Brief Answer:
Pemphigus; increase Wysolone to 1-2 mg/kg/day

Detailed Answer:
Hello and welcome to healthcaremagic

I am Dr. Kakkar. I have gone through your query and I have understood it.

Pemphigus vulgaris is an autoimmune blistering disease characterised by flaccid intraepidermal bullae, which rupture easily and leave behind painful erosions. The erosions can involve the scalp, oral mucosa, lips, trunk and abdomen, groin and genitals.

The patient has been on Wysolone, which is an oral steroid whereas Azoran is Azathioprine, an immunusupressive.

Management options for pemphigus vulgaris: Topical and systemic treatment

Topical:
-Topical steroids
-Topical antibiotics

Systemic:
-Oral steroids
-Oral antibiotics like tetracycline and erythromycin
-Cyclophosphamide
-Mycophenolate Mofetil
-Azathioprine
-Methotrexate

Since daily oral steroids have a lot of adverse effects like weight gain, weakening of the bones (osteoporosis), diabetes, high blood pressure, glaucoma, cataracts etc they should not be continued alone forever, but instead patients should be simultaneously started on various other safer but slow acting options (steroid sparing agents) like cyclophosphamide, Mycophenolate Mofetil, Azathioprine, OR Methotrexate. Steroids can be tapered gradually and finally stopped once the steroids sparing agents take full control of the disease.

In patient concerned over here, wysolone can be given at a higher dosage of 1-2 mg/kg/day. e.g in a 60 kg man, wysolone can be given in a dose of 60mg to 120mg per day to bring the disease under control. 35 mg of wysolone is too less for a 36 year old male to bring the disease under control.

Since Azoran would take around 4 weeks to take full effect, therefore round that time one can consider tapering steroids gradually and finally stop them.

*DCP Therapy (Dexamethasone cyclophosphamide pulse): Pulse therapy for pemphigus offers the only chance of long term cure/remission and is considered to be relatively safe and side effects are minor and few as compared to daily oral steroids.

regards

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Brief Answer:
Psoriasis and Pemphigus

Detailed Answer:
Hi.

There is a fairly good chance of cure following pulse therapy. However, treating pemphigus and psoriasis together, is challenging. Though DCP can be used in patients of pemphigus but consideration must be given to the age and marital status of the patient(here 36 yrs).

The use of cyclophosphamide is relatively contraindicated in patients who wish to conceive children. Although the severity of disease may demand treatment with cyclophosphamide, the patient may be rendered infertile by Cyclophosphamide based pulse therapy.

In such a scenario, one can use a modification of pulse therapy in young patients and also in this case, affected by psoriasis: DMP therapy(Dexamethasone Methotrexate Pulse Therapy). This would be a better choice than DCP Therapy because while the fertility related side effect of cyclophosphamide is avoided by this modification, Methotrexate is itself a very effective treatment of Psoriasis as well.

Pulse therapy requires the patient to get admitted for 3 days every month for the purpose of administering injections.

I would suggest that you visit a Medical College associated Teaching & Research Hospital in Bangalore/Karnataka where they can admit and give this therapy (DMP Therapy) to your patient. A Medical College associated Hospital would be experienced in handling these cases.

regards

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Brief Answer:
Pulse therapy

Detailed Answer:
Hi.

DCP therapy has 4 phases. Phase IV is an observational phase. Normally it takes between 24 months-36 months for the first 3 phases (Ist, IInd and IIIrd) to get over.

Chances of relapse are very less. Many of the patients are cured after pulse.

Side effects of immunosupressants are risk of infections, hemorrhagic cystitis(with cyclophosphamide), infertility(with cyclophosphamide). With Methotrexate, monitoring for Liver and Bone marrow functions is required because it can cause side effects related to liver and bone marrow suppression.

regards

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Brief Answer:
Pulse therapy and pemphigus

Detailed Answer:
Hi.

Dexamethasone-cyclophosphamide pulse (DCP): In phase I, dexamethasone 100 mg in 5% dextrose was given as a slow IV infusion over 2 hours for three consecutive days along with cyclophophamide 500 mg infusion on one of the days. Such pulses are repeated every 28 days till no new lesions appear between pulses. Cyclophosphamide 50 mg/day is given orally. This phase can vary from 6-9 months.

Phase II consists of the DCP schedule given for a fixed duration of 6 months.

In phase III, only oral cyclophosphamide 50 mg/day is given for 1 year, while in phase IV, all the drugs were withdrawn and the patient was followed-up for as long as possible.

The patient needs to be admitted only during the Ist and IInd phases for injections i.e for 12 months to 15 months (admitted for 3 days after every 28 days). From IIIrd phase, only oral cyclophosphamide is continued, therefore no need for admission.

Yes, the procedure is standard in every hospital.

Since, I stay very far from bangalore, therefore I wont be able to help you with a particular doctor, but as I said you should visit nearest Medical College associated Teaching & Research Hospital in Bangalore/Karnataka where they can admit and give this therapy to your patient. I could suggest a few:

-MS Ramaiah Medical College, MS Ramaiah Nagar, Near Mathikere, Bangalore - 560 054

-St.John's Medical College, Sarjapur road Bangalore - 560 034

-Bangalore Medical College, Fort, Bangalore – 560 002

Of course, he can continue his job simultaneously, if the disease allows during phase I, however during phase II and Phase III, there wont be any new lesions. He can take an off for 3 days every month for injections. Normally during the Ist phase which lasts 6-9 months, new lesions of pemphigus can appear but they become progressively less and less, as the phase I goes on, so that as he moves on to the IInd and IIIrd phases new lesions wont appear. So he can very well work in the IInd and IIIrd phases.

regards

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Brief Answer:
Pemphigus treatment

Detailed Answer:
Hi.

As far as his present treatment is concerned, Azoran has been started just 2 weeks back. Azoran takes around 4 weeks to show its full effect. So, I would have managed him on a increased does of steroids 60mg once daily instead of 35 mg once daily (which is too less for an active case of pemphigus) along with Azoran 50mg twice daily. Once his disease is brought under control, steroid can be tapered and ultimately stopped and he can be maintained on Azoran. Steroids cannot be continued forever!!

As far as switching on to pulse therapy is concerned, that is always a better option because pulse dosing of steroids has a decreased risk of steroid related side effects like diabetes, hypertension, osteoporosis etc as compared to daily oral steroids. If, side effects like infertility are not an issue(e.g for a person who has completed his family), then pulse therapy is preferable over daily oral steroids in terms of both side effects as well as response to treatment.

On the other hand, if he is continued on daily steroids as he has been till now, then of course it will never get cured. It will keep coming back time and again. Treatment of pemphigus with daily oral steroids will in fact cause diabetes!! as a side effect of daily oral steroids.

Hope this helps

regards

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Brief Answer:
Pulse therapy

Detailed Answer:
Hi.

Cyclophosphamide destroys the sperm generating cells resulting in permanent male infertility.

DCP (if infertility is not an issue) OR DMP is a good option for him. With daily oral steroids there are more chances of a person getting impaired glucose tolerance(diabetes) than with pulse therapy. DCP OR DMP therapy can be given even in patients of diabetes. Insulin is added to the infusion to control the raised blood sugar.

regards

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Brief Answer:
Rituximab in pemphigus is a last resort!!

Detailed Answer:
Hi.

Rituximab is a chimeric monoclonal antibody that targets CD20 molecule on B cell membranes resulting in cell death. Since Pemphigus is an antibody mediated disease. The use of Rituximab rituximab in patients with pemphigus is based on its ability to deplete CD20+ B cells that presumably produce pathogenic antibodies.

Clinical response with rituximab may be faster as compared with conventional therapy, thus it has a definite advantage but whether this control is long term , life long or of limited duration is not yet known. It is new frontier in the treatment of pemphigus.

However, Rituximab in Pemphigus is an 'Off Label' use. It has not been approved for it. It is an evolving therapy and not commonly given across many centers in India. Even with Rituximab there can be partial responders and non-responders. Relapse of pemphigus may occur months after discontinuation of therapy. Lastly, there has been a limited follow up with this drug and significant side effects like severe infections, cardiac side effects and even mortality can occur during therapy. So, it is not without serious risks!!

Presently, the indications for using rituximab in pemphigus could be as follows.

-Failure of conventional therapy for minimally 6 months
-Conventional therapy producing significant side effects

DCP therapy on the other hand is a tried and tested therapy for years. Many patients respond well on it and many are ultimately off all treatment after completing the phases, in contrast to daily oral steroids which obviously has a lot of adverse effects.

Pasricha et al from AIIMS new delhi first gave this therapy in pemhigus years ago and they even claim that pemphigus can be cured with DCP pulse.

My suggestion is to first try DCP therapy OR may be DMP therapy in view of the fertility related side effects of cyclophosphamide in DCP pulse. Patients fair far much better on pulse therapy rather than daily oral steroids.

Rituximab is the last resort, when everything fails.

regards

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Brief Answer:
IVIg for pemphigus

Detailed Answer:
Hi.

IVIg can rapidly control active Pemphigus by causing a selective and very rapid decline in the autoantibodies that mediate the disease by increasing the catabolism of pathogenic autoantibodies, responsible for pemphigus. This it provides an alternate and rapidly effective treatment for patients with active pemphigus unresponsive to conventional treatment.

IVIg is generally very safe. It should be more commonly utilized being a safe and effective therapy, however, the high cost of IVIg limits its widespread use.

regards

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Brief Answer:
Pemphigus treatment

Detailed Answer:
Hi

1) IVIg is a good option, if you can afford it out of the three, because it is relatively safe. It is given in a dose of 2g/kg/cycle, given monthly until clinical control, with a progressive increase of the intervals between the cycles thereafter to 6, 8, 10, 12 and 14 weeks. The last cycle is given after a 16-week interval, and is considered as the end of therapy.

2) IVIg produces long term sustained remission. In studies, long term sustained remission for up to 2 years follow up, after discontinuing IVIg has been reported.

3)Nonetheless, there is a chance of relapse after IVIg treatment.

4)It is safe in term of risk of infection from donors and properly screened for HIV, Hep B etc

5)I am not aware of the exact cost but it would be in lacs/cycle.

6)Renal failure is a risk for those who have underlying renal insufficiency like diabetes, those on nephrotoxic drugs etc

7)Second best option in my view is DCP therapy because of its availability and experience. Rituximab, IVIG are still experimental and may be in future they would replace current treatment modalities but presently they are not first choice.

Hope this helps you

regards

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Brief Answer:
Pemphigus treatment

Detailed Answer:
Hi

1)IVIg is not related to steroids. It is steroid sparing agent.

2)I personally don't have any experience with IVIg because it is not freely given to patients. Yes, it does rapidly control the disease within a matter of few days or weeks because it specifically targets the pathogenic autoantibodies(anti desmoglein antibodies)

3)IVIg, is given only in monthly cycles. After adequate control is achieved, subsequent IVIg treatment cycles are spaced progressively less frequently rather than every month(say at 6 weeks, then at 8 weeks, 10 weeks and so on).

4)Of course as a dermatology student we have all heard about him and read his articles and books as a student. If you can take your patient to PGI Chandigarh, it would be a good choice.

regards

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Brief Answer:
Pemphigus treatment

Detailed Answer:
Hi.

Of course, you can take your patient to him. He has years of experience. Though it would be a lot farther from your place also since he is into private practice now, so I guess the cost of therapy would be high depending on how he treats pemphigus patients, whether he would choose to give.. DCP Pulse or IVIg or Rituximab in your patient, but my guess is DCP Pulse.

All the best
take care
regards

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Brief Answer:
Pemphigus treatment

Detailed Answer:
Hi.

Ok, that's good. IVIg is very promising treatment of pemphigus.

Yes, no one can guarantee a cure for pemphigus. Since it is autoimmune.

IVIg will bind to pemphigus autoantibodies already circulating in the blood and inactivate them but since new antibodies can always be produced by the B cells/Antibody producing cells (these B cells are the target of Rituximab) so there is always a chance of relapse. However, the relapse is not that frequent as it is with steroids because high dose IVIg is postulated to inhibit the production of new pathogenic autoantibodies from B cells. That explains long term remission with IVIg (upto 2 years)

Not much precautions, except the patient should be well hydrated.

regards

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Brief Answer:
Pemphigus treatment

Detailed Answer:
Hi.

It "may" relapse. Studies have shown long term remission and no relapse even after 2 years of follow up, with patients off all treatments. But for obvious reasons, studies don't follow up for the entire life time of a patient OR else they would not get reported for decades. Each study has a 2 year or 5 year end point. 2 years follow up with no relapse, is a very good thing to expect with any treatment modality for pemphigus. As I told you before, No study claims 'permanent cure'. We can only treat the disease to the best of our capabilities and knowledge and constantly try to find newer and better treatment modalities, so that ultimate one day, sometime in future, we are able to find an ideal treatment modality which can offer permanent cure.

As of now, IVIg, Rituximab and DCP offers the best chance of long term remission and least relapse rate. However, safety wise IVIg is the safest.

We can only manage the patient with the best available treatment options, weighing the risks and benefits, and hope for the best for him.

regards

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Brief Answer:
Pemphigus treatment

Detailed Answer:
Hi.

The literature does'nt support this view. IVIg is expensive, that is the only drawback. See, your main concern is that the patient disease is steroid dependent, which is going to do more harm than good in terms of side effects like diabetes, hypertension, osteoporosis etc. You you want the patient to be off steroids as soon as possible. So your options are:

1)Immunosuppressant drugs like cyclosporin, Azathioprine, Methotrexate etc,
3)DCP or DMP pulse which is anyways safer than daily dose of steroids.
2)IVIg
3)Rituximab

IVIg is good choice. It can be given either as monothaerapy OR in combination with Immunosuppresant drugs like Cuclophosphamide/Azathioprine. At least the patient is Off steroids!! which are actually a double edged sword and moreover IVIg with or without Imunosuppressants, offers a chance of long term remission unlike steroids!!.

At last, I would suggest that you go with what your treating doctor has suggested.

You can go through these link for information:

http://www.ncbi.nlm.nih.gov/pubmed/0000

http://www.jaad.org/article/S0190-9622(01)66733-1/abstract

Hope this helps
regards
take care

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