Tag Archives: immunosuppressant

Pemphigus is a chronic, muco-cutaneous autoimmune blistering disorder; two main variants being pemphigus vulgaris (PV) and pemphigus foliaceus (PF). PV is the most common subtype, varying between 75 to 92% of total pemphigus patients. Although no community based studies are undertaken to estimate the incidence of pemphigus in India, it is relatively common. A questionnaire based survey in Thrissur district of south India estimated pemphigus incidence to be 4.4 per million population. Mortality due to pemphigus has decreased remarkably with the aggressive and widespread use of corticosteroids, prior to which it was as high as 90%. High dose corticosteroids were once used in combination with other immunosuppressants with good improvement, but such high doses of corticosteroids were often associated with severe side effects, and were responsible for the death of nearly 10% of the patients. With the aim of reducing the adverse effects of long term, high dose steroid administration dexamethasone cyclophosphamide pulse (DCP) therapy was introduced in 1984. Since then DCP or oral corticosteroids with or without adjuvant immunosuppressants (azathioprine, cyclophosphamide, mycophenolatemofetil, and cyclosporine) have been the corner-stone of therapy for these disorders in India. Despite the benefits associated with DCP therapy compared to high dose oral steroids, it cannot be denied that even DCP therapy with or without adjuvants can lead to numerous adverse events, which account for majority of deaths in pemphigus. Moreover there are few patients who fail to improve with these conventional treatments or have contraindications for their usage. Thus there has been a constant search for newer therapeutic modalities in pemphigus. Rituximab (Reditux. Dr. Reddy’s, Hyderabad, India and MabThera TM , Roche, Basel, Switzerland), a monoclonal chimeric IgG1 antibody targeting the B cell specific cell-surface antigen CD20, is one such newer novel therapy for pemphigus (an off-label indication for its use. It has so far been approved by FDA for use only in CD 20+ B cell non-Hodgkin’s lymphoma, treatment resistant rheumatoid arthritis, Wegener’s granulomatosis and microscopic polyangiitis).

There is currently no consensus on the optimal dosage and schedule of rituximab in treatment of pemphigus. The various treatment protocols followed include:

  1. Lymphoma protocol- Most commonly followed protocol. Rituximab is administered at a dose of 375mg/m 2 body surface area weekly for four weeks.
  2. Rheumatoid arthritis protocol- Two doses of rituximab 1g is administered at an interval of 15 days. Increasingly used by dermatologists and is the protocol currently followed in our institute. Advantage over the lymphoma protocol include less cost and fewer infusions.
  3. Combination therapy- Rituximab has been used in combination with IVIG, immunoadsorption and dexamethasone pulse therapy
  4. Long-term rituximab treatment with regular infusions every 4 or 12 weeks following an induction cycle of infusions every week

Full article can be viewed at: http://www.ijdvl.com/article.asp?issn=0378-6323;year=2012;volume=78;issue=6;spage=671;epage=676;aulast=Kanwar

Background  The classic treatment for pemphigus vulgaris is prednisolone. Immunosuppressive drugs can be used in association.

Objective  To compare the efficacy of Azathioprine in reducing the Disease Activity Index (DAI).

Patients and methods  A double blind randomized controlled study was conducted on 56 new patients, assigned to two therapeutic groups: (i) prednisolone plus placebo; (ii) prednisolone plus Azathioprine. Patients were checked regularly for 1 year. ‘Complete remission’ was defined as healing of all lesions after 12 months, and prednisolone <7.5 mg daily, (DAI ≤ 1). Analysis was done by ‘Intention To Treat’ (ITT) and ‘Treatment Completed Analysis’ (TCA).

Results  Both groups were similar in age, gender, disease duration, and DAI. Primary endpoint: By ITT and TCA, the mean DAI improved in both groups with no significant difference between them. The difference became significant for the last trimester (3 months; ITT:P = 0.033, TCA: P = 0.045). Secondary endpoint: The total steroid dose decreased significantly in both groups, with no significant difference between them, except for the last trimester (ITT: P = 0.011, TCA: P = 0.035). The mean daily steroid dose decreased gradually in both groups becoming statistically significant in favour of azathioprine, in the last trimester, especially at 12th months (ITT: P = 0.002, TCA:P = 0.005). Complete remission was significant at 12 months only for TCA (AZA/Control: 53.6%/39.9%, P = 0.043).

Limitations  Sample size was rather small to demonstrate all differences. Other limitations include the choice of primary and secondary endpoints and the unavailability to measure thiopurine methyltransferase activity.

Conclusion  Azathioprine helps to reduce prednisolone dose in long-run.

Full article available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1468-3083.2012.04717.x/abstract;jsessionid=4F8C646E8902BB54AC0026B542EF91FD.d03t01

  This article reviews the use of MMF for the treatment of several bullous conditions, and assesses the evidence gathered from clinical trials and case series. According to numerous case series, MMF could be of value in treating refractory disease. The few randomized clinical trials conducted to date of patients with pemphigus and bullous pemphigoid report a similar efficacy for MMF to other immunosuppressants. (Source: Immunology and Allergy Clinics of North America)

from MedWorm: Pemphigus http://www.medworm.com/index.php?rid=6018247&cid=c_297_3_f&fid=33229&url=http%3A%2F%2Fwww.immunology.theclinics.com%2Farticle%2FPIIS0889856112000252%2Fabstract%3Frss%3Dyes

by Sarah Brenner, MD, Jacob Mashiah, MD, Einat Tamir, MD, Ilan Goldberg, MD and Yonit Wohl, MD, Department of Dermatology, Tel Aviv Sourasky Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Israel

Pemphigus is generally considered to stem from a genetic predisposition to the disease triggered and/or aggravated by one or more external factors. An acronym has been suggested from the name of the disease, PEMPHIGUS, to encompass those factors:

by Dr. Neal Halsey, Department of International Health, Johns Hopkins School of Medicine, and Dr. Noel Rose, Autoimmune Disease Research Center, Johns Hopkins University

1. What is the risk of developing smallpox?

Smallpox does not exist as a naturally occurring disease anywhere in the world. The only risk of smallpox would come from the use of smallpox as a weapon of bioterrorism. Government security experts believe that bioterrorists in several countries may have smallpox. No one knows for certain whether or not they have smallpox or if smallpox will be used as a weapon. Most infectious disease experts believe that the risk of any individual being exposed to smallpox is extremely low.

2. How good is this vaccine?

No vaccine is perfect. The smallpox vaccine provides approximately 95 percent protection against smallpox. This is about as effective as most other live viral vaccines.

3. What kinds of adverse reactions can occur?

The smallpox vaccine causes a local infection on the arm. A small group of blisters or vesicles develop associated with inflammation, swelling and tenderness that lasts for one to two weeks. About 10 percent of people develop an exaggerated reaction with more marked swelling, redness and tenderness and decreased use of the arm for a few days. Some people develop red streaks going around the arm, which resolve spontaneously, but this reaction is sometimes mistakenly assumed to be a secondary bacterial infection. Headache, fever, and feeling poorly for a few days occur frequently. About one-third of healthy young adults who were vaccinated reported missing at least one day of work, school, or participating in usual activities. More serious reactions occur much less commonly.

The vaccine virus can be transmitted from the vaccination site to some other part of the body or to people who have direct contact with a vaccinated person. The virus is transmitted on hands after touching the vaccine site. There is no evidence that the virus is transmitted through respiratory droplets or that there is any risk from being in the same room as a vaccinated person. If the vaccine virus is put on an area where the skin is broken or on a mucous membrane such as the mouth, eye, vagina, or rectum, then sores develop that are similar to the sore at the vaccination site. This can create serious problems if the viruses are placed in or around the eye or the genital area. The vaccine is not recommended for anybody with acute or chronic skin conditions that could predispose to this problem. People with eczema are at particularly high risk of developing severe reactions. Any person with eczema, atopic dermatitis, or any household member who has these conditions should not be vaccinated.

When the smallpox vaccine was given to pregnant women, the vaccine virus was sometimes transmitted to their unborn babies and caused serious infections and sometimes premature birth. When the vaccine was given to children under a year of age, they had a higher risk of developing encephalitis than older children and adults. The risk in adults is about one to two per million and this complication can lead to long-term brain damage or death.

4. Are there special risks for patients with immune disorders?

Yes, patients with immune deficiency disorders and their household contacts should not be vaccinated. Persons with defects in lymphocyte function, including people with leukemia and other forms of cancer, are at high risk of developing a serious and frequently fatal complication called progressive vaccinia. Although patients with mild defects in the immune system that do not affect lymphocyte function may not be at increased risk, there is no reason for these people to be vaccinated at this time. If there were to be outbreaks of smallpox associated with bioterrorism, these people should check with their doctors before considering smallpox vaccination.

5. I am being treated with prednisone. Should I take the vaccine?

Any person with a condition that requires the use of prednisone or other immunosuppressive agents should not receive the smallpox vaccine at this time. Although low doses of prednisone do not usually cause any problems with live viral vaccines, these persons might require higher doses of prednisone if their underlying condition became more severe. We do not have any data on what doses of prednisone might be safe for people who receive the smallpox vaccine.

6. If I have an autoimmune disease, should members of my family take the vaccine?

If you have an autoimmune disease that might require the use of steroids or other therapy that could affect the immune system, no one in your family who lives in the same household should receive smallpox vaccine because you might acquire the smallpox vaccine virus from your family member.

7. If I have an autoimmune disease, should I stay away from my place of employment if there are people there who have been vaccinated? If so, how long should I stay away?

You do not need to stay away from your place of work where people have received the smallpox vaccine. We do not have the same physical contact with people in the workplace that we have with family members. Vaccinated individuals in the workplace should have their smallpox vaccine site covered with special bandages that will markedly reduce, if not eliminate, the risk of their transmitting the virus to you. If vaccinated people take appropriate precautions with regard to care of the vaccine site, then they can continue to shake hands and have other minimal contact with other persons.

8. Are there any special precautions that I as an autoimmune disease patient should take if there is a national vaccination program?

If your disorder puts you at increased risk, you should take care to minimize direct touching contact with people who may have received the smallpox vaccine and who have an open sore that could contain the virus. If your job requires direct physical contact with people, such as people who do massage therapy, then you might consider asking clients who have been vaccinated not to come for therapy during the time when they have an open sore from the vaccine.

9. If I have an autoimmune disease that affects the skin, should I take the vaccine?

If you have active lesions from psoriasis, cutaneous vasculitis, bullous pemphigoid, Behçet's disease, discoid lupus, Mooren's ulcer, or any other skin disorder, you should not receive the vaccine. If your skin disorder is under control, you do not have any open lesions, and the vaccine is highly recommended for you because of your occupation, then you might consider receiving the vaccine after consultation with your physician. If it is not essential for you to be immunized, then we would advise against it.

10. Is there any way of treating the adverse reactions if they occur?

Some adverse reactions can be treated with a special immune globulin preparation that appears to help patients with eczema vaccinatum, severe inoculation around the eye or other sites, and possibly for progressive vaccinia. There is one antiviral drug that is available for investigational purposes, but it has a high rate of serious side effects. These drugs are available through the Centers for Disease Control and Prevention.

11. Is there a safer vaccine available for patients with autoimmune disease?

A new smallpox vaccine is currently being tested and should become available sometime during 2003. This vaccine is made from the same virus that is in the current smallpox vaccine. The new vaccine will be grown in cell culture rather than on the calf skin. Since the viruses are the same, the new vaccine will probably have the same risk of adverse reactions as the current vaccine. Scientists are working on developing safer vaccines against smallpox, but it will take at least five to ten years before these vaccines might become available.

12. Is the situation likely to change with regard to the risk of exposure to smallpox?

Almost all infectious disease experts recommend against routine vaccination of the civilian population because the risks of exposure to smallpox are very small and probably close to zero. Experts are constantly reevaluating the potential for exposure from bioterrorism. As the United Nations investigations in Iraq continue, we should learn whether or not this country has produced smallpox for possible use as a weapon. If there was one small event in a single location, this may not change the equation with regard to balancing the risks and benefits from this vaccine for the general population. Experts would contact everyone who had been exposed to be sure that they were immunized, but it would not require immunization of the general population. Smallpox vaccine can protect against smallpox even when it's administered up to four days after exposure. If someone has a known exposure to smallpox, then there are very few contraindications to using the vaccine and people with skin disorders and mild immune deficiency disorders would be immunized. If there was a confirmed large outbreak in your local community, then many experts believe that almost everyone in that community should receive the vaccine. We must always weigh the potential benefits of vaccines against the potential risks. At this time smallpox vaccination is not warranted for the general public.

American Autoimmune Related Diseases Association
22100 Gratiot Avenue
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by Edward Tenner, M.D.


The autoimmune bullous skin diseases, pemphigus (with major subsets pemphigus vulgaris, pemphigus foliaceus and paraneoplastic pemphigus) and the more common bullous pemphigoid (with variant disease phenotypes of cicatricial pemphigoid and gestational pemphigoid) each may have ocular manifestations.

by Dr. David Rowe, DC, Dr. Nicholas Hall, DC

The following article is one in a series we are publishing about complementary medical approaches to living with pemphigus. These treatments are not meant to replace the therapies administered by your physician.

What is Chiropractic?

Chiropractic is a drugless healing art built on a very simple principle: the body is a self-healing, self-regulating organism that is under the complete control of the central nerve system. When vertebrae of the spine misalign and lose their ability to move freely in all directions, they often put pressure on the delicate nerves that carry vital nerve impulses from the brain to the body. This condition is called a Vertebral Subluxation Complex (VSC), and is the cause of many of the unwanted conditions that people suffer from every day. In fact, the damaging effects of VSC are further reaching than most people are aware of, and although chiropractic has come to be a mainstay for the treatment of headaches and musculoskeletal conditions such as low back pain and neck pain, the importance of us all maintaining a healthy spine has become more apparent as research continues to reveal the devastating effects of VSC on our health.

By Robert Jordon, M.D.
Professor and Chairman, Department of Dermatology,
University of Texas
Houston, Texas

Historical Perspective

The term pemphigus was most likely in use in the ancient world, but the first recorded instance was by Hippocrates (460-370 BC) who described pemphigoid fever as “pemphigodes pyertoi.” Galen (AD 13 1-201) named a pustular disease of the mouth as “febris pemphigodes.” In 1637, Zacutus again uses the term “febris pemphigodes” to describe patients with blisters of short duration. DeSauvages (1760) described patients with high fever and blisters of short duration as having “pemphigus maior.” None of the above conditions is considered to be true pemphigus, as their disease was of short duration and all patients recovered.


By Jay Glaser, M.D.

Dr. Glaser is a board-certified internist, researcher and medical director at the Lancaster Ayurveda Medical Centers based in Sterling, MA. He can be reached at 978-422-5044. Answers to many questions about Ayurveda can be found on the Lancaster web site, www.AyurvedaMed.com, where you can subscribe to their free online newsletter, The Spirit of Health.

Sufferers of pemphigus are in a good position to aid well meaning administrators in politics, social policy, security, intelligence and defense who are currently grappling with how to re-engineer a free society immune to disruption from within or without, because this disorder recapitulates issues in domestic security. Understanding the immunology of autoimmune disorders sheds light on critical issues of individual and societal health, so we will examine immunology from both a western and eastern perspective.

By Vincenzo Ruocco, M.D., Sarah Brenner, M.D., and Eleonora Ruocco, M.D., from the Department of Dermatology, 2nd University of Naples, Naples, Italy, Department of Dermatology, Tel-Aviv Sourasky Medical Center, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Correspondence: Vincenzo Ruocco, MO, Department of Dermatology, 2nd University of Naples, Via Sergio Pansini, 5, 1-80131 Naples, Italy.


In dermatology, there are typical examples of disorders related to dietary factors. The pathogenic, links between nutritional factor(s) and skin disease may be different.

Nutrient deficiency and nutrient excess are the simplest causes of specific diet-related cutaneous changes: scurvy (vitamin C deficiency) and acrodermantis enteropathica (zinc deficiency) are examples of the first type, and caronenoderma (carotene excess) is an example of the second type. Genetic metabolic defects or enzyme deficiencies, although subtle, may pave the way for the onset of diet-related skin disorders, where a toxic effect is exerted by the dietary factor(s): alcohol intake is responsible for porphyria curanea tarda, and the ingestion of choline- and lecithin-containing foods is the cause of eccnine bromhidrosis, with the typical “fishy” odor that features trimethylaminuria. More often, an immune (and complex) mechanism is involved in the pathogenesis of strictly diet-dependent skin disorders, e.g. atopic dermatitis and food-induced urticaria (related to several foods), dermatitis herpetiformis (gluten), and allergic contact dermatitis (nickel). Finally, cutaneous disorders exist where the pathogenic interference of dietary factors has repeatedly been advocated, but without convincing evidence: psoriasis, seborrheic dermatitis, and acne are the commonest examples of this type.