- Email: [email protected]
A European perspective on the challenges of managing psoriasis
A European perspective on the challenges of managing psoriasis Rosita Saraceno, MD,a,b and Christopher E. M. Griffiths, MD, FRCPa Manchester, United Kingdom, and Rome, Italy
P
soriasis affects approximately 2% of the world’s population and results in disability similar to or exceeding that associated with other major illnesses such as diabetes mellitus, rheumatoid arthritis (RA), depression, and cancer.1,2 It is chronic and incurable and can develop at any age. The disease is characterized by unpredictable periods of remission and relapse. As an added complication, the nature and morphology of the disease may be altered by therapy such as psoralen plus UVA. The lifelong nature of psoriasis invariably means a requirement for therapy that may be used long term. Clinical management is currently dictated by the physical and psychologic aspects of the disease coupled with historic response to therapy, with physical aspects identified as mild to severe. Perhaps we should instead consider psoriasis as easy or difficult to treat. This philosophy is exemplified by the holistic tool used for psoriasis measurement, the Salford Psoriasis Index.3 New systemic therapies require reconsideration of psoriasis treatment paradigms.
PSYCHOLOGIC ASPECTS Psoriasis is emotionally disabling, carrying with it significant psychosocial difficulties.4,5 Emotional difficulties arise from concerns about appearance, resulting in social rejection, guilt, embarrassment, emptiness, sexual problems, and impairment of From the Dermatology Centre, The University of Manchester, Hope Hospital,a and Dermatology Department, University of Rome ‘‘Tor Vergata.’’b Supported by Amgen Inc and Wyeth Research. Disclosure: This review article was solicited for this supplement by Amgen Inc. Dr Griffiths has received consulting fees, lecture fees, and research grants from Wyeth, Schering-Plough, Serono, Novartis, Galderma, Leo, and Biogen. Reprints not available from the authors. Correspondence to: Christopher E. M. Griffiths, MD, FRCP, Dermatology Centre, Irving Bldg, Hope Hospital, Salford, Manchester M6 8HD, United Kingdom. E-mail: christopher. [email protected]. J Am Acad Dermatol 2006;54:S81-4. 0190-9622/$32.00 ª 2006 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2005.10.051
professional ability.5,6 Those who experience psoriasis from an early age are most vulnerable to anticipating rejection and having feelings of guilt and shame.5 Psychologic aspects can modify the course of illness; in particular, feeling stigmatized can lead to treatment noncompliance and worsening of psoriasis.5 Psychologic stress can also lead to depression and anxiety.7 The prevalence of suicidal ideation and depression in patients with psoriasis is higher than that reported in other medical conditions and the general population.8,9 Patients may use alcohol and tobacco to alleviate the emotional consequences of living with such an intrusive and incurable disease.10 The anticipation by patients with psoriasis of others’ reactions to their disease leads to avoidance behavior and excessive worrying, which imbue considerable constraint on patients’ lives.11 Rapp et al2 suggested that, although not threatening to life itself, psoriasis can very significantly impair quality of life. These observations are consistent with those of Finlay et al,12 who used quantitative measures to compare disability and found that patients with psoriasis have disability at least equivalent to that of patients with angina or hypertension. Elsewhere, most patients with psoriasis who also had asthma, diabetes, or bronchitis replied that it would be ‘‘the same’’ or ‘‘better’’ to have one of these diseases than to have psoriasis.13 A further study compared illness perceptions and coping strategies in patients with psoriasis, chronic obstructive pulmonary disease, or RA.14 In the chronic diseases examined, perceived constancy of illness and fear of disease exacerbation influenced social functioning. The authors suggested that interventions aimed at increasing beliefs in personal control and changing beliefs about the course and consequence of illness could improve physical and social functioning. Active coping strategies including expression of emotion, distraction, and seeking social support are linked to better psychologic and physical adjustment in chronic diseases including psoriasis. Coping strategies used by patients with psoriasis, spinal cord injury, chronic fatigue syndrome, atrial fibrillation, cancer, or myocardial infarction are remarkably similar.15 S81
S82 Saraceno and Griffiths
J AM ACAD DERMATOL MARCH 2006
Although clearance of psoriasis reduces factors specific to psoriasis (such as disability and stress), it has no impact on psychologic distress or on patients’ beliefs about psoriasis.16 Patients are concerned about disease relapse once therapy is withdrawn. These findings underscore the need for a biopsychosocial model of long-term control of psoriasis, thereby minimizing the chance of relapse.
DISEASE MODIFICATION IN PSORIASIS Psoriasis shares many characteristics with RA, a chronic autoimmune disease with frequent progression to joint destruction and disability.17 Proinflammatory cytokines, such as interleukin-1 and tumor necrosis factor-a, play important roles in RA by mediating the inflammatory process that leads to joint damage.18 The resultant physical disability in RA is of overriding concern among rheumatologists and patients, and has inevitably shaped therapeutic strategy for this condition; once bony erosions have occurred, joint damage and deformities are difficult to reverse.19 The key is to diagnose early and treat aggressively to modify or nullify the inflammation that leads to joint erosion and subsequent destruction. The concept of early, aggressive treatment with disease-modifying antirheumatic drugs (eg, methotrexate, prednisolone, cyclosporine) was introduced into rheumatology about 15 years ago.19 With the development of tumor necrosis factor-a inhibitors, such as etanercept, infliximab, and adalimumab, the modern disease-modifying aim of treatment for RA is to reduce or prevent intra-articular inflammatory cell trafficking, cytokine production, and angiogenesis. This principle is also true for psoriatic arthritis. As Gottlieb20 has observed, dermatologists are in the vanguard of diagnosing early psoriatic arthritis and have the opportunity, perhaps even responsibility, to prevent joint destruction by timely intervention with disease-modifying antirheumatic drugs, including the new biologic agents. The concept of disease modification in psoriasis is new and not as intuitive as for RA. The principle of physical joint destruction is obvious, but is there such a concept as skin destruction? We speculate that significant cutaneous inflammation, as in psoriasis, could lead to permanent susceptibility and recurrence of disease and may irrevocably alter cutaneous leukocyte trafficking by making the dermal vascular endothelial cells more receptive to adherence by circulating leukocytes. Indeed, dermatologists who are responsible for long-term management of psoriasis are familiar with the frequent residual ‘‘blush’’ of erythema after clearance of plaques. This blush most probably represents persisting angiogenesis
and a proinflammatory state permissive of vascular leakage. An analogous situation is the recurrence of fixed drug eruptions at the same anatomic site, a phenomenon that is in part caused by persistence of the adhesion molecule intercellular adhesion molecule-1 on endothelial cells and epidermal keratinocytes.21 Moreover, increased oxidative damage with formation of reactive oxygen species has been described in fibroblasts of lesional and nonlesional skin and is believed to contribute to the skin degeneration process.22 An alteration of adhesion molecule expression could be involved in the skin changes, compounded by certain treatments (eg, overuse of topical high-potency steroids and phototherapy).23,24 Thus, we propose a scenario of microscopic skin modulation that might be reduced or prevented by early use of disease-modifying antirheumatic drugs. It will admittedly be difficult to prove whether such an approach is truly disease modifying, as we have a poor understanding of natural disease progression in psoriasis. The long-term sequel of guttate psoriasis is relatively unknown; in 1 of the few studies in this area, only 1 in 3 patients progressed to chronic plaque psoriasis within 15 years of a first episode of acute guttate psoriasis.25 Currently, the treatment strategy for psoriasis is one of a staged approach, gradually working up to systemic therapies. We should consider using systemic therapies early in the course of psoriasis, perhaps, and provocatively, even during the first episode of guttate psoriasis.
MOVING TOWARD LONG-TERM THERAPY The aim of chronic treatment is a balance between preventing disease-associated morbidity and disability, and minimizing side effects and organ toxicity consequent to prolonged use of a single agent. Unfortunately, cure of inflammatory disease such as psoriasis remains a significant unmet medical need; as in many chronic diseases, psoriasis needs lifetime treatment, but this is often difficult and unsatisfactory.26,27 In chronic skin conditions, patients directly experience the ineffectiveness of treatments by the inherent visibility of any recurrence. In contrast, many other chronic diseases are characterized by a gradual worsening, imperceptible to patients and evident only by medical monitoring. Traditional treatments, although effective in mildto-moderate psoriasis, have numerous shortcomings, including inconvenience and local intolerance, which may limit their use. Treatment for more extensive psoriasis includes monotherapy and combination therapies. Systemic drugs available for the treatment of moderate-to-severe plaque psoriasis
J AM ACAD DERMATOL
Saraceno and Griffiths S83
VOLUME 54, NUMBER 3
include photochemotherapy, retinoids, cyclosporine, methotrexate, and fumarates. Methotrexate, fumarates, and acitretin may be regarded as appropriate for continuous use. However, short- and longterm courses of many such therapies do not provide sufficient periods of remission, and very few patients are ever completely disease free, making clearance an unrealistic expectation.28 In addition, although many patients are able to achieve disease control with currently available nonbiologic systemic therapies or strategies, some are ineligible because of side effects or comorbidities. For example, short-term use of cyclosporine allows very rapid control of psoriasis, but its long-term use is associated with toxicities including hypertension and impairment of renal function.29,30 Thus, cyclosporine may best be used as a ‘‘sprint therapy’’ in acute situations, followed by a switch to safer, long-term maintenance or ‘‘marathon’’ therapies. Using therapies in rotation, or intermittently, reduces the danger of toxicity to any one organ. Indeed, dermatologists sometimes remove patients from a highly effective treatment to avoid prolonged exposure to a given set of side effects (rotational therapy).31 This strategy may include so-called ‘‘treatment holidays’’ allowing the patient respite from a particular drug until relapse of disease necessitates further treatment (intermittent therapy). However, as a consequence, many patients are unable to maintain uninterrupted control of their psoriasis, leading to dissatisfaction with treatment and contempt for their physician.32 The psychologic morbidity produced by psoriasis cannot be overemphasised and may also lead to noncompliance with treatment. It is, therefore, our belief that this approach is no longer appropriate for the management of psoriasis. Because psoriasis is chronic and essentially incurable, safe, long-term (preferably mono-) therapies that can achieve control of psoriasis are required. Recently, there has been a significant advance in devising newer medications that may be used safely over the long term for psoriasis. Laboratory science has advanced our understanding of the immunopathogenesis of psoriasis, and a number of key cytokines and immune cells, notably tumor necrosis factor-a and T cells, have been identified as critical to the biology of the disease. The so-called biologics have revolutionized the management of chronic diseases such as RA, Crohn’s, and more recently have started to impact significantly the management of psoriasis. The clear advantage of biologic agents is that they may be less toxic than other traditional systemic therapies when administered over the long term.20 The biologics era may represent an important
transition from short- to long-term continuous therapy in the management of psoriasis. Biologics hold the tantalizing promise of providing long-term, safe control for patients with psoriasis who have until recently been denied this opportunity. REFERENCES 1. Christophers E. Psoriasiseepidemiology and clinical spectrum. Clin Exp Dermatol 2001;26:314-20. 2. Rapp SR, Feldman SR, Exum ML, Fleischer AB Jr, Reboussin DM. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol 1999;41:401-7. 3. Kirby B, Fortune DG, Bhushan M, Chalmers RJG, Griffiths CEM. The Salford Psoriasis Index: a holistic measure of psoriasis severity. Br J Dermatol 2000;142:728-32. 4. Fortune DG, Richards HL, Griffiths CEM, Main CJ. Psychological stress, distress and disability in patients with psoriasis: consensus and variation in the contribution of illness perceptions, coping and alexithymia. Br J Clin Psychol 2002;41:157-74. 5. Ginsburg IH, Link BG. Feelings of stigmatization in patients with psoriasis. J Am Acad Dermatol 1989;20:53-63. 6. Richards HL, Fortune DG, Chong SL, Mason DL, Sweeney SK, Main CJ, et al. Divergent beliefs about psoriasis are associated with increased psychological distress. J Invest Dermatol 2004; 123:49-56. 7. Gupta MA, Gupta AK. Psychodermatology: an update. J Am Acad Dermatol 1996;34:1030-46. 8. Cooper-Patrick L, Crum RM, Ford DE. Identifying suicidal ideation in general medical patients. JAMA 1994;272:1757-62. 9. Fortune DG, Richards HL, Griffiths CEM. Psychologic factors in psoriasis: consequences, mechanisms and interventions. Dermatol Clin 2005;23:681-94. 10. Poikolainen K, Reunala T, Karvonen J, Lauharanta J, Karkkainen P. Alcohol intake: a risk factor for psoriasis in young and middle aged men? BMJ 1990;300:780-3. 11. Griffiths CEM, Richards HL. Psychological influences in psoriasis. Clin Exp Dermatol 2001;26:338-42. 12. Finlay AY, Khan GK, Luscombe DK, Salek MS. Validation of sickness impact profile and psoriasis disability index in psoriasis. Br J Dermatol 1990;123:751-6. 13. Finlay AY, Coles EC. The effect of severe psoriasis on the quality of life of 369 patients. Br J Dermatol 1995;132:236-44. 14. Scharloo M, Kaptein AA, Weinman J, Hazes JM, Willems LN, Bergman W, et al. Illness perceptions, coping and functioning in patients with rheumatoid arthritis, chronic obstructive pulmonary disease and psoriasis. J Psychosom Res 1998; 44:573-85. 15. Fortune DG, Richards HL, Main CJ, Griffiths CEM. Patients’ strategies for coping with psoriasis. Clin Exp Dermatol 2002; 27:177-84. 16. Fortune DG, Richards HL, Kirby B, McElhone K, Main CJ, Griffiths CEM. Successful treatment of psoriasis improves psoriasis-specific but not more general aspects of patients’ well-being. Br J Dermatol 2004;151:1219-26. 17. Wolfe F, Zwillich SH. The long-term outcomes of rheumatoid arthritis: a 23-year prospective, longitudinal study of total joint replacement and its predictors in 1,600 patients with rheumatoid arthritis. Arthritis Rheum 1998;41:1072-82. 18. Odeh M. Role of cytokines in rheumatoid arthritis. Drug News Perspect 1998;11:331-41. 19. O’Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med 2004;350:2591-602. 20. Gottlieb AB. Psoriasis: emerging therapeutic strategies. Nat Rev Drug Discov 2005;4:19-34.
S84 Saraceno and Griffiths
J AM ACAD DERMATOL MARCH 2006
21. Teraki Y, Moriya N, Shiohara T. Drug-induced expression of intercellular adhesion molecule-1 on lesional keratinocytes in fixed drug eruption. Am J Pathol 1994;145:550-60. 22. Dimon-Gadal S, Gerbaud P, Therond P, Guibourdenche J, Anderson WB, Evain-Brion D, et al. Increased oxidative damage to fibroblasts in skin with and without lesions in psoriasis. J Invest Dermatol 2000;114:984-9. 23. Edwards BD, Andrew SM, O’Driscoll JB, Chalmers RJ, Ballardie FW, Freemont AJ. Changes in numbers of epidermal cell adhesion molecules caused by oral cyclosporin in psoriasis. J Clin Pathol 1993;46:713-7. 24. Vazquez-Lopez F, Marghoob AA. Dermoscopic assessment of long-term topical therapies with potent steroids in chronic psoriasis. J Am Acad Dermatol 2004;51:811-3. 25. Martin BA, Chalmers RJ, Telfer NR. How great is the risk of further psoriasis following a single episode of acute guttate psoriasis? Arch Dermatol 1996;132:717-8. 26. de Rie MA, Goedkoop AY, Bos JD. Overview of psoriasis. Dermatol Ther 2004;17:341-9.
27. Rapp SR, Feldman SR. The promise and challenge of new biological treatments for psoriasis: how do they impact quality of life? Dermatol Ther 2004;17:376-82. 28. Al-Suwaidan SN, Feldman SR. Clearance is not a realistic expectation of psoriasis treatment. J Am Acad Dermatol 2000; 42:796-802. 29. Griffiths CEM, Dubertret L, Ellis CN, Finlay AY, Finzi AF, Ho VC, et al. Ciclosporin in psoriasis clinical practice: an international consensus statement. Br J Dermatol 2004;150(Suppl 67):11-23. 30. Zachariae H, Kragballe K, Hansen HE, Marcussen N, Olsen S. Renal biopsy findings in long-term cyclosporin treatment of psoriasis. Br J Dermatol 1997;136:531-5. 31. Weinstein GD, White GM. An approach to the treatment of moderate to severe psoriasis with rotational therapy. J Am Acad Dermatol 1993;28:454-9. 32. Krueger G, Koo J, Lebwohl M, Menter A, Stern RS, Rolstad T. The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey. Arch Dermatol 2001;137:280-4.
P
soriasis affects approximately 2% of the world’s population and results in disability similar to or exceeding that associated with other major illnesses such as diabetes mellitus, rheumatoid arthritis (RA), depression, and cancer.1,2 It is chronic and incurable and can develop at any age. The disease is characterized by unpredictable periods of remission and relapse. As an added complication, the nature and morphology of the disease may be altered by therapy such as psoralen plus UVA. The lifelong nature of psoriasis invariably means a requirement for therapy that may be used long term. Clinical management is currently dictated by the physical and psychologic aspects of the disease coupled with historic response to therapy, with physical aspects identified as mild to severe. Perhaps we should instead consider psoriasis as easy or difficult to treat. This philosophy is exemplified by the holistic tool used for psoriasis measurement, the Salford Psoriasis Index.3 New systemic therapies require reconsideration of psoriasis treatment paradigms.
PSYCHOLOGIC ASPECTS Psoriasis is emotionally disabling, carrying with it significant psychosocial difficulties.4,5 Emotional difficulties arise from concerns about appearance, resulting in social rejection, guilt, embarrassment, emptiness, sexual problems, and impairment of From the Dermatology Centre, The University of Manchester, Hope Hospital,a and Dermatology Department, University of Rome ‘‘Tor Vergata.’’b Supported by Amgen Inc and Wyeth Research. Disclosure: This review article was solicited for this supplement by Amgen Inc. Dr Griffiths has received consulting fees, lecture fees, and research grants from Wyeth, Schering-Plough, Serono, Novartis, Galderma, Leo, and Biogen. Reprints not available from the authors. Correspondence to: Christopher E. M. Griffiths, MD, FRCP, Dermatology Centre, Irving Bldg, Hope Hospital, Salford, Manchester M6 8HD, United Kingdom. E-mail: christopher. [email protected]. J Am Acad Dermatol 2006;54:S81-4. 0190-9622/$32.00 ª 2006 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2005.10.051
professional ability.5,6 Those who experience psoriasis from an early age are most vulnerable to anticipating rejection and having feelings of guilt and shame.5 Psychologic aspects can modify the course of illness; in particular, feeling stigmatized can lead to treatment noncompliance and worsening of psoriasis.5 Psychologic stress can also lead to depression and anxiety.7 The prevalence of suicidal ideation and depression in patients with psoriasis is higher than that reported in other medical conditions and the general population.8,9 Patients may use alcohol and tobacco to alleviate the emotional consequences of living with such an intrusive and incurable disease.10 The anticipation by patients with psoriasis of others’ reactions to their disease leads to avoidance behavior and excessive worrying, which imbue considerable constraint on patients’ lives.11 Rapp et al2 suggested that, although not threatening to life itself, psoriasis can very significantly impair quality of life. These observations are consistent with those of Finlay et al,12 who used quantitative measures to compare disability and found that patients with psoriasis have disability at least equivalent to that of patients with angina or hypertension. Elsewhere, most patients with psoriasis who also had asthma, diabetes, or bronchitis replied that it would be ‘‘the same’’ or ‘‘better’’ to have one of these diseases than to have psoriasis.13 A further study compared illness perceptions and coping strategies in patients with psoriasis, chronic obstructive pulmonary disease, or RA.14 In the chronic diseases examined, perceived constancy of illness and fear of disease exacerbation influenced social functioning. The authors suggested that interventions aimed at increasing beliefs in personal control and changing beliefs about the course and consequence of illness could improve physical and social functioning. Active coping strategies including expression of emotion, distraction, and seeking social support are linked to better psychologic and physical adjustment in chronic diseases including psoriasis. Coping strategies used by patients with psoriasis, spinal cord injury, chronic fatigue syndrome, atrial fibrillation, cancer, or myocardial infarction are remarkably similar.15 S81
S82 Saraceno and Griffiths
J AM ACAD DERMATOL MARCH 2006
Although clearance of psoriasis reduces factors specific to psoriasis (such as disability and stress), it has no impact on psychologic distress or on patients’ beliefs about psoriasis.16 Patients are concerned about disease relapse once therapy is withdrawn. These findings underscore the need for a biopsychosocial model of long-term control of psoriasis, thereby minimizing the chance of relapse.
DISEASE MODIFICATION IN PSORIASIS Psoriasis shares many characteristics with RA, a chronic autoimmune disease with frequent progression to joint destruction and disability.17 Proinflammatory cytokines, such as interleukin-1 and tumor necrosis factor-a, play important roles in RA by mediating the inflammatory process that leads to joint damage.18 The resultant physical disability in RA is of overriding concern among rheumatologists and patients, and has inevitably shaped therapeutic strategy for this condition; once bony erosions have occurred, joint damage and deformities are difficult to reverse.19 The key is to diagnose early and treat aggressively to modify or nullify the inflammation that leads to joint erosion and subsequent destruction. The concept of early, aggressive treatment with disease-modifying antirheumatic drugs (eg, methotrexate, prednisolone, cyclosporine) was introduced into rheumatology about 15 years ago.19 With the development of tumor necrosis factor-a inhibitors, such as etanercept, infliximab, and adalimumab, the modern disease-modifying aim of treatment for RA is to reduce or prevent intra-articular inflammatory cell trafficking, cytokine production, and angiogenesis. This principle is also true for psoriatic arthritis. As Gottlieb20 has observed, dermatologists are in the vanguard of diagnosing early psoriatic arthritis and have the opportunity, perhaps even responsibility, to prevent joint destruction by timely intervention with disease-modifying antirheumatic drugs, including the new biologic agents. The concept of disease modification in psoriasis is new and not as intuitive as for RA. The principle of physical joint destruction is obvious, but is there such a concept as skin destruction? We speculate that significant cutaneous inflammation, as in psoriasis, could lead to permanent susceptibility and recurrence of disease and may irrevocably alter cutaneous leukocyte trafficking by making the dermal vascular endothelial cells more receptive to adherence by circulating leukocytes. Indeed, dermatologists who are responsible for long-term management of psoriasis are familiar with the frequent residual ‘‘blush’’ of erythema after clearance of plaques. This blush most probably represents persisting angiogenesis
and a proinflammatory state permissive of vascular leakage. An analogous situation is the recurrence of fixed drug eruptions at the same anatomic site, a phenomenon that is in part caused by persistence of the adhesion molecule intercellular adhesion molecule-1 on endothelial cells and epidermal keratinocytes.21 Moreover, increased oxidative damage with formation of reactive oxygen species has been described in fibroblasts of lesional and nonlesional skin and is believed to contribute to the skin degeneration process.22 An alteration of adhesion molecule expression could be involved in the skin changes, compounded by certain treatments (eg, overuse of topical high-potency steroids and phototherapy).23,24 Thus, we propose a scenario of microscopic skin modulation that might be reduced or prevented by early use of disease-modifying antirheumatic drugs. It will admittedly be difficult to prove whether such an approach is truly disease modifying, as we have a poor understanding of natural disease progression in psoriasis. The long-term sequel of guttate psoriasis is relatively unknown; in 1 of the few studies in this area, only 1 in 3 patients progressed to chronic plaque psoriasis within 15 years of a first episode of acute guttate psoriasis.25 Currently, the treatment strategy for psoriasis is one of a staged approach, gradually working up to systemic therapies. We should consider using systemic therapies early in the course of psoriasis, perhaps, and provocatively, even during the first episode of guttate psoriasis.
MOVING TOWARD LONG-TERM THERAPY The aim of chronic treatment is a balance between preventing disease-associated morbidity and disability, and minimizing side effects and organ toxicity consequent to prolonged use of a single agent. Unfortunately, cure of inflammatory disease such as psoriasis remains a significant unmet medical need; as in many chronic diseases, psoriasis needs lifetime treatment, but this is often difficult and unsatisfactory.26,27 In chronic skin conditions, patients directly experience the ineffectiveness of treatments by the inherent visibility of any recurrence. In contrast, many other chronic diseases are characterized by a gradual worsening, imperceptible to patients and evident only by medical monitoring. Traditional treatments, although effective in mildto-moderate psoriasis, have numerous shortcomings, including inconvenience and local intolerance, which may limit their use. Treatment for more extensive psoriasis includes monotherapy and combination therapies. Systemic drugs available for the treatment of moderate-to-severe plaque psoriasis
J AM ACAD DERMATOL
Saraceno and Griffiths S83
VOLUME 54, NUMBER 3
include photochemotherapy, retinoids, cyclosporine, methotrexate, and fumarates. Methotrexate, fumarates, and acitretin may be regarded as appropriate for continuous use. However, short- and longterm courses of many such therapies do not provide sufficient periods of remission, and very few patients are ever completely disease free, making clearance an unrealistic expectation.28 In addition, although many patients are able to achieve disease control with currently available nonbiologic systemic therapies or strategies, some are ineligible because of side effects or comorbidities. For example, short-term use of cyclosporine allows very rapid control of psoriasis, but its long-term use is associated with toxicities including hypertension and impairment of renal function.29,30 Thus, cyclosporine may best be used as a ‘‘sprint therapy’’ in acute situations, followed by a switch to safer, long-term maintenance or ‘‘marathon’’ therapies. Using therapies in rotation, or intermittently, reduces the danger of toxicity to any one organ. Indeed, dermatologists sometimes remove patients from a highly effective treatment to avoid prolonged exposure to a given set of side effects (rotational therapy).31 This strategy may include so-called ‘‘treatment holidays’’ allowing the patient respite from a particular drug until relapse of disease necessitates further treatment (intermittent therapy). However, as a consequence, many patients are unable to maintain uninterrupted control of their psoriasis, leading to dissatisfaction with treatment and contempt for their physician.32 The psychologic morbidity produced by psoriasis cannot be overemphasised and may also lead to noncompliance with treatment. It is, therefore, our belief that this approach is no longer appropriate for the management of psoriasis. Because psoriasis is chronic and essentially incurable, safe, long-term (preferably mono-) therapies that can achieve control of psoriasis are required. Recently, there has been a significant advance in devising newer medications that may be used safely over the long term for psoriasis. Laboratory science has advanced our understanding of the immunopathogenesis of psoriasis, and a number of key cytokines and immune cells, notably tumor necrosis factor-a and T cells, have been identified as critical to the biology of the disease. The so-called biologics have revolutionized the management of chronic diseases such as RA, Crohn’s, and more recently have started to impact significantly the management of psoriasis. The clear advantage of biologic agents is that they may be less toxic than other traditional systemic therapies when administered over the long term.20 The biologics era may represent an important
transition from short- to long-term continuous therapy in the management of psoriasis. Biologics hold the tantalizing promise of providing long-term, safe control for patients with psoriasis who have until recently been denied this opportunity. REFERENCES 1. Christophers E. Psoriasiseepidemiology and clinical spectrum. Clin Exp Dermatol 2001;26:314-20. 2. Rapp SR, Feldman SR, Exum ML, Fleischer AB Jr, Reboussin DM. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol 1999;41:401-7. 3. Kirby B, Fortune DG, Bhushan M, Chalmers RJG, Griffiths CEM. The Salford Psoriasis Index: a holistic measure of psoriasis severity. Br J Dermatol 2000;142:728-32. 4. Fortune DG, Richards HL, Griffiths CEM, Main CJ. Psychological stress, distress and disability in patients with psoriasis: consensus and variation in the contribution of illness perceptions, coping and alexithymia. Br J Clin Psychol 2002;41:157-74. 5. Ginsburg IH, Link BG. Feelings of stigmatization in patients with psoriasis. J Am Acad Dermatol 1989;20:53-63. 6. Richards HL, Fortune DG, Chong SL, Mason DL, Sweeney SK, Main CJ, et al. Divergent beliefs about psoriasis are associated with increased psychological distress. J Invest Dermatol 2004; 123:49-56. 7. Gupta MA, Gupta AK. Psychodermatology: an update. J Am Acad Dermatol 1996;34:1030-46. 8. Cooper-Patrick L, Crum RM, Ford DE. Identifying suicidal ideation in general medical patients. JAMA 1994;272:1757-62. 9. Fortune DG, Richards HL, Griffiths CEM. Psychologic factors in psoriasis: consequences, mechanisms and interventions. Dermatol Clin 2005;23:681-94. 10. Poikolainen K, Reunala T, Karvonen J, Lauharanta J, Karkkainen P. Alcohol intake: a risk factor for psoriasis in young and middle aged men? BMJ 1990;300:780-3. 11. Griffiths CEM, Richards HL. Psychological influences in psoriasis. Clin Exp Dermatol 2001;26:338-42. 12. Finlay AY, Khan GK, Luscombe DK, Salek MS. Validation of sickness impact profile and psoriasis disability index in psoriasis. Br J Dermatol 1990;123:751-6. 13. Finlay AY, Coles EC. The effect of severe psoriasis on the quality of life of 369 patients. Br J Dermatol 1995;132:236-44. 14. Scharloo M, Kaptein AA, Weinman J, Hazes JM, Willems LN, Bergman W, et al. Illness perceptions, coping and functioning in patients with rheumatoid arthritis, chronic obstructive pulmonary disease and psoriasis. J Psychosom Res 1998; 44:573-85. 15. Fortune DG, Richards HL, Main CJ, Griffiths CEM. Patients’ strategies for coping with psoriasis. Clin Exp Dermatol 2002; 27:177-84. 16. Fortune DG, Richards HL, Kirby B, McElhone K, Main CJ, Griffiths CEM. Successful treatment of psoriasis improves psoriasis-specific but not more general aspects of patients’ well-being. Br J Dermatol 2004;151:1219-26. 17. Wolfe F, Zwillich SH. The long-term outcomes of rheumatoid arthritis: a 23-year prospective, longitudinal study of total joint replacement and its predictors in 1,600 patients with rheumatoid arthritis. Arthritis Rheum 1998;41:1072-82. 18. Odeh M. Role of cytokines in rheumatoid arthritis. Drug News Perspect 1998;11:331-41. 19. O’Dell JR. Therapeutic strategies for rheumatoid arthritis. N Engl J Med 2004;350:2591-602. 20. Gottlieb AB. Psoriasis: emerging therapeutic strategies. Nat Rev Drug Discov 2005;4:19-34.
S84 Saraceno and Griffiths
J AM ACAD DERMATOL MARCH 2006
21. Teraki Y, Moriya N, Shiohara T. Drug-induced expression of intercellular adhesion molecule-1 on lesional keratinocytes in fixed drug eruption. Am J Pathol 1994;145:550-60. 22. Dimon-Gadal S, Gerbaud P, Therond P, Guibourdenche J, Anderson WB, Evain-Brion D, et al. Increased oxidative damage to fibroblasts in skin with and without lesions in psoriasis. J Invest Dermatol 2000;114:984-9. 23. Edwards BD, Andrew SM, O’Driscoll JB, Chalmers RJ, Ballardie FW, Freemont AJ. Changes in numbers of epidermal cell adhesion molecules caused by oral cyclosporin in psoriasis. J Clin Pathol 1993;46:713-7. 24. Vazquez-Lopez F, Marghoob AA. Dermoscopic assessment of long-term topical therapies with potent steroids in chronic psoriasis. J Am Acad Dermatol 2004;51:811-3. 25. Martin BA, Chalmers RJ, Telfer NR. How great is the risk of further psoriasis following a single episode of acute guttate psoriasis? Arch Dermatol 1996;132:717-8. 26. de Rie MA, Goedkoop AY, Bos JD. Overview of psoriasis. Dermatol Ther 2004;17:341-9.
27. Rapp SR, Feldman SR. The promise and challenge of new biological treatments for psoriasis: how do they impact quality of life? Dermatol Ther 2004;17:376-82. 28. Al-Suwaidan SN, Feldman SR. Clearance is not a realistic expectation of psoriasis treatment. J Am Acad Dermatol 2000; 42:796-802. 29. Griffiths CEM, Dubertret L, Ellis CN, Finlay AY, Finzi AF, Ho VC, et al. Ciclosporin in psoriasis clinical practice: an international consensus statement. Br J Dermatol 2004;150(Suppl 67):11-23. 30. Zachariae H, Kragballe K, Hansen HE, Marcussen N, Olsen S. Renal biopsy findings in long-term cyclosporin treatment of psoriasis. Br J Dermatol 1997;136:531-5. 31. Weinstein GD, White GM. An approach to the treatment of moderate to severe psoriasis with rotational therapy. J Am Acad Dermatol 1993;28:454-9. 32. Krueger G, Koo J, Lebwohl M, Menter A, Stern RS, Rolstad T. The impact of psoriasis on quality of life: results of a 1998 National Psoriasis Foundation patient-membership survey. Arch Dermatol 2001;137:280-4.