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Doctors caring for patients with psoriasis should consider exploring early screening and treatment for comorbidities, while the impact of early intervention cannot be underestimated.
Key points
- Psoriasis is associated with musculoskeletal, metabolic, cardiovascular and psychological morbidities.
- Every patient encounter is an opportunity to screen for comorbidities.
- There is emerging evidence that systemic treatments for psoriasis reduce systemic inflammatory burden and associated damage.
- Early intervention in psoriasis has the potential to modify the course of disease.
Although the skin is the most visibly affected organ in psoriasis, we now recognise that the impact of psoriasis goes well beyond the skin. In 2020, my colleagues and I published a review of the evolving body of literature that has demonstrated psoriasis to be a complex, systemic immune-mediated disorder (here).
We continue to advocate for all health care providers to have an understanding of the various systemic associations with psoriasis to inform holistic patient care. Doctors caring for patients with psoriasis should consider exploring early screening and treatment for comorbidities, such as psoriatic arthritis, cardiovascular disease, metabolic syndrome and psychological disorders.
Even though topical therapies can lead to great outcomes in limited psoriasis, considering what we now know about the comorbidities, we need to consider whether there should be a greater focus on commencing systemic therapy.
Cardiovascular and metabolic disease
In other immune-mediated diseases, such as rheumatoid arthritis, there is evidence to suggest that early treatment with systemic immunomodulators can improve vascular inflammation and reduce the risk of myocardial infarction (here and here).
A meta-analysis of patients with psoriasis demonstrated that tumour necrosis factor inhibitors (TNFi) and methotrexate are associated with a decreased risk of cardiovascular events (here).
Data published this year from more than 250 000 patients with psoriasis in a Korean nationwide database showed that systemic therapy, including both conventional and biologic therapies, was inversely associated with cardiocerebrovascular disease (here). Further, analysis from an international psoriasis registry has shown that methotrexate, TNFi and interleukin (IL)-12/23 inhibitors are associated with reduced mortality risk in patients with moderate to severe psoriasis (here).
Several prospective randomised controlled trials of moderate to severe psoriasis have recently been performed to evaluate the effects of ustekinumab (IL-12/23 inhibitor; here), secukinumab (IL-17A inhibitor; here and here) and apremilast (phosphodiesterase type 4 [PDE4] inhibitor; here) on aortic inflammation as measured by fluorodeoxyglucose–positron emission tomography (FDG-PET), computed tomography, and biomarkers of cardiometabolic disease. These trials suggest that systemic agents generally have either neutral or beneficial association with aortic vascular inflammation and cardiometabolic biomarkers.
Psoriatic arthritis
About one in four individuals with psoriasis will develop psoriatic arthritis over their lifetime. Once psoriatic arthritis is established, modern treatment still has relatively modest efficacy; on average, only 20–47% of patients achieve 50% improvement (here).
Although psoriatic arthritis can precede or develop concurrently with skin psoriasis, the majority (85%) of psoriatic arthritis presents after the onset of skin psoriasis. Therefore, a strategy to prevent psoriatic arthritis in patients at the time of cutaneous diagnosis would be ideal.
A retrospective cohort study (here) was published this year showing that treatment with IL-12/23 or IL-23 inhibitors were associated with reduced risk of development of psoriatic arthritis compared with TNFi. However, a systematic review of four other retrospective cohort studies showed conflicting results in regards to the ability of biologic agents to prevent psoriatic arthritis (here). It is worth noting that there are limitations with the data analysis of retrospective cohort studies. Evidently, prospective clinical trials are required to confirm whether psoriatic arthritis can be prevented with biologic therapy. A prospective randomised controlled trial on psoriatic arthritis prevention using an IL-23 inhibitor is currently underway (here).
We do not know why some people with psoriasis develop psoriatic arthritis while others do not. The European HIPPOCRATES project is an exciting new initiative that aims to advance our ability to stratify patients at risk for psoriatic arthritis development through better understanding of molecular biomarkers (here).
Psychological disorders
Depression and anxiety are more common in individuals with psoriasis. We know that up to 20% of people with psoriasis have concomitant depression (here). The social impact of psoriasis and skin symptoms were traditionally thought to be the cause of psychiatric symptoms, but more recent evidence suggests that elevated inflammatory cytokines and neuroinflammation may be a major driver (here).
Interestingly, psoriatic arthritis is associated with a depressive burden three times higher than those without joint involvement. It is thought that this not only reflects pain and physical disability but the effects of systemic inflammation (here).
In addition to psychotherapy and antidepressants, anti-IL-23 and anti-IL-17A biologic agents (but not traditional systemic agents) have been shown to significantly improve depressive symptoms (here).
Psoriasis early intervention: is there a role?
Early intervention is an emerging concept in the management of psoriasis. Early intervention involves screening for comorbidities, education about psoriasis and lifestyle management, as well as early implementation of systemic therapy. Although the benefits of early intervention have been well established in rheumatoid arthritis and Crohn’s disease, the benefit has not yet been proven in psoriasis.
You might wonder why psoriatic plaques keep recurring in previously affected areas. This is due to the resident memory T cells in the skin. It is hypothesised that a “hit hard and early” therapeutic approach has the potential to modify the disease by preventing these memory T cells to accumulate in the skin (here).
In two randomised controlled trials published this year, administering biologic agents to patients with disease duration less than two years resulted in a higher likelihood of achieving complete skin clearance, compared with patients with longer disease duration (here and here).
Early introduction of biologic agents may modify the long term natural course of disease. Unfortunately, the current median time to commencement of biologic therapy in patients with severe skin psoriasis in Australia and New Zealand is 8.9 years (here). A pilot early access psoriasis clinic has recently been set up in the United Kingdom (here) and we await real-world outcomes from this early intervention model.
Lastly, pharmaco-economic review of newer agents needs to be considered. This should take into account the direct cost of treatments and the potential savings gained from the prevention of long term sequelae. Of note, patents on the biologic agent ustekinumab (IL-12/23 inhibitor) are expiring in the near future. This means cheaper biosimilar agents could enter the market in early 2025 and be more accessible to more patients with psoriasis.
Dr Tom Kovitwanichkanont is an Australian Dermatology Fellow at St John’s Institute of Dermatology in London, UK. He has a special interest in medical dermatology, having completed basic physician training prior to commencing dermatology training.
The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.
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If IL 23 is expressed in the ileum, why is a modified diet not investigated as an option to taking drugs? Is it that there is no money in it? As with the experience of people with T2D and low carb diets. Has dermatology teamed up with gastroenterology? Are there studies that a modified diet can have a similar effect to anti IL23 drugs? Anecdotally my son’s psoriasis’s clears up when on an elimination diet diet ie carnivore.