Pemphigus vulgaris
BMJ 2007; 335 doi: https://doi.org/10.1136/bmj.39374.504884.BE (Published 29 November 2007) Cite this as: BMJ 2007;335:1152
All rapid responses
Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
I was particularly distressed and anguished by the fact that in the year 2007, this lady is still feeling desperate about the cure for pemphigus, whereas we have been curing pemphigus patients in India for the last 25 years and published several papers in a variety of International and Indian journals.1-8
Following our reports several centres in India 9-15 have also been using the same method and obtaining similar results, although those who have not used the parameters properly are not expected to achieve the optimum results.8,16
Our method of treatment is called the Dexamethasone Cyclophosphamide Pulse (DCP) therapy regimen and is administered in 4 phases. During phase I, the patient receives aggressive treatment to recover from the disease, and after the patient has recovered, all the additional drugs are step-wise withdrawn completely. This phase generally lasts 3-6 months though in some patients it may last longer. During the second and the third phases, the patient remains clinically completely alright, but has to complete these phases (9 months each). These phases of treatment are considered necessary to eradicate the auto-immunity and thus prevent a relapse in the future. The fourth phase is only a post-treatment follow up period to ensure that the patient has actually not developed the disease again. We like to have a follow up of at least 10 years to ensure that the patient has indeed been cured.
We first used the DCP regimen for pemphigus in 1982 and during the next 15 years or so, we enrolled 500 pemphigus patients for this treatment. (Pemphigus is far more common among the Indians and we get patients referred to us from far and wide). Meticulous records were maintained for each of these patients and an attempt has been made to follow up as many of these patients for as long as possible.
In this batch of 500 patients, 57 patients did not take our treatment and 18 patients died, but all the remaining 425 patients are in complete remission without any maintenance treatment and are living like normal individuals. In 236 (55.6%) of these patients, it has been possible to confirm that they are indeed living like normal individuals without taking any treatment for pemphigus and have not developed a relapse for at least 10 years after complete withdrawal of all treatment. In several of these patients the confirmed duration of post-treatment follow up period is 20 years (maximum 22 years). In another 77 (18.1%) patients, the duration of post-treatment disease free period is between 5 and 10 years, and in 33 (7.8%) patients between 2-5 years. In the remaining patients, the duration of post-treatment follow up is less than 2 years because we have lost further contact with them but presumably they are also in remission.
In this group, most of the patients did not follow our instructions strictly (some of them did not even complete the treatment, some others were irregular in reporting for the treatment and a few were treated with only one drug). The relapse rate therefore in this group was high (A total of 108 patients so far developed a relapse), but a second course led to recovery all over again.
After retirement from the AIIMS in 1998, the DCP regimen is being administered in the private clinic which is only a Day-care centre. The procedure is as simple as reporting to the clinic for receiving the infusion and going back home to attend to the routine duties, and report back the next day for the next dose. Most of the patients do not require even admission into the hospital or any specific monitoring.
We have recently analysed our results in 143 pemphigus patients who reported to us between 1998 and 2002. Of these, 17 patients did not take the treatment and 3 patients died. The remaining 123 patients received the treatment and the compliance was better. The duration of phase I in this group was 3 months in 62 patients and 4-5 months in 28. The remaining patients needed more treatment to recover. A total of 11 patients (some of them defaulters and a few treated with only dexamethasone pulses) have developed a relapse, but have recovered again on further treatment. All these patients are also in remission at present and the duration of post-treatment disease-free period in this group has been more than 5 years in 62 patients, 3-5 years in 41 patients, and 2-3 years in 3 patients.
The side effects with the DCP regimen are far infrequent and insignificant if the regimen is used as per our parameters.
We would like to ask all the dermatologist colleagues that if a pemphigus patient does not develop a relapse of the disease for 5 years without any maintenance treatment, is this not sufficient evidence that pemphigus has been cured in this patient. And if the duration of post-treatment follow up is more than 10-20 years, should there be any doubt that the disease has indeed been eliminated. And in case such a result can be produced in almost every patient does anybody require a better evidence.
We would leave it to the dermatologists to make up their mind, but they should remember that their prejudices and other considerations, do effect the lives of their patients as has unfortunately happened to Ms Lowe. The patients also have their right to take their own decisions.
If any dermatologist is interested in learning the technique and see the patients recovering from pemphigus, they are most welcome.
J. S. Pasricha, Poonam
Skin Diseases Centre, 1-A, Masjid Moth, DDA Flats, Phase I, Outer Ring Road, Near Chirag Delhi Flyover, New Delhi-110048, India.
Address for correspondence: Dr. J. S. Pasricha, Skin Diseases Centre, 1-A, Masjid Moth, DDA Flats, Phase I, Outer Ring Road, Near Chirag Delhi Flyover, New Delhi-110048, India.
E-mail:j_s_pasricha@hotmail.com
REFERENCES
1. Pasricha JS, Gupta Ramji. Pulse therapy with dexamethasone-cyclophosphamide in pemphigus. Indian J Dermatol Venereol Leprol 1984; 50: 199-203.
2. Pasricha JS, Srivastava G. Cure in pemphigus – a possibility. Indian J Dermatol Venereol Leprol 1986; 52: 185-186.
3. Pasricha JS, Thanzama J, Khan UK. Intermittent high dose dexamethasone-cyclophosphamide pulse therapy for pemphigus. Brit J Dermatol 1988; 119: 73-77.
4. Pasricha JS, Seetharam KA, Das Urmimala. Further studies on pemphigus patients treated with dexamethasone-cyclophosphamide pulse therapy for pemphigus. Indian J Dermatol Venereol Leprol 1989; 55: 98-104.
5. Pasricha JS, Das SS. Curative effect of dexamethasone-cyclophosphamide pulse therapy for the treatment of pemphigus vulgaris. Internat J Dermatol 1992; 31: 875-877.
6. Pasricha JS, Khaitan BK, Shantha Raman R, Chandra M. Dexamethasone-cyclophosphamide pulse therapy for pemphigus. Internat J Dermatol 1995; 34: 875-882.
7. Pasricha JS, Khaitan BK. Curative treatment for pemphigus. Arch Dermatol 1996; 132:1518-1519.
8. Pasricha JS. Pulse Therapy in Pemphigus and Other Diseases. Third ed. Pulse Therapy and Pemphigus Foundation. New Delhi; 2006.
9. Surrinder K, Kanwar AJ. Dexamethasone-cyclophosphamide pulse therapy in pemphigus. Internat J Dermatol 1990; 29: 371-374.
10. Roy R, Kalla G. Dexamethasone-cyclophosphamide pulse (DCP) therapy in pemphigus. Indian J Dermatol Venereol Leprol 1997; 63: 354-356.
11. Singh IP, Mehta SD. Pulse therapy in pemphigus vulgaris. Indian J Dermatol 1996; 41: 31-32.
12. Masood Q, Hassan I, Majid I et al. Dexamethasone cyclophosphamide pulse therapy in pemphigus. Experience in Kashmir Valley. Indian J Dermatol Venereol Leprol 2003; 69: 97-99.
13. Narasimha Rao P, Laxmi TSS. Pulse therapy and its modification in pemphigus. A six year study. Indian J Dermatol Venereol Leprol 2003; 69: 329-333.
14. Kanwar AJ, Kaur S, Thami GP. Long-term efficacy of dexamethasone- cyclophosphamide pulse (DCP) therapy in pemphigus. Dermatology 2002; 204: 228-231.
15. Sacchidanand S, Hiremath NC, Natraj HV et al. Dexamethasone cyclophosphamide pulse therapy for autoimmune vesiculobullous disorders. Dermatology Online Journal 9 (5): 2.
16. Toth GG, Van der Meer JB, Jonkman MF. Dexamethasone pulse therapy in pemphigus. J Eur Acad Dermatol Venereol 2002; 16: 607-611.
Competing interests:
None declared
Competing interests: No competing interests
SIR,
the “Patient’s journey” on pemphigus vulgaris (PV) on the 1st December
issue has impressed us (1). The way Siri has faced the disease should
serve as a model for all the patients affected by PV. We have been studying
pemphigus for years, and know well that despite the impressive progress in
dealing with PV, no current treatment addresses the basic pathophysiology
of the disease (2). We are sceptical, in fact, about the actual
effectiveness of novel therapies such as rituximab and intravenous
immunoglobulin (IVIg), that are mentioned in the cited article. Our doubts
refer both to the scientific and economic aspect. Although the treatment
options available for PV patients are expanding, there are still few
randomized, controlled trials to evaluate the true effectiveness of such
therapies. To complicate matters, disparity exists regarding the general
interest in the alternative treatments. For instance, clinical studies on
novel immunosuppressants such as mycophenolate mofetil, that has shown
beneficial effects in multiple case series, are not adequately funded by
pharmaceutical industry. On the contrary, both industry and medical
literature appear to care more about rituximab and IVIg, which are to date
considered fully effective, despite the lack of strong scientific evidence
and large follow-up studies. May the expensiveness of IVIg and rituximab
be relevant to this regard? In addition, despite having a public National
Health Service, in UK (as all over the world) the chances of getting them
paid for are very slim. As a consequence, “biologic” treatment is actually
an elite treatment.
Pemphigus therapy could rely on alternative drug regimens that, if
adequately substantiated by further scientific evidence, would be of great
benefit for patients. For instance, Grando has described 6 patients with
PV who were treated with the cholinergic agonist pyridostigmine bromide
(Mestinon) (3). Nevertheless, neither NIH nor industry are currently
investing on such a dug.
To date, novel potential therapies intercepting intracellular
signaling evoked by PV IgG include p38MAPK inhibitors (4) and the cyclin-
dependent kinase inhibitor roscovitine (Lanza et al, submitted). Both
drugs have been shown to prevent blister formation in mice. Therefore, we
are confident that these recent discoveries will be able to give new hopes
to all patients with PV.
References
1. Lowe S. Pemphigus vulgaris. BMJ 2007;335:1152-4.
2. Lanza A, Cirillo N, Femiano F, Gombos F. How does acantholysis occur in
pemphigus vulgaris: a critical review. J Cutan Pathol 2006;33:401-12.
3. Grando SA. New approaches to the treatment of pemphigus. J Invest
Dermatol Symp Proc 2004;9:84-91.
4. Berkowitz P, Hu P, Warren S, Liu Z, Diaz LA, Rubenstein DS. p38MAPK
inhibition prevents disease in pemphigus vulgaris mice. Proc Natl Acad Sci
U S A 2006;103:12855-60.
Competing interests:
None declared
Competing interests: No competing interests
Pemphigus is Responding to DCP
Our patients at Nisarg Skin Institute and My Skin City at Surat-Gujarat-India have been responding very well to Dexamethasone Cyclophosphamide Pulse (DCP) therapy regimen since 1988. We have treated nearly 88 patients with this Dexamethasone Cyclophosphamide Pulse (DCP) therapy regimen and barring a few side effects they are doing really well. You may find plenty of references to this Dexamethasone Cyclophosphamide Pulse (DCP) therapy regimen various Indian and International Journals.
Dr. Rajesh M. Buddhadev
E mail- buddhadev1@gmail.com
Competing interests:
None declared
Competing interests: No competing interests