Comorbidities in Psoriasis: Part Two
Tuesday, November 06, 2007
Psoriasis is a common chronic inflammatory
disease of the skin that has been associated with a variety of
comorbidities. More recent work has focused on how comorbid
diseases and exposures can be risk factors for the development of
psoriasis, as well as how chronic psoriasis can be a risk factor
for the development of other diseases that share a common immune
A risk factor is an exposure or characteristic
that increases an individual's chance for developing a certain
outcome, and by definition, the association is not explained by
confounding (e.g. third factors that explain the association) or
bias (e.g. systematic error in how patients are selected or
information is collected). A risk factor may suggest a causal
relationship based on strength of study design (randomized
controlled trial is the gold standard), temporal relationship,
strength of the association, consistency of studies, and biological
In this review, I will summarize some of the
major comorbidities associated with psoriasis, highlighting recent
studies that evaluate risk factors for onset of psoriasis or
exacerbation of psoriasis, and studies that evaluate psoriasis as a
risk factor for developing diseases that share a similar immune
This commentary will address cancer,
cardiovascular and metabolic disease, psychiatric disease, and
Part One addresses infection, body mass index (BMI), and
smoking and alcohol.
The immunologic nature of psoriasis, as well
as therapies that are immunosuppressive or mutagenic, may
predispose patients with psoriasis to an increased risk of cancer.
A higher incidence of non-melanoma skin cancer (NMSC) has been
reported in psoriasis patients, and there are conflicting findings
regarding internal cancers such as lung, breast, colon and
prostate.1-7 Lymphoma has been of special interest as
inflammatory conditions may be associated with a higher risk of
lymphoproliferative diseases. Studies of the risk of internal
lymphoma in psoriasis patients have yielded inconsistent
results.8-15 The largest study to date found no
increased risk of non-Hodgkin's lymphoma but did observe an
increased risk of Hodgkin's lymphoma and a markedly increased
relative risk for cutaneous T-cell lymphoma (CTCL).16
The association of psoriasis with CTCL may be due to misdiagnosis
of early CTCL as psoriasis or may be related to chronic
lymphoproliferation leading to CTCL.16 Recently, the
results of 30 years of follow-up of psoriasis patients treated with
PUVA found that patients who received PUVA and were exposed to high
levels of methotrexate (≥36 months) had an increased incidence of
lymphoma compared to the general population (IRR 4.39, 95% CI
1.59-12.06).17 Patients who received >300 UVB
treatments, were skin types 1 or 2, or received >200 PUVA
treatments also had increased rates of lymphoma, but these were not
statistically significant, possibly due to limitations of
statistical power and incomplete ascertainment of outcomes.
Cardiovascular and Metabolic Disease
Epidemiologic studies in Sweden, Germany, and
the Unites States have demonstrated an association between
psoriasis and cardiovascular disease (CVD).18-20
Mallbris and colleagues found that a Swedish cohort of patients
with a history of hospital admission for psoriasis had an overall
increased risk of CV mortality compared to the general population
(SMR 1.52; 95% CI: 1.44-1.60).20 However, this finding
was not supported by Stern et al. who found no evidence of
increased cardiovascular mortality in psoriasis patients receiving
psoralen and long-wave ultraviolet radiation (PUVA) treatment
compared to the general population (SMR 0.83, 90%
0.7-1.0).21 These studies are limited in that they are
of highly selected patient populations, utilized an external
comparison group (which can introduce bias), and did not control
for other cardiac risk factors that may confound the relationship
between psoriasis and CVD.
In addition to smoking and obesity, several
studies suggest that cardiovascular risk factors such as diabetes,
hypertension, and hyperlipidemia are more prevalent in psoriasis
patients.18,19,22-28 In particular, diabetes has
shown an association with severe psoriasis (OR 1.62, 95% CI
1.3-2.01) independent of other risk factors for diabetes such as
obesity.7 Although evolving evidence suggests that
psoriasis is associated with a variety of cardiovascular risk
factors, recent studies suggest that psoriasis itself is an
independent risk factor for developing coronary artery disease and
myocardial infarction (MI), possibly due to shared immunologic
pathways that function abnormally in both diseases.29-31
For example, a large cohort study of more than 130,000 patients
with psoriasis demonstrated that psoriasis was associated with an
increased risk of MI even when controlling for major cardiovascular
risk factors such as diabetes, hypertension, hyperlipidemia,
smoking, and BMI. The increased risk of MI attributable to severe
psoriasis (N=3837) was similar in magnitude to the risk of MI
conferred by other major risk factors such as
diabetes.29 A smaller study of 32 severe psoriasis
patients selected from a referral practice demonstrated a higher
prevalence of coronary artery disease even when controlling for
multiple risk factors for atherosclerosis.32
Multiple studies, the majority of which are
descriptive, have examined psychological characteristics of
patients with psoriasis.33-35 A wide range of problems
have been described, such as depression, anxiety, obsessive
behavior, sexual dysfunction, and suicidal
ideation.36-41 Suicidal ideation was found to be present
in 7.2% of patients hospitalized for psoriasis, 2.5% of psoriasis
outpatients and 2.4-3.3% of general medical patients, suggesting
that patients with more severe disease may have greater emotional
impairment.33 Psychological distresses may also impair
response to psoriasis therapies. For example, in a cohort of
psoriasis patients treated with PUVA, pathological or high-level
worry was a significant predictor of time taken for PUVA to clear
psoriasis, whereas clinical severity of psoriasis, skin phenotype,
alcohol intake, anxiety, and depression were not.42
Joint diseases are common among patients with
psoriasis.43 Psoriatic arthritis is defined as a
rheumatoid factor-negative inflammatory arthritis associated with
psoriasis.44 Estimates of the prevalence of
psoriatic arthritis among patients with psoriasis vary from 6% up
to 30%.43,45 Population-based studies, which are
broadly representative of all patients with psoriasis, have found a
prevalence of psoriatic arthritis in patients with psoriasis to be
6.25% in Olmstead County, Minnesota, and 11% in the continental US
population.8 Additionally, the population-based studies
and clinic-based studies have indicated that the prevalence of
psoriatic arthritis increases significantly based on the BSA
affected by psoriasis.8,9
In general, psoriatic arthritis tends to
appear several years after the onset of skin lesions in the
majority of patients; however, it can precede the skin disease in
approximately 13-17% of cases.10 Nail lesions may help
to identify those patients with psoriasis who are at higher risk of
developing arthritis as these lesions occur in 80-90% of patients
with psoriatic arthritis compared to 46% in those with psoriasis
uncomplicated by arthritis.11 Although the severity of
skin psoriasis predicts the prevalence of psoriatic arthritis, it
does not reliably correlate with the severity of psoriatic
arthritis symptoms and signs.11 Broadly representative
population-based studies suggest that the incidence of structural
damage in psoriatic arthritis is low (<10%) and that the disease
does not impact mortality.45 Studies from tertiary care
centers, which are skewed toward patients with more severe disease,
have shown a higher risk of mortality for patients with psoriatic
arthritis and have found higher overall frequencies of destructive
joint changes.10,12 Several HLA types have been
associated with psoriatic arthritis, suggesting a genetic
predisposition to developing this disease.13, 14, 46
Psoriasis is associated
with a variety of comorbidities and adverse health behaviors such
as smoking and alcohol use. Evolving data suggests that some
conditions and behaviors may increase a patient's risk of
developing psoriasis (such as smoking and obesity). For patients
with psoriasis, evolving data suggests that smoking, alcohol, and
excessive worry may result in more severe skin disease, treatment
non-compliance, and treatment resistance, respectively, and that
psoriasis itself may be an independent risk factor for having
diabetes and atherosclerosis and for developing a subsequent MI.
The cumulative impact of severe chronic psoriasis and its
associated comorbidities is demonstrated by recent data showing
that severe psoriasis is associated with a 50% increased risk in
all-cause mortality and that these patients die approximately 3-4
years younger than patients without psoriasis.15
The emerging data highlight
the importance of comprehensive medical care for patients with
psoriasis. Patients should be counseled on the importance of
maintaining a healthy body weight, not smoking, and not drinking
alcohol to excess. Furthermore, screening for symptoms of psoriatic
arthritis and risk factors for cardiovascular disease in psoriasis
patients and appropriate treatment of these conditions when
identified is encouraged. Additional studies are necessary to
determine if treating psoriasis will result in a decrease in the
incidence of adverse health outcomes (e.g. MI), as well as to more
clearly determine how psoriasis skin severity and treatment relate
to morbidity rates.
- Paul CF, Ho VC, McGeown C, et al. Risk of malignancies
in psoriasis patients treated with cyclosporine: a 5 y cohort
study. J Invest Dermatol. 2003;120:211-6.
- Stern RS, Vakeva LH. Noncutaneous malignant tumors in the PUVA
follow-up study: 1975-1996. J Invest Dermatol.
- Hannuksela-Svahn A, Sigurgeirsson B, Pukkala E, et al.
Trioxsalen bath PUVA did not increase the risk of squamous cell
skin carcinoma and cutaneous malignant melanoma in a joint analysis
of 944 Swedish and Finnish patients with psoriasis. Br J
- Frentz G, Olsen JH, Avrach WW. Malignant tumours and psoriasis:
climatotherapy at the Dead Sea. Br J Dermatol.
- Boffetta P, Gridley G, Lindelof B. Cancer risk in a
population-based cohort of patients hospitalized for psoriasis in
Sweden. J Invest Dermatol. 2001;117:1531-7.
- Hannuksela-Svahn A, Pukkala E, Laara E, et al.
Psoriasis, its treatment, and cancer in a cohort of Finnish
patients. J Invest Dermatol. 2000;114:587-90.
- Frentz G, Olsen JH. Malignant tumours and psoriasis: a
follow-up study. Br J Dermatol. 1999;140:237-42.
- Gelfand JM, Gladman DD, Mease PJ, et al.
Epidemiology of psoriatic arthritis in the population of the United
States. J Am Acad Dermatol. 2005;53:573.
- Stern RS. The epidemiology of joint complaints in patients with
psoriasis. J Rheumatol. 1985;12:315-20.
- Gladman DD, Shuckett R, Russell ML, et al.
Psoriatic arthritis (PSA) - an analysis of 220 patients. Q
- Cohen MR, Reda DJ, Clegg DO. Baseline relationships between
psoriasis and psoriatic arthritis: analysis of 221 patients with
active psoriatic arthritis. Department of Veterans Affairs
Cooperative Study Group on Seronegative
- Wong K, Gladman DD, Husted J, et al. Mortality
studies in psoriatic arthritis: results from a single outpatient
clinic. I. Causes and risk of death. Arthritis
- Eastmond CJ. Psoriatic arthritis. Genetics and HLA
antigens. Baillieres Clin
- Gladman DD, Anhorn KA, Schachter RK, et al. HLA
antigens in psoriatic arthritis. J
- Gelfand JM, Troxel A, Lewis JD, et al. Severe
psoriasis patients have an increased risk for mortality: Results
from a population-based study. Arch
Dermatol. 2007;In press.
- Gelfand JM, Shin DB, Neimann AL, et al. The risk of
lymphoma in patients with psoriasis. J Invest Dermatol.
- Stern RS. Lymphoma risk in psoriasis: results of the PUVA
follow-up study. Arch Dermatol. 2006;142:1132-5.
- Ena P, Madeddu P, Glorioso N, et al. High prevalence
of cardiovascular diseases and enhanced activity of the
renin-angiotensin system in psoriatic patients. Acta
- Henseler T, Christophers E. Disease concomitance in psoriasis.
J Am Acad Dermatol. 1995;32:982-6.
- Mallbris L, Akre O, Granath F, et al. Increased risk
for cardiovascular mortality in psoriasis inpatients but not in
outpatients. Eur J Epidemiol. 2004;19:225-30.
- Stern RS, Lange R. Cardiovascular disease, cancer, and cause of
death in patients with psoriasis: 10 years prospective experience
in a cohort of 1,380 patients. J Invest Dermatol.
- Lindegard B. Mortality and causes of death among psoriatics.
- McDonald CJ. Cardiovascular disease in psoriasis. J Invest
- McDonald CJ, Calabresi P. Thromboembolic disorders associated
with psoriasis. Arch Dermatol. 1973;107:918.
- McDonald CJ, Calabresi P. Complication of psoriasis.
- McDonald CJ, Calabresi P. Occlusive vascular disease in
psoriatic patients. N Engl J Med. 1973;288:912.
- Mallbris L, Granath F, Hamsten A, et al. Psoriasis is
associated with lipid abnormalities at the onset of skin disease.
J Am Acad Dermatol. 2006;54:614-21.
- Lindegard B. Diseases associated with psoriasis in a general
population of 159,200 middle-aged, urban, native Swedes.
- Gelfand JM, Neimann AL, Shin DB, et al. Risk of
myocardial infarction in patients with psoriasis. JAMA.
- Ludwig RJ, Herzog C, Rostock A, et al. Psoriasis: a
possible risk factor for development of coronary artery
calcification. Br J Dermatol. 2007;156:271-6.
- Hansson GK. Inflammation, atherosclerosis, and coronary artery
disease. N Engl J Med. 2005;352:1685-95.
- Ludwig RJ, Herzog C, Rostock A, et al. Psoriasis: a
possible risk factor for development of coronary artery
calcification. Br J Dermatol. 2007;156:271-6.
- Gupta MA, Gupta AK. Depression and suicidal ideation in
dermatology patients with acne, alopecia areata, atopic dermatitis
and psoriasis. Br J Dermatol. 1998;139:846-50.
- Gupta MA, Schork NJ, Gupta AK, et al. Suicidal
ideation in psoriasis. Int J Dermatol.
- Polenghi MM, Molinari E, Gala C, et al. Experience
with psoriasis in a psychosomatic dermatology clinic. Acta Derm
Venereol Suppl (Stockh). 1994;186:65-6.
- Gupta MA, Gupta AK, Haberman HF. Psoriasis and psychiatry: an
update. Gen Hosp Psychiatry. 1987;9:157-66.
- Rubino IA, Sonnino A, Pezzarossa B, et al. Personality
disorders and psychiatric symptoms in psoriasis. Psychol
- Vidoni D, Campiutti E, D'Aronco R, et al. Psoriasis
and alexithymia. Acta Derm Venereol Suppl (Stockh).
- Gupta MA, Gupta AK, Watteel GN. Early onset (<40 years age)
psoriasis is comorbid with greater psychopathology than late onset
psoriasis: a study of 137 patients. Acta Derm Venereol.
- Richards HL, Fortune DG, Weidmann A, et al. Detection
of psychological distress in patients with psoriasis: low consensus
between dermatologist and patient. Br J Dermatol.
- Ginsburg IH, Link BG. Feelings of stigmatization in patients
with psoriasis. J Am Acad Dermatol. 1989;20:53-63.
- Fortune DG, Richards HL, Kirby B, et al. Psychological
distress impairs clearance of psoriasis in patients treated with
photochemotherapy. Arch Dermatol. 2003;139:752-6.
- Zachariae H. Prevalence of joint disease in patients with
psoriasis: implications for therapy. Am J Clin Dermatol.
- Gladman DD. Psoriatic arthritis. Rheum Dis Clin North
- Shbeeb M, Uramoto KM, Gibson LE, et al. The
epidemiology of psoriatic arthritis in Olmsted County, Minnesota,
USA, 1982-1991. J Rheumatol. 2000;27:1247-50.
- Gladman DD, Cheung C, Ng CM, et al. HLA-C locus
alleles in patients with psoriatic arthritis (PsA). Hum