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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 5  |  Issue : 1  |  Page : 26-29

Oral ranitidine: A promising novel therapeutic option in molluscum contagiosum in children


1 Department of Skin and VD, Smt SCL General Hospital, Ahmedabad, Gujarat, India
2 Department of Skin and VD, Jawaharlal Nehru Medical College, AVBR Hospital, Wardha, Maharastra, India

Date of Web Publication22-Jul-2019

Correspondence Address:
Dr. Bhushan Madke
Department of Skin and VD, Jawaharlal Nehru Medical College, AVBR Hospital, Sawangi, Wardha, Maharastra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_41_18

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  Abstract 


Background: Molluscum contagiosum(MC) is one of the most common cutaneous viral infection observed in children. Though, it is benign and self-limiting, treatment is often sought for cosmetic reasons. Existing invasive therapeutic modalities are generally not well tolerated in children because of pain and risk of scarring. Immunomodulatory potential of cimetidine is well established. We thus extrapolated the same to ranitidine and conducted this study. Aim: To assess the efficacy of oral ranitidine in treatment of molluscum contagiosum in immunocompetent children. Methods: A multicentre longitudinal study was conducted in the dermatology departments of tertiary care hospitals in Ahmedabad and Wardha, India over a period of 4 months. 24 children with MC were included. Oral ranitidine was started in dose of 5 mg/kg/day in two divided doses for 8 weeks. Follow up was done very 15 days and changes in number and size of lesions were noted. Results: Mean age of patients was 5.08 years. 19 patients completed the study. 15 patients had improvement in the lesions at the end of 8 weeks while 4 patients did not show any improvement. Complete clearance was seen in 14 patients(73.6%) and 1 patient had decrease in size of the lesions without change in the number. Mean duration of complete clearance of lesion was 6.5 weeks. Conclusion: Oral ranitidine may be considered as a safe and effective alternative therapeutic option in widespread MC in immunocompetent children where invasive painful procedures are less desirable.

Keywords: Immunomodulators, molluscum contagiosum, pediatric dermatology, ranitidine


How to cite this article:
Agarwal P, Madke B, Bodar P. Oral ranitidine: A promising novel therapeutic option in molluscum contagiosum in children. Indian J Drugs Dermatol 2019;5:26-9

How to cite this URL:
Agarwal P, Madke B, Bodar P. Oral ranitidine: A promising novel therapeutic option in molluscum contagiosum in children. Indian J Drugs Dermatol [serial online] 2019 [cited 2019 Nov 13];5:26-9. Available from: http://www.ijdd.in/text.asp?2019/5/1/26/263101




  Introduction Top


Molluscum contagiosum (MC) is a common cutaneous viral infection observed predominantly in children. It is caused by MC virus, a member of the Poxviridae family. The infection usually presents as single or multiple small whitish or skin-colored papules with a typical central umbilication.[1] Although the infection is benign and self-limiting, treatment is often sought for mainly cosmetic reasons and fear of transmission to other contacts.[2] Various modalities have been used for treatment, though a systematic Cochrane review in 2009 concluded that there was insufficient evidence supporting the use of any single treatment as being definitively effective.[3] Existing therapeutic modalities include cryotherapy, curettage, and application of topical cauterizing agents such as trichloroacetic acid, potassium hydroxide, and phenol.[4] As mainly the T-cell-mediated immunity is effective in viral infections, drugs with an immunomodulatory action seem to be a promising therapeutic option in such diseases. Cimetidine and ranitidine are histamine receptor antagonists which are classically administered to suppress gastric acid secretion in peptic ulcer disease.[5] They have been found to have immunomodulatory effects by stimulation of delayed-type hypersensitivity. Cimetidine has been used with variable success in the treatment of verruca plana[6],[7] and molluscum[8],[9] with variable efficacy. The present study was undertaken to study the effectiveness of oral ranitidine in the treatment of MC in childhood.


  Materials and Methods Top


This multicenter longitudinal study was conducted in the dermatology departments of two tertiary care hospitals in Ahmedabad and Wardha, India, over a period of 4 months from June 2018 to October 2018. All the children visiting the dermatology outpatient department (OPD) were screened for MC and were included in the study after written informed consent of the parent/guardian. Informed consent was obtained for enrollment in the study as well as for photographic documentation. Detailed clinical history including age of onset, sex, duration of disease, any predisposing factors, and any prior treatment taken was noted. Clinical examination was done to note the distribution of lesions, number and average size of lesions, and any associated feature like inflammation or eczematization. Pediatrician opinion was sought for complete systemic examination to rule out any underlying illness. Patients with any underlying systemic disease or malnutrition were excluded from the study. The patients were started on oral ranitidine syrup at a dose of 5 mg/kg/day in two divided doses for 8 weeks and were called for follow-up every 15 days. On every follow-up visit, changes in the number and size of lesions were noted. No adjunctive treatment was given. Clinical photographs were taken at the initiation of therapy and every follow-up visit.


  Results Top


Twenty-four patients were included in this study in the age group between 1.5 and 12 years (mean age: 5.08 years). The number of male patients was higher and male-to-female ratio was 1.4:1. The clinical profile of patients is detailed in [Table 1]. At the beginning of the study, molluscum lesions were evaluated in terms of number and size. The number of lesions ranged from minimum 7 to maximum 47 in a single patient. The size of the lesions ranged between 0.5 mm and 2 mm. Out of the 24 patients enrolled in the study, 19 patients completed the study and 5 patients were lost to follow-up at various stages of the study. Out of these 19 patients, 15 patients had improvement in the size as well as the number of lesions, whereas 4 patients did not show any improvement even after 8 weeks and were hence switched to other modes of therapy [Table 2]. Complete clearance of lesions was seen in 14 patients (73.6%) and the remaining 1 patient had a decrease in the size of the lesions with no change in the number of lesions at the end of 8 weeks [Figure 1], [Figure 2], [Figure 3], [Figure 4]. Improvement was noticed as early as 2 weeks after initiation of therapy and complete clearance was seen in 8 weeks. The mean duration of complete clearance of lesion was 6.5 weeks. Observations revealed that the size of the individual lesions decreased earlier than decrease in numbers. We also observed that children younger than 5 years showed a better response. Patients were followed up for 2 months after complete clearance of lesions. Recurrence was seen only in 2 patients. In one patient, new lesions appeared within 20 days, and in the other, it was toward the end of the 2nd month of stopping ranitidine. On probing, it was revealed that their close contacts had untreated molluscum lesions.
Table 1: Clinical profile of patients with molluscum contagiosum

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Table 2: Clinical response in molluscum lesions after treatment

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Figure 1: Multiple tiny pearly-white papules over the face (a) baseline, (b) decrease in number after 4 weeks of therapy, and (c) clearance after 8 weeks of therapy

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Figure 2: Widespread molluscum at (a) baseline and (b) complete clearance after 8 weeks of therapy

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Figure 3: Decrease in the number of molluscum lesions from (a) baseline to (b) 2 weeks posttherapy, (c) 4 weeks posttherapy, and (d) 6 weeks posttherapy

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Figure 4: Decrease in size of lesions from (a) baseline to (b) 8 weeks of therapy

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  Discussion Top


Although molluscum is one of the most common skin infections in children, scientific evidence does not clearly favor a specific treatment for it.[3] Procedures which cause pain or have a significant risk of scarring are generally avoided in the pediatric age group. Oral cimetidine (an H2 receptor antagonist) is a well-known oral immunomodulator which has been tried in the various cutaneous viral infections.[6],[7],[8],[9] It acts by stimulating delayed hypersensitivity. It has been used in the treatment of MC by Dohil et al. where 13 children with MC were treated with 40 mg/kg/day of oral cimetidine for 2 months, and complete resolution was observed in 9 of 13 patients.[10] However, a double-blind trial comparing the efficacy of cimetidine versus placebo treatment showed no statistically significant differences between the two treatment groups.[11] Ranitidine differs in chemical structure from both histamine and cimetidine and works as H2 receptor antagonist.[12] It is a more potent inhibitor than cimetidine with added advantage of sharing none of the cimetidine's antiandrogenic and hepatic enzyme-inhibiting effects.[13] It has a better safety profile in children, pregnancy and lactation, and elderly. The drug is very well tolerated without any serious adverse reactions or any clinically significant drug interactions.[14] Due to its favorable efficacy, tolerability profile as well as better availability than cimetidine, oral ranitidine was chosen as the therapeutic option in this study. While going through the literature for researching for its immunomodulatory action, multiple studies showed its utility as an immunomodulator in trauma as well as malignant cases.[15],[16],[17] Treatment with ranitidine in patients with head injury was seen to be associated with a significant increase in CD4+ lymphocytes (33%–49%; P <.05) and a significant decrease in CD8+ lymphocytes (41%–27%; P <.05) compared to placebo. Furthermore, the interferon-gamma production increased from 121 to 269 pg/mL (P<.05) in patients treated with ranitidine compared to placebo.[16] Another study of oral ranitidine in colorectal cancer patients revealed that the natural killer, lymphokine-activated killer, and interferon-alpha-stimulated killer cell activity increased significantly in the ranitidine patients compared to the placebo patients (P < 0.02, P < 0.03, and P < 0.05, respectively).[17]

In the pediatric age group, the fear of needle in children made us look for any other safer and noninvasive modality of treatment. It was surprising that 73.6% of our patients had complete clearance of molluscum lesions over a course of 8 weeks of oral ranitidine syrup (5 mg/kg/day). Four patients who still had no response in the size as well as the number of lesions at the end of 8 weeks were then taken for needle extraction under topical anesthesia. New lesions were observed only in 2 out of 15 patients and both had a positive history of coming in contact with a patient with molluscum. Hence, it is difficult to ascertain whether these new lesions were due to reinfection or recurrence. Spontaneous clearance of molluscum lesions is seen sometimes, but it usually takes 6–9 months,[18] whereas in this study, lesions were cleared in 2 months in most cases.


  Conclusion Top


Oral ranitidine may be considered as a safe and effective alternative therapeutic option in widespread MC in immunocompetent children. It is particularly useful in young children where painful procedures such as cryotherapy or curettage are not desirable. The drug is thought to have an immunostimulatory effect by increasing the helper CD4+ lymphocytes and decreasing the CD8+ lymphocytes. To rule out the spontaneous resolution of molluscum lesions, a double-blind, placebo-controlled study is suggested to confirm the efficacy of ranitidine.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sladden MJ, Johnston GA. Common skin infections in children. BMJ 2004;329:95-9.  Back to cited text no. 1
    
2.
Janniger CK, Schwartz RA. Molluscum contagiosum in children. Cutis 1993;52:194-6.  Back to cited text no. 2
    
3.
van der Wouden JC, van der Sande R, van Suijlekom-Smit LW, Berger M, Butler CC, Koning S. Interventions for cutaneous molluscum contagiosum. Cochrane Database Syst Rev 2009;4:CD004767.  Back to cited text no. 3
    
4.
Epstein WL. Molluscum contagiosum. Semin Dermatol 1992;11:184-9.  Back to cited text no. 4
    
5.
Mavligit GM, Talpaz M. Cimetidine for herpes zoster. N Engl J Med 1984;310:318-9.  Back to cited text no. 5
    
6.
Orlow SJ, Paller A. Cimetidine therapy for multiple viral warts in children. J Am Acad Dermatol 1993;28:794-6.  Back to cited text no. 6
    
7.
Choi YS, Hann SK, Park YK. The effect of cimetidine on verruca plana juvenilis: Clinical trials in six patients. J Dermatol 1993;20:497-500.  Back to cited text no. 7
    
8.
Sharma AK. Cimetidine therapy for multiple molluscum contagiosum lesions. Dermatology 1998;197:194-5.  Back to cited text no. 8
    
9.
Cunningham BB, Paller AS, Garzon M. Inefficacy of oral cimetidine for nonatopic children with molluscum contagiosum. Pediatr Dermatol 1998;15:71-2.  Back to cited text no. 9
    
10.
Dohil M, Prendiville JS. Treatment of molluscum contagiosum with oral cimetidine: Clinical experience in 13 patients. Pediatr Dermatol 1996;13:310-2.  Back to cited text no. 10
    
11.
Antony F, Cliff S, Ahmad A, Holden C. Doubleblind placebo-controlled study of oral cimetidine treatment for molluscum contagiosum. Br J Dermatol 2001;145:122-9.  Back to cited text no. 11
    
12.
Dawson J, Richards DA, Stables R, Dixon GT, Cockel R. Ranitidine – Pharmacology and clinical use. J Clin Hosp Pharm 1983;8:1-3.  Back to cited text no. 12
    
13.
Brogden RN, Carmine AA, Heel RC, Speight TM, Avery GS. Ranitidine: A review of its pharmacology and therapeutic use in peptic ulcer disease and other allied diseases. Drugs 1982;24:267-303.  Back to cited text no. 13
    
14.
Pahwa R, Shilpa Sharma S, Kumar V, Kohli K. Ranitidine hydrochloride: An update on analytical, clinical and pharmacological aspects. J Chem Pharm Res 2016;8:70-8.  Back to cited text no. 14
    
15.
Nielsen HJ, Nielsen H, Moesgaard F, Tvede N, Klarlund K, Mansa B, et al. The effect of ranitidine on cellular immunity in patients with multiple myeloma. Cancer Immunol Immunother 1990;32:201-5.  Back to cited text no. 15
    
16.
Rixen D, Livingston DH, Loder P, Denny TN. Ranitidine improves lymphocyte function after severe head injury: Results of a randomized, double-blind study. Crit Care Med 1996;24:1787-92.  Back to cited text no. 16
    
17.
Nielsen H, Hammer J, Gronvall S, Monrad H, Grindsted J. The effect of ranitidine on immune function, tumor response and survival in patients with liver metastases from colorectal cancer. GI Cancer 1996;1:183-90.  Back to cited text no. 17
    
18.
Hawley TG. The natural history of molluscum contagiosum in Fijian children. J Hyg (Lond) 1970;68:631-2.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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