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BRIEF REPORT
Year : 2018  |  Volume : 9  |  Issue : 6  |  Page : 422-425  

Prospective study of pulse therapy in childhood pemphigus disorders


Department of Dermatology, Venereology, and Leprosy, Gandhi Medical College, Hyderabad, Telangana, India

Date of Web Publication5-Nov-2018

Correspondence Address:
Bhumesh Kumar Katakam
Department of Dermatology, Venereology, and Leprosy, Gandhi Medical College, Hyderabad - 500 003, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/idoj.IDOJ_9_18

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   Abstract 


Background: Pemphigus disorders are a group of immunobullous diseases affecting skin and/or mucus membranes. Dexamethasone cyclophosphamide pulse (DCP)/dexamethasone only pulse (DOP) therapy has shown promising results in the management of pemphigus group of diseases in adults. Aim: To evaluate the outcome of pulse therapy (PT) in pediatric cases diagnosed with pemphigus vulgaris (PV). Materials and Methods: Prospective study of 12 pediatric cases of PV from 2010 to 2015 and treated with PT in Gandhi Hospital. The patients were treated with DOP therapy, with a dose of 50 mg of dexamethasone in 250 ml of 5% dextrose in pediatric patients below the age of 12 years and 100 mg of dexamethasone in 500 ml of 5% dextrose for above 12 years, for three consecutive days. No interpulse steroids or rituximab were given to any patients in our study. Results: Out of 12 cases, 10 were female and 2 were male children. Four cases were below the age of 12 years and 8 cases were above the age of 12 years. The lowest age was 11 years female and highest age was 16 years male child. Average duration of illness is between 4 and 6 months. Six cases completed three phases, four cases were in phase II cycle 7, and two cases were in phase IV. In majority of cases clinical improvement was observed between 2 and 4 pulses in phase I. No significant adverse effects were observed in any case except in two cases who developed headache, shivering, and nausea in first one to two pulses of phase I and managed conservatively. Conclusion: Our study shows that PT gives good response in the management of pemphigus in children, in terms of remission and side effects. There was no significant major adverse effect as observed in adults. In low-resource centers such as government institution, PT would be one option. Further studies and long-term follow-up are required to weigh the risks and benefits of PT in pediatric age group.

Keywords: Children, dexamethasone pulse therapy, pemphigus vulgaris


How to cite this article:
Katakam BK, Kavitha S B, Rao Netha G N, Shahana M, Sri T S, Vani D S. Prospective study of pulse therapy in childhood pemphigus disorders. Indian Dermatol Online J 2018;9:422-5

How to cite this URL:
Katakam BK, Kavitha S B, Rao Netha G N, Shahana M, Sri T S, Vani D S. Prospective study of pulse therapy in childhood pemphigus disorders. Indian Dermatol Online J [serial online] 2018 [cited 2018 Dec 12];9:422-5. Available from: http://www.idoj.in/text.asp?2018/9/6/422/245018




   Introduction Top


Pemphigus disorders are a group of serious and potentially life-threatening disorders characterized by asymptomatic blisters in the skin and/or mucus membranes.[1] Dexamethasone cyclophosphamide pulse (DCP) therapy was designed by Pasricha et al., at All India Institute of Medical Sciences (AIIMS), New Delhi, that revolutionized the management of pemphigus since its introduction in 1986.[2],[5] If properly used, DCP therapy has the potential of effective lifelong remission from these diseases.[3] Apart from pemphigus disorders, DCP therapy was also found to be effective in pemphigoid disorders, systemic sclerosis, systemic lupus erythematous, etc.[4] Here, we report the outcome of dexamethasone only pulse (DOP) therapy in 12 pediatric patients with pemphigus vulgaris (PV) in terms of remission, side effects, and relapse.


   Materials and Methods Top


In this prospective study of 12 pediatric cases of PV, treatment was started on pulse therapy (PT) in Gandhi Hospital from 2010 to 2015.

Inclusion criteria

Children up to the age of 18 years were taken up for the study.

Exclusion criteria

Those who are not willing to participate were excluded from the study. Predesigned and pretested proforma was filled after taking informed consent. Privacy and confidentiality were maintained. Detailed history and thorough clinical examination were carried out in each patient. Information was recorded using semi-structured questionnaire guidelines by using local vernacular language. A total of 12 pediatric (below 18 years of age) cases of PV were diagnosed based on clinical features of asymptomatic flaccid blisters, spreading erosions and positive Nikolsky's sign, Tzanck smear (acantholytic cells), histopathology (intraepidermal cleft with or without acantholytic cells and row of tomb stone appearance of basal keratinocytes), and direct immunofluorescence of the skin or mucosal lesions. The severity of skin involvement was categorized as mild, with <20 blisters, moderate with 20–40 blisters, and severe with >40 blisters. Mucosal involvement was categorized as mild, with 1–5 lesions, moderate with 5–10 lesions, and severe with >10 lesions or extensive erosions.[5] All cases were admitted in hospital for prepulse basic evaluation based on investigations such as complete blood picture (CBP), erythrocytic sedimentation rate (ESR), blood urea, sugar, liver function tests (LFT), serum electrolytes, chest X-ray, complete urine examination (CUE), stool analysis, electrocardiography (ECG), and two-dimensional echo along with cardiology opinion for fitness to carry out PT. Bacterial culture and sensitivity were done from infected skin lesions. Patients were started on DOP with 50 mg of dexamethasone in 250 ml of 5% dextrose in children below the age of 12 years, and 100 mg of dexamethasone in 500 ml of 5% dextrose in above 12 years children for three consecutive days, which was designed by Pasricha.[5] Drip was administered as a slow intravenous infusion over 2 h for three consecutive days. DOP therapy was repeated every 28 days for 18 months (phases I and II). Patients were followed up in the third (9 months) and fourth phase (2 years) without PT. Intrapulse monitoring was done by way of pulse rate, blood pressure (BP), temperature, and general condition. Postpulse monitoring was done by detailed evaluation of CBP, ESR, serum electrolytes, LFT, renal function tests, ECG, and CUE. We monitored the complications such as focus of infections either in blood (leukocytosis or raised ESR) or in urine (pus cells), hemoglobin level, platelet count, and serum electrolytes and treated accordingly. We discharged the patients only after fitness based on clinical and laboratory evaluation. During the first 1–3 months (phase I), patients continued to develop clinical lesions in-between DOPs. We assured the patients and continued PT for 9 months. Later, the patient was shifted to phase II. In phase II, nine more DOPs were administered. In phase III, DOPs were stopped and the patients were advised for follow-up every month. In phase IV, all treatments were stopped, and patients were followed up as long as possible to look for any tendency to relapse. If a patient did not develop a relapse for 2 years after complete withdrawal of treatment, he was declared to be cured of disease. Data regarding the age, gender, age of onset of disease, clinical details about the disease, previous treatment details, phases of therapy, remission, relapse, cure, default and reasons for default, death and causes of death, and adverse effects of therapy were recorded in pulse monitoring chart. After completion of 3 days pulse laboratory investigations were repeated such as urine analysis, stool analysis, hemoglobin, total and differential leukocyte counts, platelet counts, blood sugar, blood urea, serum creatinine, serum electrolytes, and LFTs. Any alterations from the standard normal values were noted.


   Results Top


Out of 12 cases, 10 were females and 2 were male children [Chart 1]. Four cases were below the age of 12 years and eight cases were above the age of 12 years [Chart 2]. The lowest age was 11 years female and highest age was 16 years male child. Average duration of illness is between 4 and 6 months. Six cases were mild, four cases were moderate, and two cases were severe [Chart 3]. Eleven cases were associated with mucosal and skin lesions and in one case presented with only mucosal lesion of mild variety. The gap between mucosal and skin lesions was about 3–6 months. Four cases were in phase II cycle 7 without any lesions, six cases in phase III cycle 8, and two cases were in phase IV [Chart 4] beyond 3 years with good remission (no new lesions in 2 years). Clinical improvement was assessed based on clinical features such as appearance of no new bullae, absence of spreading erosions, negative Nikolsky's sign, clearing of oral erosions, and improvement of general condition of the patients. Clinical improvement was observed by the end of 2, 3, and 4 pulses (phase I) in mild, moderate, and severe cases [Figure 1]a and b, before and after treatment], respectively. Skin lesion improvement was seen earlier than mucosal lesions. During intrapulse no significant adverse effects were observed in any case, except in two cases headache, shivering, and nausea in first one to two pulses of phase I were observed and managed conservatively. In two cases we observed hypokalemia (3 mEq/l) in postpulse, and such cases were treated with syrup potassium chloride 5 ml (tid) mixed with water or milk along with plenty of oral fluids and supplemented with tender coconut water, bananas. We discharged the patients based on clinical and laboratory monitoring. We advised the patients to follow strictly 28 days cycle to decrease relapses and prolong remission. For all children and their parents counseling was given during early cycles of phase I, where they were suffering with clinical lesions. The reason behind was no patient is going to follow the instructions of doctor when they are free from disease. In spite of proper counseling, we observed two relapses in phase II, they missed three cycles. We restarted PT from phase I. Now they are doing well. No interpulse steroids or rituximab were given to any patients in our study. But in our institution, those who are not responding with PT, we will give intermittent rituximab in adults. The results are encouraging. All patients were under follow-up from 2010 to 2015. Relapse is seen even after DCP and rituximab therapy.
Figure 1: Severe PV – 9-year-old female child: Erosions in oral cavity. (b) Severe PV – 9-year-old female child: All lesions were cleared after four pulses (phase I)

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   Discussion Top


PT means administration of large (supra-pharmacologic) doses of drugs in an intermittent manner to enhance the therapeutic effect and reduce the side effects. PT in pediatric age (below 12 years of age) is DOP only, with half of the adult dose (50 mg of dexamethasone in 250 ml of 5% dextrose) for three consecutive days was given. The pulses are repeated strictly every 28 days. The insistence on a strict 28-day cycle for pulses is based on the observation that relapses were commoner in those who took pulses irregularly as observed in two cases of our study. PT has been used mainly in autoimmune diseases, and found to be an effective therapy. DCP is the preferred mode of therapy in adults with pemphigus group of disorders in India because it is relatively cost-effective and free from side effects in comparison with oral steroids.[5]

In our study, children with pemphigus who did not respond to conventional steroid therapy were started on PT (DOP), which showed good response after two cycles with minimal side effects, because the PT regimen virtually cures every pemphigus patient for the rest of his life and there are almost no side effects, as observed in our study also, in terms of prolonged remission (four cases in phase II, six in phase III, and two cases in phase IV) and without major side effects. All pemphigus patients deserve to be treated with this regimen irrespective of age, sex, or severity of disease. Patients on conventional steroid therapy and under remission may be started on PT with gradual tapering of oral steroids.[5]

There are almost no contraindications for PT. It can be given to all pediatric patients but the doses have to be reduced to half for children (DOP) below the age of 12 years. To achieve good response in pemphigus, the standard course of PT has to be followed strictly. If the treatment is stopped after completing phase I as noted in two cases of our study, almost every patient is expected to develop a relapse. Compromises of any kind lead to inferior results and increase the chances of a relapse. The relapse rates during follow-up were 53.8% with incomplete treatment, 18.2% with irregular intervals, and 8% with regular intervals (exactly 28-day cycles), as observed by Pasrichaalso.[5]

Clinical improvement was observed based on severity of disease. There was early improvement noted in mild cases compared with moderate to severe cases.

PT is useful in almost all the autoimmune and several other corticosteroid responsive dermatoses, and the side effects are less common than conventional daily dose regimens of corticosteroid administration. (From authors' personal experience, PT treatment has been given for adults and children since more than 10 years in their institution.) To achieve optimum results, it is important to strictly follow the regimen. Any compromises have produced inferior results. There are no significant major adverse effects as compared to adults in our study. Further studies are required to weigh the risks and benefits of PT in pediatric age group, though it has a prolonged remission for autoimmune diseases.[5]

The major limitation of this study is the very small sample size of 12. Large cohort studies are required for clinical assessment and to observe side effects.


   Conclusion Top


Systemic corticosteroids are main stay of therapy for PV but long-term use is often necessary for adequate control. Adverse effects from therapy can have devastating effects during the critical period of growth that occurs during adolescence. In low-resource centers such as government institutions, PT would be one option.

Newer therapies must be designed to adequately treat juvenile patients while also limiting serious adverse effects. PT (DP) in children appears to be advantageous by inducing remission than the conventional therapy in pemphigus patients. Our study shows that PT gives good response in the management of pemphigus in children, in terms of remission, side effects, and cost-effectiveness. There were no significant major adverse effects compared to adults. Further studies are required to weigh the risks and benefits of PT in pediatric age group.

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.
Huilgol SC, Black MM. Management of the immunobullous disorders. II. Pemphigus. Clin Exp Dermatol 1995;20:283-93.  Back to cited text no. 1
    
2.
Rao PN, Lakshmi TS. Pulse therapy and its modifications in pemphigus: A six year study. Indian J Dermatol Venereol Leprol 2003;69:329-33.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Pasricha JS, Poonam. Current regimen of pulse therapy for pemphigus: Minor modifications, improved results. Indian J Dermatol Venereol Leprol 2008;74:217-21.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Ramam M, Bhat R. Pulse therapy in other diseases. In: Pasricha JS, editor. Pulse Therapy in Pemphigus and Other Diseases. 3rd ed. New Delhi: Mehta Publishers; 2006. p. 91-5.  Back to cited text no. 4
    
5.
Pasricha JS. Pulse therapy as a cure for autoimmune diseases. Indian J Dermatol Venereol Leprol 2003;69:323-8.  Back to cited text no. 5
[PUBMED]  [Full text]  


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