Comorbidities
An interesting way of starting the interactive workshop sessions was by asking the question: “What do patients want?”
Invariably the answer will include long-term resolution of the underlying dermatological disorder, possibly using a single agent. This will include rapid remission of the disease to a point where the patient can live a normal life and this effect should be maintained without constant disease flares.
To achieve this requires a combination of pharmacological therapy, patient education, removal of trigger factors (including drugs) and an approach to managing comorbidities. With regards to the latter, which is the main focus of this part of the workshop, some of the more common comorbidities associated with psoriasis include anxiety and depression, psoriatic arthritis (PsA), the metabolic syndrome (abdominal obesity, hypertension, atherogenesis and dyslipidemia), diabetes and hyperhomocysteinemia. The metabolic changes result in an overall increased risk of cardiovascular disease and this has recently been confirmed in large registry studies. Regarding comorbidities associated with conventional systemic therapy for psoriasis, drugs such as methotrexate (homocysteinemia, hepatotoxicity and teratogenicity), ciclosporin (nephrotoxicity, dyslipidemia, hypertension and diabetes) and retinoids (dyslipidemia, diabetes, hepatotoxicity and diabetes) all have their problems. The more recently introduced TNF-α antagonists appear better in this regard.
What is the evidence that the inflammation of the skin in patients with psoriasis can affect the body as a whole?
• Psoriasis is associated with increased levels of C-reactive protein (a marker for cardiovascular risk), which has been linked to the development and progression of atherosclerosis;
• Psoriasis is associated with increased homocysteine levels, an independent risk factor for cardiovascular disease.
There is accumulating evidence that moderate-to-severe psoriasis increases susceptibility to cardiovascular disease, and patients should be encouraged to aggressively correct modifiable cardiovascular risk factors, such as weight, smoking habits, alcohol consumption and dyslipidemia. An interesting discussion regarding psoriasis and obesity ensued between the workshop participants. Psoriasis patients have low self esteem and a higher risk of depression/anxiety and these exacerbate the likelihood of weight gain. Most delegates agreed that the first priority of treatment was to resolve the underlying skin pathology since this was the best method of alleviating secondary conditions such as depression, anxiety and low self esteem, and then the focus could turn to the reduction of risk factors such as obesity. Even relatively simple measures, such as routine monitoring of blood pressure and lipid profiles, were not performed by the majority of dermatologists in the meeting. In an environment of evidence-based clinical practice and a holistic approach to patient care, more attention will need to be placed upon risk reduction in the future.
Psoriatic arthritis
Psoriatic arthritis is relatively common and easy to diagnose, and it generally occurs approximately 10 years after the psoriasis is first diagnosed. This places the dermatologist in a prime position to diagnose PsA and, with the advent of drugs that can prevent x-ray progression of the arthritis (e.g., the TNF antagonists), the earlier the treatment the better the clinical outcome. PsA presents with a range of characteristics/symptoms, including morning stiffness (∼50%), America College of Rheumatology functional class III/IV (11%), inflammatory neck pain and stiffness (23%), inflammatory back pain and stiffness (19%), actively inflamed joints (97%), deformities (≥1 43%; ≥5 16%), dactylitis (33%), distal interphalangeal joint disease (54%), sacroiliac stress pain (10%), skin and joints flaring simultaneously (35%), iritis (7%), psoriasis pattern (vulgaris 94%; guttae 4%) and nail lesions (83%).
When should the dermatologist refer PsA to a rheumatologist? The answer to this question differs from country to country and even within individual physician groups. Most cases of PsA are easily diagnosed and easily treated, but if there is any doubt, they should be refered to a rheumatologist. Irrespective of whoever takes responsibility, they need to be well versed in the use of systemic immunosuppressive therapy.
Given the natural history of psoriasis and PsA, the dermatologist has a critical role to play in the management of the two diseases since early diagnosis of joint involvement and immediate initiation of treatment can alleviate pain and prevent longer term damage.
So, who takes responsibility for the patient when they are first diagnosed with PsA? It probably does not matter so long as somebody does. One of the most important considerations is that drugs are administered that can treat both conditions equally well, since these will represent first-line choices in this class of patient. In this regard, we already have more effective drugs available to us, such as the TNF blockers, and they can be used long term because they are generally safer than conventional therapies. An exciting next step is to investigate whether their use in psoriasis has any impact on the development of PsA during long-term continuous treatment. Is it possible that we can prevent or delay PsA occurring?
Financial & competing interests disclosure
G Girolomoni has previously received honoraria for attending advisory boards and as a speaker for Abbott, Schering-Plough, Wyeth, Novartis, Merck Serono, UCB Pharma, Janssen-Cilag and Astellas. A Gottlieb is a member of the Speakers’ Bureau for Amgen, Inc. and Wyeth Pharmaceuticals. A Gottlieb has current consulting/advisory board agreements with Amgen, Inc., Centocor, Inc., Wyeth Pharmaceuticals, Celgene Corp., Bristol Myers Squibb Co., Beiersdorf, Inc., Warner Chilcott, Abbott Labs, Roche, Sankyo, Medarex, Kemia, Celera, TEVA, Actelion, UCB, Novo Nordisk, Almirall, Immune Control, RxClinical, Dermipsor Ltd, Medacorp, DermiPsor, Can-Fite, Incyte and Corgentech, and most of the income is payed to the employer. Writing assistance was provided by Steve Clissold PhD (Content Ed Net), with funding by Schering-Plough, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
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