, 2013; accepted March 31, 2014
Abstract
Background: Psoriasis is a chronic inflammatory skin disease known to be associated with obesity and metabolic syndrome. Single case reports and small series suggest remission or improvement after bariatric surgery, hypothetically through a GLP-1 mediated mechanism. The objective of this study was to investigate on the effect of bariatric surgery on the clinical behavior of psoriasis in obese patients. Methods: A total of 33 morbidly obese individuals with psoriasis who were on active medical treatment were identified. Demographic characteristics and follow-up data were extracted from our database. Medication usage and percentage of affected body surface area (%ABSA) were recorded preoperatively and at least 6 months after bariatric surgery. Results: Nine (27.2%) patients were on systemic therapy at baseline. At a mean follow-up time of 26.2 ⫾ 20.3 months, a mean excess weight loss (EWL) of 48.7 ⫾2 6.6% was achieved. This was associated with improvement of psoriasis based on downgrade of medication and %ABSA in 30.3% and 26.1% of patients, respectively. In total, 13 of 33 patients (39.4%) had improvement based on either criteria. Eight (24.2%) patients were not on any psoriasis medication at the latest follow-up (P ¼ .001). Older age at the time of surgery (54.8 ⫾ 8.1 versus 48.1 ⫾ 10.4 years, P ¼ .047), Roux-en-Y gastric bypass versus nonbypass procedures (52.4% versus 16.7%, P ¼ .043), and greater EWL (64.2 ⫾ 26.0% versus 43.4 ⫾23.6%, P ¼ .036) predicted improvement. Only 1 (3%) patient experienced worsening after surgery. Conclusion: Almost 40% of our cohort showed improvement of psoriasis several months after bariatric surgery. Improvement is directly related to the degree of postoperative weight loss and is associated with the Roux-en-Y configuration. (Surg Obes Relat Dis 2014;]:00–00.) r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Bariatric surgery; Psoriasis; GLP-1; Metabolic syndrome; Gastric bypass
Psoriasis is a chronic inflammatory skin disease that affects 1–4% of the world’s population [1]. Patients with psoriasis are affected by chronic skin lesions that may involve any part of their body and usually require long-term treatment that negatively affects their quality of life [2]. It is well known that obesity is a risk factor for psoriasis and increased body *
Correspondence: Dr. Stacy Brethauer, Cleveland Clinic, Bariatric and Metabolic Institute, 9500 Euclid Avenue, M61, Cleveland, OH 44194. E-mail: [email protected]
mass index (BMI) is associated not only with greater extent of the disease, but also more refractory disease [3,4]. The association between psoriasis and obesity has been postulated as a complex interplay between the immune system, adiposity and metabolic dysregulation [5]. Although the exact mechanism of this relationship is unknown, investigators hypothesize that an increase in proinflammatory cytokines such as (tumor necrosis factor α), interleukin (IL)-1, IL-6, IL-8, and leptin) synthesized by adipose tissue in obese individuals plays a central role. Obesity is linked with low-grade
http://dx.doi.org/10.1016/j.soard.2014.03.025 1550-7289/r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.
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systemic inflammation that in theory may precipitate and/or exacerbate psoriatic lesions in overweight and obese individuals [1]. The obesity epidemic continues to grow worldwide and surgery remains the only effective and durable therapy for many individuals [6]. Bariatric surgery has been shown to induce weight loss, improve quality of life, and reduce co-morbidities [7]. Currently, the effect of bariatric surgery on psoriasis has not been well studied. Case reports suggest that Roux-en-Y gastric bypass (RYGB) in patients with psoriasis could result in complete resolution of the disease [8]. Further small series support the benefits of weight loss surgery on the behavior of psoriasis. The aim of this study is to further clarify these findings and identify predictive factors of psoriasis resolution after bariatric surgery. Methods This was an Investigative Research Board approved retrospective chart review of all morbidly obese individuals with psoriasis who underwent bariatric surgery at our center between January 2004 and December 2012. We identified morbidly obese patients with psoriasis who were on active medical treatment at the time of surgery. Demographic characteristics (age, sex, and related co-morbidities) and follow-up data were extracted and analyzed to assess preoperative and postoperative parameters and outcomes. Psoriasis medication types and status and the percentage of affected body surface area (%ABSA) were recorded before surgery and at least 6 months after the intervention. The %ABSA was calculated based on the dermatologist’s assessment, according to the National Psoriasis Foundation’s palm method (the surface area of the hand corresponds to 1%) [9]. Improvement of psoriasis was defined as a decrease in %ABSA and/or a downgrade in 1 or 2 of the 3 treatment classes (no treatment, local and systemic therapy). The presence of a Koebner lesion (development of isomorphic pathologic psoriatic lesions at the operative site scar) was recorded, if present during follow-up [10]. Remission of type 2 diabetes mellitus (T2DM) was defined as glycated hemoglobin (HbA1 c) o 6.5% and fasting blood glucose (FBG) o 126 mg/dL without diabetic medications. Clinical improvement of T2DM was defined as significant reduction in HbA1 c (by 4 1%), FBG (by 4 25 mg/dL), or diabetes medication requirement [11]. Treatment goals of co-morbidities were defined based on the American Diabetes Association criteria for control of diabetes (HbA1 c o 7%), blood pressure (o 130/80 mm Hg), and cholesterol (LDL o 100 mg/dL). Data were analyzed using SPSS version for Windows (SPSS, Inc., Chicago, IL, USA). Results were expressed in mean ⫾ SD, and frequency (%). Statistical significance of means and proportions was tested with T test and Z-test, respectively. Categorical variables were analyzed with Χ2
or Fisher’s exact tests. Statistical significance was considered at P o .05. Results A total of 33 patients with psoriasis were identified. Most patients were female (60.6%). Mean age of the studied population was 50.8 ⫾ 10.0 years and the mean duration of psoriasis before bariatric surgery was 24.0 ⫾ 9.0 months. Psoriatic arthropathy and family history of psoriasis were present in 24.2% and 9.1%, respectively. Presurgical treatment of psoriasis included local therapies in 24 (72.7%) patients and systemic medication in 9 patients (27.2%). Systemic agents included Methotrexate, oral corticosteroids, and biologics (tumor necrosis factor α blockers). Metabolic co-morbidities included T2DM (63.6%), hypertension (69.7%), and dyslipidemia (75.7%). Bariatric procedures included RYGB (n ¼ 21), sleeve gastrectomy (SG) (n ¼ 8), and laparoscopic adjustable gastric banding (n ¼ 4). There were no conversions to open surgery in our cohort, and no major postoperative complications occurred. Mean BMI at the time of surgery was 50.2 ⫾ 10.1 kg/m2, and BMI decreased to 38.5 ⫾ 9.8 at a mean follow-up period of 26.2 ⫾ 20.3 months (range, 6–77), which corresponded to mean percent excess weight loss (EWL) of 48.7 ⫾ 26.6%. Table 1 summarizes the metabolic profile of patients at baseline and follow-up. A total of 13 patients (39.4%) reported improvement in psoriasis after the surgical intervention based on downgrade in medication category (30.3%) and %ABSA (26.1%). Eight patients (24.2%) were not on any medication at the latest follow-up point (P ¼ .001). Six (75%) of them underwent RYGB, 1 (12.5%) had a SG, and 1 (12.5%) a laparoscopic adjustable gastric banding. Only 1 patient (3%), who underwent a SG, experienced worsening of psoriasis after bariatric surgery. Five (15.1%) patients were on a systemic medication at follow-up. A significant reduction in %ABSA was observed after bariatric surgery Table 1 Metabolic profile of patients with psoriasis after bariatric surgery (n¼33) Metabolic parameters*
Baseline
BMI (kg/m ) 50.2 ⫾ 10.1 A1C (%) 7.9 ⫾ 1.3 FBG (mg/dL) 138.3 ⫾ 58.9 LDL cholesterol (mg/dL) 111.2 ⫾ 29.2 HDL cholesterol (mg/dL) 55.5 ⫾ 23.7 Triglycerides (mg/dL) 140.9 ⫾ 86.4 American Diabetes Association goals A1C o 7% (%) 23.1 BP o 130/80 mmHg (%) 19.4 LDL o 100 mg/dL (%) 35.7 2
Follow-up
P value
38.5 ⫾ 9.8 6.4 ⫾ 1.2 101.3 ⫾ 27 81.5 ⫾ 29.2 66 ⫾ 20.1 116.9 ⫾ 116
o.001 .007 .005 .001 .002 .236
61.5 51.6 78.6
.038 .005 .014
BMI ¼ body mass index; BP ¼ blood pressure; FBG ¼ fasting blood glucose; HbA1c ¼ glycated hemoglobin A1c; HDL ¼ high density lipoprotein; LDL ¼ low density lipoprotein * Values are mean ⫾ SD.
125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 T1150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179
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(5.7 ⫾ 4.1% versus 1.7 ⫾ 2.1%, P ¼ .04). No patient developed Koebner phenomenon within surgical scars during the follow-up period. Predictors of psoriasis improvement were older age at the time of surgery (54.8 ⫾ 8.1 versus 48.1 ⫾ 10.4 years, P ¼ .047), RYGB versus nonbypass procedures (52.4% versus 16.7%, P ¼ .043) and greater %EWL (64.2 ⫾ 26.0 versus 43.4 ⫾ 23.6, P ¼ .036). Discussion Psoriasis is an immune-mediated disease characterized by increased epithelial turnover. Patients with psoriasis present with erythematous scaly patches and plaques that can involve any part of their anatomy. The negative effect of psoriasis on patient’s quality of life is significant, similar to that of T2DM [12]. Psoriasis is also associated with metabolic syndrome that may lead to hypertension, T2DM, and myocardial infarction [13]. The association between psoriasis and obesity has been well established in several epidemiologic studies. A systematic review and meta-analysis of 16 observational studies including 4200,000 psoriasis patients has shown that individuals with psoriasis have a higher incidence and prevalence of obesity compared to the general population (OR 1.66, CI95% CI 1.46–1.89) [14]. The same meta-analysis demonstrated that patients with severe psoriasis have a higher risk of being obese (OR 2.23, CI95% 1.63–3.05) than patients with a mild form of the disease (OR 1.46, CI95% 1.17–1.82). A recent cohort study by Love et al. [15] involving 75,395 individuals with psoriasis reports an increased risk of psoriatic arthritis with increased BMI (relative risk of 1.48 in patients with a BMI Z 35 kg/m2). Currently, the role of weight loss as a treatment modality for psoriasis in obese patients is under investigation. There are a few randomized trials that investigate the clinical effects of weight loss on the severity of this skin disease [16,17]. Gisondi et al. [16] observed that weight loss induced by a low-calorie diet improved the response to low-dose cyclosporine therapy in patients with psoriasis. A prospective randomized controlled trial conducted by Jensen et al. [17] also recently addressed the effect of weight loss reduction in overweight psoriasis patients. In this study, the intervention group, which received a low energy diet (800–1000 kcal/d) for 8 weeks, experienced a significant improvement in clinical response and quality of life over the control group. Given this scenario, it seems reasonable to surmise that weight loss surgery could be a treatment option in obese patients with psoriasis. The literature regarding bariatric surgery and psoriasis is limited to a few case reports and small case series describing improvement of the skin lesions after surgery [18–21]. Conversely, 1 case report showed psoriasis worsening after surgery, although the type of procedure was not specified [22]. Herein, we report the
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outcomes of 33 consecutive morbidly obese patients after weight loss surgery. Forty percent of patients showed improvement in psoriasis after surgical intervention based on %ABSA affected and medication downgrade. The clinical improvement observed in our study was inferior to that published by other authors; however, there are several points that must be taken into consideration. Farias et al. [19] reported a 70% psoriasis resolution rate at 6 months follow-up and this is currently the highest rate ever published. However, the study included only 10 patients and there is no mention of how improvement was measured. In addition, 4 of the 7 patients who had initially achieved remission relapsed at mid-term follow-up (0.5–2.5 yr), bringing the resolution rate to a 30%. Hossler et al. [23] observed improvement of the skin lesions in 62% (n ¼ 34) of patients undergoing bariatric surgery (88% had RYGB). Data was collected retrospectively using a telephone survey and no follow-up parameters were described. Differences in type of bariatric procedures, follow-up time, and the lack of documentation of medication status after surgery make the comparison between studies difficult. Our study presents the longest reported follow-up to date on this topic (26.2 ⫾ 20.3 mo). The differences in methods used to determine psoriasis improvement after surgery might also explain different results among the published series. In our study, we demonstrated psoriasis improvement in 40% based on % ABSA and medication class reduction. We used the simple and reproducible palm method to calculate the extent of disease based on the dermatologist description. The palm method scores 1% for each palm (100% of BSA corresponds to 100 palms) but fails to evaluate local severity. In our cohort who were on active pharmacotherapy at the time of surgery, 8 patients (24.2%) were not on any psoriasis medication at the latest follow-up visit (P ¼ .001), while 19 patients were being treated by topical medications only, compared with the 24 individuals at baseline. It is also important to mention that only 1 patient worsened after surgery (3%). This was a 60-year-old man who developed more widespread psoriasis 1-year after SG, despite EWL of 50% and significant improvement of T2DM. Our analysis identified greater EWL (P ¼ .036), RYGB (P ¼ .043), and advanced age at time of surgery (P ¼ .047) as predictors of psoriasis improvement. It has been reported that surgical and medical weight loss has a clear beneficial effect over the activity of the disease. This hypothesis was supported by our analysis, which showed a significant correlation between degree of EWL and psoriasis improvement after surgery. RYGB was also associated with significant improvement in our analysis. The 12 patients who did not undergo RYGB (8 sleeve gastrectomy, 4 gastric banding) had inferior outcomes in terms of improvement compared with the RYGB group, a finding that is supported by results observed by other authors [19]. Interestingly, the only patient that had worsening of the
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disease had a laparoscopic sleeve gastrectomy as his bariatric procedure. On this note, several studies have shown that the gastrointestinal rearrangement after RYGB (duodenal exclusion with rapid food transit to the distal ileum) is associated with T2DM and lipid profile improvement by endocrine-mediated mechanisms [24]. Because an increase in GLP-1 seen after RYGB and sleeve has been associated with resolution of some metabolic conditions, some researchers have hypothesized that GLP-1 could play a role in psoriasis improvement after RYGB through an anti-inflammatory effect [25]. There are recently published reports of significant and rapid improvement of psoriasis in patients treated with a GLP-1 receptor agonist (exenatide, liraglutide) [26,27], probably due to a direct antiinflammatory effect on invariant natural killer T-cells [28]. Furthermore, the presence of GLP-1 receptors has been identified in biopsies of psoriasis plaques demonstrating the possibility of direct interaction between the lesion and the peptide [29]. Further studies are required to explore the relationship between psoriasis resolution and GLP-1. In conjunction with obesity, metabolic syndrome contributes to the development of a chronic systemic inflammatory state and has been associated with psoriasis [22]. Significant improvement in proinflammatory profiles (CRP, IL-6, leptin) and insulin sensitivity has recently been reported after RYGB and this could certainly play an important role in the improvement of psoriasis [30]. The improved metabolic profiles in our cohort support this concept. Surprisingly, advanced age at the time of surgery was also identified as a predictor of psoriasis improvement after surgery. We expected advanced age to negatively affect outcomes secondary to the chronicity of wellestablished disease; however, we found the exact opposite. The positive effect of advanced age on outcomes has been reported by Hossler et al. [23], but a possible mechanism remains to be clarified. There are some limitations in our retrospective study. First, the estimation of %ABSA by relying on clinical records was not ideal and does not account for other important clinical aspects of disease, including plaque thickness and amount of scale. Second, the sample size is relatively small but sufficient to determine significant improvement and predictors of it. Third, we were unable to assess whether other indirect factors may have also contributed to psoriasis improvement, including increased physical activity, dietary changes, or decreases/discontinuation in nonpsoriatic medications. Also, a psoriasis-related quality of life assessment could have enhanced this report and should be included in future studies examining this obesity-related co-morbidity. Conclusion Nearly 40% of our cohort showed improvement of psoriasis several months after bariatric surgery, confirming
the beneficial effect that these procedures have on psoriasis. Improvement appears to be directly related to the degree of postoperative weight loss of the individual as well as to the choice of procedure. Psoriasis should be added to the list of medical conditions that improve after bariatric surgery. Further prospective research is warranted to evaluate the mechanism by which these outcomes are achieved. Disclosures xx References [1] Schon MP, Boehncke WH. Psoriasis N Engl J Med 2005;352: 1899–912. [2] Johnson MA, Armstrong AW. Clinical and histologic diagnostic guidelines for psoriasis: a critical review. Clin Rev Allergy Immunol 2013;44:166–72. [3] Naldi L, Chatenoud L, Linder D, et al. Cigarette smoking, body mass index, and stressful life events as risk factors for psoriasis: results from an Italian case-control study. J Invest Dermatol 2005;125:61–7. [4] Setty AR, Curhan G, Choi HK. Obesity, waist circumference, weight change, and the risk of psoriasis in women: Nurses' Health Study II. Arch Intern Med 2007;167:1670–5. [5] Hamminga EA, van der Lely AJ, Neumann HA, Thio HB. Chronic inflammation in psoriasis and obesity: implications for therapy. Med Hypotheses 2006;67:768–73. [6] Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010. JAMA 2012;307:483–90. [7] Buchwald H, Estok R, Fahrbach K, Banel D, Sledge I. Trends in mortality in bariatric surgery: a systematic review and meta-analysis. Surgery 2007;142:621–32. [8] Halawi A, Abiad F, Abbas O. Bariatric surgery and its effects on the skin and skin diseases. Obes Surg 2013;23:408–13. [9] Bremmer S, Van Voorhees AS, Hsu S, et al. Obesity and psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol 2010;63:1058–69. [10] Mendez-Fernandez MA. Koebner phenomenon: what you don't know may hurt you. Ann Plast Surg 2000;44:644–5. [11] Brethauer SA, Aminian A, Romero-Talamas H, et al. Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg 2013;258: 628–36. [12] Grozdev I, Kast D, Cao L, et al. Physical and mental impact of psoriasis severity as measured by the compact Short Form-12 Health Survey (SF-12) quality of life tool. J Invest Dermatol 2012;132: 1111–6. [13] Yeung H, Takeshita J, Mehta NN, et al. Psoriasis severity and the prevalence of major medical comorbidity: a population-based study. JAMA Dermatol 2013;149:1173–9. [14] Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and obesity: a systematic review and metaanalysis of observational studies. Nutr Diabetes 2012;2:e54. [15] Love TJ, Zhu Y, Zhang Y, et al. Obesity and the risk of psoriatic arthritis: a population-based study. Ann Rheum Dis 2012;71:1273–7. [16] Gisondi P, Del Giglio M, Di Francesco V, Zamboni M, Girolomoni G. Weight loss improves the response of obese patients with moderate-to-severe chronic plaque psoriasis to low-dose cyclosporine therapy: a randomized, controlled, investigator-blinded clinical trial. Am J Clin Nutr 2008;88:1242–7.
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