British Journal of Dermatology {1978) 99, 469.

Clinical and Laboratory Investigations

Psoriasis and occlusive vascular disease

CHARLES J.MCDONALD AND PAUL CALABRESI
Section of Medicine, Division of Biology and Medicine, Brown University, Department of Medicine, Roger
Williams General Hospital, 825 Chatkstone Avenue, Providence, RI 02908, U.S.A.

Accepted for publication 17 April 1978

SUMMARY

To test the hypothesis that psoriasis is associated with an increased incidence of occlusive vascular
disease (thrombophlebitis, myocardial infarction, pulmonary cmbolization, and ccrebrovascular
accident), the clinical records of 323 psoriatic and 325 non-psoriatic patienrs admitted to the dermatology service of the Roger Williams General Hospital were examined. The data obtained in this
study suggest that (i) the occurrence rate of occlusive vascular disease is significantly greater in the
psoriatic than in the non-psoriatic dermatological patient. This is particularly true in the male population; (2) psoriasis predisposes to occlusive vascular disease; and (3) the psoriatic patient with certain
predisposing factors is at greater risk of experiencing an occlusive vascular episode than both the nonpredisposed psoriatic and the non-psoriadc dermatological patient.

It is well known among dermatologists and dermatopathologists that patients with psoriasis have
microvascular abnormalities in normal skin as well as in the skin affected with psoriasis (Braverman,
Cohen & O'Kcefe, 1972; Braverman, 1972; Levi & Curri, 1973). However, no one has previously
associated psoriasis with an increased incidence of large vessel disease. Reed et al. (1973) proposed an
association between psoriatic arthritis and occlusive vascular disease. Our present interest in this
area was stimulated by a number of uncontrolled observations that appeared to associate the administration of a specific antimetabolic agent to patients having severe, recalcitrant psoriasis and an
increased occurrence of occlusive vascular episodes in these patients. These observations led us to
search the current literature for reports of psoriasis and occlusive vascular disease occurring in both
treated and untreated patients and to a rapid review of a representative sample of the clinical records of
our untreated psoriatic patients. Both reviews indicated that psoriatic patients experienced more
episodes of occlusive vascular disease than would be expeaed in a normal population (Reed et al.y
1961; Nyfors, 1968; Black et ai^ 1964; Roenigk, Fowler-Bergfeld & Curtis, 1969; Ryan & Baker,
1969). These findings led us to hypothesize that there is a greater than normal incidence of occlusive
vascular disease associated with psoriasis (McDonald & Calabresi, I973a,b,c).
Presented at the 58th Annual Session of the American College of Physicians April 1977.
Reprint requests to: Dr Charles J.McDonald, Department of Medicine, Roger Williams General Hospital,
825 Chalkstone Avenue, Providence, RI 02908, U.S.A.
0007-0963/78/1100-0469102.00 '0 1978 British Association of Dermatologists

469

470

C.y.McDonald and P.Calabresi

We then reviewed the clinical records of all psoriatic patients and a similar number of non-psoriatic
dermatological patients seen and examined by one of us (C.J.M.) at the Roger Williams General
Hospital from i July 1968 to 31 December 1972. We now wish to repon the findings of a retrospective
study designed to test the hypothesis that the psoriatic patient suffers an abnormally high incidence of,
and has a greater predisposition to, occlusive vascular disease {i.e. coronary thrombosis, thrombophlebitis, cerebrovascular accidents, and pulmonary embolization).
MATERIALS AND METHODS

A total of 648 patients' records from the Roger Williams General Hospital were sequentially selected
and examined using information entered in each record from 1 July 1968 to 31 December 1972. The
study was limited to the number of occlusive vascular episodes which were recorded as occurring
between i January 1968 and 31 December 1972. All occlusive vascular episodes had been previously
documented by appropriate clinical and laboratory examinations. Typical diseases of the nonpsoriatic patient group included atopic eczema, ec2ematous dermatitis, acute and chronic allergic
contact dermatitis, urticarias (acute and chronic), collagen vascular diseases, alopecias, ichthyoses,
etc.
The data retrieved from the records consisted of the following : (a) sex, (b) age, (c) age at the onset
of psoriasis, (d) percent of body coverage of psoriasis, (e) history of predisposing factors other than
psoriasis, (f) the type of occlusive vascular incident (repeated episodes of the same disease were
totalled and counted as a single occurrence. Occurrences of dissimilar diseases in the same patient
were identified separately and recorded as such), and (g) age at the time of the occlusive vascular
event.
Data retrieval for non-psoriatic patients followed the same format except for items (c) and (d).
Each psoriatic patient was matched with a non-psoriatic patient of similar age (within 5 years) and
having a recorded general medical history of similar completeness. The study population contained
approximately equal numbers of males and females. Females receiving birth control pills were not
admitted to the study.
Several analytical approaches were employed in examining the hypothesis: (a) the incidence of
occlusive vascular disease in the psoriatic patient was contrasted with that of the non-psoriatic patient
population, (b) the predisposition of the psoriatic population to occlusive vascular disease was contrasted with that of the non-psoriatic population, (c) the psoriatic population was examined alone to
see if a relationship existed between the extent and duration of psoriasis and the likelihood of occlusive
vascular disease. Additional information obtained for analysis included: (a) association between age,
sex, predisposition, and the incidence of occlusive vascular disease, (b) relative frequency of different
occlusive vascular episodes, (c) relative significance of psoriasis in the event that it proved to be a
predisposition towards occlusive vascular disease.
To stratify the populations into predisposed and non-predisposed groups, a list of faaors predisposing and possibly predisposing to occlusive vascular episodes was derived from the literature
(Sartwell, 1969). Predisposing factors included a past or present history of heart disease (angina,
valvular heart disease, cardiac arrhythmias, arteriosclerotic heart disease, congestive heart failure,
etc.), hypertension, deep vein varicosities, chronic venous stasis and peripheral oedema, obesity,
anaemia, diabetes mellitus, extensive abdominal surgery, cirrhosis of the liver with peripheral oedema,
previously elevated serum clotting factors such as elevated fibrinogen levels, and abnormal lipid
profiles. Possible predisposing factors included family history of diabetes mellitus, previous limited
abdominal surgery, liver disease, rheumatic heart disease with and without valvular defects, family
history of clotting episodes, and family history of cardiovascular disease.

Psoriasis and occlusive vascular disease

471

An analysis of the separate categories of occlusive vascular disease was not performed because the
number of positive responses within each category was small.
RESULTS

Table i shows the occurrence rate of venous and arterial occlusive vascular disease in predisposed and
non-predisposed psoriatic and non-psoriatic males and females above and below 50 years of age. In
each age/sex group rates of occurrence of occlusive vascular disease were significantly higher (P <o-O5)
TABLE I . Occlusive vascular disease occurrence rate per patient group (648 patients)*
Type of occurrence

Sex and
age group
(years)

Male

Arierial
Predisposition
Predisposed

Age < 50
Non-predisposed

Psoriatic

Non-psoriatic

Psoriatic

Non-psoriatic

3/St

1/10(3-75)
IO-O
0/60 (0-98)

0/8

o/io (0)

0-0

0-0

0-0

I/6I
1-6

O'O

3/24 (9-6)

r/30

4/24 (O'S)

37-5*
1/61
1-6

Male,
Age> 50

Predisposed
Non-predisposed

Female,
Age < 50

Predisposed
Non-p redisposed

Female,
Age > 50

Predisposed
Non-predisposed

Venous

0/60 (0-98)

Combined
(arterial and venous)
Psoriatic
3/8
37-5
2/61

3 3

12/30
40 0
0/42

125

o-o
r/ii
9-1

1/23 (2-09J
43

0/71

0/77 (0)

0/71

0/77 (0)

0/71

0 0

00

0-0

0-0

0-0

6/49

3/40 (4-90)
7-S
0/54 Co)
O-o

9/49
18-4
0/51

o-o

13/30

3-3

167

0/37 (0)

0/42

0/37 (0)

0/42

00

0-0

O'O

0-0

4/11

2/23 (8-36)
8-7

5/II

4/40 (7-35)
10-o
0/54 (0)

o-o

36-4

12-2
0/51
0-0

433

454

15/49
306

0/51
0-0

Non-psoriatlc
i/io (375)
I o-o
0/60 (1-97)
0-0

7/24 (ro-4)
29-2
0/37 (0)
0-0

3/23 (I0-5)
13-0
0/77 (0)

o-o
7/40 (12-2)
17-5
0/54 (0)
0 0

* P-values (a) Psoriasis vs non-psoriasis

P<ooo5
(b) Predisposed psoriasis vs predisposed non-psor.
7^ < 0-005
(c) Predisposed psoriasis vs non-predisposed psor.
P<o-ooo5
(d) Predisposed psoriasis vs non-predisposed non-psor. / ' < 0-0005
(e) Non-predisposed psoriasis vs predisposed non-psor./'<00005
t 3/8 = 3 out of 8 patients
t 37-5 = 37'5"o
Numbers in parentheses would be expected number of occurrences if psoriatics' occurrence rates applied to
non-psoriatics.

in predisposed psoriatic patients than in predisposed non-psoriatic patients. Virtually no occlusive

vascular episodes occurred in non-predisposed patients, whether psoriatic or not. In predisposed
psoriatic males arterial episodes predominated. In predisposed psoriatic females below 50 years of age
venous disease predominated, whereas arterial disease predominated in females over 50.
Additionally, Table i shows that there is a significant difference in the number of occlusive vascular
episodes experienced by non-psoriatic patients versus the number of occurrences tlaat would have been
expected among them if they had experienced the same disease rate as psoriatics. For example, if the

C.J.McDonald

472

and P.Calabresi

predisposed non-psoriatic group of lo male patients below age 50 had experienced the same rate of
occurrence of arterial disease as was observed in the same age group of predisposed psoriatics, they
would have suffered approximately 375 clotting episodes instead of a single episode.
TABLE 2. Observed vs expected occlusive vascular occurrences (325 nonpsoriatics)

Arterial
Venous
Combined

Observed

Expected

9
9

238

18

388

150

Observed
rate (" )

Expected
rate (")

2-8
2-8
5-5

7-3

Relative
risk
x-6

11-9

22

Table 2 summarizes the observed versus expected occurrence of arterial and venous disease among
the combined group of 325 non-psoriadc patients (i.e. the amount of vascular disease actually observed in the group of non-psoriatic patients versus what they would have been expected to have
experienced if vascular disease was as prevalent in the group as it was in the psoriatic population).
Once the significance of various factors was demonstrated, the relationship between occurrence of
thrombosis and age and percent body coverage of the psoriatic patients was estimated. Contour graphs
in Figs 1 and 2 are helpful in understanding the relationships between the variables of age^ duration,

DURATION OF PSORIASIS IN YEARS

FIGURE I. Relationship between age and duration of disease and the occurrence of occlusive
vascular disease in 323 psoriatic patients.

Psoriasis and occlusive vascular disease

473

percent body coverage, and occlusive vascular disease. Duration of psoriatic disease did not appear
to have an effect on the patients' likelihood of experiencing an occlusive vascular episode. The per
cent of the body covered by psoriasis, while not appearing to be as significant as age in effecting an
increase in occlusive vascular occtirrences, does appear to have some effect, especially in the older
age group.
90 r

0.55

15

30

45

60

75

90

PERCENTAGE COVERAGE OF PSORIASIS

FIGURE 2. Relationship between age and percent body coverage of psoriasis and the occurrence of
occlusivc vascular disease in 323 psoriatic patients. In order to determine this relationship in any age
group and any degree of body coverage using this graph, a straight line is drawn perpendicular to
the axis of the age and percent body coverage selected. These two lines will intersect at some point
on the graph This point of intersection will correspond to the expected occurrence rate of occlusive
vascular disease.
E.\ample, A 65-year-old male with 15",. body coverage has a 15",, chance of having an occlusive
episode. With 35?u body coverage his chances rise to 25".

DISCUSSION

Using retrospective data, we have attempted to study the hypothesis that patients who have psoriasis
suffer an abnormally high prevalence of various occlusive vascular diseases. We recognize the many
criticisms of retrospectively gathered data in supporting or refuting a hypothesis (Feinstein, 1973).
However, there is broad support for the use of retrospectively gathered data, and it is our belief that
such data can, and in this situation do, indicate that our original conjecture is valid and worthy of
rigorous testing in a well-planned and properly designed prospective study (Sartwell, 1974).
The data obtained in this study suggest (a) the occurrence rate of occlusive vascular episodes is
significantly greater in the psoriatic than in the non-psoriatic patient. In averaging data from the five

474

C.J.McDonald and P.Calabresi

age/sex/predisposition categories in which ai least one arterial occlusive vascular incident took place,
the association between the presence of psoriasis and the occurrence of occlusive vascular disease is
statistically highly significant (P<o-oo5). There appear to be no statistically significant differences
among each of the five age/sex/predisposition cells with respect to the degree with which psoriasis and
arterial occlusive vascular disease are associated, (b) The predisposed patient not only experienced
virtually all of the occlusive vascular episodes reported in this study, but is also at greater risk of
developing occlusive vascular disease than the non-predisposed, (c) Females tend to have less arterial
but more venous occlusive vascular disease than males, (d) The type and distribution of predispositions
in psoriatic patients did not differ to any great degree from those in non-psoriatics. (e) In general, age
does not appear to have a cumulative effea on the total incidence of occlusive vascular disease. However, age does appear to produce a greater effect on arterial than on venous disease, ff) Although the
evidence is not conclusive, it appears that percent body coverage seems to have an effect on older
psoriatic patients' incidence rates, (g) Psoriasis in itself may be a predisposition to occlusive vascular
disease.
Why are patients with psoriasis more prone to develop occlusive vascular disease than other dermatological patients ? Is it because these patients suffer from an abnormally large number of other
diseases which make them more susceptible to occlusive vascular disease? Are there hereditary
factors involved ? Psoriasis has been demonstrated to be a hereditary disease that can be modified by a
number of internal as well as environmental factors. Are psoriatics more prone to develop occlusive
vascular disease because there are yet to be described abnormalities in the entire cardiovascular system
of the psoriatic patient? Braverman ei al. (1972), Braverman (1972) and Levi (1973) have described
microscopic abnormalities in the cutaneous blood vessels of psoriatic patients. These abnormal blood
vessels tend to revert to normal with appropriate antipsoriatic therapy. Many other questions may be
asked; yet at present there are no definitive answers.
Although confirmation of the hypothesis that psoriasis is associated with an increased predisposition
to and an increased incidence of occlusive vascular disease awaits further testing in controlled prospective studies, we feel that the data presented here add immensely to the unfolding evidence that
psoriasis is a generalized metabolic disease with multisystem involvement. The association of psoriasis
and joint disease is well known (Baker, Golding & Thompson, 1963; Wright, 1971)- R^^d et al.
(1961) described postmortem findings and causes of death in 16 of 86 patients with psoriasis and
psoriatic arthritis. Five of the 16 patients died of myocardial infarction (pulmonary embolization
was listed as a contributing cause of death in one of the five), and one died of pulmonary haemorrhage
and infarction. Reed ei al. (1961) postulated the association of psoriasis, arthritis, and vascular disease
in this manner'The acute exudative nature of psoriasis may be merely a reflection of severe inflammation seen elsewhere in synovial membranes of the joints, iris, urethra, and the collagen-elastic
tissues of the heart and aorta.' Two recently published reports indicate that we should probably
rethink the association of psoriasis, methotrexate, and liver disease (Reese ei al, 19745 Shapiro ei ai.,
1974). Both studies show that on biopsy the livers of patients with severe psoriasis, whether treated
with antimetabolic agents or untreated, demonstrate significant non-specific liver damagedamage
that, like arthritis and vascular disease, may very well be associated with a 'psoriasis and systemic
disease syndrome.'
ACKNOWLEDGMENTS

The statistical analyses in this study were performed by Dr Donald Roy McNeil, Princeton University
and Dr Mel K. Langman, Annandale, New Jersey.
Supported in part by USPHS grant nos GM 16538, GM 21535-01 and CA 13943-02.

Psoriasis and occlttsive vascular disease

475

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