Psoriasis is a common condition, frequent in primary care. Its estimated prevalence in Australia is 2.3 to 6.6%. While the skin is the most visible part of the organ affected by psoriasis, there is increasing evidence to support that psoriasis is a chronic multisystem inflammatory disease with many associated conditions.
Recognition and understanding of the relationship between psoriasis and other diseases is important to provide optimal care. Primary care providers and general practitioners are prepared to identify and manage these comorbid diseases.
Although the majority of patients are treated in primary care, the management of extracutaneous manifestations has not yet been fully explored in this context.
| Psoriatic arthritis |
Psoriatic arthritis is a form of inflammatory arthritis, the prevalence of which is 6% to 41% in people with psoriasis.
Almost all patients with psoriatic arthritis have skin psoriasis. In most people, skin manifestations precede arthritis, but it is estimated that 15% of cases present joint symptoms prior to or concurrent with skin lesions. Psoriatic nail dystrophy has been found to correlate with an almost 3-fold increase in the risk of joint disease.
The severity of the skin disease appears to be associated with an increased risk of psoriatic arthritis. However, skin and joint manifestations may not be temporally correlated since psoriasis flares do not necessarily precede arthritis flares. Furthermore, obesity was found to be an independent risk factor for the development of psoriatic arthritis in patients with psoriasis, reinforcing the importance of weight reduction in these individuals, who often also have an associated metabolic disorder.
Psoriatic arthritis can also present with enthesitis (inflammation of the tissue that connects the ligament or tendon to the bone) and dactylitis (sausage-shaped swelling of the digit). Dactylitis most commonly affects the feet, with an asymmetrical pattern. and is associated with greater radiological damage. Unlike other causes of inflammatory arthritis, psoriatic arthritis does not show sexual predilection. However, differences have been observed in the clinical phenotypes of psoriatic arthritis. Men are more likely to develop axial disease and radiographic joint damage while women are more likely to develop severe limitation in function and respond less favorably to treatment with tumor necrosis factor-α (TNF-α) inhibitors.
Early treatment of psoriatic arthritis can significantly improve joint outcomes and quality of life, as well as prevent permanent joint damage. Even a 6-month delay in rheumatological consultation from the onset of symptoms resulted in joint erosions and a greater likelihood of long-term disability.
With a strong emphasis on early diagnosis of psoriatic arthritis, many self-administered questionnaires have been developed and validated to screen for psoriatic arthritis. In general, they are moderately accurate in identifying psoriatic arthritis in individuals with psoriasis. A recent meta-analysis found that the Early Psoriatic Arthritis Screening Questionnaire (EARP) was the most accurate screening instrument, with the highest sensitivity and specificity.
Given the significant heterogeneity of psoriatic arthritis, the response to systemic therapy may be different for skin disease compared to joint disease. For example, while ustekinumab is very effective for the treatment of skin psoriasis, it is considered less effective than TNF-α inhibitors for psoriatic arthritis. This highlights the importance of multidisciplinary care to achieve optimal outcome in patients with psoriasis and comorbidities.
> Management in primary care - Use of validated screening tools based on questionnaires. Patients with psoriasis should be proactively screened for psoriatic arthritis and, if so, referred to a rheumatologist. Since these screening tools are designed to be self-administered by patients, they can be done routinely while patients are in the waiting room. - Given that concomitant psoriatic nail alterations are one of the strongest predictors of psoriatic arthritis, patients with psoriasis whose nails are affected should be exhaustively evaluated so as not to overlook psoriatic arthritis. |
| Cardiovascular disease |
Psoriasis is an independent risk factor for myocardial infarction, stroke, and peripheral vascular disease.
It is important to highlight that the disease is one of the main causes of excess death in patients with severe psoriasis, but not in patients with mild psoriasis.
Although the mechanism of this association is unclear, it is likely related to inflammatory mediators that are important in the pathogenesis of both psoriasis and atherosclerotic diseases. Therefore, it is important to identify psoriasis patients who are at high cardiovascular risk, in order to promote early interventions, such as lifestyle and pharmacological modifications. However, almost 15-50% of patients are aware of their increased risk of cardiovascular disease. A smaller proportion of these patients (15-25%) are aware of the association with obesity.
On the other hand, it has been shown that traditional cardiovascular risk calculators underestimate the real cardiovascular risk and that of cardiovascular and subclinical atherosclerosis in patients with psoriatic arthritis. This underestimation may result in inadequate management of risk factors in these patients.
Taking into account the established relationship between psoriasis and cardiovascular disease, it is necessary to determine if there is any treatment for psoriasis that can reduce the risk of cardiovascular events and mortality.
There is some evidence to suggest that methotrexate and TNF-α inhibitors may be associated with a lower risk of cardiovascular events compared to other systemic therapies. In contrast, no cardioprotective effect was observed for acitretin, cyclosporine, or interleukin (IL)-12 and IL-23 inhibitors. In fact, hyperlipidemia is a known adverse effect of both acitretin and cyclosporine. Cyclosporine is also known to cause hypertension, particularly in older patients, compared to younger individuals.
Although the evidence for methotrexate is limited in psoriasis and psoriatic arthritis, a meta-analysis of observational studies has shown that methotrexate decreases the risk of cardiovascular events in patients with rheumatoid arthritis.
A recent randomized controlled trial demonstrated that methotrexate did not reduce cardiovascular events in patients with stable atherosclerotic disease without any systemic inflammatory conditions. This may suggest that the reported cardiovascular benefits of methotrexate may apply only to patients with pre-existing inflammatory conditions, such as rheumatoid arthritis and psoriasis.
On the other hand, TNF-α inhibitors are associated with fewer cardiovascular events in patients with psoriasis and/or psoriatic arthritis. However, the results of these studies should be interpreted with caution due to the risk of selection bias and confounding effects. In 2 randomized controlled trials, the TNF-α inhibitor failed to reduce aortic vascular inflammation but improved inflammatory markers, including serum C-reactive protein and glycoprotein acetylation, providing a plausible biological basis for the potential cardiovascular benefits of TNF-α. TNF-α inhibitor.
The relationship between the use of TNF-α inhibitors and congestive heart failure is less certain. Studies evaluating TNF-α inhibitors in patients with congestive heart failure demonstrated an increase in mortality compared to the control group. Currently, TNF-α inhibitors are not recommended in patients with moderate to severe congestive heart failure.
> Management in primary care - Primary care providers should be aware that traditional cardiovascular risk assessment algorithms to be applied in the general population may underestimate the risk in patients with psoriasis. There is compelling evidence to consider psoriasis as a cardiovascular risk factor in its own right. - People with psoriasis should be encouraged to work with their primary care providers to optimize their cardiovascular risk factors according to national guidelines, such as lifestyle modifications (smoking cessation, alcohol counseling, and weight reduction ). |
| Obesity and insulin resistance |
Psoriasis is associated with several metabolic risk factors, including obesity, type 2 diabetes mellitus, hypertension, and dyslipidemia.
These metabolic abnormalities are also more common in patients with more severe psoriasis than in those with milder disease. The mechanisms underlying this association are complex and multifactorial, and involve both genetic and environmental factors.
Accumulating evidence suggests that, through proinflammatory cytokines secreted by white adipocytes, obesity predisposes to the development of psoriasis and worsens already existing psoriasis. Weight loss interventions using low-calorie diets (800-1000 kcal/day) and gastric bypass were shown to improve psoriasis outcomes.
Of note, gastric bypass did not achieve the same antipsoriatic effect, suggesting that the observed discrepancies may be due to factors other than weight loss, such as postoperative hormonal changes.
It is estimated that for every 10% increase in body surface area affected by psoriasis, there is an additional 20% increase in the risk of developing diabetes. Furthermore, patients with diabetes and psoriasis have a higher risk of developing micro- and macrovascular complications compared to patients with diabetes alone.
> Management in primary care - People with psoriasis should undergo routine monitoring of their body mass index, fasting blood glucose, blood pressure and lipid panel. |
| Excessive consumption of alcohol and tobacco |
Beyond its harmful cardiovascular effect, smoking was found to increase the risk of developing psoriasis and increasing its severity.
Smoking has a close association with the psoriatic palmoplantar pustulosis variant. Smoking cessation was associated with significant clinical improvement in patients with this variant.
Regarding joint disease, there is some controversial evidence surrounding the inverse association of smoking and psoriatic arthritis, often known as the “smoking paradox.” However, rather than a true association, the main reasons for the paradox are now thought to be probably methodological limitations.
Excessive alcohol consumption has been linked to the development of psoriasis, more severe skin involvement, and a less favorable response to treatment. Excessive alcohol intake also limits some of the systemic therapeutic options for the treatment of psoriasis, such as methotrexate. There is evidence to show that severe psoriasis leads to excessive tobacco and alcohol use. There are no randomized trials examining whether alcohol abstinence and smoking cessation are effective in treating psoriasis.
> Management in primary care - People with psoriasis should receive advice on quitting smoking and limiting alcohol consumption to improve their overall health. |
| Psychosocial impact and effect on quality of life |
People with psoriasis have been found to have a significantly increased risk of depression and anxiety compared to unaffected individuals.
The attributable risk of depression, but not anxiety, is greater in patients with severe psoriasis than with mild psoriasis. However, it is important to recognize that the psychosocial impact experienced by patients is not always proportional to or anticipated by the severity of the skin disease. Therefore, it should not be assumed that people with the same objective severity of psoriasis will have the same level of psychological distress from their condition. There is also evidence to suggest that depression and anxiety are associated with the development of atherosclerosis, beyond traditional risk factors.
Although it is unclear whether the psychiatric symptoms associated with psoriasis are related to the elevation of inflammatory cytokines or the social impact of psoriasis, several studies have shown that the use of biological therapies in patients with moderate to severe psoriasis results in improvement significant depression and anxiety score.
It was found that biological therapy was associated with a lower incidence of depressive symptoms than conventional systemic therapy and phototherapy. Evidence from these studies suggests that mental health symptoms improve along with improvement in skin disease.
Psoriasis affects several factors that contribute to worse quality of life, including fear of stigmatization, problems in social life, higher unemployment rates, and sexual dysfunction. Genital psoriasis occurs in up to 60% of people affected by the disease. The studies also found that sexual dysfunction occurred regardless of the presence of genital psoriasis. Effective systemic therapy has been associated with greater work productivity and lower rates of sexual dysfunction.
Based on these observations, the question arises whether psoriasis is associated with suicidality at the population level. Two systematic reviews and meta-analyses addressed this research gap, but their conclusions are contradictory. From the critical evaluation of these findings, it was deduced that specific recommendations for clinical practice cannot be made based on the low-quality evidence obtained to date. However, doctors should be alert to the warning signs of suicidality.
> Management in primary care - Primary care providers must take into account the burden of health problems in people with psoriasis. They should be screened and managed with depression and anxiety in mind. - People with moderate to severe psoriasis should undergo dermatological evaluation, biological treatment, conventional systemic therapy and phototherapy, which have been shown to improve psoriasis and, at the same time, improve psychiatric symptoms and quality of life. |
| Malignancy |
People with psoriasis have been found to have a higher incidence of certain malignancies compared to age-matched controls without psoriasis, including lymphoproliferative disorder (the strongest association occurring with cutaneous T-cell lymphoma and Hodgkin lymphoma). ), non-melanoma skin cancer and malignant tumors of the gastrointestinal tract, bladder, lung, head and neck.
The relative risk of developing cancer increases with the severity of psoriasis, which may be partly explained by the comorbid risk factors of smoking, alcohol consumption, and obesity.
Higher rates of malignancy are also attributed to the tumor-promoting effect of a chronic systemic inflammatory state. Elevated risk of nonmelanoma skin cancer appears to be associated with the use of cyclosporine, psoralen, and ultraviolet A (PUVA) TNF-α inhibitors. In Australia, PUVA is currently used very little and has largely been replaced by narrow band ultraviolet B (NBUVB), a safer form of phototherapy, without the demonstrated carcinogenic risk of PUVA. Current evidence suggests that IL-12 and IL-23 do not appear to increase the risk of malignancy.
Acitretin does not increase the risk of carcinogenesis and also protects against non-melanoma skin cancer and cutaneous T-cell lymphoma. Considering the abundant evidence from the dermatological and rheumatological literature, there is little evidence of an association between non-cutaneous malignant tumors. and systemic immunomodulators for psoriasis. Optimizing comorbidities, well-established risk factors such as obesity, smoking, and alcohol consumption, has a greater impact on reducing cancer risk than cessation or avoidance of immunosuppressive therapy for psoriasis.
> Primary care management - Primary care providers should be aware that psoriasis is associated with increased relative risk of certain types of cancers. Clinical characteristics suggestive of occult malignancy should be investigated and, if appropriate, the patient should be referred for further management. - Ensure that people with psoriasis are up to date with appropriate cancer screening appropriate to their age. - It is recommended that patients who have received more than 100 PUVA treatments, especially if they were administered in combination with cyclosporine, have regular skin cancer surveillance. - Atypical skin lesions that do not respond to psoriasis treatment should be studied by biopsy or referred for screening for non-melanoma skin cancer and cutaneous T-cell lymphoma. |
| Inflammatory bowel disease and other immune-mediated diseases |
Psoriasis and psoriatic arthritis have been associated with inflammatory bowel disease and several other immune-mediated conditions, including celiac disease, alopecia areata, vitiligo, rheumatoid arthritis, autoimmune thyroid disease, and systemic sclerosis . Studies demonstrated that psoriasis and inflammatory bowel disease are associated in a significant bidirectional manner and share several genetic susceptibility loci .
The prevalence of Crohn’s disease and ulcerative colitis in patients with psoriasis was 0.7% and 0.5%, respectively. The incidence of Crohn’s disease and ulcerative colitis was 1.55 and 3.17/10,000 person-years among psoriasis patients, respectively. Several therapies, such as TNF-α and IL-23 inhibitors, are effective in both diseases, highlighting the existence of common immunological mechanisms. Patients with inflammatory bowel disease may develop a paradoxical psoriasiform reaction after use of TNF-α inhibitors, occurring with an incidence rate of 5/100 person-years.
The pathophysiology of this paradoxical skin reaction may be related to a cytokine imbalance. There is also information that happens with other biological products. In contrast to the link between severe psoriasis and increased risk of psoriatic arthritis and cardiovascular disease, patients with concomitant psoriasis and inflammatory bowel disease have a mild psoriasis phenotype similar to that of psoriasis patients without inflammatory bowel disease. Patients with psoriatic arthritis were more likely to have an autoimmune disease than those who only had skin disease. According to the authors, this may be explained by the higher level of systemic inflammation in patients with psoriatic arthritis compared to those with psoriasis alone.
> Management in primary care - Primary care physicians should take into account that people with psoriasis have a higher incidence of diseases mediated by the immune system. The clinical characteristics of these disorders should be recognized and suspicious symptoms should be further investigated and then, if possible, the patient should be referred appropriately. |
| Liver disease |
There appears to be an association between psoriasis and non-alcoholic fatty liver disease.
The occurrence of this disease was greater in patients with psoriatic arthritis and moderate to severe psoriasis than in patients with a mild degree of psoriasis. On the other hand, psoriasis patients treated with systemic therapy, including methotrexate, had an increased risk of alcoholic fatty liver disease. This risk was more pronounced than in patients with rheumatoid arthritis.
> Primary care management - People with moderate to severe psoriasis, psoriatic arthritis and/or metabolic syndrome should be investigated for the presence of non-alcoholic fatty liver disease. - In this at-risk population, hepatotoxic medications should be used with caution. |
| Renal insufficiency |
Even after adjusting for other psoriasis-associated comorbidities that can negatively affect the kidneys (cardiovascular and metabolic disorders, and use of nonsteroidal anti-inflammatory drugs), moderate to severe psoriasis was found to be an independent risk factor for kidney disease. chronicle .
No association was found with mild psoriasis. Although the precise mechanism of this relationship is unclear, possible explanations in these patients include accelerated atherosclerosis, renal injury from chronic psoriatic inflammation, and increased incidence of glomerulonephritis, particularly IgA nephropathy.
> Management in primary care - Nephrotoxic medications should be used with caution in people with moderate to severe psoriasis. - Impaired kidney function can cause methotrexate accumulation and subsequent myelosuppression. In patients with a glomerular filtration rate <50 ml/min/1.73 m2, the dose of methotrexate must be reduced and it is contraindicated if it is <20 ml/min/1.73 m2. |
| Conclusion |
The authors state that “we should not treat psoriasis purely as a skin disease.”
The chronic inflammatory nature of psoriasis contributes to the comorbidities of this complex multisystem disorder.
In general, psoriasis severity is associated with the occurrence of most comorbid conditions, warranting increased vigilance when evaluating patients with a more severe clinical phenotype.
Given the interdependent relationship between various comorbidities and psoriasis, effective treatment in moderate to severe cases is likely to provide benefits in comorbidities and overall patient outcome.
Primary care providers and general practitioners play an important role in the recognition and management of these comorbid conditions.
