Journal of Dermatological

Science,

1 (1990) 211-282

Elsevier
DESC 00032

Inverse relation between severity of psoriasis and serum 1,25=dihydroxyvitamin D level

Shigeto Morimoto, Kunihiko Yoshikawa, Keisuke Fukuo, Tsunehito Shiraishi, Eio
Koh, Shunji Imanaka, Shoichi Kitano, and Toshio Ogihara
Department of Geriatric Medicine, and Department

of Dermatoloo,

Osaka University Medical School, Fukushima-ku,

Osaka,

Japan

(Received 6 May 1989; accepted

Key words: 1,25-Dihydroxyvitamin

14 March 1990)

D; Psoriasis;

Clinical severity

Abstract

The serum levels of calcium, inorganic phosphate, parathyroid hormone, calcitonin, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 34 patients with psoriasis vulgaris and compared with the severity of skin lesions. Severity of
psoriasis was evaluated by three indices, the area-severity index (ASI), the area index (AI) and the severity index (SI), determined
as the product of the area and severity, the area, and the severity of the individual skin lesions, respectively. The mean basal
levels of these serum parameters were within the normal range. AS1 and SI showed significant inverse correlations (r = - 0.387,
P < 0.05 and r = - 0.638,P < 0.01, respectively) with the serum level of 1,25-dihydroxyvitamin D, but not with any other serum
parameters, but AI was not correlated with any of these serum parameters. These data suggest that psoriatic patients are not
deficient in 1,25-dihydroxyvitamin D, but that development of this skin disease may be related to a slightly decreased level of
active metabolites of vitamin D or abnormalities in the responsiveness of the skin cells to them.

Introduction
Psoriasis is a chronic inflammatory skin disease characterized by rapid turnover of epidermal
keratinocytes,
and showing topical symptoms
such as erythema, infiltration, and desquamation
of the skin lesions. Some cases of various forms
of this skin disease have been found to show
disturbances
in systemic calcium metabolism
[l-3].
Association of mild hypocalcemia with
Correspondence
to: Shigeto
Morimoto,
Department
of
Geriatric Medicine, Osaka University Medical School,
Fukushima-ku, Osaka 553, Japan.

0923-181 l/90/$03.50

0 1990 Elsevier Science Publishers

pustular psoriasis of von Zumbush, a rather

severe form of psoriasis, has been observed [ 11.
Reportedly, hypoparathyroidism
may cause the
onset or aggravate psoriasis in patients with surgical hypoparathyroidism
and primary hypoparathyroidism [2]. Association of the disease with
pseudohypoparathyroidism
was also reported

[31.
Moreover, we showed that topical application
of 1,25dihydroxyvitamin
D, [ 1,25-(OH),D,],
a
well known calcitropic hormone, improved skin
lesions of psoriatic patients [4,5]. Although the
basal levels of calcium-related factors in the circulation were within normal ranges in our previous

B.V. (Biomedical

Division)

218

cases [4,5], we did not study their relation to the

severity of the skin lesions in patients with psoriasis vulgar-is, the most common form of psoriasis.
In the present work, we examined the serum
levels of calcium-related
factors,
including
1,25_dihydroxyvitamin D
[ 1,25-(OH),D]
in
patients with psoriasis vulgaris, as possible factors related to the severity of the skin lesions, A
significant
negative
correlation
was found
between the serum concentration of 1,25-(OH),D
and the degree of severity of the skin lesions.
Materials and Methods
Patients
Studies were made on 34 patients with psoriasis vulgar-is who visited the dermatology clinic of
Osaka University Hospital. These patients consisted of 19 males and 15 females with a mean
(k SD) age of 47.5 k 16.1 years (range 16-77 years; mean for males, 49.5 _+ 14.0 years;
mean for females, 44.9 f. 18.6 years). They had
been suffering from psoriasis
vulgar-is for
9.6 + 7.4 years (range 0.2-37 years). None of
them received and systemic or topical medication
that might alter calcium or vitamin D metabolism.
Physical
examination
and laboratory
tests
showed no abnormalities except psoriasis vulgaris. The diagnosis of psoriasis was made by
experienced dermatologists on the basis of macroscopic observation of the skin lesions, characterized by erythematous plaques of various sizes
with silver-white scales. At the time of blood
sampling, all other medications for psoriasis had
been stopped for at least two months, except topical application of white petrolatum. No medication that might alter Ca metabolism was given
to any of these patients. Blood sampling for
assays was done between 8 : 00 and 9 : 00 a.m.
after the patients had fasted overnight. Sera
obtained by centrifugation were frozen and kept
at - 20 C until assayed.
Determination of clinical severity of psoriasis
The severity of psoriasis was determined on
the basis of total area of the skin lesions and

severity of the individual psoriatic skin lesions by

a modification of a previous method [ 61. Briefly,
the three main body areas were assessed as the
trunk (t), the upper extremities (u) and the lower
extremities (l), corresponding to 30, 20 and 40%
of the total body area, respectively. The head area,
corresponding to the remaining 10%) was not
included, because skin lesions in this area are not
easy to evaluate correctly. The area of psoriatic
involvement of these three main areas (At, Au and
Al) was assigned a numerical value: 0 = no
involvement ;
1= <10x;
2= 10<30%;
3=30<50%;
4=50x70%;
5=70<90%
and 6 = 90-100%.
Three target symptoms,
namely erythema (E), infiltration (I), and desquamation (D) were assessed for evaluation of the
severity of the psoriatic lesions according to a
scale of O-4, where 0, 1, 2, 3 and 4 represent no,
slight, moderate, severe and very severe involvement, respectively. The area-severity index (ASI),
area index (AI) and severity index (SI) were calculated according to following formulae :
AS1 = 0.3x(Et + It + Dt)xAt
+ 0.2x(Eu + Iu + Du)xAu
+ 0.4x(El + 11 + Dl)xAl.
AI = 0.3xAt + 0.2xAu + 0.4xA1,
SI = 0.3x(Et + It + Dt) + 0.2x(Eu + Iu + Du)
+ 0.4x(El + 11 + Dl).
Measurement of serum parameters
The serum levels of 25-hydroxyvitamin
D
(25-OHD) and 1,25-(OH),D were determined by
competitive protein binding assay (7) and radioreceptor assay (8) respectively, after separation of
these compounds
by HPLC,
as previously
described. The overall recoveries of 25-OHD and
1,25-(OH),D
were 72 + 10% and 65 + 9%,
respectively, and the coefficients of variation
within and between assays were, respectively 8
and 15% in the 25-OHD assay and 12 and 18%
in the 1,25-(OH),D assay. Serum parathyroid
hormone (PTH) was measured with a commercially available radioimmunoassay
kit (Eiken
Immunochemical Lab., Tokyo, Japan) using antiserum directed towards the carboxy-terminal
portion of the peptide [9]. The sensitivity of the

assay was 100 pg/ml and within and between

assay coefficients of variation were 5 and 172,
respectively. Plasma calcitonin (CT) was measured by radioimmunoassay
as described previously [9] with antiserum directed towards the
mid-portion of the peptide; the sensitivity was
25 pg/ml, and the within and between assay
coefficients of variation were 8 and 22 %, respectively. The serum levels of Ca and Pi were measured with a multichannel Technicon autoanalyser.
The serum levels of these parameters in the
psoriatic patients were compared with those of
24 age-matched normal subjects [ 19 males and
5 females; mean ( + SD) age, 45.4 & 11.4 years
(range, 28-60 years)]. All samples from patients
were examined in the same assay to reduce
between assay variation. Values are expressed as
means
+ SD. Statistical analyses were performed by Students two-tailed t test for comparison for levels of serum parameters between
psoriatic group and normal group, and by
Spearmans rank correlation analysis for correlation between severity of psoriasis and levels of
serum parameters. P values of less than 0.05 were
considered to be significant.

Table I. There was no significant difference in the

mean basal values of any of these parameters in
the two groups, or in their values in males and
females in the psoriatic group. Moreover their
values were not correlated with the age of the
psoriatic patients or the duration of skin disease.
The ASI, AI and SI for the patients in the
present study varied from 2.6 to 24.3, 0.5 to 2.7
and 3.2 to 12.0, with mean + SD values of
12.6 + 6.2, 1.7 _+0.7 and 7.3 + 1.8, respectively.
Table II and Figs. 1, 2 and 3 show the correlations between the indices of clinical severity of
the skin lesions, ASI, AI and SI, and the various
serum parameters. The serum levels of Ca, Pi,

. . :

ASI

a.

Y=-0.273x+21.9
r = -0.367

.
.

P<O.OS

10

,
20

.*.

30

>

40

50

60

Serum 1,254OHhD (w/ml)

Results
The basal levels of serum Ca, Pi, PTH, CT,
25-OHD
and 1,25-(OH),D
in the psoriatic
patients and normal subjects are summarized in
TABLE

..
.

01

Fig. 1. Correlations
between individual values for serum 1,25-(OH),D level and AS1 determined as the product
of the area and severity of the psoriatic skin lesions. Statistical analysis was performed by Spearmans rank correlation
analysis.

Serum levels of calcium-related

factors in patients with psoriasis vulgaris and normal subjects

Serum parameter

Psoriatic group
Mean f SD
(N = 34)

Normal group
(N = 24)

P"

Normal range

Ca (mg/dl)
Pi (mg/dl)
PTH (pg/ml)
CT (pgiml)
25-OHD (ng/ml)

9.1
3.8
270
45
22
37

9.3
3.1
270
55
21
41

5 0.4
5 0.4
k 60
+ 17
f 15
& 14

NS
NS
NS
NS
NS
NS

8.4-10.2
3.0-4.5
180-460
< 150
7-35
20-60

1,2WOW,D (pdml)

+
+
+
f
+
f

0.4
0.4
80
14
I
9

a Significance of difference in the basal levels of serum parameters

I test, NS: not significant.

between the psoriatic and normal groups by the unpaired

280

PTH, CT and 25-OHD showed no significant

correlation with ASI, AI or SI (Table II). The
serum level of 1,25-(OH),D was not correlated
with AI (P > 0.1, r = - 0.167 ) (Fig. 2), but
showed a significant negative correlation with
AS1 (P < 0.05, Y= - 0.387) (Fig. 3), and an even
closer correlation with SI (P < 0.01, Y= - 0.638)
(Fig. 3). There was no significant difference
between the ASI, AI or SI of male and female
psoriatic patients. There was no correlation
between ASI, AI or SI and the age of patients or
the duration of psoriasis.

lo-

st 5-

.L

Y=-o.i3ox+n.7

r = -0.636

P<O.ol

10

60

60

Serum 1,254OHhD Wmt)

TABLE II
Correlation coeffeicients between severity of the skin disease
and the serum parameters

Fig. 3. Correlation between individual values for serum

1,25-(OH),D level and SI determined as the severity of the
skin lesions.

Discussion
Severity of the skin disease

Serum
Parameter

Ca
Pi
PTH
bCT
25-OHD

AS1

AI

SI

- 0.086
- 0.220
- 0.172
0.029
0.037

- 0.058
- 0.212
- 0.152
0.034
- 0.020

- 0.188
- 0.124
- 0.204
0.136
0.125

Values were not statistically

parameters.

significant

between

the two

3.0 -

2.0 -

Al

lo

. :

.. ..
.. .
.
.
.
.

:_.;

,,.._

20

ho

30

Serum 1,254OH)~D (w/ml)

Fig. 2. Correlation between individual values for serum

1,25-(OH),D level and AI determined as the area of the skin
.
lesions.

Previously, we reported that the levels of calcium-related factors were within the normal range
in a small number of patients with psoriasis vulgaris [ 4,5]. In the present work also, we could not
detect any significant difference in the mean basal
levels of circulating Ca, Pi, PTH, CT, 25-OHD or
1,25-(OH),D in groups of psoriatic patients and
age-matched normal subjects. Thus the mechanisms for maintenance of the circulating levels of
Ca, Pi, PTH, CT and vitamin D metabolites are
apparently not grossly disturbed in patients with
psoriasis vulgaris.
However, in this study we found that the serum
concentration of 1,25-(OH),D, but not the other
serum parameters measured, showed a significant
negative correlation with the clinical severity of
psoriatic skin lesions assessed as the ASI and
more particularly as the SI, but not as the AI.
Thus we conclude 1) that skin lesions are more
severe in patients with psoriasis vulgaris with relatively low serum levels of 1,25-(OH),D, although
these levels are within the normal range, and
2) that low levels of serum 1,25-(OH),D
are
related more closely to the severity of the individual skin lesions, such as erythema, infiltration
and desquamation,
than to the area of the
psoriatic skin involvement.

281

Recent studies revealed that 1,25-(OH),D participated in the regulation of the normal skin.
1,25-(OH),D,,
an active form of vitamin D,
besides affecting calcium metabolism, suppresses
proliferation and induces differentiation of certain
cells, including epidermal keratinocytes [ 10-121,
that have a specific receptor for it. Epidermis from
patients with psoriasis vulgar-is, a disease characterized by increased epidermal proliferation of
unknown etiology [ 131, and reportedly topical or
oral application of 1,25-(OH),D,
[4,5,14] or its
analogs [ 15,161 may improve the psoriatic skin
lesions. Moreover, MacLaughlin et al. found that
cultured dermal fibroblasts from these patients
have partial
resistance
to the effect
of
1,25-(OH),D, in suppressing proliferation [ 171.
The present data provide further evidence that
1,25-(OH),D in the circulation of patients with
psoriasis vulgaris is closely related to the development of psoriatic skin lesions. Recently, Staberg
et al. [ 181 also observed that psoriatic patients
with psoriatic involvement of more than 20% of
the total skin area showed significantly reduced
levels of circulating 1,25-(OH),D compared to
those with lesser severe involvement. Our observations were partially compatible with the result
of Staberg et al. [ 181.
The slightly decreased levels of circulating
1,25-(OH),D
in psoriatic patients with more
severe topical lesions can be interpreted in two
ways : decreased
production,
and increased
degradation of this sterol. The production of
1,25-(OH),D
is, however, rather complicated.
The kidney is known to produce 1,25-(OH),D,
but cultured keratinocytes
were also found to
have 1-hydroxylase, the key enzyme for production of the active form of vitamin D, 1,25-(OH),D
[ 191. Moreover, the enzyme activity in cultured
keratinocytes was found to be decreased by addition of 1,25-(OH),D,
to the medium. Thus
studies are required on the production
of
1,25-(OH),D and its regulation in the epidermis
of psoriatic patients. The degradation of the
active forms of vitamin D in the circulation of
these patients should also be examined.
Moreover, possible participation of vitamin A

and glucocorticoids in the growth- and differentiation-properties

of Keratinocytes has been also
reported [20,21]. Although, we did not measure
the circulating levels of vitamin A or gluescorticoids, studies are also needed about the possible involvement of circulating levels of vitamin A
and glucocorticoids
in the severity of the skin
lesions to elucidate the mutual effects of
vitamin A and/or glucocorticoids with the active
form of vitamin D on this skin disease.
Acknowledgments
This work was supported by grants from The
Research Program on Cell Calcium Signals in the
Cardiovascular System and from the Ministry of
Education,
Science and Culture of Japan
(No 63570505). We are grateful to MS Yumiko
Mayumi for secretarial assistance.
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