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CASE REPORT
Ahead of print publication  

Risperidone-induced maculopapular rashes in a child


 Department of Psychiatry, ESIC Medical College and Hospital, Faridabad, Haryana, India

Date of Submission06-Nov-2021
Date of Decision25-Nov-2021
Date of Acceptance25-Nov-2021
Date of Web Publication04-Feb-2022

Correspondence Address:
Enub Ali,
Department of Psychiatry, ESIC Medical College and Hospital, NH-3, NIT, Faridabad - 121 001, Haryana
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aip.aip_135_21

  Abstract 


We report the case and the literature focusing on dermatological problems as a possible side effect of risperidone. A 10-year-old boy with attention deficit hyperactivity disorder, who was maintaining well on atomoxetine, developed rashes on addition of risperidone for behavioral problems. This prompted us to evaluate the relationship between skin rashes and risperidone. Maculopapular rashes resolved after risperidone was stopped following 3 days of treatment and resurfaced after rechallenge. These dermatological side effects were possibly induced by risperidone. Possible association of antipsychotics with dermatological side effects was explored and discussed. Antipsychotic use may present with maculopapular rashes as a side effect.

Keywords: Antipsychotics, management, rashes, risperidone



How to cite this URL:
Ali E, Sachdeva A, Passi S. Risperidone-induced maculopapular rashes in a child. Ann Indian Psychiatry [Epub ahead of print] [cited 2022 Aug 17]. Available from: https://www.anip.co.in/preprintarticle.asp?id=337218




  Introduction Top


Risperidone is an effective second-generation antipsychotic. It is indicated in multiple childhood problems including schizophrenia, bipolar disorder, and controlling disruptive behavior including hyperactivity, aggression, low frustration tolerance, impulsivity, and temper tantrums. Behavioral disturbances are often associated with pervasive developmental disorder and mental retardation in children. It is usually well tolerated in therapeutic doses, with a few patients experiencing adverse reactions such as weight gain, extrapyramidal symptoms, somnolence, galactorrhea, and headache.[1] Dermatological side effects such as rashes and pruritus are uncommonly associated with antipsychotic use. Pigmentation, erythema multiforme, and alopecia have also been reported in a few cases due to the use of atypical antipsychotics.[2] Chlorpromazine and clozapine have been the most implicated medicines with dermatological problems.[2],[3] Risperidone has not been studied extensively with regard to dermatological adverse effects. Here, we present a case of acute hypersensitivity reaction in a child treated with risperidone for behavioral problems.


  Case Report Top


A 10-year-old male child diagnosed with attention deficit hyperkinetic disorder had been on treatment with atomoxetine 10 mg daily for the past 5 years and was maintaining well. As per the family members, significant relief was reported in hyperactivity, inattention, and scholastic performance. Due to the change in residence, the patient gradually developed oddities in behavior such as increased irritability and agitation, especially toward family and peers. His intellectual capacity and developmental history did not reveal anything significant. The family consulted a doctor for the same where he was started on 1 mg of risperidone tablet and was advised behavior therapy. However, the family refused to comply with behavioral therapy. The patient took risperidone for 3 days when he started developing rashes over the limbs and abdomen and immediately consulted in the emergency department where his both medicines were stopped.

The patient presented in the psychiatry outpatient department next day. Maculopapular rashes <5 mm in diameter which did not fade on palpation were noted over the limbs and abdomen as seen in [Figure 1]. Detailed physical examination and thorough investigations were done to evaluate for systemic and infectious etiologies. The patient's leukocyte count, liver function, urea, creatinine, erythrocyte sedimentation rate, and C-reactive protein test results were normal. The viral serological test results were negative. The family did not report any allergy to food or any other drugs. He had no significant neurological or medical history. The patient was then referred to the dermatology department where all other causes for rash were excluded. With no evident systemic and dermatological cause for rashes, a thorough literature search was carried out to assess the role of antipsychotics in causing dermatological side effects. A few case reports were found which suggested antipsychotics, mainly clozapine and chlorpromazine, to be potential agents causing rashes.[2],[3] Furthermore, no significant drug–drug interaction was found between atomoxetine and risperidone. Tablet cetirizine 10 mg once a day for 5 days was advised from the dermatology department. The lesions started regressing after 4 days and completely subsided in 2 weeks. Relatives were advised to restart the patient on risperidone and atomoxetine at the same doses as the association for rashes was not significant for these two drugs. This unfortunately led to reappearance of rashes in the next 3–4 days. On further data search, a few case reports of risperidone causing skin rashes were found, following which risperidone was stopped and aripiprazole was started in view of his behavioral disturbances.[4],[5],[6] The Naranjo's causality assessment scale for adverse drug reactions is 6, so it is probable that the adverse reaction is caused by risperidone.[7]
Figure 1: Maculopapular rash on front of chest, abdomen and arm after oral intake of risperidone.

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  Conclusion Top


Risperidone is a second-generation antipsychotic which works on dopamine D2 receptors and 5-HT2A serotonin receptors. It is indicated in several psychological and behavioral problems associated with children and adolescents including bipolar disorder, schizophrenia, disruptive behavior disorder, and behavior disturbances associated with autism spectrum disorder and mental retardation.[8],[9]

Dermatological side effects of antipsychotics are generally underreported or ignored. Data regarding the dermatological side effect of antipsychotics are lacking and insufficient.[10] The most common antipsychotic drugs implicated in causing dermatological side effects are clozapine and chlorpromazine.[2],[3] Only a few other case reports highlight dermatological side effects of other antipsychotics.[11] The exact mechanisms for dermatological side effects of antipsychotics are not known, and they most likely vary between different drugs. These may include a direct effect of the drug on keratinocytes as well as immunomodulatory properties of the drug.[12]

The index case was a known case of attention deficit hyperkinetic disorder who was maintaining well on atomoxetine but developed rashes soon after the initiation of risperidone. Extensive literature search did not suggest any interaction between risperidone and atomoxetine. All other causes of dermatological side effects were also ruled out. Risperidone rechallenge also led to development of rashes associated with temporal association in a similar pattern.

Risperidone-induced dermatological side effect has been reported in the literature in all age groups. A 20-year-old male patient who was diagnosed with psychosis had excoriation of skin following initiation of oral risperidone,[4] and a 5-year-old child with disruptive behavior disorder developed diffused maculopapular rashes.[6] Risperidone-associated maculopapular rashes were also reported in a 64-year-old woman with antitubercular drug-induced psychosis.[5] It has been observed that different dermatological side effects occur with the use of different forms of risperidone.[11],[13],[14],[15] Risperidone-induced rashes have been reported in early as well as late phase of treatment.[16]

Skin rashes are uncommon yet clinically important adverse reactions to treatment with psychotropic drugs. It is a potentially dangerous medical complication in psychiatric patients if ignored and left untreated. Other important etiology of rashes in children such as infections (scarlet fever, varicella, and measles), systemic illnesses (ichthyosis tuberous sclerosis), and allergic reactions should be considered and ruled out. The rash might be due to the other binding agents in the tablet of risperidone. Hence, a challenge with other brands may be useful to know whether the rash is due to risperidone or some other binding agents in the tablet. There is a complete and rapid recovery of drug-induced rashes once the offending agent is discontinued, as happened with the index case, without any further recurrences. Clinicians need to be aware of this dangerous complication and exercise caution before starting risperidone (and antipsychotics) to avoid rashes or more severe complications such as toxic epidermal necrolysis and Stevens–Johnson syndrome.

Consent for publication

Written informed consent to publish this information was obtained from the legal guardian of the study participant.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's legal guardian has given consent for images and other clinical information to be reported in the journal. The patient's guardian understands that name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Pandina GJ, Aman MG, Findling RL. Risperidone in the management of disruptive behavior disorders. J Child Adolesc Psychopharmacol 2006;16:379-92.  Back to cited text no. 1
    
2.
Warnock JK, Morris DW. Adverse cutaneous reactions to antipsychotics. Am J Clin Dermatol 2002;3:629-36.  Back to cited text no. 2
    
3.
Yücel A, Karakuş G, Günaştı S. Dermatological side effects of psychotropic drugs and treatment approaches. Klinik psikofarnakoloji bulteni-bulletin of clinical psychopharmacology 2008;18:235-44.  Back to cited text no. 3
    
4.
Janardhana P, Nagaraj AK, Basavanna PL. Risperidone-induced skin rash. Indian J Psychiatry 2016;58:106-7.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Shah M, Karia S, Merchant H, Shah N, Sousa Ad. Risperidone-induced skin rash in an elderly female. J Geriatr Ment Health 2019;6:28-30.  Back to cited text no. 5
  [Full text]  
6.
Güler HA, Türkoğlu S, Güler D. Maculopapular rash associated with risperidone in a child. Psychiatry Clin Psychopharmacol 2019;29:527-8.  Back to cited text no. 6
    
7.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 7
    
8.
De Hert M, Dobbelaere M, Sheridan EM, Cohen D, Correll CU. Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: A systematic review of randomized, placebo controlled trials and guidelines for clinical practice. Eur Psychiatry 2011;26:144-58.  Back to cited text no. 8
    
9.
Grant S, Fitton A. Risperidone. Drugs 1994;48:253-73.  Back to cited text no. 9
    
10.
Obayi O, Okoh N. Mixed acute allergic angioedema and urticaria associated with olanzapine treatment – A rare case report. Clin Dermatol J 2018;3:000148.  Back to cited text no. 10
    
11.
Lin J. Antipsychotics and rashes. Ment Illn 2018;10:7808.  Back to cited text no. 11
    
12.
Bujor CE, Vang T, Nielsen J, Schjerning O. Antipsychotic-associated psoriatic rash – A case report. BMC Psychiatry 2017;17:242.  Back to cited text no. 12
    
13.
Chae BJ, Kang BJ. Rash and desquamation associated with risperidone oral solution. Prim Care Companion J Clin Psychiatry 2008;10:414-5.  Back to cited text no. 13
    
14.
Sidhu K, Saggu H, Lachover L, dziuba JT. Rare case report of rash associated with risperidone long-acting injection. Prim Psychiatry 2010;17:38-40.  Back to cited text no. 14
    
15.
Reeves RR, Mack JE. Allergic reaction to depot risperidone but not to oral risperidone. J Clin Psychiatry 2005;66:949.  Back to cited text no. 15
    
16.
MacMorran WS, Krahn LE. Adverse cutaneous reactions to psychotropic drugs. Psychosomatics 1997;38:413-22.  Back to cited text no. 16
    


    Figures

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