|Year : 2018 | Volume
| Issue : 6 | Page : 405-408
Factors affecting the duration of phase 1 of dexamethasone-immunosuppressant pulse therapy for pemphigus group of disorders: A 10-year retrospective study in a tertiary care center
Vidya Mundakkat, Rajiv Sridharan
Department of Dermatology, Academy of Medical Sciences, Kannur, Kerala, India
|Date of Web Publication||5-Nov-2018|
Department of Dermatology, Academy of Medical Sciences, Pariyaram, Kannur - 670 503, Kerala
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Context: Dexamethasone-immunosuppressant pulse therapy introduced by Pasricha et al. in 1981 as a treatment for long-term remission in pemphigus group of disorders has gained wide acceptance in many places, especially India. Since the overall duration of treatment is determined by the duration of phase 1 of the regime, identification of factors that influence phase 1 may be particularly helpful in addressing patient's concerns and apprehensions before initiation of treatment so that compliance can be improved. Aims: To find out factors that affect the duration of phase 1 of dexamethasone-immunosuppressant pulse therapy. Subjects and Methods: A 10-year retrospective study from medical records of 37 patients was conducted. The severity of pemphigus was assessed using Kumar's scoring system. The mean duration of phase 1 compared between the variables and significance of association was found out using Student's t-test. Patients were further classified in to two groups: with phase 1 duration ≤6 months and >6 months. Chi-squared and Fisher's exact tests were done to find out factors which significantly contribute to prolonged induction phase. Results: A significant association was noticed between total severity score and mean duration of phase 1 (P = 0.031). Significant association was also noticed between prolonged induction phase of >6 months and oral mucosal severity score >2 (P = 0.017). Other patient factors, type of pulse therapy, and comorbidities had no effects on the duration of phase 1. Conclusions: Duration of phase 1 is expected to prolong if the total severity score is >3, and when oral severity score is >2 it is likely to be more than 6 months.
Keywords: Kumar's score, oral severity score, phase 1 of dexamethasone-immunosuppressive therapy
|How to cite this article:|
Mundakkat V, Sridharan R. Factors affecting the duration of phase 1 of dexamethasone-immunosuppressant pulse therapy for pemphigus group of disorders: A 10-year retrospective study in a tertiary care center. Indian Dermatol Online J 2018;9:405-8
|How to cite this URL:|
Mundakkat V, Sridharan R. Factors affecting the duration of phase 1 of dexamethasone-immunosuppressant pulse therapy for pemphigus group of disorders: A 10-year retrospective study in a tertiary care center. Indian Dermatol Online J [serial online] 2018 [cited 2019 Feb 23];9:405-8. Available from: http://www.idoj.in/text.asp?2018/9/6/405/245015
| Introduction|| |
Pemphigus is a group of immune bullous disorders where autoantibodies are generated against the intercellular adhesion molecules (desmosomes) and as a result intraepidermal blisters are developed. It is a potentially life-threatening condition. The case fatality rate in a retrospective study conducted at Trivandrum was 7.65%. The incidence in Thrissur, Kerala was found to be 4.4 per million in one study and the incidence in India varies from 0.09% to 1.8%. Before 1981, systemic steroids in high doses were widely used for the treatment. Even though the treatment results were better, the drug-related side effects were also higher. The introduction of dexamethasone-cyclophosphamide pulse therapy (DCP) by Pasricha et al. in 1981 revolutionized the treatment for pemphigus. It is administered in 4 phases. In phase 1 (induction phase), the patient is given treatment till he/she attains clinical remission in the absence of any additional treatment, conventionally oral steroids. The duration of phases except phase 1 is fixed. Therefore, the overall duration is determined by the duration of phase 1. The regimen is followed with minor modifications such as replacing cyclophosphamide with other immune suppressants.,,,
The severity of pemphigus is assessed by different scoring systems. Autoimmune bullous skin disorder intensity score, pemphigus disease area index, pemphigus area and activity score, Ikeda index, Saraswat's oral pemphigus scoring, Harman's pemphigus grading, Kumar's scoring system, and Mahajan's scoring system are some among them.,
Studies evaluating the factors affecting the duration of induction phase and comparative studies between different combinations of dexamethasone and immune suppressants are less. Since DCP is a long-term treatment, there is a chance for poor patient compliance. If we can find out the expected duration of completion of therapy, it is possible to counsel the patient accordingly. Since the overall duration of treatment is determined by the duration of the induction phase, the identification of factors that influence the induction phase will be helpful in proper management in terms of patient counseling and modification of risk factors.
| Subjects and Methods|| |
The study was conducted in the Department of Dermatology, Venereology, and Leprosy of a tertiary care hospital. This 10-year retrospective study included 37 patients with a diagnosis of pemphigus group of disorders during the time period of January 1, 2008 to December 31, 2017. Ethical clearance was obtained from the Institutional Research and Ethics Committee.
Data collected from the old records included the demographic profile, diagnosis, extent of skin and mucosal involvement at baseline, duration of illness, treatment history, history of any comorbidities, family history of pemphigus disorder, type of pulse therapy, and duration of the induction phase. Relevant investigations were also noted. Diagnosis was made on clinical, histopathological, and/or immunofluorescence basis. Baseline clinical severity was assessed by Kumar's scoring system [Table 1].
Modified DCP regimen by Pasricha was used for the treatment with substitution of cyclophosphamide with azathioprine in 7 patients who had not completed their family, to avoid gonadal suppression. All patients received interpulse treatment with tapering doses of oral steroids to accelerate remission. Patients who took irregular treatments or who discontinued treatment were excluded from the study.
Statistical analysis was done using SPSS version 24 (Kerala State Co-operative Hospital Complex and Centre for Advanced Medical Sciences Ltd., Kannur, India). P value was calculated using t-test, Chi-squared test, and Fisher's exact test to find out the significance of association.
| Results|| |
A total of 37 patients were included in this study with a mean age of 44.54 ± 12.96 years. About 78.4% of patients were females. There were 30 (81.1%) cases of pemphigus vulgaris, 1 (2.7%) case of pemphigus vegetans, 5 (13.5%) cases of pemphigus foliaceus, and 1 (2.7%) case of pemphigus erythematosus. The median skin lesion score was 2 with interquartile range of 1. About 86.5% of patients had a skin lesion score of ≤2, whereas only 13.5% had a skin lesion score >2. The median oral lesion score was 1 with an interquartile range of 2. In addition, 75.7% of patients had an oral lesion score ≤2 and 24.3% had an oral lesion score >2. The median total score (skin lesion score + oral lesion score) was three with an interquartile range of 2. About 56.8% of patients had a total score of ≤3 and 43.2% had >3. One (5.7%) patient had conjunctival and 3 (8.1%) patients had genital mucosal involvement. None of the patients had anal mucosal involvement. Twenty-five (67.6%) patients had single mucosal involvement. Seven (18.9%) patients had 2 mucosal and 5 (13.5%) had no mucosal involvement. Twenty-four (64.9%) patients had scalp involvement. Prepulse duration of illness varied from 0.25 to 72 months with a mean duration of 11.63 ± 16.98. In total, 64.9% of patients had taken some form of specific systemic treatment for pemphigus before starting pulse therapy. About 16.2% had hypertension, 8.1% had diabetes, 2.75% had dyslipidemia, 16.2% had atopy, 10.8% had hypothyroidism, 5.4% were smokers, and 8.1% were alcoholic. None of the patients had a family history of bullous disorders. About 81.1% received DCP and 18.9% received dexamethasone-azathioprine pulse therapy (DAP). Duration of phase 1 varied from 2 to 18 months with a mean duration of 6.38 ± 2.95 months.
While looking for the factors affecting the duration of phase 1 [Table 2], a significant association was noticed between the mean duration of phase 1 and total severity score (P = 0.031, t-test). Other factors like age, sex, type of pemphigus (subcorneal, suprabasal), skin lesion score, oral lesion score, number of mucosal sites involvement, scalp involvement, prepulse duration of illness, history of other specific systemic treatment prior to pulse therapy, type of pulse therapy, history of hypertension, diabetes, dyslipidemia, atopy, hypothyroidism, smoking, and alcoholism were not found to significantly affect the duration of phase 1 even though a noticeable difference with higher duration of phase 1 was observed among patients with age >45 years, female sex, oral lesion score >2, total mucosal site involvement >1, suprabasal type of pemphigus, associated scalp involvement, prepulse duration of illness >12 months, history of diabetes mellitus (DM), and dyslipidemia. A higher duration was also observed among patients receiving DCP pulse compared to DAP pulse.
To find out the factors responsible for a prolonged induction phase (duration >6 months), patients were classified into 2 groups: those having a phase 1 duration of ≤6 months and >6 months; Chi-squared test and Fisher's exact test were done to find out the P value. A significant association was noticed with an oral lesion score of >2 and phase 1 duration of >6 months (P = 0.017) [Figure 1]. Other factors like age, sex, type of pemphigus (subcorneal or suprabasal), skin lesion score, total score, number of mucosal sites involvement, scalp involvement, prepulse duration of illness, history of other specific systemic treatment prior to pulse therapy, type of pulse therapy, history of hypertension, DM, dyslipidemia, atopy, hypothyroidism, smoking, and alcoholism were not found to contribute significantly to a prolonged induction phase.
|Figure 1: Correlation of oral lesions with duration of phase 1 of pulse therapy. IP = Induction phase|
Click here to view
| Discussion|| |
DCP is a widely followed therapy for pemphigus even in the present era of biologics. Till now only few studies are available which evaluated the factors affecting the duration of the induction phase. And the comparative studies on the effectiveness of DCP and other steroid-immunosuppressant combinations are also few. Therefore we tried to find out the factors influencing the duration of phase 1 of dexamethasone-immunosuppressant pulse therapy in this retrospective study.
In this study, our main aim was to find out the factors that affect the mean duration of the induction phase and also to find out the factors that predispose to a prolonged induction phase of >6 months. We found that the total severity score significantly increases the mean duration of phase 1 (P = 0.031). Our finding is similar to the studies by Nayak et al. and Kanwar et al. where they found a significant association between severity of disease and duration of phase 1 and contrast to the study by Manzoor et al. where they found no correlation. Age and gender di not significantly affect the mean duration even though age >45 and female sex had a higher mean duration of phase 1. Nayak et al. also noticed a similar finding.
In our study, a prolonged phase 1 of >6 months was found to be significantly associated with an oral mucosal severity score of >2 (P = 0.017) but prepulse treatment with other specific systemic drugs did not have any significant effect on phase 1, whereas no association with oral lesions but significant association with prepulse treatment with steroids was noticed by Nayak et al. In both studies, prepulse duration of illness was not found to alter phase 1 significantly. Skin lesion severity score alone was not found to influence the duration of phase 1 in this study but the total score did, which means that the mucosal severity component is the determinant factor. In our study, majority of patients (59.5) had a phase 1 duration of <6 months, similar to the study by Manzoor et al. where most patients had a phase 1 duration of 3–4 months.
Only few studies have evaluated different combinations of dexamethasone with immune suppressants. In our study, we did not find a significant association between the type of pulse (DCP and DAP) and duration of the induction phase; however, the mean duration was higher among the DCP group. In contrast to this finding, Hassan et al. in their study found a greater duration of phase 1 with DAP regimen. They also found that dexamethasone–methotrexate regimen did not have any additional benefit in poor responders.
In this study, we also evaluated the effect of a number of other variables apart from these, such as the type of pemphigus (subcorneal or suprabasal), total number of mucosal sites involved, scalp involvement, presence of comorbidities like hypertension, diabetes, dyslipidemia, atopy, hypothyroidism, addictions like smoking and alcoholism, but none was found to have any significant association with the duration of phase 1.
| Conclusion|| |
A significant association was noticed with the mean duration of the induction phase and total severity score. Patients with an oral mucosal score of >2 are more likely to have an induction phase duration of >6 months. Other factors like age, sex, type of pemphigus, skin lesion score alone, number of mucosal sites involved, scalp involvement, prepulse duration of illness, prepulse treatment with specific drugs, type of pulse therapy (DCP/DAP), comorbidities, and addictions were not found to have significant association with the duration of the induction phase in this study. We hope that the findings from our study will be helpful in counseling the patient regarding the probable duration of treatment prior to initiation of therapy itself so that the compliance is improved.
The authors acknowledge the help and support of Prof. Usha Karunakaran and Dr. Binoo Divakaran, Department of Community Medicine, Academy of Medical Sciences for statistical analysis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Schmidt E, Groves R. Immunobullous diseases. In: Griffiths CE, Barker J, Bleiker T, Chalmers R, Creamer D, editors. Rook's Textbook of Dermatology. 9th
ed. UK: Wiley Blackwell; 2016. p. 50.1-9.
Nair SP. A retrospective study of mortality of pemphigus patients in a tertiary care hospital. Indian J Dermatol Venereol Leprol 2013;79:706-9.
] [Full text]
Kumar KA. Incidence of pemphigus in Thrissur district, South India. Indian J Dermatol Venereol Leprol 2008;74:349-51.
] [Full text]
Kanwar AJ, De D. Pemphigus in India. Indian J Dermatol Venereol Leprol 2011;77:439-49.
] [Full text]
Pasricha JS. Pulse therapy as a cure for autoimmune diseases. Indian J Dermatol Venereol Leprol 2003;69:323-8.
] [Full text]
Pasricha JS, Poonam. Current regimen of pulse therapy for pemphigus: Minor modifications, improved results. Indian J Dermatol Venereol Leprol 2008;74:217-21.
] [Full text]
Abraham A, Roga G, Job AM. Pulse therapy in pemphigus: Ready reckoner. Indian J Dermatol 2016;61:314-7.
] [Full text]
Rao PN, Lakshmi TS. Pulse therapy and its modifications in pemphigus: A six year study. Indian J Dermatol Venereol Leprol 2003;69:329-33.
] [Full text]
Grover S. Scoring systems in pemphigus. Indian J Dermatol 2011;56:145-9.
] [Full text]
Daniel BS, Hertl M, Werth VP, Eming R, Murrell DF. Severity score indexes for blistering diseases. Clin Dermatol 2012;30:108-13.
Nayak CS, Ray S, Thombre A, Jain M. Factors affecting the duration of phase I of dexamethasone – Cyclophosphamide pulse therapy. Indian J Dermatol Venereol Leprol 2014;80:296-9.
] [Full text]
Kanwar AJ, Kaur S, Thami GP. Long-term efficacy of dexamethasone-cyclophosphamide pulse therapy in pemphigus. Dermatology 2002;204:228-31.
Manzoor S, Bhat Y, Ahmad S, Andleeb M, Inam K. Dexamethasone-cyclophosphamide pulse therapy in pemphigus. Indian J Dermatol Venereol Leprol 2009;75:184-6.
] [Full text]
Hassan I, Sameem F, Masood QM, Majid I, Abdullah Z, Ahmad QM, et al.
Non comparative study on various pulse regimens (DCP, DAP and DMP) in pemphigus: Our experience. Indian J Dermatol 2014;59:30-4.
] [Full text]
[Table 1], [Table 2]