- Email: [email protected]
Gastric bypass surgery improves psoriasis
Gastric bypass surgery improves psoriasis Eric W. Hossler, MD, Michele S. Maroon, MD, and Chris M. Mowad, MD Danville, Pennsylvania Recent studies have found that psoriasis is linked to a higher rate of obesity, and that obesity itself is a risk factor for the development of psoriasis. There are two recent reports of chronic severe psoriasis improving with weight loss after Roux-en-Y gastric bypass surgery. We have observed two patients with body mass indices greater than 50 kg/m2 who had marked improvement in their psoriasis after gastric bypass surgery. The common link between psoriasis and obesity may be a state of chronic inflammation, including elevated levels of T helper 1 (TH-1) cytokines such as tumor necrosis factor. More recent research has shown that the appetite suppressant leptin is also elevated in patients with psoriasis and obesity, and that levels decrease with weight loss. We conclude that weight loss may be a useful adjunctive therapy for obese patients with psoriasis. ( J Am Acad Dermatol 2011;65:198-200.) Key words: bariatric surgery; psoriasis; weight loss.
T
o our knowledge, there are only 3 prior case reports of psoriasis improving after Rouxen-Y gastric bypass surgery (RYGBP).1-3 We have observed two additional cases.
CASE REPORTS Case 1 A 34-year-old woman was followed in our dermatology clinic for many years with severe plaque psoriasis involving up to 75% of her body requiring superpotent topical steroids, ultraviolet (UV)B phototherapy, and psoralen plus UVA treatment. Her medical history included morbid obesity, with a peak body weight of 294 lb (body mass index [BMI] 52 kg/m2), type 2 diabetes mellitus, hypercholesterolemia, hypothyroidism, and mild mental retardation. Despite enrollment in a comprehensive weight management clinic for 6 months, her weight remained stable. On January 28, 2003, she underwent open RYGBP. By March 3, 2003, she had lost 45 lb, and noted that her psoriasis had markedly improved, allowing discontinuation of phototherapy. Over the following months, her psoriasis continued to improve and she reached a nadir weight of 183 lb, with a BMI of 34 kg/m2. She has been followed up for From the Department of Dermatology, Geisinger Medical Center. Funding sources: None. Conflicts of interest: None declared. Reprint requests: Eric W. Hossler, MD, Department of Dermatology, Geisinger Medical Center, 115 Woodbine Lane, Danville, PA 17822. E-mail: [email protected]. Published online July 23, 2010. 0190-9622/$36.00 ª 2010 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2010.01.001
198
Abbreviations used: BMI: RYGBP: TH: TNF: UV:
body mass index Roux-en-Y gastric bypass surgery T helper tumor necrosis factor ultraviolet
more than 6 years after RYGBP with no rebound of her psoriasis. Currently, psoriasis involves less than 5% of her body surface area, her weight is 216 lb (BMI 40.8 kg/m2), and she needs only intermittent topical steroids for therapy. She is overall very happy with her response.
Case 2 A 42-year-old woman presented to our dermatology clinic November 1, 2006, for severe plaque psoriasis involving more than 50% of her body requiring superpotent topical steroids, tazarotene, calcipotriene, UVB phototherapy, and methotrexate. She had a history of morbid obesity (214 lb; BMI 55.69 kg/m2), type 2 diabetes mellitus, hypertension, hyperlipidemia, hypothyroidism, and gastric reflux. She was started on etanercept injections, and after 19 months of therapy her body surface area involvement reduced to 25%. After unsuccessful treatment for 8 months in a comprehensive weight management clinic, she underwent open RYGBP on October 13, 2008. Six months later, her weight decreased to 145 lb (total loss 60 lb), and she noted a marked improvement in her psoriasis, with reduction of body surface area involvement to 9% plus marked thinning and lightening of her plaques. She has been
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inflammatory state associated with obesity.11 Obesity and the metabolic syndrome are associated with higher levels of tumor necrosis factor (TNF)-alfa.12,13 which plays a major role in the chronic inflammation DISCUSSION found in psoriatic plaques. Adipose tissue can seObesity is more common in patients with psoricrete TNF-alfa, and the adipose tissue of obese asis,4-8 and obese patients with psoriasis are more individuals produces 2.5 times more TNF-alfa likely to have severe skin disease.4 In addition, messenger RNA that adipose obesity is a significant risk tissue from healthy individfactor for the onset of psoriCAPSULE SUMMARY uals.14 Furthermore, weight asis, with a significant trend loss after bariatric surgery toward higher risk with inPsoriasis is a systemic disease linked with results in lower TNF-alfa excreasing BMI.9 obesity and it has been suggested that pression in adipose tissue.14 We report two patients weight loss may improve psoriasis in Improvement in psoriasis with psoriasis and comorbid obese patients. may also involve leptin, obesity who experienced We report two cases of recalcitrant a 16-kd protein secreted by dramatic improvement in psoriasis improving after weight loss adipocytes15,16 that plays a their skin disease after from gastric bypass surgery. role in appetite suppresweight loss surgery. Both of sion.17 Levels of leptin are our patients subjectively The improvement seen in psoriasis after higher in obese patients and noted improvement with weight loss in obese patients may be a directly correlate with the weight loss, and both were result of decreases in leptin or TNF-alfa percentage of body fat, sugpleased with their results. or alteration of cutaneous microflora. gesting that obese persons The improvement in their are insensitive to endogepsoriasis has been mainnous leptin.18 Several studies have now shown that tained throughout follow-up of more than 6 years leptin levels are higher in patients with psoriasis than in patient 1, and 13 months in patient 2. We believe in control subjects,15,19,20 and levels of leptin are that weight loss may have a significant impact on not higher in patients with severe psoriasis than those only the development of psoriasis, but also the with only mild psoriasis.21 Leptin levels decrease treatment of psoriasis. with weight loss16 including weight loss after bariatIn 1977, the first report of gastric bypass resulting 1 ric surgery.22 Leptin affects T lymphocytes and in improvement of psoriasis was reported. This was cytokine secretion and causes a shift toward a T a case of long-standing refractory plaque psoriasis, helper (TH)-1 phenotype (eg, that found in psoriapreviously treated with psoralen plus UVA, which sis) while suppressing TH2.17,23 In addition, leptin went into near remission after RYGBP, resulting in a 1 stimulates TNF-alfa production in peripheral blood weight loss of 54 kg. More recently, there have been monocytes.24 two cases of RYGBP causing improvement in psori2,3 Another possibility is that weight loss may alter In the first case, a 55-year-old man with asis. cutaneous microflora, which could in turn affect psoriasis on 90% of his body experienced complete antigenic stimulation driving psoriasis. According to remission after a 39-kg weight loss via RYGBP.2 In Yosipovitch et al,25 skin infections are more common the second case, a 123-kg 56-year-old man with in obese patients. Bacterial and nonbacterial infecsevere psoriasis experienced complete remission of tions are associated with obesity, including erysipehis skin disease after undergoing RYGBP and a las and cellulitis in obese patients with coexistent weight loss of 23 kg.3 None of these cases report lymphedema.25 One interesting study found that rebound flares of psoriasis during follow-up. In obesity was a significant independent risk factor for addition to these cases, a recent article showed that Staphylococcus aureus nasal carriage.26 Thus, the weight loss improved the response of psoriasis to 10 interaction between cutaneous microflora, in partictherapy with cyclosporine. To our knowledge, ular S aureus, deserves further study. there are no reports of less invasive surgical methods Despite the recent evidence supporting the posof weight loss, such as gastric banding, on the itive impact of weight loss on psoriasis, there are rare severity of psoriasis. A MEDLINE search for the case reports demonstrating worsening of psoriasis phrase ‘‘psoriasis 1 ((bariatric surgery) or (weight after weight loss surgery.27,28 In addition, one study loss))’’ failed to reveal additional reports. showed that a rapid weight reduction of 10% to 14% The reasons for this response are unknown, but of total body weight over 3 to 5 weeks caused may in part be a result of the chronic low-grade followed up for a total of 13 months after RYGBP with no rebound in her psoriasis.
d
d
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200 Hossler, Maroon, and Mowad
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worsening of psoriasis in 7 of 8 patients.29 These facts raise the possibility that our observations are spurious. Just as TNF-alfa inhibitors are used to treat psoriasis but are increasingly recognized as a cause of psoriasis in some patients,30 so too may weight loss surgery affect patients with psoriasis. Nevertheless, we agree with Hamminga et al.16 that weight loss could play a potential role in the treatment of psoriasis in patients who are obese. Reducing the inflammation from excess adipose tissue could have a therapeutic benefit in psoriatic lesions by way of reducing levels of TNF-alfa or leptin. We believe that further studies will support weight loss as a potential therapy for psoriasis, particularly in obese patients, and may play a role in adjunctive therapy with more traditional medical therapies for psoriasis. REFERENCES 1. Porres JM. Jejunoileal bypass and psoriasis. Arch Dermatol 1977;113:983. 2. Higa-Sansone G, Szomstein S, Soto F, Brasecsco O, Cohen C, Rosenthal RJ. Psoriasis remission after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Obes Surg 2004;14:1132-4. 3. de Menezes Ettinger JE, Azaro E, de Souza CA, dos Santos Filho PV, Mello CA, Neves M Jr, et al. Remission of psoriasis after open gastric bypass. Obes Surg 2006;16:94-7. 4. Herron MD, Hinckley M, Hoffman MS, Papenfuss J, Hansen CB, Callis KP, Krueger GG. Impact of obesity and smoking on psoriasis presentation and management. Arch Dermatol 2005; 141:1527-34. 5. Naldi L, Chatenoud L, Linder D, Belloni Fortina A, Peserico A, Virgili AR, 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. 6. Lindegard B. Diseases associated with psoriasis in a general population of 159,200 middle-aged, urban, native Swedes. Dermatologica 1986;172:298-304. 7. Henseler T, Christophers E. Disease concomitance in psoriasis. J Am Acad Dermatol 1995;32:982-6. 8. Brauchli YB, Jick SS, Miret M, Meier CR. Psoriasis and risk of incident myocardial infarction, stroke or transient ischemic attack: an inception cohort study with a nested case-control analysis. Br J Dermatol 2009;160:1048-56. 9. 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. 10. 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. 11. Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 2003;112:1785-8. 12. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome [comment]. Lancet 2005;365:1415-28.
13. Katsuki A, Sumida Y, Murashima S, Murata K, Takarada Y, Ito K, et al. Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1998;83:859-62. 14. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factoralpha in human obesity and insulin resistance. J Clin Invest 1995;95:2409-15. 15. Chen YJ, Wu CY, Shen JL, Chu SY, Chen CK, Chang YT, Chen CM. Psoriasis independently associated with hyperleptinemia contributing to metabolic syndrome. Arch Dermatol 2008;144: 1571-5. 16. 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. 17. Mattioli B, Straface E, Quaranta MG, Giordani L, Viora M. Leptin promotes differentiation and survival of human dendritic cells and licenses them for Th1 priming. J Immunol 2005;174: 6820-8. 18. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334:292-5. 19. Wang Y, Chen J, Zhao Y, Geng L, Song F, Chen HD. Psoriasis is associated with increased levels of serum leptin. Br J Dermatol 2008;158:1134-5. 20. Takahashi H, Tsuji H, Takahashi I, Hashimoto Y, IshidaYamamoto A, Iizuka H. Plasma adiponectin and leptin levels in Japanese patients with psoriasis. Br J Dermatol 2008;159: 1207-8. 21. Cerman AA, Bozkurt S, Sav A, Tulunay A, Elbasi MO, Ergun T. Serum leptin levels, skin leptin and leptin receptor expression in psoriasis. Br J Dermatol 2008;159:820-6. 22. Ballantyne GH, Gumbs A, Modlin IM. Changes in insulin resistance following bariatric surgery and the adipoinsular axis: role of the adipocytokines, leptin, adiponectin and resistin. Obes Surg 2005;15:692-9. 23. Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 1998;394: 897-901. 24. Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin stimulates proliferation and activation of human circulating monocytes. Cell Immunol 1999;194:6-11. 25. Yosipovitch G, DeVore A, Dawn A. Obesity and the skin: skin physiology and skin manifestations of obesity. J Am Acad Dermatol 2007;56:901-20. 26. Herwaldt LA, Cullen JJ, French P, Hu J, Pfaller MA, Wenzel RP, Perl TM. Preoperative risk factors for nasal carriage of Staphylococcus aureus. Infect Control Hosp Epidemiol 2004;25:481-4. 27. Nowlin N, Solomon H. Weight loss and psoriasis [letter]. Arch Dermatol 1976;112:1465. 28. Perez-Perez L, Allegue F, Caeiro JL, Zulaica JM. Severe psoriasis, morbid obesity and bariatric surgery. Clin Exp Dermatol 2009;34:e421-2. 29. Zackheim HS, Farber EM. Rapid weight reduction and psoriasis. Arch Dermatol 1971;103:136-40. 30. Moustou AE, Matekovits A, Dessinioti C, Antoniou C, Sfikakis PP, Stratigos AJ. Cutaneous side effects of anti-tumor necrosis factor biologic therapy: a clinical review. J Am Acad Dermatol 2009;61:486-504.
T
o our knowledge, there are only 3 prior case reports of psoriasis improving after Rouxen-Y gastric bypass surgery (RYGBP).1-3 We have observed two additional cases.
CASE REPORTS Case 1 A 34-year-old woman was followed in our dermatology clinic for many years with severe plaque psoriasis involving up to 75% of her body requiring superpotent topical steroids, ultraviolet (UV)B phototherapy, and psoralen plus UVA treatment. Her medical history included morbid obesity, with a peak body weight of 294 lb (body mass index [BMI] 52 kg/m2), type 2 diabetes mellitus, hypercholesterolemia, hypothyroidism, and mild mental retardation. Despite enrollment in a comprehensive weight management clinic for 6 months, her weight remained stable. On January 28, 2003, she underwent open RYGBP. By March 3, 2003, she had lost 45 lb, and noted that her psoriasis had markedly improved, allowing discontinuation of phototherapy. Over the following months, her psoriasis continued to improve and she reached a nadir weight of 183 lb, with a BMI of 34 kg/m2. She has been followed up for From the Department of Dermatology, Geisinger Medical Center. Funding sources: None. Conflicts of interest: None declared. Reprint requests: Eric W. Hossler, MD, Department of Dermatology, Geisinger Medical Center, 115 Woodbine Lane, Danville, PA 17822. E-mail: [email protected]. Published online July 23, 2010. 0190-9622/$36.00 ª 2010 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2010.01.001
198
Abbreviations used: BMI: RYGBP: TH: TNF: UV:
body mass index Roux-en-Y gastric bypass surgery T helper tumor necrosis factor ultraviolet
more than 6 years after RYGBP with no rebound of her psoriasis. Currently, psoriasis involves less than 5% of her body surface area, her weight is 216 lb (BMI 40.8 kg/m2), and she needs only intermittent topical steroids for therapy. She is overall very happy with her response.
Case 2 A 42-year-old woman presented to our dermatology clinic November 1, 2006, for severe plaque psoriasis involving more than 50% of her body requiring superpotent topical steroids, tazarotene, calcipotriene, UVB phototherapy, and methotrexate. She had a history of morbid obesity (214 lb; BMI 55.69 kg/m2), type 2 diabetes mellitus, hypertension, hyperlipidemia, hypothyroidism, and gastric reflux. She was started on etanercept injections, and after 19 months of therapy her body surface area involvement reduced to 25%. After unsuccessful treatment for 8 months in a comprehensive weight management clinic, she underwent open RYGBP on October 13, 2008. Six months later, her weight decreased to 145 lb (total loss 60 lb), and she noted a marked improvement in her psoriasis, with reduction of body surface area involvement to 9% plus marked thinning and lightening of her plaques. She has been
Hossler, Maroon, and Mowad 199
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inflammatory state associated with obesity.11 Obesity and the metabolic syndrome are associated with higher levels of tumor necrosis factor (TNF)-alfa.12,13 which plays a major role in the chronic inflammation DISCUSSION found in psoriatic plaques. Adipose tissue can seObesity is more common in patients with psoricrete TNF-alfa, and the adipose tissue of obese asis,4-8 and obese patients with psoriasis are more individuals produces 2.5 times more TNF-alfa likely to have severe skin disease.4 In addition, messenger RNA that adipose obesity is a significant risk tissue from healthy individfactor for the onset of psoriCAPSULE SUMMARY uals.14 Furthermore, weight asis, with a significant trend loss after bariatric surgery toward higher risk with inPsoriasis is a systemic disease linked with results in lower TNF-alfa excreasing BMI.9 obesity and it has been suggested that pression in adipose tissue.14 We report two patients weight loss may improve psoriasis in Improvement in psoriasis with psoriasis and comorbid obese patients. may also involve leptin, obesity who experienced We report two cases of recalcitrant a 16-kd protein secreted by dramatic improvement in psoriasis improving after weight loss adipocytes15,16 that plays a their skin disease after from gastric bypass surgery. role in appetite suppresweight loss surgery. Both of sion.17 Levels of leptin are our patients subjectively The improvement seen in psoriasis after higher in obese patients and noted improvement with weight loss in obese patients may be a directly correlate with the weight loss, and both were result of decreases in leptin or TNF-alfa percentage of body fat, sugpleased with their results. or alteration of cutaneous microflora. gesting that obese persons The improvement in their are insensitive to endogepsoriasis has been mainnous leptin.18 Several studies have now shown that tained throughout follow-up of more than 6 years leptin levels are higher in patients with psoriasis than in patient 1, and 13 months in patient 2. We believe in control subjects,15,19,20 and levels of leptin are that weight loss may have a significant impact on not higher in patients with severe psoriasis than those only the development of psoriasis, but also the with only mild psoriasis.21 Leptin levels decrease treatment of psoriasis. with weight loss16 including weight loss after bariatIn 1977, the first report of gastric bypass resulting 1 ric surgery.22 Leptin affects T lymphocytes and in improvement of psoriasis was reported. This was cytokine secretion and causes a shift toward a T a case of long-standing refractory plaque psoriasis, helper (TH)-1 phenotype (eg, that found in psoriapreviously treated with psoralen plus UVA, which sis) while suppressing TH2.17,23 In addition, leptin went into near remission after RYGBP, resulting in a 1 stimulates TNF-alfa production in peripheral blood weight loss of 54 kg. More recently, there have been monocytes.24 two cases of RYGBP causing improvement in psori2,3 Another possibility is that weight loss may alter In the first case, a 55-year-old man with asis. cutaneous microflora, which could in turn affect psoriasis on 90% of his body experienced complete antigenic stimulation driving psoriasis. According to remission after a 39-kg weight loss via RYGBP.2 In Yosipovitch et al,25 skin infections are more common the second case, a 123-kg 56-year-old man with in obese patients. Bacterial and nonbacterial infecsevere psoriasis experienced complete remission of tions are associated with obesity, including erysipehis skin disease after undergoing RYGBP and a las and cellulitis in obese patients with coexistent weight loss of 23 kg.3 None of these cases report lymphedema.25 One interesting study found that rebound flares of psoriasis during follow-up. In obesity was a significant independent risk factor for addition to these cases, a recent article showed that Staphylococcus aureus nasal carriage.26 Thus, the weight loss improved the response of psoriasis to 10 interaction between cutaneous microflora, in partictherapy with cyclosporine. To our knowledge, ular S aureus, deserves further study. there are no reports of less invasive surgical methods Despite the recent evidence supporting the posof weight loss, such as gastric banding, on the itive impact of weight loss on psoriasis, there are rare severity of psoriasis. A MEDLINE search for the case reports demonstrating worsening of psoriasis phrase ‘‘psoriasis 1 ((bariatric surgery) or (weight after weight loss surgery.27,28 In addition, one study loss))’’ failed to reveal additional reports. showed that a rapid weight reduction of 10% to 14% The reasons for this response are unknown, but of total body weight over 3 to 5 weeks caused may in part be a result of the chronic low-grade followed up for a total of 13 months after RYGBP with no rebound in her psoriasis.
d
d
d
200 Hossler, Maroon, and Mowad
J AM ACAD DERMATOL JULY 2011
worsening of psoriasis in 7 of 8 patients.29 These facts raise the possibility that our observations are spurious. Just as TNF-alfa inhibitors are used to treat psoriasis but are increasingly recognized as a cause of psoriasis in some patients,30 so too may weight loss surgery affect patients with psoriasis. Nevertheless, we agree with Hamminga et al.16 that weight loss could play a potential role in the treatment of psoriasis in patients who are obese. Reducing the inflammation from excess adipose tissue could have a therapeutic benefit in psoriatic lesions by way of reducing levels of TNF-alfa or leptin. We believe that further studies will support weight loss as a potential therapy for psoriasis, particularly in obese patients, and may play a role in adjunctive therapy with more traditional medical therapies for psoriasis. REFERENCES 1. Porres JM. Jejunoileal bypass and psoriasis. Arch Dermatol 1977;113:983. 2. Higa-Sansone G, Szomstein S, Soto F, Brasecsco O, Cohen C, Rosenthal RJ. Psoriasis remission after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Obes Surg 2004;14:1132-4. 3. de Menezes Ettinger JE, Azaro E, de Souza CA, dos Santos Filho PV, Mello CA, Neves M Jr, et al. Remission of psoriasis after open gastric bypass. Obes Surg 2006;16:94-7. 4. Herron MD, Hinckley M, Hoffman MS, Papenfuss J, Hansen CB, Callis KP, Krueger GG. Impact of obesity and smoking on psoriasis presentation and management. Arch Dermatol 2005; 141:1527-34. 5. Naldi L, Chatenoud L, Linder D, Belloni Fortina A, Peserico A, Virgili AR, 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. 6. Lindegard B. Diseases associated with psoriasis in a general population of 159,200 middle-aged, urban, native Swedes. Dermatologica 1986;172:298-304. 7. Henseler T, Christophers E. Disease concomitance in psoriasis. J Am Acad Dermatol 1995;32:982-6. 8. Brauchli YB, Jick SS, Miret M, Meier CR. Psoriasis and risk of incident myocardial infarction, stroke or transient ischemic attack: an inception cohort study with a nested case-control analysis. Br J Dermatol 2009;160:1048-56. 9. 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. 10. 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. 11. Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 2003;112:1785-8. 12. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome [comment]. Lancet 2005;365:1415-28.
13. Katsuki A, Sumida Y, Murashima S, Murata K, Takarada Y, Ito K, et al. Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1998;83:859-62. 14. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM. Increased adipose tissue expression of tumor necrosis factoralpha in human obesity and insulin resistance. J Clin Invest 1995;95:2409-15. 15. Chen YJ, Wu CY, Shen JL, Chu SY, Chen CK, Chang YT, Chen CM. Psoriasis independently associated with hyperleptinemia contributing to metabolic syndrome. Arch Dermatol 2008;144: 1571-5. 16. 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. 17. Mattioli B, Straface E, Quaranta MG, Giordani L, Viora M. Leptin promotes differentiation and survival of human dendritic cells and licenses them for Th1 priming. J Immunol 2005;174: 6820-8. 18. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334:292-5. 19. Wang Y, Chen J, Zhao Y, Geng L, Song F, Chen HD. Psoriasis is associated with increased levels of serum leptin. Br J Dermatol 2008;158:1134-5. 20. Takahashi H, Tsuji H, Takahashi I, Hashimoto Y, IshidaYamamoto A, Iizuka H. Plasma adiponectin and leptin levels in Japanese patients with psoriasis. Br J Dermatol 2008;159: 1207-8. 21. Cerman AA, Bozkurt S, Sav A, Tulunay A, Elbasi MO, Ergun T. Serum leptin levels, skin leptin and leptin receptor expression in psoriasis. Br J Dermatol 2008;159:820-6. 22. Ballantyne GH, Gumbs A, Modlin IM. Changes in insulin resistance following bariatric surgery and the adipoinsular axis: role of the adipocytokines, leptin, adiponectin and resistin. Obes Surg 2005;15:692-9. 23. Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 1998;394: 897-901. 24. Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin stimulates proliferation and activation of human circulating monocytes. Cell Immunol 1999;194:6-11. 25. Yosipovitch G, DeVore A, Dawn A. Obesity and the skin: skin physiology and skin manifestations of obesity. J Am Acad Dermatol 2007;56:901-20. 26. Herwaldt LA, Cullen JJ, French P, Hu J, Pfaller MA, Wenzel RP, Perl TM. Preoperative risk factors for nasal carriage of Staphylococcus aureus. Infect Control Hosp Epidemiol 2004;25:481-4. 27. Nowlin N, Solomon H. Weight loss and psoriasis [letter]. Arch Dermatol 1976;112:1465. 28. Perez-Perez L, Allegue F, Caeiro JL, Zulaica JM. Severe psoriasis, morbid obesity and bariatric surgery. Clin Exp Dermatol 2009;34:e421-2. 29. Zackheim HS, Farber EM. Rapid weight reduction and psoriasis. Arch Dermatol 1971;103:136-40. 30. Moustou AE, Matekovits A, Dessinioti C, Antoniou C, Sfikakis PP, Stratigos AJ. Cutaneous side effects of anti-tumor necrosis factor biologic therapy: a clinical review. J Am Acad Dermatol 2009;61:486-504.