By M. Elaine Husni, MD, MPH
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Although psoriatic arthritis (PsA) is associated predominantly with skin and joint manifestations, it is now recognized that patients with PsA are often affected by numerous comorbidities (Figure) that carry significant morbidity and mortality. These comorbidities frequently go unrecognized or undertreated, causing a significant clinical burden for patients and an economic burden for the healthcare system.
An overview of comorbidities most commonly seen with psoriatic arthritis.
To address this burden, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has just provided an update to its 2009 treatment guidelines that will, for the first time, include a section on managing comorbidities and extra-articular manifestations in patients with PsA.1
As the lead for this comorbidity section, our team developed the evidence-based recommendations from systematic literature reviews focused on comorbidities’ impact on PsA management and their influence on PsA therapy selection. An additional goal was to highlight research needs around these comorbidities and treatment paradigms. This article provides a general overview of key conclusions and endorsements of the new recommendations document.
Comorbidities common to systemic rheumatic disease
Cardiovascular disease (CVD) is one of the most significant comorbidities in systemic rheumatic disease. Greater awareness of the association between PsA and CVD is critical, particularly among rheumatologists, cardiologists, dermatologists and primary care providers. The association is independent of traditional CVD risk factors such as hypertension, dyslipidemia and smoking.
A recent Cleveland Clinic study2 demonstrated increased carotid intima-media thickness, a surrogate of atherosclerosis, and increased presence of carotid artery plaque in patients with PsA compared with psoriasis alone. It is hypothesized that low-grade systemic inflammation may contribute to increased insulin resistance, oxidative stress, endothelial cell dysfunction and atherosclerosis development. Thus, reducing inflammation through disease-modifying antirheumatic drug (DMARD) therapy has been hypothesized to attenuate CVD risk. To date, however, no prospective studies have specifically examined the effect of aggressive PsA treatment regimens, including DMARDs, on the risk of cardiovascular events.
Obesity, metabolic syndrome and diabetes also have been revealed as common comorbidities of rheumatic diseases, including psoriatic disease. Inflammation-mediated insulin resistance, obesity and unhealthy lifestyles may partially explain the 12 to 18.6 percent prevalence of type 2 diabetes mellitus among PsA patients. CVD, obesity, metabolic syndrome and diabetes all may impact PsA disease activity and response to therapy negatively. For these reasons, attention to traditional CVD risk factors, lifestyle changes and proper diet should be particularly vigorous in the PsA population.
Comorbidities common to psoriatic disease
Inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, has an elevated incidence in patients with PsA, as does subclinical bowel inflammation. The associated potential morbidity of coexisting IBD and PsA is high but not well-studied.
Autoimmune ophthalmic disease and its spectrum have been shown to have a significant prevalence (up to 25 percent) in PsA patients, conferring high potential morbidity. For this reason, PsA patients with ophthalmic symptoms should be evaluated early. Ocular manifestations of PsA include uveitis, keratitis, blepharitis, conjunctivitis, episcleritis and scleritis; uveitis appears to have the strongest association with PsA. Available data support the use of corticosteroids (systemic, periocular and implantable forms), methotrexate, mycophenolate, cyclosporine, azathioprine and some anti-TNF agents to treat PsA patients with uveitis. The two most frequently used biologics are infliximab and adalimumab.
Emerging comorbidities associated with psoriatic disease
Osteoporosis: A high index of suspicion for osteoporosis should be maintained in PsA patients, and those using glucocorticoids should be evaluated for osteoporosis and treated when indicated.
Malignancy: Understanding of the effect of psoriatic disease on malignancy is confounded by the use of immunosuppressive and ultraviolet therapies. Published data are insufficient and conflicting, but incidence rates generally do not differ from those in the general population. It remains unclear whether patients with PsA and a history of cancer are at greater risk of recurrent cancer with chronic anti-TNF therapy.
Liver disease, particularly nonalcoholic fatty liver disease (NAFLD), is believed to result from psoriatic disease, although this association has not been well-studied in PsA. Among patients with psoriasis, the increased prevalence of NAFLD is associated with psoriasis severity and concomitant PsA as well as other comorbidities common to PsA, such as metabolic syndrome, hypercholesterolemia, hypertriglyceridemia and obesity.
Kidney disease has been associated with psoriatic diseases. Independent of traditional risk factors, patients with moderate to severe psoriasis have a higher risk of chronic kidney disease compared with the general population. Sixteen percent of patients with seronegative arthritis (PsA and undifferentiated oligoarthritis) have been shown to have reduced estimated glomerular filtration rate, similar to the prevalence in rheumatoid arthritis (19 percent).
Special therapeutic challenges in psoriatic disease
Chronic viral infections, such as with HIV or hepatitis B or C virus, may impact therapy choice in patients with PsA, as the use of potentially hepatotoxic and immunosuppressive drugs requires caution due to the potential for increased viral replication and reactivation.
Routine vaccinations are often a concern among PsA patients on immunosuppressive therapy. The Advisory Committee on Immunization Practices (ACIP) provides a list of recommended vaccinations prior to initiation of certain immunosuppressive therapies. ACIP also recommends avoiding use of live attenuated vaccines in immunosuppressed patients. Temporary discontinuation of immunosuppressive medication before vaccination also might be considered, although no studies support this strategy.
In addition to PsA’s skin and joint manifestations, the above comorbidities and therapeutic challenges loom large in the management of these patients. It is imperative that providers be aware of the multiple comorbidities and extra-articular/cutaneous manifestations of PsA in order to provide truly comprehensive care. While much debate surrounds who should directly manage these comorbidities, patients benefit from communication among and education from both rheumatologists and other providers.
As new medications are added to the PsA armamentarium, studying their effects on comorbidities and extra-articular/cutaneous manifestations will be central to promoting better-tailored treatment options. Further studies examining the reasons for the high prevalence of comorbidities could alleviate some of this burden.
- Ogdie A, Schwartzman S, Eder L, Maharaj AB, Zisman D, Raychaudhuri SP, Reddy SM, Husni E. Comprehensive treatment of psoriatic arthritis: managing comorbidities and extraarticular manifestations. J Rheumatol. 2014;41(11):2315-2322.
- Lin YC, Dalal D, Churton S, Brennan DM, Korman NJ, Kim ES, Husni ME. Relationship between metabolic syndrome and carotid intimamedia thickness: cross-sectional comparison between psoriasis and psoriatic arthritis. Arthritis Care Res (Hoboken). 2014;66(1):97-103.
Dr. Husni is Director of the Arthritis and Musculoskeletal Treatment Center and directs Cleveland Clinic’s Psoriatic Disease Biobank. She led the writing group for the comorbidities section of the GRAPPA guidelines update.