Early-Onset Versus Late-Onset Psoriasis: A Comparative Study of Clinical Variables, Comorbidities, and Association with HLA CW6 in a Tertiary Care Center.

Background: Psoriasis is a chronic inflammatory diseaseresulting from a complex interplay of genetic and environmental factors affecting the skin, nail and joints. Two distinct types of psoriasis are said to exist (i) early onset psoriasis (EOP), beginning before the age of 40 years and (ii) late onset psoriasis (LOP), beginning ≥40 years; with the presence of Human lymphocyte antigen (HLA) Cw6, present in majority of patients with early onset. Several studies demonstrated clinical and genetic differences between EOP and LOPamong European and East Asian populations. Lack of similar study in the Indian population has prompted us to undertake the present work. Aims and
Objectives: (i) To compare the clinical patterns of early onset and late onset psoriasisin patients attending the Dermatology outpatientdepartment (OPD) and admitted in the in-patient department (IPD). (ii) To analyze the association age of onset with presence of HLA Cw6. Materials and
Methods: It was an institution-based, descriptive, cross-sectional study. Consecutive patients with psoriasis at the OPD and IPD of the department of Dermatology during the study period, were recruited in the study after obtaining informed consents. Detailed history was obtained regarding the disease, co-morbidities and complications. Through physical examination was carried out, PASI was calculated and blood samples were drawn fromconsenting adult patients (age>/=18 years) to study the presence of Cw6.
Results: The study population (n=250) wasbroadly divided into "Early onset psoriasis(EOP)" (n=138) and Late onset psoriasis (LOP)" (n=112).Significant higher occurrence of positive family history, nail involvement and koebnerization were found in EOP, but such differences were absent considering the types, patterns, joint involvement, severity and HLACW6 positivity.
Conclusion: This study supports the concept of two subtypes of psoriasis based on age of onset showing different clinical and evolutionary features. Copyright:

Introduction

Psoriasis is a chronic inflammatory disease affecting the skin, nail, and joint and is associated with a complex interplay of genetic and environmental factors or triggers. There are various types and patterns of skin manifestations but the typical presentation is symmetrical, sharply demarcated erythematous plaques with silvery-white scales located mainly on the extensors.

The prevalence of psoriatic arthritis and nail involvement leading to deformity and disability is variable, and a wide range between 1.3%[1] and 34.7%[2] and 4.2% to 69% had been, respectively, reported.[345] Patients suffering from psoriasis also have a high association with cardiovascular and other noncommunicable diseases (NCDs).[678]

There is considerable evidence that genetic factors play a key role in the development of psoriasis. The HLA-C isotype HLACw6 is strongly associated with the development of psoriasis and with a more severe form presenting at a younger age.[9101112] HLACw6 allele is an indicator for susceptibility for psoriasis development as well as early age of onset in HLACw6 positive psoriasis patients.

In 1985, Henseler and Christophers studied 2147 patients and documented the presence of two distinct types of psoriasis depending on the age of onset: (i) early-onset psoriasis (EOP), which begins before the age of 40 years and (ii) late-onset psoriasis (LOP), which begins at ≥40 years of age.[13] Subsequently, several studies have demonstrated clinical and genetic differences between EOP and LOP among European[1415] and East Asian populations.[1617] From the available studies, the prevalence of psoriasis in India ranges from 0.44% to 2.8%[18] with psoriasis constituting 2.6% of all skin outpatient department patients.[119] The objective of the present study was to explore whether there are significant differences in clinical phenotypes as well as HLACw6 positivity between Indian patients with EOP and LOP.

Aims and Objectives

(i) To compare the clinical patterns of early-onset and late-onset psoriasis in patients attending the Dermatology OPD and in those admitted in the inpatient department.

(ii) To analyze the association of age of onset with HLACw6.

Materials and Methods

Study design

We conducted an institution-based, descriptive, cross-sectional study on patients presenting with psoriasis, fulfilling the inclusion criteria, and consenting for participation in the study. Permission from the Institutional ethics committee was obtained before proceeding with the study.

Study place

The study was conducted at the outpatient and inpatient department of Dermatology of a tertiary care institute in eastern India.

Study period

January 2018 to August 2019.

Study population

All consenting outdoor and indoor patients with psoriasis.

Sample size

Based on the comparative prevalence of comorbid conditions in EOP versus LOP reported in a previous study,[16] keeping an alpha of 0.05, and power of 80%, a sample size of 76 in each group was calculated. We, however, studied 250 consecutive patients resulting in the recruitment of more than the minimum number in each group.

Sample design

Consecutive patients with psoriasis who attended the outdoor department and were admitted in the inpatient department of Dermatology during the study period were recruited to the study. The following inclusion and exclusion criteria were laid down:

Inclusion Criteria: Patients of any age group suffering from psoriasis.

Exclusion Criteria: Patients not willing to comply with the protocol requirements.

Parameters studied

Age, sex, gender, literacy, occupation, physical status, comorbidity, family history, and duration of the disease were noted.

Clinical features of psoriasis: type and morphology of lesions, involvement of palms, soles, and nails, joint involvement by using ClASsification criteria for Psoriatic ARthritis (CASPAR) criteria, extent of body involvement by PASI score, and HLACw6 of consenting patients were studied.

Study technique

After taking informed consent, detailed history was taken and a thorough physical examination was carried out. Blood samples were drawn from consenting adult patients (age>/ = 18 years) for genetic study. All the information was recorded in the case record form and digital photographs were taken by digital image recorder.

Statistical analysis

Quantitative data were described as mean, standard deviation, and 95% confidence interval (CI) for the mean and range. Qualitative variables were described as frequencies and percentages. Comparisons of quantitative data were analyzed with independent sample t-test for normally distributed data or Mann–Whitney U test if normality rejected. The Chi-square test and Fisher's exact test were used to compare qualitative variables. A P value of <0.05 was considered statistically significant. Data were managed and analyzed by using Medcalc statistical Software version 19.2.6., 2019.

Results

All the participants came from the eastern Indian state of West Bengal and were of uniform racial composition. The study population (n = 250) was broadly divided based on the age of onset with patients having an onset of disease at or before the age 40 years being grouped into “Early-onset psoriasis (EOP)” (n = 138) and those having age of onset after 40 years being grouped into “Late-onset psoriasis (LOP)” (n = 112). All the results obtained in the study have been analyzed statistically, and they are briefly discussed below. Demographic data are summarized in Table 1.

Table 1

Demographic profile of study participants: EOP vs LOP

Parameters	EOP (n=138)	LOP (n=112)	P
Age in years (Mean±S.D)	31.02±11.76	56.14±9.68	<0.0001
Median (IQR)	33 (22,40)	55 (50,60)
Sex
Male	78 (56.6%)	81 (72.3%)	0.01
Female	60 (43.4%)	31 (27.7%)
Family History
Positive	17 (12.3%)	4 (3.6%)	0.01
Negative	121 (87.7%)	108 (96.4%)
Age of onset in years			<0.0001
(Mean±S.D)	24.5±0.10.75	52.5±8.97
	26 (16-34)	50.5 (45.5-58)
Median (IQR)

SD=Standard deviation; IQR=Interquartile range. *P-value was obtained from Mann-Whitney U test for age (as the distribution rejects normality); Fisher’s exact test for gender distribution and family history

Age

The study population was comprised of patients from all ages (42.28 ± 16.56, range: 2–93 years). Patients belonging to the age group of 41–50 years were the most common (24%), in which EOP group had 17.39% and LOP group had 32.14% patients.

Sex

In the present study, male outnumbered female (M = 158, female = 91, M:F = 1.75:1). A significantly higher male:female ratio (2.6:1) was found in LOP group in comparison to EOP (1.3:1) group (P = 0.01).

Age of onset

The age of onset was widely variable (37.06 ± 17.17 years, range: 0–83 years), ranging from early in the newborn period up to ninth decade of life.

Duration

Disease duration of <5 years was mostly seen (62%). Mean duration in EOP and LOP were 6.7 ± 6.53 years and 3.58 ± 3.26 years, respectively. The statistical difference between the two groups was significant (P = 0.0006).

Family history

Positive Family history was found in only 8.4% (n = 21) of psoriasis patients, 17 (12.3%) in the EOP, and 4 (3.6%) in the LOP subset. The difference was statistically significant (P = 0.01). In EOP, 8 (47%) had a history of parental involvement, 6 (35%) had a history in their sibling, 2 (11.8%) had a history of both parent and sibling involvement, while 1 (5.9%) had a second degree relative with psoriasis. In LOP, 2 patients (1.76%) had a history of parental involvement, other 2 (1.76%) had their sibling involved, while there was no instance of involvement in both parent and sibling or a second-degree relative.

Types of psoriasis

Chronic plaque psoriasis was the most common type, (72.8%, n = 182) followed by palmoplantar psoriasis, (17.2%; n = 43). Besides the presence of guttate psoriasis in EOP only, there was no significant difference in the types of psoriasis between the two groups [Table 2] (P = 0.12).

Table 2

Clinical parameters showing comparison of EOP and LOP

Parameters	EOP (n=138)	LOP (n=112)	P
Duration in years (Mean±S.D)	6.7±6.53 4 (2-10)	3.58±3.26 2 (1-5)	0.0006
Median (IQR)
Nail involvement	77 (55.8%)	38 (34%)	0.005
Joint involvement	10 (7.2%)	9 (8%)	0.8
Koebnerization	31 (22.4%)	8 (7.14%)	0.0003
PASI (Mean±SD)	4.48±4.67	6.44±6.68	0.07
Median (IQR)	3 (0.6-6.0)	4.65 (1.05-9.5)
Types of psoriasis
Chronic plaque	103 (74.6%)	79 (71%)	0.12
Palmoplantar	25 (18.1%)	18 (16%)
Pustular	6 (4.3%)	4 (3%)
Guttate	6 (4.3%)	0
Erythrodermic	5 (3.6%)	11 (9.8%)
Sites involved			0.95
Scalp	86 (62.3%)	60 (54%)
Head - Neck	66 (48%)	58 (52%)
Trunk	96 (70%)	84 (75%)
Upper limb	96 (70%)	84 (75%)
Lower limb	101 (73.1%)	88 (79%)
Genitalia	26 (19%)	24 (21.4%)
HLACw6	11 (58%)	3 (27.3%)	0.11

**P value was obtained from Mann-Whitney U test for duration of the disease and PASI (as the distributions reject normality), Fisher’s exact test for nail involvement, joint involvement, and presence of koebnerization, Chi-square test for types of psoriasis and sites involved

Sites involved

The most common sites involved in both groups were the lower limbs, 73.1% in EOP and 79% in LOP group. Genital involvement was least common in both the groups.

There was no statistically significant difference between the two groups (P = 0.95) in terms of body site involvement.

Nail involvement

Among the study population in EOP, 77 (55.8%) had nail involvement in contrast to 38 (34%) in LOP. The presence of nail involvement was significantly higher in EOP (P = 0.005).

Koebnerization

The presence of koebnerization was considered only in patients with chronic plaque psoriasis and guttate psoriasis and it was significantly high in EOP than LOP (P = 0.0003).

PASI score

Psoriasis area and severity index (PASI) score was calculated in patients with chronic plaque psoriasis. The mean PASI score was 4.48 ± 4.67 in EOP, while it was 6.44 ± 6.68 in the LOP. There was no significant difference in mean PASI scores between the two groups (P = 0.07).

Joint involvement

Arthralgia and/or arthritis involving only the distal interphalangeal joints of hands was seen in 10 (7.2%) patients of EOP and 9 (8%) of LOP. This difference was not statistically significant (P = 0.8). In addition, 2 (1.4%) EOP patients and 1 (0.8%) LOP patient had joint deformity, which was also not statistically significant (P = 0.6).

Comorbidities

It was found that 58 (51.8%) patients had no comorbidities in LOP group compared to 121 (87.5%) in EOP group [Table 3]. The incidence of diabetes, hypertension, and dyslipidemia were significantly higher in LOP compared to EOP (P for diabetes = 0.006, hypertension <0.0001, and dyslipidemia = 0.05).

Table 3

Comparison of comorbidities in EOP vs LOP

Comorbidities	Early-onset psoriasis (n=138)	Late-onset psoriasis (n=112)	P
No comorbidities	121 (87.5%)	58 (51.8%)	<0.0001
Diabetes	4 (3%)	17 (15.1%)	0.006
Hypertension	4 (3%)	24 (21.4%)	<0.0001
Hypothyroidism	3 (2.2%)	6 (5.4%)	0.17
Dyslipidemia	0	3 (2.7%)	0.05
Vitiligo	3 (2.2%)	0	0.11
Ischemic heart disease	1 (0.7%)	3 (2.7%)	0.21
Other	2 (1.4%)	1 (0.9%)	0.7

***P value was obtained from Chi-square test

HLACW6

Blood samples for HLACw6 study could be sent for only 30 patients; out of them 19 were from EOP group and 11 from LOP group. In patients with EOP, 11 (58%) were HLACw6 positive, while in LOP, 3 (27.3%) were HLACw6 positive. This finding was not statistically significant (P = 0.11).

Discussion

Psoriasis is a common chronic NCD with polygenic predisposition. It may be associated with a number of comorbidities and may increase the risk of developing other serious clinical conditions such as cardiovascular and other NCDs.[678] The disease exists in two clinical forms, namely, (i) early-onset psoriasis (EOP) and (ii) late-onset psoriasis (LOP). Several studies had found considerable evidences in support of genetic factors, most commonly HLACw6 allele playing a key role in the development of psoriasis, an indicator for psoriasis susceptibility as well as an early age of onset.[910111213] In our study, we have tried to compare these two forms in terms of clinical variables and association of HLACw6.

All the participants came from the eastern Indian state of West Bengal and were of uniform racial composition. We observed that LOP had a male preponderance with a male:female ratio of 2.6:1 as compared to EOP (M:F = 1.3:1). A similar result was obtained in a Pakistan-based study[20] but a study from Thailand[16] showed a different gender preponderance suggesting that women might have an earlier onset of psoriasis in the Indo-Pakistan subcontinent.

The mean age at presentation of our patients was 30.54 ± 16.93 years (range: 1–93 years). In EOP, it was 31 ± 0.9 years and in LOP, group it was 56 ± 0.9 years. The mean age of onset of two groups were 24.5 ± 0.91 years and 52.5 ± 0.84 years, respectively, a result similar to that of a previous study,[20] where the onset were between 19.67 ± 7.83 years and 41.85 ± 10.37 years, respectively. Similar findings were also reported by Theodorakopoulou et al. (2016)[21] from the United Kingdom.

The two subsets of psoriasis patients having age of onset similar to our patients were also found in a Thai study with a large sample size of 1017 psoriasis patients.[16]

Duration of disease in EOP ranged from 6 months to 28 years (6.7 ± 0.6) and in LOP from 3 months to 15 years (4 years ± 0.3). A significantly higher number of patients in EOP had a disease duration of more than 10 years (P = 0.0002) pointed towards the younger age group involvement and chronic course of the disease in this group.

Positive family history was significantly more common (P = 0.01) in the EOP group, 17 (12.3%) as compared to 4 (3.6%) patients of LOP. However, previous studies showed conflicting results in this respect.[2021]

With the exception of guttate psoriasis, which was observed in EOP only, no other significant association was seen in our study between types of psoriasis and age of onset. Ejaz et al. (2009)[20] also failed to find such an association. A Thai study[16] showed a significantly higher incidence of guttate psoriasis in EOP, whereas a UK based study[21] found cases of guttate, erythrodermic, and pustular psoriasis in EOP alone, suggesting that acute manifestations tended to occur more in younger patients.

Regional involvement of psoriasis was widely variable. The most common sites involved in our study irrespective of the age of onset were the lower limbs; a study[20] done on Pakistani population found scalp as the most common site in both the groups. This differed from the results of Chularojanamontri et al. (2015)[16] who reported a significantly higher involvement of lower limbs in LOP, while the scalp was the most common site in both the groups. This variation may be due to either variation in climate, personal habits, occupation, or simply coincidental.

Consistent with the study by Henseler and Christophers (1985),[13] we observed significant nail changes more in the EOP than LOP; however, other studies[1620] had shown no significant difference.

More active and unstable disease processes in EOP might be supported by the presence of a significantly high proportion of koebnerization (28.4%) in EOP in contrast to 10% in LOP (P = 0.0003) in our study samples and that of Theodorakopoulou et al. (2016).[21]

A higher incidence of joint involvement as determined by CASPAR criteria has been reported in EOP,[1322] while others have found no such difference.[20] In our patients, it was higher in EOP but the difference was not statistically significant (P for joint pain = 0.8 and P for joint deformity = 0.6).

The severity of the disease as determined by PASI was higher in EOP, but the difference in mean PASI scores or the number of patients with PASI scores more than 10 was not statistically significant between the two groups. A similar finding was reported by Chularojanamontri et al. (2015)[16] previously.

Comorbidities were found in only 17 (12.5%) in EOP group in comparison to 54 (48.2%) in LOP. The incidence of diabetes and hypertension were significantly higher in LOP compared to EOP. In the study by Theodorakopoulou et al. (2016),[21] a significantly higher proportion of patients with LOP had type 2 diabetes (T2DM) compared to EOP. This difference remained significant after a restriction of age 50 or above was applied to both cohorts. A multivariate logistic regression model adjusted for ischemic heart disease, hypertension, dyslipidemia, central obesity, disease duration, and psoriasis severity for this restricted cohort demonstrated a three-fold higher likelihood of finding T2DM in LOP patients as compared to EOP. We found a significantly higher prevalence of diabetes, hypertension, and dyslipidemia among LOP patients. Considering that a higher mean age of the LOP group might also be a confounding factor for this observation, a multivariate logistic regression was performed with the presence of comorbidities as the binary dependent variable. Adjusted for age, gender, onset, duration, severity of disease, family history, and type of psoriasis, patients with comorbidities had a higher likelihood of belonging to the LOP group [odds ratio 7.45 (95% CI = 3.55–15.64)].

HLACw6 positivity, as a marker of genetic predisposition, was not found to be significantly raised in EOP patients (58%) as compared to LOP (27.3%) (P = 0.11), which is in contrast to the pilot study where HLACw6, known to be at disequilibrium in psoriasis, was present in 85.3% of patients with early onset versus 14.7% patients of late onset.[13]

To conclude, the present study supported the concept of two subtypes of psoriasis based on the age of onset in Indian patients also. They also showed different clinical and evolutionary features. Multicentric longitudinal studies with larger sample sizes need to be done for further strengthening of the observations.

Limitations of the study

Due to lack of resources, HLACw6 was done in a very small proportion of patients; hence, the association of it with each of the clinical parameters was not possible. For better understanding, HLACw6 testing with a greater number of patients should be done.

We have not compared the findings with healthy controls.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.