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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 17  |  Issue : 2  |  Page : 104-107

Successful treatment of refractory childhood vesiculobullous disorders with rituximab: A study of five cases


Department of Dermatology, NHL Medical College, V.S Hospital, Ahmedabad, Gujarat, India

Date of Web Publication30-Mar-2016

Correspondence Address:
Jeta Y Buch
Department of Dermatology, NHL Medical College, V.S Hospital, Ellisbridge, Ahmedabad - 380 006, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2319-7250.175664

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  Abstract 

Introduction: Rituximab, a chimeric monoclonal anti-CD20 antibody, has shown efficacy as an adjuvant in the treatment with refractory vesiculobullous disorders. We, hereby, present a study of five pediatric patients of extensive vesiculobullous disorders showing resistance to conventional therapy of 40 mg of prednisolone daily and treated effectively with rituximab as an adjuvant.
Aim of the Study: To study the efficacy, safety, and clinical outcome of rituximab in refractory autoimmune vesiculobullous disorders.
Method: Five patients (3: Pemphigus vulgaris, 1: Pemphigus foliaceous, 1: Chronic bullous disease of childhood [CBDC]) were selected for treatment with rituximab after confirmation with tzanck, biopsy, direct immunofluorescence (DIF) and desmoglein (DSG) level. Three hundred milligram intravenous infusion in children over 4–5 h duration. Two doses were given at 15 days interval. DSG 1 and 3 and differential item functioning were repeated after 1-month of the second dose of rituximab. Follow-up (weekly for 1-month, fortnightly for next 2 months). Two patients (1: Pemphigus vulgaris, 1: CBDC) showed relapse after 6 months. So, they were given two more doses of rituximab at an interval of 15 days.
Observation: All five patients showed complete remission during the 6 months follow-up period, along with a consensual decline of the serum anti-DSG titers.
Conclusion: Rituximab can be considered as an effective adjuvant therapy when treating resistant cases of autoimmune blistering diseases in pediatric patients. However, more number of patients and long-term follow-up is required to draw a definite conclusion.

Keywords: Rituximab, pediatric, vesiculobullous disorders


How to cite this article:
Buch JY, Raval RC. Successful treatment of refractory childhood vesiculobullous disorders with rituximab: A study of five cases. Indian J Paediatr Dermatol 2016;17:104-7

How to cite this URL:
Buch JY, Raval RC. Successful treatment of refractory childhood vesiculobullous disorders with rituximab: A study of five cases. Indian J Paediatr Dermatol [serial online] 2016 [cited 2019 Nov 14];17:104-7. Available from: http://www.ijpd.in/text.asp?2016/17/2/104/175664


  Introduction Top


Rituximab

A chimeric monoclonal antibody of IgG1 class acts against the protein CD20 found on the surface of immune complex B cells by complement dependent and antibody dependent cell mediated cytotoxicity. We, hereby, present a study of five pediatric patients of extensive pemphigus showing resistance to conventional therapy of 40 mg of prednisolone daily and treated effectively with rituximab as an adjuvant.


  Case Reports Top


Case 1

An 11-year-old female presented to the skin outpatient department (OPD) with fluid filled lesions over scalp, skin and oral lesions since 4 months (PAAS-16) [Figure 1]. The patient was diagnosed as having pemphigus vulgaris that was confirmed with tzanck and biopsy. The patient was given injectable dexamethasone (1 cc) intravenous (IV) twice a day that was gradually tapered along with immunosuppressant azathioprine (50) once a day for 22 days. Despite this, new lesions continued to develop, so patient was given first dexamethasone azathioprine pulse (DAP) pulse. Side effects like moon face and hyperglycemia developed due to long-term steroids and injection. Insulin was given to counteract this side effect.
Figure 1: Case 1 Pemphigus vulgaris/11yrs/F, Scalp, body, and oral erosions and crusting

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Case 2

A 12-year-old male presented to the skin OPD with fluid filled lesions over scalp and skin since 14 months and oral lesions since 6 months (PAAS-16) [Figure 2]. The patient was diagnosed as having pemphigusvulgaris that was confirmed with tzanck and biopsy. The patient was given injectable dexamethasone (1 cc) IV twice a day that was gradually tapered along with immunosuppressant azathioprine (50) once a day for 20 days. Despite this new lesions developed along with side effects of steroids such as moon face, weight gain, cushingoid features and atrophy. So, patients were given DAP pulse. On the 1st day of pulse therapy, the patient developed side effects such as tachycardia, hypertension, and chest pain. So, the pulse therapy was stopped, and the patient was considered for rituximab.
Figure 2: Case 2 Pemphigus vulgaris/12yrs/M, Scalp, body, oral and genital erosions

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Case 3

A 9-year-old female presented with fluid filled lesions over scalp and body since 6 months and oral lesions since 1-month (PAAS 16) [Figure 3]. Patient was diagnosed as having pemphigusvulgaris that was confirmed with tzanck and biopsy. The patient was given injectable dexamethasone (1 cc) IV once a day that was gradually tapered over a 30 day period. New lesions continued to develop along with steroid side effects such as weight gain and cushingoid features. So, the patient was considered for rituximab.
Figure 3: Case 3 Pemphigus vulgaris/9yrs/F, Scalp, oral and body crusts

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Case 4

A 12-year-old male presented with fluid filled lesions over scalp and skin since 7 months (99% bovine serum albumin [BSA]) [Figure 4]. The diagnosis was confirmed as pemphigus foliaceous by tzanck and biopsy. The patient was given injectable dexamethasone (1 cc) IV once a day which was gradually tapered over a 30 days period. New lesions continued to develop along with steroid side effects such as weight gain and cushingoid features. So, patient was considered for rituximab.
Figure 4: Case 4 Pemphigus foliaceous/12yrs/M, Scalp, body crusts

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Case 5

A 9-year-old boy presented with fluid filled lesions over scalp, perioral, anogenital, chest, back, abdomen and extremities in a cluster of jewel pattern since past 1½ year (70% BSA) [Figure 5]. Diagnosis of chronic bullous disease of childhood was confirmed by biopsy. The patient was given oral steroid that was gradually tapered along with oral dapsone. But, on tapering the dose of steroid, new crops continued to occur along with side effects of dapsone like hemolytic anemia. So, the patient was given four doses of rituximab at an interval of 15 days.
Figure 5: Case 5 Chronic bullous disease of childhood/9yr/M/bullous lesions arranged in a “string of pearls” pattern

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Prerituximab Investigations

  • Complete blood count (hemoglobin [Hb], total count [TC], differential count [DC], platelet count)
  • Random blood sugar
  • Complete urinalysis
  • Renal function tests
  • Liver function tests
  • Desmoglein (DSG) levels (1 and 3)
  • Serum, electrolytes (Na +, K +, Cl)
  • X-ray chest (posterioranterior printarticle.asp?issn=2319-7250;year=2016;volume=17;issue=2;spage=104;epage=107;aulast=Buch view)
  • Electrocardiogram
  • Screening for hepatitis B surface antigen, anti-Hbc, anti-hepatitis C virus, HIV-1 and HIV-2.


Treatment

Premedicate with:

  • Hydrocortisone 100 mg IV stat
  • Pheniramine maleate 22.75 mg IV stat
  • Paracetamol 500 mg orally single dose
  • Thirty minutes prior to rituximab infusion.


Method

  • Pretreatment DSG 1 and 3 and differential item functioning (DIF)
  • Three hundred milligram IV infusion in children over 5–6 h duration
  • Two doses of rituximab were given at 15 days interval
  • DSG 1 and 3 and DIF were repeated after 1-month of the second dose of rituximab
  • Follow-up (weekly for 1-month, fortnightly for next 2 months).[1]


Postrituximab Investigations

  • Complete blood count (Hb, TC, DC, platelet count)
  • Random blood sugar
  • Complete urinalysis
  • Renal function tests
  • Liver function tests
  • DSG levels (1 and 3)
  • Serum, electrolytes (Na +, K +, Cl)
  • X-ray chest (PA view)
  • Electrocardiogram.



  Results Top


[Table 1].
Table 1: Results

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Remission data

[Table 2].
Table 2: Remission data

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  Discussion Top


Rituximab, a chimeric monoclonal anti-CD20 antibody, acts by cell-mediated and complement dependent cytotoxicity.[1] All cases were treated with conventional modalities before rituximab therapy. On review of the literature, we came across only seven cases of childhood pemphigus treated with rituximab.[2],[3],[4],[5],[6],[7],[8],[9] Two of these cases were PF and five were PV. All cases of childhood pemphigus were treated with conventional modalities before rituximab therapy. These cases were generally resistant to conventional treatments or had severe adverse effects with these therapies. Most of the cases were treated with multiple infusions of rituximab with or without IV immunoglobulin. None of these cases showed any serious long-term adverse effects. In our study, all five patients were in complete remission after the 1 year follow-up period, along with a consensual decline of the serum anti DSG titers and are maintained on low dose steroid (5–10 mg) ± immunosuppressant (azathioprine/dapsone).


  Conclusion Top


Rituximab can be considered as an effective adjuvant therapy when treating resistant vesiculobullous disorders in pediatric patients. However, more number of patients and long-term follow-up is required to draw a definite conclusion.

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.

The authors have obtained appropriate patient consent for the information published in this article.

Financial Support and Sponsorship

Nil.

Conflicts of Interest

The authors have obtained appropriate patient consent for the information published in this article.

 
  References Top

1.
Kanwar AJ, Vinay K. Rituximab in pemphigus. Indian J Dermatol Venereol Leprol 2012;78:671-6.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
2.
Kanwar AJ, Sawatkar GU, Vinay K, Hashimoto T. Childhoodpemphigus vulgaris successfully treated with rituximab. Indian J Dermatol Venereol Leprol 2012;78:632-4.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
3.
Reguiai Z, Tabary T, Maizières M, Bernard P. Rituximab treatment of severe pemphigus: Long-term results including immunologic follow-up. J Am Acad Dermatol 2012;67:623-9.  Back to cited text no. 3
    
4.
Connelly EA, Aber C, Kleiner G, Nousari C, Charles C, Schachner LA. Generalized erythrodermic pemphigus foliaceus in a child and its successful response to rituximab treatment. Pediatr Dermatol 2007;24:172-6.  Back to cited text no. 4
    
5.
Kong HH, Prose NS, Ware RE, Hall RP rd. Successful treatment of refractory childhood pemphgus vulgaris with anti-CD20 monoclonal antibody (rituximab). Pediatr Dermatol 2005;22:461-4.  Back to cited text no. 5
    
6.
Schmidt E, Herzog S, Bröcker EB, Zillikens D, Goebeler M. Long-standing remission of recalcitrant juvenile pemphigus vulgaris after adjuvant therapy with rituximab. Br J Dermatol 2005;153:449-51.  Back to cited text no. 6
    
7.
Fuertes I, Guilabert A, Mascaró JM Jr, Iranzo P. Rituximab in childhood pemphigus vulgaris: A long-term follow-up case and review of the literature. Dermatology 2010;221:13-6.  Back to cited text no. 7
    
8.
Kanwar AJ, Tsuruta D, Vinay K, Koga H, Ishii N, Dainichi T, et al. Efficacy and safety of rituximab treatment in Indian pemphigus patients. J Eur Acad Dermatol Venereol 2013;27:e17-23.  Back to cited text no. 8
    
9.
Mamelak AJ, Eid MP, Cohen BA, Anhalt GJ. Rituximab therapy in severe juvenile pemphigus vulgaris. Cutis 2007;80:335-40.  Back to cited text no. 9
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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Abstract
Introduction
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