BMJ 2011;343:d7320 doi: 10.1136/bmj.

d7320 (Published 17 November 2011)

Endgames

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ENDGAMES
PICTURE QUIZ

A 41 year old man with an itchy rash

Rebekka Salgo consultant dermatologist, Wolf-Henning Boehncke professor of dermatology
Department of Dermatology, JW Goethe-University Frankfurt, 60590 Frankfurt, Germany

A 41 year old man presented with a widespread rash that had been recurrently itchy and uncomfortable for 20 years. He also had stiff and painful fingers, mainly during the morning and most pronounced towards the fingertips; these symptoms had got worse over the past few months. On examination, he showed disseminated, sharply demarcated, red, scaly plaques; these were accentuated over his elbows, knees, and trunk (fig 1). He was 166 cm tall, weighed 98 kg, and had been obese since adolescence. He had been taking zuclopenthixol because of depression for the past five years, had smoked one pack of cigarettes a day for many years, and had a daily alcohol intake of 1-2 L of beer. He had no other relevant medical history.

Questions
1 What is your diagnosis regarding the patients skin disease? 2 What other comorbidities are associated with this skin condition? 3 What is the importance of the joint symptoms?

Correspondence to: R Salgo rebekka.salgo@kgu.de

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BMJ 2011;343:d7320 doi: 10.1136/bmj.d7320 (Published 17 November 2011)

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4 How could the diagnosis of depression influence the management of this patient? 5 How would you treat this patient?

Answers

1 What is your diagnosis regarding the patients skin disease? Short answer
The patient has plaque-type psoriasis.

Fig 2 Plaque-type psoriasis

Long answer

Psoriasis is a chronic recurrent immune mediated inflammatory skin disease with a prevalence of 2-3% in Europe and northern America.1 Several different types exist. The most common manifestation, plaque-type psoriasis, is characterised by sharply demarcated red plaques covered by silvery scaling (fig 2). Lesions are typically located at the knees, elbows, lower back, and head but may at times affect the whole body surface. Children often develop rashes consisting of small red papules on the trunk, known as guttate psoriasis (fig 3), which may be triggered by streptococcal tonsillitis. Inverse psoriasis (fig 4) affects intertriginous areas and lacks scaling. Pustular forms (fig 5) may be localised or systemic, and when systemic can be potentially life threatening. In all forms, the scalp and nails can be affected.

Fig 3 Guttate psoriasis

Fig 4 Inverse psoriasis

Fig 5 Pustular psoriasis

The burden of disease caused by psoriasis is substantial and is similar to that of cancer or diabetes.2

2 What other comorbidities are associated with this skin condition? Short answer

Comorbidities of psoriasis include cardiovascular diseases and the metabolic syndrome (arterial hypertension, dyslipidaemia, atherosclerosis, abdominal obesity, abnormal oral glucose tolerance test), type 2 diabetes, depression, Crohns disease, and lymphomas.

Long answer

Multiple epidemiological studies document a higher prevalence of the metabolic syndrome (arterial hypertension, dyslipidaemia, atherosclerosis, abdominal obesity, abnormal oral glucose tolerance test), type 2 diabetes, depression, Crohns disease, and lymphomas. Cardiovascular comorbiditiesmyocardial
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BMJ 2011;343:d7320 doi: 10.1136/bmj.d7320 (Published 17 November 2011)

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ENDGAMES

infarction and strokeare clinically the most important because they contribute to the increased mortality seen in patients with severe psoriasis (those who at any point in time needed systemic treatment, phototherapy, or inpatient treatment). Regardless of the ongoing controversy about the reasons for the high prevalence of the metabolic syndrome in these patients (severe psoriasis is considered an independent cardiovascular risk factor by several studies, with the odds ratio for myocardial infarction being in the range of 1.53 4; others suggest that this association might be the result of confounding5 6), doctors managing patients with severe psoriasis should know of the association and be ready to try to help with modifiable risk factors. All of these patients need comprehensive monitoring with a focus on early detection of traditional cardiovascular risk factors (table).7 8 Our patient is obese with a body mass index of 36. As well as obesity being a cardiovascular risk factor, patients with a body mass index greater than 30 are less responsive to systemic treatment for psoriasis, even when body weight dependent dosing is used.9

stigmatisation. Recent data suggest, however, that proinflammatory cytokines known to drive psoriasis (such as TNF and interferon ) may also be involved in depression.15 In line with this concept, systemic treatments for psoriasis have also shown efficacy for depression.

Finally, some antidepressive drugs, such as lithium or fluoxetine, can exacerbate psoriasis.16

5 How would you treat this patient? Short answer

Systemic treatment is needed because the disease is widespread. Methotrexate would be a good choice, but the patients excessive alcohol intake may be a contraindication. Leflunomide has little effect on the skin, so ciclosporin would be an alternative. If conventional systemic drugs cannot be used, tumour necrosis factor inhibitors would be the biological agents of choice.

Long answer

3 What is the importance of the joint symptoms? Short answer

The goal of treatment is to clear the skin as much as possible from visible symptoms and then to maintain a symptomless state. Patients with frequent rashes therefore often require long term maintenance treatment.

About 20% of patients with psoriasis develop psoriatic arthritis. Involvement of the distal interphalangeal joints is a common pattern, and morning stiffness points towards an inflammatory joint disease.

Long answer

About 20% of patients with psoriasis develop psoriatic arthritis,10 most of them within 10 years after manifestation of the disease. Patients whose nails and scalp are affected have a higher risk of developing psoriasis. Psoriatic arthritis typically affects the distal interphalangeal joints, all joints of a toe or finger (dactylitis), insertion points of tendons (enthesitis), or the insertion point of one sacroiliacal joint (asymmetric sacroiliitis). Oligoarticular and polyarticular arthritis can also occur, as well as spinal involvement or uveitis. Because around 40% of patients with psoriatic arthritis will encounter structural damage and loss of function, early diagnosis and treatment are essential. Several patient based questionnaires, including the Toronto psoriatic arthritis screening questionnaire (TOPAS) and the psoriatic arthritis screening and evaluation (PASE) tool, are available for this purpose.11 Disease modifying antirheumatic drugsnamely, methotrexate, are the therapeutic gold standard, but only tumour necrosis factor (TNF) inhibitors have been proved to stop progressive structural damage and are useful if disease modifying antirheumatic drugs fail.12

Mild forms of psoriasis that affect 10% or less of the body surface area may be treated topically. Start with a fixed combination of a glucocorticosteroid and a vitamin D derivative (such as betamethasone/calcipotriol). If this is not effective or if areas that are difficult to treat such as the scalp, face, palms, soles, and genitals are affected, or if the disease is too widespread to allow topical treatment, refer the patient to secondary care.1

More widespread disease necessitates phototherapy or systemic treatments. In some areas phototherapy is often not feasible for practical reasons (time consuming). The most widely used systemic drugs are fumaric acid esters (although not licensed all over Europe), methotrexate, ciclosporin, and retinoids. Retinoids are not recommended as monotherapy because of insufficient efficacy, whereas ciclosporin can be used for periods of a few months only, which limits its use for long term maintenance treatment. Biological agents can be used in patients who do not respond to, do not tolerate, or have contraindications to phototherapy or conventional systemic treatments. Currently, three TNF inhibiting biological agents (adalimumab, etanercept, and infliximab), as well as ustekinumab, which blocks interleukins 12 and 23, are approved to treat psoriasis. The presence or absence of psoriatic arthritis also influences the treatment decision. Although numerous studies have shown methotrexate and biological agents to be efficacious in the treatment of psoriatic arthritis,17 good quality evidence on the effects of ciclosporin and fumaric acids is limited,18 and controversy on the efficacy of ciclosporin is ongoing. Several organisations have developed evidence based guidelines for the treatment of psoriasis.19 20

4 How could the diagnosis of depression influence the management of this patient? Short answer

Some antidepressants and mood stabilisers such as lithium can exacerbate psoriasis. Psoriasis is also an independent risk factor for depression.

Long answer

Patients with psoriasis have an increased risk of depression, anxiety, and suicidality.13 Multivariate models controlling for age, sex, and consulting behaviour indicate that psoriasis is independently associated with depression (odds ratio 1.49).14 Psychological distress has long been regarded to result from
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Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Provenance and peer review: Commissioned; externally peer reviewed. Patient consent obtained.

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BMJ 2011;343:d7320 doi: 10.1136/bmj.d7320 (Published 17 November 2011)

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1 2 3 4 5 6 7 8 9 10 11 12

Smith CH, Barker JN. Psoriasis and its management. BMJ 2006;333:380-4. 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. Prodanovich S, Kirsner RS, Kravetz JD, Ma F, Martinez L, Federman DG. Association of psoriasis with coronary artery, cerebrovascular, and peripheral vascular diseases and mortality. Arch Dermatol 2009;145:700-3. Gelfand, JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA 2006;296:1735-41. Wakkee M, Meijer W, Neumann HA, Herings RM, Nijsten T. Psoriasis may not be an independent predictor for the use of cardiovascular and anti-diabetic drugs: a 5-year prevalence study. Acta Derm Venereol 2009;89:476-83. Stern RS. Psoriasis is not a useful independent risk factor for cardiovascular disease. J Invest Dermatol 2010;130:917-9. Kimball AB, Gladman D, Gelfand JM, Gordon K, Horn EJ, Korman NJ; National Psoriasis Foundation. National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening. J Am Acad Dermatol 2008;58:1031-42. Boehncke WH, Boehncke S, Schn MP. Managing comorbid disease in patients with psoriasis. BMJ 2010;340:b5666. Naldi L, Addis A, Chimenti S, Giannetti A, Picardo M, Tomino C, et al. Impact of body mass index and obesity on clinical response to systemic treatment for psoriasis. Evidence from the Psocare project. Dermatology 2008;217:365-73. Radtke MA, Reich K, Blome C, Rustenbach S, Augustin M. Prevalence and clinical features of psoriatic arthritis and joint complaints in 2009 patients with psoriasis: results of a German national survey. J Eur Acad Dermatol Venereol 2009;23:683-91. Qureshi AA, Dominguey P, Duffin KC, Gladman DD, Helliwell P, Mease PJ, et al. Psoriatic arthritis screening tools. J Rheumatol 2008;35:1423-5. Ritchlin CT, Kavanaugh A, Gladman DD, Mease PJ, Helliwell P, Boehncke WH, et al. Treatment recommendations for psoriatic arthritis. Ann Rheum Dis 2009;68:1387-94.

13 14 15 16 17

18 19 20

Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol 2010;146:891-5. Schmitt J, Ford DE. Psoriasis is independently associated with psychiatric morbidity and adverse cardiovascular risk factors, but not with cardiovascular events in a population-based sample. J Eur Acad Dermatol Venereol 2010;24:885-92. Van Voorhees AS, Fried R. Depression and quality of life in psoriasis. Postgrad Med 2009;121:154-61. Basavaraj KH, Ashok NM, Rashmi R. The role of drugs in the induction and/or exacerbation of psoriasis. Int J Dermatol 2010;49:1351-61. Heiberg MS, Kaufmann C, Rdevand E, Mikkelsen K, Koldingsnes W, Mowinckel P, et al. The comparative effectiveness of anti-TNF therapy and methotrexate in patients with psoriatic arthritis: 6 month results from a longitudinal, observational, multicentre study. Ann Rheum Dis 2007;66:1038-42. Peeters AJ, Dijkmans BA, van der Schroeff JG. Fumaric acid therapy for psoriatic arthritis. A randomized, double-blind, placebo-controlled study. Br J Rheumatol 1992;31:502-4. Pathirana D, Ormerod AD, Saiag P, Smith C, Spuls PI, Nast A, et al. European S3 guidelines on the systemic treatment of psoriasis vulgaris. J Eur Acad Dermatol Venereol 2009;23(suppl 2):1-70. Burden AD, Hilton Boon M, Leman J, Wilson H, Richmond R, Ormerod AD. Diagnosis and management of psoriasis and psoriatic arthritis in adults: summary of SIGN guidance. BMJ 2010,341:c5623.

Cite this as: BMJ 2011;343:d7320

BMJ Publishing Group Ltd 2011

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BMJ 2011;343:d7320 doi: 10.1136/bmj.d7320 (Published 17 November 2011)

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ENDGAMES

Table
Table 1| Monitoring of patients with severe psoriasis
Parameter Blood pressure Body mass index Heart rate Fasting blood lipids Fasting blood glucose Recommendation Measure every 2 years Measure every 2 years Measure every 2 years Measure every 5 years; measure every 2 years in patients with additional risk factors* Measure every 5 years; measure every 2 years in patients with additional risk factors*

*For example, a family history of cardiovascular disease or metabolic disease; patient smokes or has diabetes.

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