**2.1 The earlier the better or time is joint function**

66 Psoriasis

**Ankylosing Spondylitis** 

**(AS) Association** 

**with Crohn´s Disease / Colitis ulcerosa** 

> **Psoriasis Arthritis (PsA)**

**Spondyloarthritis (SpA)** 

**Reactive Arthritis (ReA)** 

Fig. 1. Clinical entities of Spondyloarthritis. The overall disease group is the

entity of the group. Common abbreviations are given in parenthesis.

**Undifferentiated Spondylitis**

**Juvenile forms** 

Spondyloarthritis, which comprises 6 distinct diseases. Psoriasis Arthritis is one disease

In clinical practice, articular and extraarticular manifestations overlap quite frequently among the SpA diseases. Initially, the clinical manifestations of PsA were collected and a set of manifestations was proposed as classification criteria by Moll and Wright in 1973 (Moll, 1973). These described clinical features were considered to be "Psoriatic Arthritis". However, over the following years, 6 modified classification criteria for PsA (Bennet, 1979; Dougados, 1991; Fournie, 1999; Gladman, 1987; McGonagle, 1999; Vasey, 1984) have been proposed by different research groups in order to differentiate between the different disease entities (Taylor, 2002). As in the Moll and Wright criteria proposal, these criteria mainly have been established in groups of patients with classical and fully developed disease manifestations. The validity of these criteria have never been formally proven in studies. Formal prove of PsA criteria was done in 2006 with the publication of the CASPAR (Classification of Psoriasis Arthritis Study Group)-Criteria (Taylor, 2006) as a joint project of the EUAR and ACR. As with the other above mentioned 7 criteria sets, the CASPAR criteria also were established in a group of patients with long standing psoriasis arthritis (mean disease duration of greater than 10 years (Taylor, 2006). As we know that chronic inflammatory arthritis like Rheumatoid Arthritis (RA) and PsA can destroy joints and cause significant disability (see Tab. 1) we need to diagnose arthritis before destruction of tissue has taken place. For this reason, in RA, arthritis classification criteria have just been revised to also classify early RA (Aletaha, 2010). Next to the new RA early classification criteria, the newly proposed classification criteria for spinal spondyloarthritis now include MRI Early detection and treatment of chronic inflammatory joint disease has been shown in numerous reports to correlate with better long-term outcome in rheumatoid arthritis (van der Bijl, 2007; Verstappen, 2007). Severity of joint destruction and loss of quality of life in PsA has been shown to be similar to RA (Husted, 2001; Rahman, 2001). Therefore, many aspects in PsA may be compared with aspects in RA. As depicted in figure 2, the chronic inflammatory process begins with an undulating situation of clinical and subclinical manifestations of joint pain with or without swelling. A trigger event then sets off the clinical manifest chronic inflammatory course. Joint destruction begins very early after this event. If the inflammatory process is not stopped, the natural disease course will occur with more or less destruction of joint structures.

Fig. 2. Time course of the development of PsA. The earlier detection and treatment of arthritis takes place, the better the outcome in the following years will be, adapted according to (Machold, 1998).

Detecting Psoriasis Arthritis Early in the Disease Course – Why This

first cardiovascular event (Cugno, 2010).

Ps/PsA add to an enhanced cardiovascular risk.

**2.3 Health care costs of PsA are high** 

70% or HAQ less than 1,2) (Zink, 2006).

modern treatment with biologics.

**2.4 Psychosomatic comorbidity is important to consider** 

**2.2 Chronic inflammation confers a cardiovascular risk factor by itself** 

is Important and How Dermatologists and Rheumatologists Can Successfully Cooperate? 69

An upcoming discussion is that chronic inflammatory processes enhance the cardiovascular risk to a similar extend like the classical known risk factors diabetes, hypertension, hyperlipidemia, obesity, smoking and genetics (van Halm, 2009). This implies that treatment of inflammation may be similar important to the treatment of the classical cardiocascular risk factors in order to reduce the overall cardiovascular risk. Prospective studies on reduction of cardiovascular risk by anti-inflammatory treatment are still pending but it was shown retrospectively that effective reduction of inflammation with combination therapy of methotrexate and anti-TNF (Tumor Necrosis Factor) medication may reduce the risk for the

As in RA the cytokine TNF plays an important role in the pathophysiological mechanism of Ps and PsA. The prothrombotic effects of TNF in cardiovascular disease are discussed in a recent review and may play an important role in the about 4 fold enhanced cardiovascular risk compared with the normal population (Jacobsson, 2005). However, Ps and PsA patients seem to additionally have an increased prevalence of cardiovascular risk factors such as smoking, hypertension, raised levels of homocysteine, excessive alcohol consumption and metabolic syndrome compared to the normal population (Tobin, 2010). Therefore, it cannot be finally answered to what extend chronic inflammation of the skin, joints, and spine in

Another reason for early detection of PsA is health care costs. PsA shows increasing costs with the duration of the disease. This seems to mainly be due to the rising risk of work disability. However, the association of work disability and disease duration has not very well been studied up to day. Only 3 studies were published on this topic (Mau, 2005; Verstappen, 2010) and one review gets to the conclusion that the data is too heterogeneous to draw hard conclusions (Tillett, 2011). Nevertheless the study of Mau et al. describes a reduction of the standard employment rate in PsA patients from 0,94 to 0,7 within 5 years. Functional status seems to be the most important factor to predict total costs. Zink et al. summarize that patients with a poor functional status of 50% (HAQ of more than 1,7) cost more than double compared to patients with a good functional status (functional status of

Finally, the psychological and psychiatric comorbidities resulting from the cutaneous stigmatization and the painful, debilitating arthritic manifestations of joint and spine add to the disease burden of PsA (Devrimci-Ozguven, 2000; Esposito, 2006). There seems to be no difference in depression rate among sex and age of patients with PsA. Effective therapy of cutaneous manifestations and arthritis may reduce depressive disorders, which will significantly reduce health costs and therefore needs to be balanced against the high costs of

In clinical practice, psoriatic patients with a dominant skin manifestation primarily consult dermatologists and patients with a dominant peripheral or spinal manifestation primarily

**3. How can patients with PsA be identified in daily clinical routine?** 

However, if we treat to the target of remission and control the inflammatory process, it is possible to prevent or slow down the destructive process. We have plenty of evidence for this targeted approach for RA as reviewed elsewhere (Schoels, 2010). Furthermore, recommendations for physicians (Smolen, 2010) and patients (de Wit, 2011) on how to treat to the target of remission have recently been published. Very likely, the targeted approach is also true for PsA, because PsA also shows destructive disease courses and we use the same outcome measures than for RA. However, this has not yet been formally proven as has been for RA.

Inflammation of articular structures always is coupled with loss of function. Early in the disease course inflammation and loss of function correlate very well. This means, if inflammation is suppressed, function is completely regained. However, the longer the inflammatory process goes on, the more fibrotic and destructive changes occur which are not reversible (Aletaha, 2006). This implies that effective suppression of inflammation will not result in full regain of function anymore (figure 3). Furthermore, fibrotic tissue may cause destruction by itself thus uncoupling the destructive process from classic immune mediated mechanisms (Neumann, 2006).

Fig. 3. Correlation of inflammation (black), loss of function (yellow) and joint destruction (blue) with time. Very early in the inflammatory process loss of joint function is tightly correlated with the degree of inflammation. In this phase, complete reduction of joint inflammation will restore joint function. However, the longer the inflammatory process goes on, the more destruction of joint structures will occur along with continuously more irreversible loss of function and destruction. Finally, there may occur an uncoupling of inflammation and irreversible joint destruction with loss of function, adapted according to (Kirwan, 2001).

#### **2.2 Chronic inflammation confers a cardiovascular risk factor by itself**

An upcoming discussion is that chronic inflammatory processes enhance the cardiovascular risk to a similar extend like the classical known risk factors diabetes, hypertension, hyperlipidemia, obesity, smoking and genetics (van Halm, 2009). This implies that treatment of inflammation may be similar important to the treatment of the classical cardiocascular risk factors in order to reduce the overall cardiovascular risk. Prospective studies on reduction of cardiovascular risk by anti-inflammatory treatment are still pending but it was shown retrospectively that effective reduction of inflammation with combination therapy of methotrexate and anti-TNF (Tumor Necrosis Factor) medication may reduce the risk for the first cardiovascular event (Cugno, 2010).

As in RA the cytokine TNF plays an important role in the pathophysiological mechanism of Ps and PsA. The prothrombotic effects of TNF in cardiovascular disease are discussed in a recent review and may play an important role in the about 4 fold enhanced cardiovascular risk compared with the normal population (Jacobsson, 2005). However, Ps and PsA patients seem to additionally have an increased prevalence of cardiovascular risk factors such as smoking, hypertension, raised levels of homocysteine, excessive alcohol consumption and metabolic syndrome compared to the normal population (Tobin, 2010). Therefore, it cannot be finally answered to what extend chronic inflammation of the skin, joints, and spine in Ps/PsA add to an enhanced cardiovascular risk.

### **2.3 Health care costs of PsA are high**

68 Psoriasis

However, if we treat to the target of remission and control the inflammatory process, it is possible to prevent or slow down the destructive process. We have plenty of evidence for this targeted approach for RA as reviewed elsewhere (Schoels, 2010). Furthermore, recommendations for physicians (Smolen, 2010) and patients (de Wit, 2011) on how to treat to the target of remission have recently been published. Very likely, the targeted approach is also true for PsA, because PsA also shows destructive disease courses and we use the same outcome measures than for RA. However, this has not yet been formally proven as has been

Inflammation of articular structures always is coupled with loss of function. Early in the disease course inflammation and loss of function correlate very well. This means, if inflammation is suppressed, function is completely regained. However, the longer the inflammatory process goes on, the more fibrotic and destructive changes occur which are not reversible (Aletaha, 2006). This implies that effective suppression of inflammation will not result in full regain of function anymore (figure 3). Furthermore, fibrotic tissue may cause destruction by itself thus uncoupling the destructive process from classic immune

Fig. 3. Correlation of inflammation (black), loss of function (yellow) and joint destruction (blue) with time. Very early in the inflammatory process loss of joint function is tightly correlated with the degree of inflammation. In this phase, complete reduction of joint inflammation will restore joint function. However, the longer the inflammatory process goes

on, the more destruction of joint structures will occur along with continuously more irreversible loss of function and destruction. Finally, there may occur an uncoupling of inflammation and irreversible joint destruction with loss of function, adapted according to

for RA.

(Kirwan, 2001).

mediated mechanisms (Neumann, 2006).

Another reason for early detection of PsA is health care costs. PsA shows increasing costs with the duration of the disease. This seems to mainly be due to the rising risk of work disability. However, the association of work disability and disease duration has not very well been studied up to day. Only 3 studies were published on this topic (Mau, 2005; Verstappen, 2010) and one review gets to the conclusion that the data is too heterogeneous to draw hard conclusions (Tillett, 2011). Nevertheless the study of Mau et al. describes a reduction of the standard employment rate in PsA patients from 0,94 to 0,7 within 5 years. Functional status seems to be the most important factor to predict total costs. Zink et al. summarize that patients with a poor functional status of 50% (HAQ of more than 1,7) cost more than double compared to patients with a good functional status (functional status of 70% or HAQ less than 1,2) (Zink, 2006).

#### **2.4 Psychosomatic comorbidity is important to consider**

Finally, the psychological and psychiatric comorbidities resulting from the cutaneous stigmatization and the painful, debilitating arthritic manifestations of joint and spine add to the disease burden of PsA (Devrimci-Ozguven, 2000; Esposito, 2006). There seems to be no difference in depression rate among sex and age of patients with PsA. Effective therapy of cutaneous manifestations and arthritis may reduce depressive disorders, which will significantly reduce health costs and therefore needs to be balanced against the high costs of modern treatment with biologics.
