YousufAbd
Mallick,1 Ahsun Jiwani2
1-2:
Dermatology Unit1/ Department of Research Center2 / The Indus Hospital Karachi, Pakistan.
Running
Title: Vitamin D and chronic plaque psoriasis
Correspondence to: Dr. Yousuf Abd Mallick, Email: dryousuf2006@yahoo.com, ORCiD: 0000-0002-8250-3319
ABSTRACT
Objective: To
determine 25-hydroxy vitamin D levels in patients of chronic plaque psoriasis
and to assess any relationship between vitamin D deficiency and other disease
parameters.
Methods: This
case-control study included 140 subjects (70 with chronic plaque psoriasis and
70 controls), and conducted in out-patient department of Dermatology Unit of
The Indus Hospital, Karachi, Pakistan from 12th September 2018 to 18th
November 2019. Body mass index (BMI) calculated and 25-hydroxy vitamin D
(25-HVD) levels were checked in all subjects. Psoriasis Area and Severity Index
(PASI) was calculated in psoriasis patients.
Results: Serum
concentration of 25-HVD in psoriasis patients is lower as compared to controls
(17.1 + - 9.1 vs 18.3 + - 10.7) but it is not statistically significant
(P=0.66). Similarly, age, gender and BMI were not statistically different
between cases and controls. On comparative analysis, type I plaque psoriasis
patients had more lower levels of 25-HVD (P=0.03), especially those who had
disease for < 5 years (P=0.01). Stratified analysis revealed males of
type I plaque psoriasis had significantly lower levels of 25-HVD as compared to
males from type II group (P=0.003).
Conclusion: 25-HVD
levels were almost similar in both cases and controls. There was no significant
25-HVD deficiency found in chronic plaque psoriasis patients, neither any
relation with age, gender, BMI or PASI. However, 25-HVD levels were much lower
in males, type I cases and with shorter duration of disease.
Keywords: Psoriasis,
body mass index, case control study
INTRODUCTION
Psoriasis is a chronic, life-long,
multisystem, inflammatory and proliferative condition which predominantly
involves skin.1It has a typical relapsing and remitting course. The
estimated world population which is known to be affected with psoriasis is
around 3.2%.2Psoriasis affects adult women and men equally. In 75%
of cases, the disease first manifests before 46 years of age.3
Several environmental factors along
with paramount genetic influencing components played their all-important
crucial role in the development of psoriasis. Among the various
notified genes and HLA associations, PSORS-1 gene is the prime determinant for
psoriasis which is alone accountable for almost half of the inherited cases.4
Psoriasis
is an immune-mediated disorder and involves both innate and acquired immune
systems. Cutaneous T-lymphocytes, keratinocytes, histiocytes, mastocytes,
dendritic cells and vascular endothelial cells play their complex roles in
development of inflammation, leading to an imbalance between Th1/Th2 immune
responses with a diversion towards Th1 response.5
Vitamin D is an oil-soluble vitamin
which was discovered in cod liver oil during the first quarter of the 20th
century. Later on, vitamin D deficiency responsible for rickets in children and
osteomalacia in adults were confirmed and subsequently Adolf Windaus, a German
chemist, received the Nobel Prize in 1928 for his breakthrough discovery.6
Vitamin D, also known as calciferol, can be produced in the body by the help of
ultraviolet B (UVB) radiation and also obtain from diet.Two major and natural
precursors of vitamin D are vitamin D2 (ergocalciferol) and
vitamin D3 (cholecalciferol). Both are biologically inert and need activation
before functioning.7
It is reported that psoriasis patients
having low levels of vitamin D are more prone to arthritis, joint deformities,
increase severity of psoriasis and a higher Psoriasis Area and Severity Index
(PASI) score.8 During last two decades all major CVD risk factors
have been associated with vitamin D deficiency (VDD) like diabetes,
hypertension and hyperlipidemia.9-12 Furthermore, psoriatic patients
with VDD are more prone to develop CVD complications, MetS
and other comorbidities with subsequent increased mortality and reduced life
span.13
Thepurpose to conduct this study was to
determine 25-hydroxy vitamin D levels in patients of chronic plaque psoriasis;
and to assess any relationship between vitamin D deficiency and other disease
parameters. Early identification and prompt treatment of VDD might help in
reducing or controlling CVD comorbidities in psoriatic subjects.
METHODS
This case-control study was conducted
in out-patient department of Dermatology Unit of The Indus Hospital, Karachi,
Pakistan from 12th September 2018 to 18th November 2019.
All patients aged ≥ 18 years of either gender were consecutively
enrolled. Whereas patients with other types of psoriasis (like pustular,
erythrodermic, guttate),with concomitant inflammatory bowel diseases (i.e. Crohn s disease and ulcerative colitis) and malabsorption,
with chronic liver and chronic kidney diseases, taking any medication which is
known to affect serum vitamin D levels (like corticosteroids, bisphosphonates,
multivitamin supplements, fish oil), pregnant and lactating mothers,infections
(like T.B, active hepatitis) and debilitating illnesses (like HIV & AIDS
and cancers), and patients and controls who were on vitamin D supplements were
excluded.
The sample size was calculated using
open epi web-based sample size calculator with the following assumptions:
confidence interval: 95%, power: 80%, Mean + - SD of 25-HVD level in psoriasis
patients (cases): 18.24 + - 4.55, Mean + - SD of 25-HVD level in non-psoriasis
patients (controls): 22.13 + - 10.64 and required sample size was estimated to
be 70 per group.
Cases was defined as clinically diagnosed patients who were
having plaque psoriasis for more than 6 months. These patients were
either never treated with oral and/or topical vitamin D analogues or stopped
their treatment at least 3 months before the investigation. While controls were defined aspatients
without psoriasis coming to dermatology OPD for other skin diseases like acne,
melasma, and fungal infections.
70 cases and 70 controls meeting the
selection criteria for this study were selected after obtaining informed
consent. Approval
from the institutional review board (IRB) was taken prior
to conduct the study. Study IRB # IRD_IRB_2018_08_001.
After enrolment; age, gender, weight, height
and body mass index (BMI) in kg/m2 were noted in all subjects. In
psoriasis cases; duration of disease, type of plaque psoriasis and PASI were
calculated. 25-hydroxy vitamin D levels were performed in all subjects.
Chronic was defined as the disease with
a minimum of 6 months. A plaque is a circumscribed, superficial, elevated area
of more than 1.0 cm in diameter. Its surface is usually flat. Plaque psoriasis
consists of erythematous, scaly, sharply demarcated, indurated plaques present
particularly over the extensor surfaces and scalp.
Obesitywas defined by WHO Western
Pacific Regional Office for Asians was used.14Patients having BMI of
< 18.5 kg/m2 were labeled as underweight, 18.5 - 22.9 kg/m2 ashealthy, 23.0 - 24.9 kg/m2 as overweight, and
obesity was labeled when BMI > 25.0 kg/m2.
Henseler
and Christophers division3 was used to
define type of plaque psoriasis i.e. those who developed plaque psoriasis
before 40 years were labelled as type 1 while those who developed plaque
psoriasis at or after 40 years were labelled as type 2.
Serum levels of 25-hydroxy vitamin D
(25-HVD) were categorized as: 25-hydroxy vitamin D level > 30 ng/mL
as sufficient, < 30 but > 20 ng/mL as insufficient, while < 20
ng/mL as deficient.15
Categorization of severity of psoriasis
on the basis of PASI was done as: PASI score of less than 7 was labeled as mild
psoriasis, PASI score from 7 to 12 was
labeled as moderate psoriasis, and PASI score of more than 12 was labeled as
severe psoriasis.16
Data were entered and analyzed by using
version 26.0 of statistical package of social sciences (SPSS) software. Median
(IQR) and Mean + - SD were computed for quantitative variables while frequency
and percentages were computed for categorical variables. Independent sample
T-test, Mann-Whitney U test, Chi Square and Fisher s exact tests were applied
as appropriate to assess significant difference in 25-HVD level between both
the groups. p-value ≤0.05 was considered as
statistically significant.
RESULTS
Out of 70 psoriatic patients; male to
female ratio of 1:1. Mean age of cases was 41.3 + 13.2 years. 2 (2.8%),
19 (27.1%), 14 (20%) and 35 (50%) patients were underweight, normal (healthy),
overweight and obese respectively. Mean 25-hydroxy vitamin D level of cases was
17.1 + 9.1 ng/mL.
Median (IQR) 25-HVD level of cases was 15.1 (10.1-23.2) ng/mL.
On categorization; 25-HVD was deficient in 47 (67.1%), insufficient in 19
(27.1%) and sufficient in 4 (5.7%) psoriatic patients (Table 1).
Out of 70 selected controls; 40 (57%)
were male and 30 (43%) were female. Mean age of controls was 29.4 + 10.3
years. 4 (5.7%), 22 (31.4%), 24 (34.2%) and 20 (28.5%) patients were
underweight, normal (healthy), overweight and obese respectively. Mean
25-hydroxy vitamin D level of controls was 18.3 + 10.7 ng/mL. Median (IQR) 25-HVD level
of controls was 15.1 (11.7-21.9) ng/mL. On categorization;
25-HVD was deficient in 50 (71.4%), insufficient in 8 (11.4%) and sufficient in
12 (17.1%) controls (Table 1).
On comparative analysis; more psoriatic
patients were found to have obesity as compared to controls (P-value 0.05). The
mean value of 25-HVD level of cases was lower than controls (17.1 ng/mL vs 18.3
ng/mL) but value was not statistically significant (P-value 0.66). No
statistically significant association was found with respect to gender, BMI and
25-HVD levels between cases and controls upon analysis (Table 1).
Upon stratification of duration in
psoriasis patients; 40 (57.1%) had disease for < 5 years while 30
(42.9%) had disease for > 5 years. 42 (60%) and 28 (40%) were classified as
Type 1 and Type 2 plaque psoriasis respectively. The median PASI score was 4.45
(minimum = 0.8 and maximum = 43.8). Regarding severity; 46 (32.9%), 9 (6.4%)
and 15 (10.7%) were categorized as mild, moderate and severe psoriasis
respectively (Table 2).
Median (IQR) value of 25-hydroxy
vitamin D level of type I plaque psoriasis group was notably lower than type II
plaque psoriasis group (13.2 ng/mL vs 18.1 ng/mL). Statistically significant
difference was detected between the 25-HVD levels (P-value 0.03), age (P-value
<0.001), and duration of psoriasis (P-value 0.01) of the two study groups,
while no association was detected between the gender, BMI and PASI score of the
two study groups (Table 3).
Stratified analysis was performed to
assess the relationship between the outcome i.e. 25-hydroxy vitamin D levels
and the exposure variable i.e. type of plaque psoriasis after controlling for confounders. Statistically
significant associations were detected between the 25-HVD levels and the type
of plaque psoriasis after controlling for confounders i.e. gender and duration
of psoriasis. When controlled for gender we found that males having type I
plaque psoriasis had lesser median (IQR) 25-HVD levels as compared to the males
of type II plaque psoriasis group (P-value 0.003). Similarly, the patients who
had a ≤ 5 years duration of psoriasis in type I plaque psoriasis group
had a lower median (IQR) 25-HVD level as compared to those who were in the type
II plaque psoriasis group (P-value 0.01). No statistical association was
detected with other confounders i.e. age, BMI and PASI
score (Table 4).
Table 1: Patient demographics among study groups
|
Variable |
Cases (Psoriasis +ve) |
Controls (Psoriasis -ve) |
P-value |
|
Age (years) |
|||
|
Mean + SD |
41.3 + - 13.2 |
29.4 + - 10.3 |
<0.001 |
|
Gender; n (%) |
|||
|
Male |
35 (50%) |
40 (57%) |
0.13 |
|
Female |
35 (50%) |
30 (43%) |
|
|
Body Mass Index (BMI); n (%) |
|||
|
Underweight |
02 (2.8%) |
04 (5.7%) |
0.05 |
|
Normal |
19 (27.1%) |
22 (31.4%) |
|
|
Overweight |
14 (20%) |
24 (34.2%) |
|
|
Obese |
35 (50%) |
20 (28.5%) |
|
|
25-hydroxy vitamin D categories; n
(%) |
|||
|
Deficient |
47 (67.1%) |
50 (71.4%) |
0.01s |
|
Insufficient |
19 (27.1%) |
08 (11.4%) |
|
|
Sufficient |
04 (5.7%) |
12 (17.1%) |
|
|
25-hydroxy vitamin D (ng/mL) |
|||
|
Median (IQR) |
15.1 (10.1 - 23.2) |
15.1 (11.7 - 21.9) |
0.66 |
T-test, Mann-Whitney U test, s
Chi-Square, Fisher Exact
Table 2: Disease parameters in psoriatic patients
|
Disease parameter |
Values |
|
PASI Score |
|
|
Median (IQR) |
4.45 |
|
Min-Max |
0.8-43.8 |
|
Division of PASI Score |
|
|
Mild |
46 (32.9%) |
|
Moderate |
09 (6.4%) |
|
Severe |
15 (10.7%) |
|
Duration of Psoriasis |
|
|
≤ 5 Years |
40 (57.1%) |
|
> 5 Years |
30 (42.9%) |
|
Types of Plaque Psoriasis |
|
|
Type I |
42 (60%) |
|
Type II |
28 (40%) |
Table 3: Comparative analysis between
type I and type II plaque psoriasis patients
|
Variable |
Plaque Psoriasis Type I Group |
Plaque Psoriasis Type II Group |
P-value |
|
Vitamin D (ng/mL) Median (IQR) |
13.2 (8.6 - 22.3) |
18.1 (13.3 - 24.6) |
0.03* |
|
Age (years) (Mean+ SD) |
32.8 + - 8.4 |
53.9 + - 7.6 |
<0.001T* |
|
Gender; n (%) |
|||
|
Male |
18 (42.9%) |
17 (60.7%) |
0.14S |
|
Female |
24 (57.1%) |
11 (39.3%) |
|
|
Body Mass Index; n (%) |
|||
|
≤ Normal |
14 (33.3%) |
07 (25%) |
0.80T |
|
Overweight |
08 (19.1%) |
06 (21.4%) |
|
|
Obese |
20 (47.6%) |
15 (53.6%) |
|
|
Duration of Psoriasis; n (%) |
|||
|
≤ 5 Years |
17 (40.5%) |
23 (82.1%) |
0.01S* |
|
> 5 Years |
25 (59.5%) |
05 (17.9%) |
|
|
PASI Score |
|||
|
Mild |
29 (69.0%) |
17 (60.7%) |
0.76S |
|
Moderate |
05 (11.9%) |
04 (14.3%) |
|
|
Severe |
08 (19.1%) |
07 (25%) |
|
T-test, Mann-Whitney U test, s Chi-Square, ƚ Fisher Exact, *
p-value <0.05
Table 4: Difference
in vitamin D levels between characteristics of patients with psoriasis
|
Variables |
Study
Groups |
P-value |
|
|
Psoriasis
Type I Group |
Psoriasis
Type II Group |
||
|
Median
& IQR |
Median
& IQR |
||
|
Gender |
|||
|
Male |
13.2
(9.6 - 16.2) |
18.2
(15.2 - 24.6) |
0.003Ŧ* |
|
Female |
13.4
(7.9 - 25.3) |
14.4
(8.9 - 23.1) |
0.66Ŧ |
|
Age |
|||
|
≤
40 |
12.9
(8.4 - 18.6) |
17.8
(16 - 19.8) |
0.31Ŧ |
|
>
40 |
24.3
(11 - 27.7) |
18.1
(13.3 - 24.6) |
0.56Ŧ |
|
Body
Mass Index (BMI) |
|||
|
≤
Normal |
13
(10.1 - 15) |
15.5
(13.3 - 22.4) |
0.1Ŧ |
|
Overweight |
12.7
(10.1 - 21.9) |
21.6
(18.2 - 24.6) |
0.15Ŧ |
|
Obese |
15.8
(6.7 - 23.6) |
18
(9.6 - 24.8) |
0.2Ŧ |
|
Duration
of Psoriasis |
|||
|
≤
5 Years |
11.6
(8.2 - 17.4) |
18.2
(13.4 - 24.6) |
0.01Ŧ* |
|
>5
Years |
14.2
(10.1 - 24.3) |
14.4
(13 - 24.8) |
0.71Ŧ |
|
PASI |
|||
|
Mild |
13.9
(7.7 - 24.2) |
16
(13.4 - 24.8) |
0.16Ŧ |
|
Moderate |
13.3
(13.1 - 15) |
18.1
(13.4 - 27.5) |
0.14Ŧ |
|
Severe |
11.3
(9.8 - 18.5) |
19.78
(13.3 - 24.6) |
0.22Ŧ |
Ŧ
Mann-Whitney U Test, * p-value <0.05
DISCUSSION
The traditional causative element of
rickets, stunted growth, osteoporosis, fractures and osteomalacia,
the vitamin D deficiency, has already taken the shape of a pandemic.8
VDD is now known to affect all ages, genders, races, religions, ethnicities,
social classes and geographical zones. Besides above-mentioned ailments, VDD
has also been coupled with several systemic, autoimmune and metabolic diseases,
supported byinnumerable accumulating and growing literature
evidences.8,16,17Among the several clinical types, plaque psoriasis
is the most frequently encountered one. All types have many localized and
generalized morphological variants which are known to affect all races across
the globe. The systemic inflammatory condition produces erythematous, scaly
plaques of psoriasis over skin and scalp, while on the other side it is also
responsible for development of PsA, CVD and metabolic
syndrome.1
The mean age of psoriatic cases in this
study was 41.3 + 13.2 years. Similar ages of psoriatic patients were
also reported by Maleki et al. from Iran (42.8 +
13.68 years), Srirama from India (47.8 + 12.8
years), Hassab-El-Naby et
al. from Egypt (31.3 + 7 years), and Zuchi et
al. from Brazil (46.4 + 14.9 years) and in their respective case-control
studies.18-21
In this study; no association of
vitamin D deficiency was found in relation to age, gender, BMI and PASI score
in psoriatic subjects. Studies carried out by Srirama,19Gisondi
et al,17Orgaz-Molina et al,5Hassab-El-Naby et al,20Zuchi
et al,21 and Ricceri et al,22
which also evaluated these variables, but did not discover any notable
correlation between vitamin D levels and age, gender, BMI and PASI scores.
However, Pavlov et al. reported positive correlation with high PASI score and
lower 25-HVD levels but not with other variables.23
This study showed no difference of
statistical significance between 25-HVD levels of cases and controls. Maleki et al. compared serum 25-HVD levels in 50 psoriasis
patients & 50 healthy controls, and failed to detect any statistically
significant difference in serum 25-HVD levels between the two groups.18Authors
suggested dressing habits and skin phenotype as possible causative factors for
VDD in cases and controls. Zuchi and colleagues reported
no difference between serum 25‑HVD levels of psoriasis cases and healthy
controls in their case-control study which involved 20 subjects in each group.21Solak
et al. delineated in their study of 43 psoriasis patients without arthritis and
41 healthy controls that there was no statistically significant difference
between 25‑HVD levels of the two studied groups.24Romani and
colleagues described lower levels of 25-HVDboth among psoriasis cases and
controls in their age and gender matched case-control study involving 50
subjects in each group.25This deficiency was independent of duration
of sun exposure, Fitzpatrick s skin photo type, age of subjects and month of
blood testing.
Srirama
highlighted difference between 25‑HVD levels of psoriatic cases and
controls in her case-control study, although both groups showed low levels. The
study had 30 subjects in each arm, and mean 25-HVD of cases and controls were
18.24 +- 4.55 and 22.13 +- 10.64 respectively.19 Presumed reasons
were poor diet, sun-avoidance and inadequate exposure. Wilson performed a cross‑sectional
analysis of 5841 participants and found no difference in serum levels of 25-HVD
between subjects with and without psoriasis.26 Moreover, Morimoto et
al. documented no significant differences in the mean basal values of 25-HVD
and 1,25-dihydroxyvitamin
D between psoriasis cases and controls.27 Furthermore,
Merola et al. notified that there is no preventive role of dietary or
supplemental vitamin D intake against development of psoriasis.28All
above mentioned studies are in accordance with this study.
This study reported that 25-HVD level
of type I plaque psoriasis group is lower than type II plaque psoriasis group
and it was also statistically associated with age and duration of psoriasis, while
it was not correlated with gender, BMI and PASI score. Pavlov et al. in their
cross-sectional analysis, described no differences in
25-HVD levels between two types of plaque psoriasis. In addition, no
correlation was found with gender, waist circumference and BMI but 25-HVD
levels were inversely correlated with PASI scores.23
CONCLUSION
This study concluded that vitamin D
level of psoriatic cases is similar to that of controls. Both of them were
detected with VDD. Psoriatic cases might have 25-HVD deficiency as a part of
community problem and overall altered or affected nutritional status. But
whenever vitamin D deficiency is detected in psoriasis, it should be
immediately replaced. The group among psoriasis patients which was more
affected with 25-HVD deficiency were males, type 1 cases and those with shorter
duration of disease.
AUTHORS
CONTRIBUTION: UAM:
Designed the study, collected and analyzed the data and manuscript writing, and
final approval of the manuscript. AJ: Literature search and helped in
manuscript writing.
ETHICAL APPROVAL: This
study was approved by Interactive Research & Development, the Indus
Hospital Karachi, Pakistan.
CONFLICT
OF INTEREST: None declared
by author.
FUNDING:
None declared
by author.
Received:
July 06, 2020
Accepted:
August 21, 2020
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