Serum prolactin levels in psoriasis and its association with disease activity: a case-control study.

BACKGROUND: Psoriasis is a T-cell-mediated autoimmune chronic skin disorder in which an environmental factor, perhaps a viral antigen, induces T cells to produce cytokines. These cytokines stimulate keratinocyte proliferation and production of antigenic adhesion molecules in the dermal blood vessels. Several mediators and hormones have been implicated in keratinocyte hyperproliferation and among these hormones, prolactin (PRL) has been found to have an effect on epithelial cells, lymphocytes and keratinocytes, thus an effect on the etiopathogenesis of psoriasis. AIM: The present study was designed to compare serum PRL levels in psoriatic patients with a control group. SETTINGS AND
DESIGN: This study was a hospital-based case control study, conducted in the department of Dermatology, STD and Leprosy, SMHS Hospital (Associated teaching hospital of Government Medical College Srinagar) over a period of 1 year, from September 2012 to 2013.
MATERIALS AND METHODS: The present study included 60 patients of psoriasis (42 males and 18 females) and 60 controls matched for age and sex. Serum PRL levels of patients and controls were measured by ECLIA and inferences were drawn. STATISTICAL ANALYSIS USED: Statistical significance of the results was carried out by the Chi-square test and the independent samples t-test. Statistical significance was determined at a level of P < 0.05.
RESULTS: Serum PRL levels were significantly increased in patients as compared to the control group (P value: 0.002). There was a positive correlation between pretreatment serum PRL levels and PASI score (r value: 0.379; P value: 0.003). An insignificant association was found between the pretreatment PRL level and serum PRL level after treatment (P value: 0.22). Also, a negative correlation between the duration of psoriasis and serum PRL was seen (r value: -0.008; P value: 0.954).
CONCLUSION: PRL may have a role to play in the etiopathogenesis of psoriasis. However, further studies with large sample size should be carried out so as to validate this hypothesis.

What was known?

Prolactin may play a role in the pathogenesis of psoriasis and may serve as a biological marker of psoriatic activity. Its role may represent a cause and/or a consequence of psoriasis pathology.

Introduction

Psoriasis is an inflammatory disease characterized by hyperproliferation of keratinocytes as well as accumulation of T cells in epidermis and dermis of psoriatic lesions.[1] The etiopathogenesis of psoriasis is complex and not well known. Lately, besides many different factors that are regarded to play a role in psoriasis pathology, hormones have also been taken into consideration. There is some evidence that psoriasis worsens at age increases when hormonal changes such as puberty and menopause are taking place, and may also worsen or improve during pregnancy.[2]

Prolactin (PRL), a neuropeptide secreted by the anterior pituitary gland, possesses a variety of physiological actions, including growth-promoting activity in vivo and proliferative response to different normal and neoplastic cell types including epithelial cells and lymphocytes in vitro. It has been reported that PRL exerts a proliferative effect on human keratinocytes via specific receptors. Some studies have indicated an increase in serum PRL levels in psoriasis and exacerbation of psoriasis in the presence of a prolactinoma.

There is a paucity of data available in the literature regarding the role of PRL in the etiopathogenesis of psoriasis. So, the present study was designed to compare the serum levels of PRL in patients of psoriasis and the control group.

Materials and Methods

This study was a hospital-based case control study conducted in the department of Dermatology, STD and Leprosy, SMHS Hospital (Associated teaching hospital of Government Medical College Srinagar) in collaboration with the Department of biochemistry, over a period of 1 year from September 2012 to 2013.

Sixty consecutive patients with plaque-type psoriasis (32 men; 18 women), with a mean and median age of 33 years and 31 years respectively were enrolled in the study. At the time of enrolment in the study, none of the patients had received any topical or systemic treatment for their psoriasis for at least 4 weeks. The control group comprised 60 healthy volunteers, matched for sex and age (40 men; 20 women), with a mean and median age of 30 and 33 years, respectively. The controls had no history of any skin abnormalities or any chronic-debilitating disease.

Diagnosis of psoriasis was based on clinical findings and history of the disease. A complete dermatological examination was done for each patient so as to determine the extent and distribution of the disease. Clinical severity of psoriasis was assessed by using the psoriasis area severity index (PASI) score.

Exclusion criteria were pregnancy, breast-feeding, and evidence of renal, hepatic, endocrinopathy (Prolactinoma, Hypothyroidism) or psychiatric disease. Patients who were receiving any medications affecting PRL such as phenothiazines (chrompromazine), antidopaminergic agents (metaclopromide), antihypertensive agents (calcium channel blockers, methyldopa) and H2 blockers (cimetidine) were also excluded from the study with an aim to avoid instances of secondary hyperprolactinaemia. Informed written consent was obtained from all the participants.

Blood samples were taken in the morning between 8.00 and -10.00 A.M in both patients and controls in regard to the circadian variation of PRL secretion. In women, measurements were taken in the premenstrual phase of the cycle. Levels of PRL were quantitatively estimated using electro-chemiluminescence immunoassay (ECLIA). Reference range for PRL was 2-18 ng/ml for males and 2-29 ng/ml for females.

All the patients were put on topical treatment for a period of 6 weeks and after that serum PRL was again measured by ECLIA.

Statistical analysis of the data was performed by using Statistical Package for Social Sciences (SPSS Version 17). Statistical significance of the results was carried out by the Chi-square test and the independent samples t-test. Statistical significance was determined at a level of P < 0.05.

Results

The present study comprised of 60 patients and 60 controls. In the patient group, there were 42 males and 18 females, while as in the control group, there were 40 males and 20 females. Thus, a male predominance was seen in our study. In the patient group, age ranged from 8 to 62 years, with a mean of 33 ± 13.02 years, while as in the control group, the mean age was 30 ± 14 years. On comparing the age and sex of cases and controls, the P value was found to be >0.05 [Tables 1 and 2]. Thus, the two groups were both age and gender matched.

Table 1

Comparison of age (in years) of cases and controls

Table 2

Sex distribution of cases and controls

Serum PRL levels in the patient group before treatment ranged from 3.80 to 39.60 ng/ml, with a mean of 11.29 ± 8.05 ng/ml. In the control group, serum PRL levels ranged from 2.80 to 18.60 ng/ml, with a mean of 7.9 ± 3.93 ng/ml. Thus, serum PRL levels were higher in patients than in controls and the difference was statistically significant (P value 0.002) [Table 3].

Table 3

Comparison of serum prolactin (ng/ml) of cases and control group

Mean serum PRL levels in patients after treatment was 7.21 ± 3.52 ng/ml, with a range of 16.00 ng/ml. Our study demonstrated that mean pre-treatment serum PRL (11.29 ± 8.05 ng/ml) level in cases was higher than the post-treatment PRL level (7.21 ± 3.52 ng/ml). The significance of this difference was tested using Student's t-test, which revealed an insignificant association (P value of 0.23) [Table 4].

Table 4

Comparison between pretreatment and posttreatment serum prolactin level (ng/ml) in cases

PASI score in the patients ranged from 0.90 to 44.70, with a mean value of 7.12 ± 8.41 [Table 5]. In our study, we found a positive correlation between PRL levels and the severity of psoriasis. Pearson regression test showed positive correlation between PRL levels and severity of psoriasis (r = 0.379, P = 0.003) [Figure 1].

Table 5

PASI score of cases

Figure 1

Scatter diagram depicting correlation between the severity of psoriasis (PASI) and serum prolactin level

The range of psoriasis duration among the patients was found to be 0.6 years to 15 years, with a mean of 5.18 ± 3.24. Statistical analysis revealed a negative correlation between the duration of psoriasis and the serum levels of PRL (r value:-0.008, P value: 0.954) [Figure 2].

Figure 2

Scatter diagram depicting the correlation between duration of psoriasis and serum prolactin level

Discussion

The polypeptide hormone PRL produced by lactotrophic cells in the anterior pituitary gland is best known as the pituitary modulator of lactation and reproduction. Recently, a vast range of PRL actions “beyond the mammary horizon” has been documented or claimed. It has become apparent that PRL may influence both humoral and cell-mediated immune reactions, and may play an important role in the expression of autoimmune diseases.[3]

More than two decades ago it was first claimed that the potent dopaminergic inhibitor of pituitary PRL secretion, bromocriptine, induced remission of psoriatic epidermal lesions and even psoriatic arthritis.[4] This resulted in postulation of a role for PRL in the pathogenesis of this chronic, inflammatory, hyperproliferative skin disease.[5] PRL exerts its actions in several target organs via specific receptors that are expressed on many cells, including T and B lymphocytes.[6] PRL exerts a proliferative effect on cultured human keratinocytes and enhances the production of VEGF production in vitro.[78] Thus, PRL may contribute to psoriasis pathogenesis by stimulating keratinocyte proliferation, T-lymphocyte IFN-γ production, and by promoting angiogenesis.[910] At the same time, the inhibition of T-suppressor cell functions by PRL may serve to promote psoriatic plaque development.[11] PRL enhances IFN-γ-induced transcription and secretion of key chemokines (for example, CXCL9, CXCL10, CXCL11), thus promoting the infiltration of type 1 T-helper cells into psoriatic lesions.[12]

Psoriasis is often triggered or exacerbated by psycho-emotional stress.[13] During pregnancy, psoriasis tends to be stable in most of the affected female patients. However, it may subsequently worsen during the early months of postpartum period, reflecting the relative physiological hyperprolactinemia associated with lactation.[14]

Our study was aimed to study the possible role of PRL in the pathogenesis of psoriasis and its correlation with the disease activity. In the present study, we investigated serum level of PRL in 60 patients with plaque type psoriasis and 60 healthy control subjects for comparison. Our study revealed that serum level of PRL was higher in psoriatic patients than controls and the difference was statistically significant (P < 0.05). Our results also revealed a positive correlation between serum PRL levels and PASI score. Also, serum PRL levels were found to be reduced after treatment although the difference was statistically insignificant.

The results of our study were consistent with the study conducted by Giasuddin et al. in the year 1998, which revealed that serum PRL levels were increased in psoriatic patients as compared to controls.[15] This suggested that raised serum PRL level may have a role in the hyperproliferation of keratinocytes in vivo, the hallmark of the psoriasis disease process.

A study conducted by Dilme-carreras et al. included 20 patients of psoriasis and 20 healthy controls. PRL levels were measured in serum of psoriatic patients before and after treatment with tacalcitol ointment and disease severity was assessed by PASI in all patients. Serum levels of PRL were found to be significantly higher in patients than controls before treatment. They also found that PRL levels were significantly reduced after treatment with tacalcitol and there was a correlation between pretreatment serum PRL levels and PASI score.

El-Khateeb et al. carried out a study that included 15 psoriasis patients and 15 controls, PASI score was evaluated, and PRL levels in serum and blister fluid were assessed. They found that PRL levels were significantly elevated in blister fluid of psoriatic lesional skin. They also noted a positive correlation of serum PRL level between lesional and non-lesional skin in psoriasis and between serum and clinically normal skin in both psoriasis and control subjects.[16]

There are reports available in the literature suggesting that psoriasis can be aggravated during the development of prolactinoma, whereas bromocriptine therapy improves the psoriatic skin symptoms in these prolactinoma patients.[17]

Gorpelioglu et al. in their study estimated PRL levels in 39 patients with psoriasis and compared these levels with 36 control subjects. Nine patients and five controls had slightly increased PRL levels but below 100 ng/ml. In their study, they could not find any significant difference in serum PRL levels between patients and controls. Also, their study did not reveal any statistical correlation between the PASI score of patients and their PRL levels.[18]

In yet another study, Hedman et al. measured the levels of PRL and other hormones in blood and synovial fluid in patients with arthritis of the knee associated with psoriasis (seven cases), and reported that there were no significant differences between patient and control groups.[19]

Priestley et al. in their study did not find any significant difference in PRL and growth hormone levels between patients and controls.[20]

In one open-label study, 35 patients with psoriatic arthritis refractory to conventional therapy were treated with bromocriptine (started at 2.5 mg and titrated up to 30 mg/day). Significant improvement was seen in 77%, with 34% showing complete remission and 43% with ~50% improvement in articular symptoms.[21]

In our study, we found an association between serum PRL levels and psoriasis. Our study also revealed an association between PRL levels and the severity of disease. On the basis of our study results, the role of PRL in the pathogenesis of psoriasis cannot be ruled out. Additional studies with larger sample size and including patients with severe psoriasis are needed in order to confirm our hypothesis and validate our findings.

Conclusion

In view of the results from both the present study and the other studies mentioned, it can be concluded that the serum PRL levels may serve as a biological marker of psoriatic disease activity. Further, studies with large sample size are needed to determine whether PRL plays a part in the etiopathogenesis of psoriasis. On the basis of the findings of our study, we recommend that controlled therapeutic trials of bromocriptine should be carried out in psoriatic patients especially in severe cases, even if prolactin levels are normal. Lastly, further studies should also be done in future to develop more specific therapy using antibodies against PRL.

What is new?

PRL may offer a novel future therapeutic target in psoriasis and other skin diseases that worsen in response to psychological distress, an assumption that must be researched more extensively.