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Research Article ISSN:2277-4564

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Alekhya et al /International Journal of Pharmaceutical Sciences Letters 2012 Vol. 2 (3)| 60-65

Drug Treatments in Development for Pemphigus Vulgaris (Pv) - A Review


Alekhya P*1, Subash vijayakumar1, Ramchandra dharak2
1
Department of Pharmacy Practice, Vaagdevi College of Pharmacy, MGM Hospital, Warangal.2 Department of
Dermatology, MGM Hospital, KMC, Warangal.

ABSTRACT:
New therapies are needed to combat the symptomatic underlying disease processes in the pemphigus vulgaris
(PV). The author examine the rapid increase in the management of disease by using systemic corticosteroid have
dramatically reduce complication of the disease, current therapeutic options are limited by toxicity profiles. In this
review, potentially new symptomatic and disease modifying therapies will be described. We undertook a review of
observational study of intervention which could reduce the burden of PV, particularly in low income and middle
income countries. So we identified several interventions which sufficient evidence to recommend implementation
in health system, including calcium supplementation with the corticosteroid. The most promising novel treatment
includes KC706, a p38 mitogen active proteinkinase (p38 MAPK) inhibitor. The pharmacological treatments for
disease continue to change, with many exciting possibilities for the future.

Introduction 1. Topical therapy


The term pemphigus refers to a group of autoimmune The topical therapy is mainly used if the mucosal sur-
blistering diseases of the skin and mucous membranes. face is involved “huilgol and black” have reviewed
The three primary sub-sets of pemphigus are: pemphigus topical therapy for pemphigus and pemphigoid in detail
vulgaris (PV), pemphigus foliaceus and paraneoplastic [2, 3] show in table no1: Topical therapy of pemphigus
pemphigus. Each type of pemphigus has distinct clinical vulgaris and its various formulation.
and Immuno-pathological features. PV accounts for ap- Formulation Drug name Dose Category
proximately 70% of pemphigus cases. Common symp-
toms include blisters in the mouth and on the skin, with Topical Benzydamine hcl 0.15%
the skin lesions forming erosions which tend to develop analgesic or (difflam oral rinse) Oral
excessive granulation and crusting. Genetic factors, old anaesthetics hygiene
age and the presence of autoimmune disorders are risk Antiseptic Chlorhexidine glu- 0.1%
factors for this condition. mouth- conate (corsodyl)
GOALS washes Hexetidine (Oral
The goal of managing pemphigus is to induce and main- dene)
tain remission with the lowest possible doses of medica- Mouth- Soluble be- 0.5mg For mul-
tion and to minimize the risk of serious and potentially washes tamethasone sodium tiple oral
fatal adverse effects [1] phosphate 0.5mg erosions
Treatments: It includes/involves tablet dissolved in
10ml water (QID)
1. Topical therapy
2.Systemictherapy Topical Triamanolone 0.1% For iso-
agent acetonide 0.1% in lated oral
Adjuvant therapy Conventional therapy adhesive paste erosion
3. Biological therapy (Adcortyl in orabase)
4. Emerging therapy.

For oral pemphigus measures such as soft diets and soft


Key words: Corticosteroid, Immunoglobulins, KC706, toothbrushes help minimize local trauma . Others :
Pemphigus vulgaris 2.5mg hydrocortisone lozenges or sprayed directly with
an asthma aerosol inhaler. Eg: Beclomethasone
Received 7 April 2012; accepted 28 April 2012; dipropionate 50-200µg or budenoside 50-200µg. Topi-
*Corresponding Author: Alekhya cal cyclosporine – 100mg/ml –oral pemphigus [4].
Department of Pharmacy Practice, Vaagdevi College of 2. Conventional therapy
Pharmacy, MGM Hospital, Warangal. It includes both the systemic therapy and the adjuvant
therapy. It has been depict in table no :2. Systemic
E-mail: alekhyapabba@gmail.com therapy of pemphigus vulgaris and its mechanism of
action.
Copyright ©2011 Published by IJPSL. All rights reserved
Alekhya et al /International Journal of Pharmaceutical Sciences Letters 2012 Vol. 2 (3)| 59-64
Systemic agent Mechanism of Route of ad- Dose and frequency Advantage Disadvantage
action ministration
Prednisolone   Oral 1-2mg/kg/d Effective Osteoporosis
Directly inhibit rapid onset 
pemphigus sera- Inexpensive
induced acan-
Dexamethasone tholysis 26  Oral or IV 50-200mg/d for Rapid onset IV admini-
pulse 33-5day inexpensive stration

(b) Conventional adjuvant therapy [1,5,6]


It includes Immunosuppressive agents: Azathiprine, Mycophenolate mofetil, Methotrexate, Cyclophosphamide,
Chlorambucil, and Cyclosporine respectively.
Anti-inflammatory agents: Gold, Dapsone, Colchicine
Antibiotics: Tetracycline, Erythromycin, Minocycline.It has been shown in Table no : 3 conventional adju-
vant therapy of pemphigus vulgaris, mechanism of action and its advantages and disadvantage.
3.Biological therapy ; It includes
Tumour Necrosis Factor-alpha antagonists : Eternacept, Infliximab
Intravenous Immunoglobulins
IgG1 anti-CD20 monoclonal antibody : Rituximab
It has been depict in the table no. 4 Biological therapy of pemphigus vulgaris and its characteristic of drug.
Drug Mechanism of Route of Dose and Side effects Advantage Disadvantage
action admini- frequency
stration

Etanercept Tumor necrosis SC 50mg  


[12,13] factor- alpha injec- weekly  
(TNF-α) An- tion  
tagonists- role Under clinical trial
Infliximab in acantholytic IV 5mg/kg/
[14,15] process [10,11] infu- cycle
sion
Intravenous Rapid & selec- IV 2g/kg/ During infusion chills, Rapid IV admini-
Immu- tive decline in infu- cycle HTN, Tachycardia, action stration ex-
noglobulin the serum lev- sion Pyrexia, Nausea & pensive, risk
(IvIg) [20] els of patho- headache of blood-
genic PV auto borne virus
antibodies infection

Rituximab Chimeric mur- IV 375mg/ Systemic infections Rapid Expensive


[21] ine/Human infu- M2 action
IgG1 anti-CD sion weekly
20 monoclonal for 4
antibody tar- weeks;
gets pre-β & or
mature B- 1,000mg
lymphocytes on days
results comple- 1&15
ment & anti-
body depend-
ent cytotoxicity
and apoptosis

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Alekhya et al /International Journal of Pharmaceutical Sciences Letters 2012 Vol. 2 (3)| 59-64
Table no : 3
Drug type Systematic Mechanism of action Mode of Dose and Side effects Advantages Disadvan-
agent administra- frequency tages
tion
Immuno- Azathioprine Block DNA replication Oral 3-4mg/ Myelosup- Inexpensive Slow onset
suppresive (inhibits lymphocyte kg/d pression & side effects
agents I proliferation and activa- nausea profiles
tion by interfering with
several enzymes required
for nucleotide replication

Mycophe- Inhibits the proliferation Oral 30-45mg/ Arterial Well tolerated Expensive
nolate of lymphocytes by inter- kg/d Hyperten- & relatively
fering with DNA replica- sion, GI less toxic
tion abrogate β-cell pro- disturbances
liferation [7,8]
Methotrexate Folate antagonist Oral 12mg/ Myelosup- Oral admini- Slow onset
weekly pression stration, inex-
hepatotoxic- pensive
ity pneu-
monitis
Cyclophos- It has pronounced effect Oral IV 2-3mg/ Neutropenia, Inexpensive Potential
phamide on lymphocytes, and can pulse im- kg/d alopecia, GI risk of
also used as immunosup- munoablati 0.5-1g/m disturbances haemor-
presant ve high- (2Monthl raised rhagic cysti-
dose (IV) y) transami- tis & carci-
50mg/kg/ nases noma of
d for 4 bladder
days
Chlorambucil Steroid sparing effect Oral 0.05- Myelosup- Inexpensive Minimal
0.2mg/ pression data
kg/d
Cyclosporine Steroid sparing effect Oral 2-5mg/ Hyperten- Inexpensive Side effect
kg/d sion, renal profile ex-
impairment, pensive
hypertrophic
gingivitis

Gold Steroid sparing agent Intramuscu- 25-50mg/ Rashes; Inexpensive IM admini-


Anti- lar biweekly Nephrotic stration slow
inflam- syndrome, onset
matory Oral 6-9mg/d Myelosup-
agents pression
Dapsone Steroid Sparing action Oral 50- Haemolysis: Inexpensive
200mg/d Methaemo-
globinemia,
Hypersensi-
tivity reac- Minimal
tions data
Colchicine Steroid sparing diuretic Oral 1.2- Anorexia Inexpensive
1.8mg/d

Tetracycline Oral 1-2g/d Flushing & Inexpensive


Antibiotics ± Nicotina- 1500- headache
mide 2000mg/ due to vaso-
d dilator with
nicotinamide
It is acts as an adjuvant GI upset Intake of
discolour- pills more
ation of than re-
teeth quired quan-
Erythromycin Oral 1,200mg/ Headache Inexpensive tity
d
Minocycline Oral 100- Hyper pig- Inexpensive
200mg/d mentation
particularly
at the sites
of blistering
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Alekhya et al /International Journal of Pharmaceutical Sciences Letters 2012 Vol. 2 (3)| 59-64
4. Emerging therapy
It includes
Plasmapheresis
Immunoadsorption
Extracorporeal photochemotherapy (ECP)
Cholinergic agonists
Other experimental therapies such as desmoglein 3 peptides & KC706. It has been shown in Table no: 5 Emerg-
ing therapy of pemphigus vulgaris.
Table no:5
Drug Mechanism of action Side effects Advantages Disadvantages
Plasmapheresis It is the process by Septicemia; flu- Direct & imme- Central venous ac-
which plasma is re- ids &Electrolyte diate removal of cess; Specialist
moved in the removal imbalance IgG & therefore equipment; trained
of the pathogenic PV removal of PV staff; expensive re-
antibodies [16] antibodies bound production of
PV antibodies
Immunoadsorption It is the process by No side effects Rapid decline in Specialist equipment;
(IA) which plasma is passed safe & well toler- desmoglein- trained staff; expen-
through an absorber ated specific IgG sive venous access
column (ie Protein A) auto antibodies can be problem
to remove circulating
immune complexes &
IgG [17]
Extracorporeal Photo- Process by which No side effects Used for refrac- Specialist equipment
chemotherapy (ECP/ white blood cells are were noted tory PV can be trained staff expen-
Photopheresis) collected performed via sive venous access
(Leukaphresis) ex- peripheral ve- can be problem lim-
posed to 8- nous access ited availability
methoxypsoralen irra-
diated with UV- light.
It involve inhibition of
pathogenic autoanti-
body production by β-
lymphocytes [6]
Cholinergic agonists Acantholytic process Only 2 clinical studies have been performed
of pemphigus .
[1,18,19,26] eg: Pyri-
dastigmine bromide
(Mestinon@, valent
pharmaceuticals)
Combination Therapy
Other experimental therapy Dexamethasone- Cyclophosphamide pulse therap. [9]/
Selective therapy using intravenous desmoglein 3 The pulse consisted of 136 mg dexamethasone dis-
peptides suppress the production of anti-desmoglein 3 solved in 5% dextrose given in a drip over a period of
antibodies through inactivation and/or deletion of 1–2 hours on 3 consecutive days. In addition, 500 mg
disease associated CD4 +T lymphocytes [22] cyclophosphamide was added in the drip on the first
Novel therapy KC 706 (Kernia Inc) is an oral allos- day. Such pulses were given at monthly intervals. In
teric p38 mitogen- activated protein (P 38 MAPK) between the pulses patients were given 50 mg cyclo-
inhibitor. phosphamide orally each day. The results were encour-
P38 MAPK Inhibition – Prevents blister formation aging, the chief advantage being freedom from side
[23], under clinical trial to determine the safety and effects of corticosteroid therapy. The lesions healed in
efficacy of KC 706 in the management of PV. 3–4 days and the patients were able to resume their
work within one week.
Alekhya et al /International Journal of Pharmaceutical Sciences Letters 2012 Vol. 2 (3)| 59-64
AYURVEDIC TREATMENT [24] -and help in managing sleeplessness. Find an experi-
The Ayurvedic treatment of PV is aimed at reducing enced massage therapist to give you the right massage.
blister formation, promoting healing of blisters and Apples
erosions, and boosting the immune system of the Eating three apples a day are reported to be effective
body. Medicines like Arogya-Vardhini, Panch-Tikta- in treating the symptoms of pemphigus vulgaris. Some
Ghrut-Guggulu, Punarnavdi-Guggulu, Gokshuradi- who are afflicted drink two glasses of apple juice a
Guggulu, Mahamanjishthadi-Qadha, Saarivasav, day instead of eating three apples. Applesauce and
Usheerasav and Chandanadi-Qadha are used to treat fruit leather are other sources for apple therapy. One
blister formation. Herbal medicines like Punarnava healthy treat is to pour applesauce in a food dehydra-
(Boerhaavia diffusa), Manjishtha (Rubia cordifolia), tor and run the machine. This makes homemade fruit
Saariva (Hemidesmus indicus), Chandan (Santalum leather. No dietary restrictions are needed, but patients
album), Haridra (Curcuma longa), Daruharidra with oral disease may benefit from avoiding certain
(Berberis aristata), Yashtimadhuk (Glycerrhiza foods (eg, spicy foods, tomatoes, orange juice) and
glabra), Gokshur (Tribulus terrestris), Kutki hard foods that may traumatize the oral epithelium
(Picrorrhiza kurroa) and Mandukparni (Centella asiat- mechanically (eg, nuts, chips, hard vegetables and
ica) can also be used to treat the blisters. In order to fruit).
promote healing of the blisters and erosions, local CONCLUSION
application of Chandanadi oil, Chandan- Bala-Laxadi Pemphigus vulgaris is a life threatening disease, it can
oil, Jatyadi oil, Yashtimadhuk-Ghrut, Panch-Tikta- be treated with the various type of therapies. Corti-
Ghrut and Shatadhout-Ghrut can be used. An ointment costeroid therapy remains the mainstay of treatment
containing Manjishtha, Saariva, Chandan, Haridra and for PV, the number of side effects with its use is to be
Mandukparni can also be used for this purpose. monitored. Conventional immunosuppressive and
In order to improve the immune status of the body, anti-inflammatory therapies are further associated
medicines like Suvarna-Malini-Vasant, Suvarna- with serious and potentially life-threatening adverse
Parpati, Tulsi (Ocimum sanctum), Bhrungraj (Eclipta effects. Today, a number of novel therapies have been
alba), Ashwagandha (Withania somnifera), Shatavari developed and these therapies appear promising, ran-
(Asparagus racemosus), Bala (Sida cordifolia) and domized controlled trials are needed to establish their
Naagbala (Grewia hirsuta) are used. All medicines safety and efficacy in the management of PV. This
need to be given long term in order to have a good review reported the treatment modalities in Ayurvedic
therapeutic effect. Ayurvedic medicines can be given and Herbal system of medicine.
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Pharm. Sci. Lett. 2012 : 2: (3) 60-65
Source of Support: Nil. Conflict of interest: None declared.

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