Journal of Pharmaceutical Negative Results

ORIGINAL ARTICLE
Year
: 2016  |  Volume : 7  |  Issue : 1  |  Page : 1--3

Propylthiouracil in treating psoriasis, a promise that failed: A hospital-based prospective study of propylthiouracil in the treatment of psoriasis


Murugaiyan Rangaraj, Kaliaperumal Karthikeyan 
 Department of Dermatology, Sri Manakula Vinayagar Medical College and Hospital, Pondicherry, India

Correspondence Address:
Murugaiyan Rangaraj
Department of Dermatology, Sri Manakula Vinayagar Medical College and Hospital, Kalitheerthalkuppam, Madagadipet - 605 107, Pondicherry
India

Abstract

Introduction: Psoriasis is a common skin disorder with no cure and definite treatment options. Propylthiouracil (PTU), an antithyroid drug, has been found to be effective in treating psoriasis in certain studies. This prompted us to conduct a study to assess the effectiveness of PTU in treating patients with psoriasis. Aims: The primary objective of our study was to assess the efficacy of PTU as a safe and effective agent in the management of psoriasis. Settings and Design: This study was a clinical prospective study conducted over a period of 3 months. Materials and Methods: Thirty one patients with psoriasis and those fulfilling the inclusion criteria were treated with PTU (100 mg thrice a day) and topical emollient, and were followed up for 12 weeks. Psoriasis Area Severity Index (PASI) at the baseline and at the end of the study were compared. Patients who attained PASI score 50 were considered to respond to the treatment. Statistical Analysis Used: Mean values of variables. Results: The mean PASI score at the beginning of the treatment with PTU was 17.6. The mean PASI score at the end of the study was 16.06. Conclusions: We found PTU to be ineffective in reducing both the symptoms and severity of psoriasis. It is also intriguing to note that PTU, which was found to be effective in treating psoriasis almost two decades ago, has never been used widely in practice. Probably, this bears testimony to the fact that PTU is not as effective as it was promised to be.



How to cite this article:
Rangaraj M, Karthikeyan K. Propylthiouracil in treating psoriasis, a promise that failed: A hospital-based prospective study of propylthiouracil in the treatment of psoriasis.J Pharm Negative Results 2016;7:1-3


How to cite this URL:
Rangaraj M, Karthikeyan K. Propylthiouracil in treating psoriasis, a promise that failed: A hospital-based prospective study of propylthiouracil in the treatment of psoriasis. J Pharm Negative Results [serial online] 2016 [cited 2017 Jul 25 ];7:1-3
Available from: http://www.pnrjournal.com/text.asp?2016/7/1/1/177046


Full Text

 Introduction



Psoriasis is a common skin disorder with no cure and definite treatment options; further, the chronic and relapsing course of the disease throws open a wide array of treatment options. Though drugs used for treating psoriasis like methotrexate , retinoids, cyclosporine and biologicals have their own merits, yet none of them are free of demerits. The search for a drug that is ideal for the treatment of psoriasis is on, and a list of treatment options is a testimony for this fact. In the past decade, many new drugs have been tried in treating psoriasis. Propylthiouracil (PTU), an antithyroid drug, has been found to be effective in treating psoriasis in certain studies. [1],[2],[3],[4] This prompted us to conduct a study to assess the effectiveness of PTU in treating patients with psoriasis.

 Materials And Methods



The primary objective of our study was to assess the efficacy of PTU as a safe and effective agent in the management of psoriasis. Our study was conducted with patients diagnosed to have psoriasis and attending our outpatient department.

The patients with history suggestive of psoriasis were subjected to a detailed clinical examination, followed by a skin biopsy. Those who had both clinical and histopathological features of psoriasis were considered for this study. Among these patients, those who had Psoriasis Area Severity Index (PASI) score more than 10 were included in the study. A total of 31 cases were recruited in the study after obtaining an informed consent. An approval from the Ethics Committee was obtained before starting the study.

Patients with unstable psoriasis, erythroderma, pustular psoriasis; pregnant and lactating women; and children were not included in the study. Moreover, those who have thyroid disorders and systemic illnesses or those who have received any form of systemic therapy for the past 3 months were excluded from the study.

The study was a clinical prospective study conducted over a period of 3 months with a follow-up. The study was conducted after obtaining consent from the Ethics Committee of the insitution.

All the recruited patients were explained about the study. They were also explained about PTU and its possible side effects. The patients were subjected to baseline investigations like hemogram, blood sugar, liver, renal, and thyroid function tests; human immunodeficiency virus (HIV) serology; throat swab culture; and antistreptolysin O (ASLO) titer.

The patients were administered oral PTU 100 mg tablets thrice a day. The patients did not receive any medication other than the topical liquid paraffin. If the patient had itching, he/she was prescribed oral cetirizine to reduce itching.

After the baseline assessment, the patients were also assessed at 2 weeks, 6 weeks, 8 weeks, and 12 weeks by a single observer who calculated their PASI score. The patients' PASI score were confirmed by another independent observer.

The therapeutic response to the drug was assessed based on serial PASI scores. PASI score 50 was considered as complete response to the treatment.

The patients were also enquired about any untoward incident (s) and were subjected to thyroid profile at 2 weeks, 6 weeks, and 12 weeks.

 Results



A total of 31 patients were included in the study out of which 20 patients were males and 11 were females. About five patients were dropped at various stages during the follow up. The remaining 26 patients completed the study. The patients who completed the study did not complain of any side effects of the drug. The thyroid function was normal and no adverse effects were noted in the study. The drug was well-tolerated.

The mean PASI score at the beginning of the treatment with PTU was 17.6. At the end of the study, it was 16.06 [Figure 1].{Figure 1}

None of the patients attained PASI score 50, confirming the lack of adequate response to PTU.

None of the patients while on treatment with PTU had reduction in scaling and erythema of the lesions. Further, in three persons, the lesions worsened in spite of the treatment.

All the patients were shifted to other modalities of therapy, based on the severity and presentation of the disease.

Analysis

All statistical evaluations were done using trial version of SPSS version 16.0. The results are expressed as mean ± standard deviation (SD). Student's paired t-test was used for statistical analysis of the data. Level of significance was P < 0.05.

 Discussion



Psoriasis is a chronic inflammatory disorder characterized by hyperproliferation and abnormal differentiation of keratinocytes. The exact mechanism of pathogenesis remains an enigma although treatment strategies such as topical treatments, phototherapy, and treatment using methotrexate, cyclosporine, and biologic agents are available. No permanent curative therapy exists, and the localized treatments are laborious and ineffective in a significant proportion of psoriatic patients.

The quests for a new drug probably lead to the use of PTU in treating psoriasis. The mechanism of PTU, a thioureylene, treating psoriasis is unclear and poorly studied. PTU has been proposed to treat psoriasis by virtue of its antiproliferative effect. [5] PTU, a thioureylene, is also found to act as a free radical scavenger, thus, inhibiting the oxidative events in the skin that play important role in initiating psoriasis. Elias et al. postulates that this drug can potentially reduce the cytokine signals that lead to keratinocyte proliferation. [6] The antithyroid drugs, PTU (6-n-propyl-2-thiouracil), and the related thioureylene, methimazole (1-methyl 2-mercaptoimidazole) have been used for decades as a medicine for first-line treatment of patients with hyperthyroidism. The roles of these drugs in the treatment of psoriasis have been addressed for several years. PTU has been shown to cause significant reduction in PASI scores within 4-6 weeks of commencement of the therapy. [7]

Most of the studies with PTU have been done by Elias et al.[3],[4],[5],[6],[7],[8] Gnanaraj et al. have found PTU to significantly clear lesions in all patients with psoriasis. Chowdhury et al. studied four patients with resistant plaque psoriasis and found moderate clinical improvement. [1] Elias et al., in their open trial, found that out of 10 patients studied two had near complete resolution and the remaining showed moderate improvement. Only one patient had mild abnormality of thyroid-stimulating hormone TSH. [7]

Kose et al. studied the effect of PTU and correlated it with adenosine deaminase levels. In this study, they found that all patients had significant clinical improvement in PASI score and their skin lesions improved.

Most of the studies included a very small number of patients. Though we had planned a larger group, the study was prematurely concluded due to very poor response to the treatment. We found PTU to be ineffective in reducing both the symptoms and severity of psoriasis. It is also intriguing to note that PTU, which was found to be effective treating in psoriasis almost two decades ago, has never been used widely in practice. Probably, this bears testimony to the fact that PTU is not as effective as it was promised to be.

Moreover, PTU is not free of any side effects, other than causing hypothyroidism it can also precipitate vasculitis in certain patients. [11] PTU has been associated with various inflammatory conditions such as agranulocytosis, aplastic anemia, hepatitis, interstitial pneumonitis, and others. In the present day, the scenario will the availability of drugs with proven efficacy and rotational therapy, and PTU will remain in the list as one of the drugs used to treat psoriasis rather than in the therapeutic armamentarium of the dermatologists.

Acknowledgments

We acknowledge the Department of Community Medicine, Department of Dermatology, Ethics Committee of the institution of Sri Manakula Vinayagar Medical College and Hospital, Pondicherry for their inputs.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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