Elsevier

Clinical Biochemistry

Volume 44, Issues 14–15, October 2011, Pages 1209-1213
Clinical Biochemistry

Clinical efficacy of propylthiouracil and its influence on prolactin in psoriatic patients

https://doi.org/10.1016/j.clinbiochem.2011.07.009Get rights and content

Abstract

Objective

Propylthiouracil (PTU) is an effective drug for psoriasis treatment. Prolactin (PRL) is increased during psoriasis which has hyperproliferative effect on keratinocytes. Hence, the objective is to find the effect of PTU on PRL level in psoriatic patients.

Design and methods

25 psoriatic patients and 10 control subjects were involved in the study. Serum PRL, hematological and biochemical parameters, thyroid profile and histopathological examination were performed.

Results

PTU treatment for 6 weeks and 12 weeks cleared psoriatic lesions indicated by decreased PASI score (p < 0.001). Patients before treatment showed significantly increased PRL levels (male p < 0.01, female p < 0.001) when compared to controls, which was found to decrease significantly (male p < 0.01, female p < 0.001) after 12 weeks. Hematological and biochemical parameters showed no significant change. Histopathology showed reduced thickening of the epidermis and acanthosis after PTU treatment.

Conclusion

Since PRL is a growth hormone involved in hyperproliferation of keratinocytes, this study reveals the antiproliferative effect of PTU. Furthermore, no major side effects were observed following PTU treatment.

Introduction

Psoriasis, a common hyper proliferative skin T-cell disorder, is a chronic disease with exacerbations and remissions [1]. It is a relatively common skin disorder affecting 1–3% of individuals worldwide [2]. Psoriasis generally occurs in adults, affecting both males and females equally [3]. The prevalence and incidence estimates of psoriasis show ethnic and geographic variations [4]. The prevalence rate being 0.8–5.6% in India is merely based on the hospital data, hence, does not reflect the true picture of psoriasis in the general population [5]. Among the different subtypes of psoriasis (such as guttatte psoriasis, pustular psoriasis and palmoplantar psoriasis) psoriasis vulgaris is implicated as the most commonly seen subtype affecting 90% of the psoriasis patients. Histologically, keratinocytes show abnormal differentiation, hyper proliferation, inflammatory infiltrates invasion in the dermis and epidermis, and a marked neoangiogenesis [6].

Psoriasis has been associated with several triggering factors. Cutaneous trauma (sunburn, surgery, trauma from scratching) can cause the development of psoriatic plaque in about 40% of psoriatic cases (Koebner's phenomenon) [7]. According to many patients and clinicians, psoriasis is exacerbated by psychological stress (probably via neuro-immunological mechanisms) [8], [9], [10] and emotional disturbances (lead to hyperprolactinaemia) [11]. The possible role of PRL, sex hormones and stress hormones was emphasized in etiology of psoriasis [12]. PRL plays a vital role in keratinocytes proliferation and is involved in the pathogenesis of psoriasis via its effect on the immune system [14]. Therefore, serum PRL levels may serve as biomarker for psoriatic disease activity [15].

Although treatment strategies like topical treatments, phototherapy, methotrexate, cyclosporine and biologic agents [5] are available. No permanent curative therapy exists, and the localized treatments are laborious and ineffective in a significant proportion of psoriatic patients. Patients with mild disease may benefit from topical agents and targeted phototherapy. However, psoriasis involving more than 20% body surface area requires systemic therapy over long periods and this often leads to toxicity [16]. For example, long-term treatment with psoralen plus ultra violet light A (PUVA) may result in cutaneous malignancies [17]. The traditional agents, methotrexate and cyclosporine, are effective in many patients, but long-term use is limited by the potential development of serious adverse events such as hepatotoxicity and nephrotoxicity [18].

More recently, anti-thyroid drugs such as PTU (6-n-propyl- 2-thiouracil) and the related thioureylene, methimazole (1-methyl 2-mercaptoimidazole, MMI), have been used for the treatment of psoriasis and have been found useful, though the mechanism is not known [19]. These drugs were earlier used as first line treatment for patients with hyperthyroidism [20]. PTU shows complete or near complete clearing of psoriatic lesions in 20–30% of the patients and more than 50% clearing seen in about half of all patients after therapy for 2 to 3 months. PTU is generally well-tolerated, except for some common side effects (abnormal hair loss, nausea, vomiting, joint or muscle aches, numbness and headache, allergic reactions) [21], [22]. Agranulocytosis [23] and hepatotoxicity [24] seldom occurs following PTU treatment. The objective of this study is to assess clinical efficacy of PTU and effect of PTU on serum PRL levels in psoriatic patients.

Section snippets

Materials and methods

For this study, 25 patients with stable plaque psoriasis were recruited from Dermatology Department at SRM Hospital, Kattankulathur. Mean patient's age was 45.4 ± 12.6 Years (15 men and 10 women, aged 19–73 years). Those who had hypothyroidism and other systemic diseases were excluded from the study. Children, pregnant and lactating women were also excluded from the study. Psoriatic patients with lesions covering more than 20% body surface area and those patients who did not receive any topical or

Results

Two patients were dropped out of the study. The medication was well tolerated in rest of the 23 patients. Patients showed significant clinical improvement as seen in Fig. 1, Fig. 2. Fig. 1 shows the representative photographs of a psoriatic patient before (a) and after treatment (b) with PTU. Fig. 2 shows the representative photographs of Hematoxylin and Eosin stained biopsy sections before and after PTU treatment (12 weeks). Fig. 2a shows increased epidermal thickening and acanthosis which is

Discussion

Pathogenesis of psoriasis is subject to control by neuro-hormonal systems [36]. Recently it has been reported that PRL which possesses a variety of physiological action including growth promoting activity, exerts a proliferative effect on human keratinocytes. PRL may therefore, play an important role in pathogenesis of psoriasis [37].

Our result shows that PTU is highly effective in clearing psoriatic lesions as shown by decreased PASI score and histopathological findings. Three patients showed

Conflict of interest

The authors state that there is no conflict of interest.

Acknowledgment

The authors thank SRM University for their Financial Support.

Glossary

1. PTU
- Propylthiouracil
2. PRL
- Prolactin
3. PASI
- Psoriatic Area Severity Index score
4. ELISA
- Enzyme Linked Immunosorbent Assay
5. rpm
- Revolutions per minute
6. LFT
- Liver function test
7. SGOT
- Serum Glutamate Oxaloacetate Transaminase
8. SGPT
- Serum Glutamate Pyruvate Transaminase
9. RFT
- Renal function test
10. TFT
- thyroid function test
11. Gp
- group

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