Approaching our patient
The patient described earlier highlights important clinical points regarding the complex management of psoriasis. First, we must recognize that her obesity, hypertension, dyslipidemia, and non-insulin-dependent diabetes indicate she most likely has metabolic syndrome. Metabolic syndrome and the systemic burden of inflammation caused by her psoriasis increase her risk for infection, cardiovascular disease, and overall mortality.
Additionally, although she has decreased her daily cigarette smoking, complete cessation of tobacco intake should be advised with the reasoning explained to the patient—that is, that smoking has been shown to exacerbate psoriasis and increase risk of cardiovascular disease and myocardial infarction. The patient should also be encouraged to decrease her daily alcohol intake, as excessive alcohol ingestion is also associated with cardiovascular disease.
Given these risk factors, many of which are modifiable, patients should see their primary care providers regularly for better control of these comorbidities and to inspire healthy lifestyle changes.
Although her psoriasis may have been mild in the past, it is now moderate-to-severe given the distress it is causing her and the large percentage of BSA it now covers. She has a history of not adhering to phototherapy treatment regimens and has expressed that it is a burden to come into the clinic weekly for treatment. Furthermore, her recent history of skin cancer is a relative contraindication to phototherapy, which heightens the risk of skin cancer with increased ultraviolet light exposure. She is thus a good candidate for systemic therapies.
Let us consider the conventional systemic therapies. Although the patient in this vignette is postmenopausal, it is always important to perform urine pregnancy tests and to ascertain the female patient’s potential and desire for pregnancy while medicated. Acitretin, an oral retinoid, has been shown to elevate serum transaminases and triglycerides in a significant number of patients. Furthermore, to be used as a monotherapy, it must be given in high doses that cause many patients significant mucocutaneous xerosis and other side effects. It is not a wise option in a patient who already has several laboratory abnormalities, especially when more effective monotherapies are available.
Methotrexate and cyclosporine have the lowest monthly costs per number of patients needed to treat to achieve PASI 75, whereas biologic agents such as infliximab and ustekinumab have costs that are more than 10 times greater.33 As previously stated, cyclosporine has many risk factors that could exacerbate chronic illnesses that our patient already has. That is, renal damage, hypertension, hypertriglyceridemia, electrolyte abnormalities, and increased risk of squamous and basal cell carcinomas. Furthermore, cyclosporine could interfere with her current medications, particularly simvastatin, which is also metabolized through the cytochrome P450 system in the liver. Although none of these are absolute contraindications to the use of cyclosporine, it is, nonetheless, typically reserved as a rescue medication rather than being utilized for long-term maintenance.
Methotrexate is one of the oldest and most commonly used systemic agents for moderate to severe psoriasis. However, this patient’s obesity indicates she may already have steatohepatitis, which would further increase her risk of liver toxicity from the methotrexate. Furthermore, her moderate alcohol intake and use of simvastatin may have already elevated her liver enzymes, which also increases her risk for liver toxicity from methotrexate and is a relative contraindication. Methotrexate, like cyclosporine and acitretin, is no longer a favorable option.
Biologics are advantageous in patients with significant comorbidities and complex medical histories, because they show no cumulative toxicity or significant interactions with other drugs. For many patients, cost may be the distinguishing factor, and their insurance plans should be taken into account. TNF-α inhibitors are a good choice for this patient, because they will not further exacerbate her existing conditions. Infliximab has weight-based dosing and may be more effective in an obese patient, though etanercept and adalimumab are both options. Should a TNF antagonist not result in adequate disease remission, newer biologic agents remain as options. TNF-α inhibitors increase the risk for infection, so patients should be screened appropriately prior to and during treatment. Apremilast is tempting to use in an obese patient given its potential side effect of weight loss, but it is not as effective in eliminating disease and has a lower PASI 75 than the other biologic agents. Nonetheless, some patients may find its oral form more favorable than an injectable medication, even if it offers partial control.
As more patients are diagnosed with chronic diseases, it is wise to understand psoriasis in their context and to be able to identify the nuances of treating psoriasis in patients with many comorbid conditions. The list of medications used to treat psoriasis continues to grow, with several other drugs having recently completed phase 3 clinical trials, providing hope and more personalized options for patients with this serious cutaneous disease.
Eman Bahani, BA, is a medical student. Maura Holcomb, MD, is a dermatology resident at Baylor College of Medicine in Houston.
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