Autoimmune disease articles

[LIGA girl]

Welcome to the thread for those who want to find out more about autoimmune disease which is the underlying cause of many of the diseases we all suffer from.
I've spoken to Nick and other members about starting this thread ¦. All think it will benefit a lot of us here ¦..

My idea is that we will post articles, or links to articles, about autoimmune disease, its causes, things that aggravate or alleviate symptoms, the way it works, how it manifests itself etc. A brief summary or critique posted before the article would also be helpful in some cases.

If you gain information via a different source, eg a radio program, a TV show or newspaper article, and would like to write up a brief account of the info you found out, that would also be useful.

If you find a previous poster's article particularly useful, put up a posting saying so, but we would rather that the thread stay clear of personal recounts.

I hope this thread becomes a valuable resource for SkinCell members interested in learning about, and controlling, their skin disease.

Vicki

[LIGA girl]

This extract from Wikipedia gives a general introduction, along with a list of autoimmune diseases. They are believed to run in families, so if you have family members with some of these, it increases the chance of you having one of them too ...I have taken out the non skin related diseases from the lists.

Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body attacks its own cells. Today there are more than 40 human diseases classified as either definite or probable autoimmune diseases, and they affect 5% to 7% of the population. Almost all autoimmune diseases appear without warning or apparent cause, and most patients suffer from fatigue.

The causes of autoimmune diseases are still obscure: Some are thought to be either examples of or precipitated by diseases of affluence. For example, arthritis and obesity are acknowledged to be related, and the World Health Organisation states that arthritis is most common in developed countries. Most autoimmune diseases are probably the result of multiple circumstances, for example, a genetic predisposition triggered by an infection.

Women tend to be affected more often by autoimmune disorders; nearly 79% of autoimmune disease patients in the USA are women. Also they tend to appear during or shortly after puberty. It is not known why this is the case, although hormone levels have been shown to affect the severity of some autoimmune diseases such as multiple sclerosis [1]. Other causes may include the presence of fetal cells in the maternal bloodstream. [2]

Diseases with a complete or partial autoimmune etiology:

   
    * Coeliac disease is a disease characterised by chronic inflammation of the proximal portion of the small intestine caused by exposure to certain dietary gluten proteins.
   

    * Pemphigus is an autoimmune disorder that causes blistering and raw sores on skin and mucous membranes.
   
Suspected

Diseases suspected to be linked to autoimmunity are:

    * Alopecia universalis is a suspected autoimmune disease in which the body's white blood cells attack hair and result in total baldness.
   
    * Hidradenitis suppurativa is a rare skin disease in which apocrine sweat glands become severely inflamed. Researches have found an improvement in case studies with Remicade and other biologics.
   
    * Psoriasis is a skin disorder in which rapidly-multiplying skin cells produce itchy, scaly inflamed patches on the skin.
    * Sarcoidosis is a disease wherein granulomas can form anywhere in the body but particularly in the lungs.
    * Scleroderma is a chronic disease characterized by excessive deposits of collagen. Progressive systemic scleroderma, the serious type of the disease, can be fatal. The local type of the disease is not serious.

    * Vitiligo is the spontaneous loss of pigment from areas of skin. The pigment-free areas have few or no melanocytes. Researchers have detected anti-melanocyte antibodies in some cases of vitiligo, so it seems likely that at least some instances of this condition are the result of autoimmune problems.

[LIGA girl]

From the Health Encyclopedia:


Causes and Risk Factors of Autoimmune Diseases and Disorders
Scientists believe multiple factors such as environmental toxins, heredity, viruses, and certain drugs may play a role in causing an autoimmune disease.

Stress, poor diet, lack of exercise, lack of sleep, abuse of alcohol and use of tobacco can also weaken the immune system and may play some role as well.

Diagnosis of Autoimmune Diseases and Disorders
Your doctor will take a complete medical history, perform a physical examination, and may order blood tests, radiological studies, and other studies.

Your doctor may also order tests to rule in or rule out specific autoimmune diseases. For example: for rheumatoid arthritis, the rheumatoid factor test; for myasthenia gravis, the acetylcholine receptor antibody test; and for thyroid disorders, thyroid function tests.

Treatment of Autoimmune Diseases and Disorders
Most autoimmune diseases cannot yet be treated directly, but are treated according to symptoms associated with the condition.

Doctors may prescribe corticosteroid drugs, non-steroidal anti-inflammatory drugs (NSAIDs) or more powerful immunosuppressant drugs such as cyclophosphamide, methotrexate and azathioprine that suppress the immune response and stop the progression of the disease.

Radiation of the lymph nodes and plasmapheresis (a procedure that removes the diseased cells and harmful molecules from the blood circulation) are other ways of treating an autoimmune disease.

Self Care
Boost your immunity naturally by altering your eating and exercise habits.

Nutritionists recommend a diet high in fresh vegetables and fruit, whole grains, brown rice, low-fat dairy products, fish and poultry. A daily multivitamin should be taken. Exercise daily if possible.

Questions To Ask Your Doctor About Autoimmune Diseases and Disorders
What caused this autoimmune disorder?

What type of treatment do you recommend?

What medications will you prescribe?

What are the side-effects?

Will changing current eating habits and beginning an exercise program help?

Can this condition be reversed with lifestyle changes?

[LIGA girl]

I heard a radio show about a possible link between early life experiences (at age 4 and under) and autoimmune diseases later in life. They said that kids who have exposure to more germs early in life (eg they eat dirt and get out in the open more and mix with people) are less likely to develop an autoimmune disease and that those kids who are exposed to tobacco smoke are more likely to develop an autoimmune disease.

[LIGA girl]

 Autoimmune Diseases
Very simply stated, autoimmune disorders occur when the immune system confuses normal body tissue, "self", with a foreign intruder, and attacks it. How can this happen? As a way to avoid being attacked by the immune system, some infectious organisms, such as bacteria and viruses, learn to expose only those parts of themselves that mimic "self" tissue. Bacteria and viruses are made from chains of protein as are our bodies. The foreign invader exposes a segment of it's protein chain (called an antigen) that looks something like the protein chain of self tissue; and when the immune system mounts it's attack against these foreign organisms by detecting it's antigen, it inadvertently targets the "self tissue" to be attacked and destroyed..........
..................................................................................................................................................................................

Skin is targeted in pemphigus vulgaris characterized by blistering of the skin and mouth; and psoriasis characterized by thick, scaling plaques of skin. An unidentified antigen causes sarcoidosis, a inflammation disease appearing in multiple organs, such as the lungs, livers, skin and eyes. System lupus erythematosus or Lupus affects the collagen, the connective tissue, and in turn that can affect almost every organ system in the body. Ulcerated colitis and Crohns disease affects the digestive systems.

There is no cure for stopping autoimmunity. Most treatment of autoimmune diseases is usually aimed at lessening the severity of symptoms and replacing the missing hormones when a gland is destroyed. If the immune system becomes too hyperactive, immunosuppressive drugs are administered.

Approximately half of all persons afflicted with autoimmune diseases experience periods of spontaneous remission. It is known that stress can tend to exacerbate symptoms.

[nicolespeanut]

Vicki,
Thanks for starting this thread.  I have to look back in my file to see if I can find the links between digestion and autoimmunity.  I have read a great deal of literature regarding possible causes of autoimmune diseases that explain how proteins can leak through the gut and enter the blood stream wreaking all sorts of havoc.  I will post it when I find it.  It is a theory but seems to make sense to me. 

Fondly,
Nicole

[LIGA girl]

I will be revisiting this thread in a week or so with some articles to post..... I have other issues at the moment which i need to attend to. Please anyone who is interested in posting on here continue to do so .... wil be adding to it soon

Vicki

[nicolespeanut]

Here is a helpful checklist:

http://www.thyroid-info.com/articles/autoimmune-checklist.htm

[LIGA girl]

An article on treatment of Bullous diseases, not sure of the date, but think it is around 8 years old .....


Bullous Disease Treatment

by
   

Grant J. Anhalt, MD
Head, Dermatoimmunology Department
Johns Hopkins University
Baltimore, Maryland
Vice President in charge of Scientific Affairs, The International Pemphigus Foundation
Pemphigus Vulgaris

Prior to the introduction of an effective therapy with oral corticosteroids in the 1950s, the disease had a dismal natural course with a 50% mortality rate at 2 years and 100% mortality rate by five years after the onset of the disease.

The mortality rate now is estimated at about five percent and death is almost invariably due to the complications of immunosuppressive therapy. This disease is rare enough so as to render large scale controlled treatment trials impractical.

Therefore, treatment recommendations are based on information gleaned from uncontrolled small series, case reports and the personal experience and biases of the author.

Long-term therapy for pemphigus vulgaris must be directed toward reducing autoantibody synthesis, because as long as significant levels of antiepithelial antibodies are present, the disease will persist. Therefore, topical treatments are of secondary importance, and sustained improvement occurs only with treatment of the hematipoietic system. Those that have resistant disease or are intolerant of corticosteroids should receive a second, steroid-sparing agent. In decreasing order of efficacy, these agents are cyclophosphamide, azathioprine, chlorambucil, methotrexate and gold.

Oral corticosteroids remain the first line of treatment for all cases of PV. Some individuals with PV respond rapidly and completely to treatment with moderate doses of oral corticosteroids, others are rather refractory. About one-half of patients respond to oral corticosteroids alone (prednisone 1.0 mg per kg per day, tapered slowly over 6 to 9 months).

Almost all individual treated with prednisone require every-other-day maintenance indefinitely to control their disease. It had been standard practice to use very large doses of corticosteroids in refractory cases. Typically, an individual would be treated initially with 60 or 80 mg of prednisone per day. It there was not a rapid response to therapy, the dose of corticosteroids would be doubled and often doubled again. Under this regimen, patients would be treated with several hundred milligrams of prednisone per day, often with devastating or fatal complications. With the advent of effective immunosuppressive agents, it is generally not necessary to use such massive doses of costico-steroids.

Cyclophosphamide (Cytoxan), is an extremely effective agent in the treatment of PV, but it is also very toxic. It is very effective in reducing autoantibody synthesis, and has a preferential cytotoxic affect on proliferative plasma cells. It is generally reserved for patients who have the most therapy-resistant forms of PV in a dose of 1 or 2 mg per kg per day of by intermittent intravenous pulse. Major side effects include a predictable leukopenia, toxic effects of urinary metabolites causing hemorrhagic cystitis, and an increased lifetime risk of malignancy. The precise risk of lymphoma, leukemia, or bladder carcinoma secondary to treatment with cyclophophamide has not been established for patients with PV, but in patients treated with similar dosed for Wegener's granulomatosis, the lifetime risk may approach 5% to 10%. In addition, treatment may produce sterility in patients with childbearing potential. Chlorambucil (Leukeran) is a useful alternative to cyclophosphamide if a patient has developed hemorrhagic cystitis due to cyclophoshamide therapy but still requires an alkylating agent to reduce anitbody synthesis. Major potential problems of chlorambucil include its carcinogenic potential, and prolonged and unpredictable neutropenia.

Azathioprine (Imuran) is more widely used for the control of corticosteroid-resistant pemphigus. It is preferentially used under several circumstances: 10 In young individuals, it is more desirable to use a less toxic agent to reduce the lifetime risk of malignancy and potential for sterility. 20 If a patient cannot be monitored closely by complete blood counts and urinalysis or is not compliant. 3) If the patient is intolerant of cyclophosphamide due to profound leukopenia, thrombocytopenia or hemorrahagic cystitis. Azathioprine, however must be used in adequate doses for proper effect. Initial doses of 2 to 3 mg per kg per day are usually required to produce reduction of anitbody synthesis. Again, it should be used in conjunction with a low dose of oral corticosteroids.

Methotrexate was used for the treatment of pemphigus before other agents were available. It is a less effective but generally well-tolerated therapy for patients who cannot use alkylating agents or azathioprine.

Intramuscular gold has also been reported widely to be effective in management of both PV and pemphigus foliaceus. Response to this therapy has not been generally recognized, and the drug is not uniformly beneficial in everyone's experience. The incidence of allergic phenomena, such as nephritis and cutaneous or pulmonary hypersensitivity reactions, is very high and approaches 25%. Therefore gold is being used with much less enthusiasm now than it has been in the past.

The side effects appear to be the same whether one administers gold by mouth or intramuscularly.

Plasmapheresis has been used with mixed results in the therapy of pemphigus. If plasmapheresis alone is used, it can produce a short-term decrease in circulating autoantibody levels with subsequent clinical improvement. However, it must be recognized that the levels with subsequent clinical improvement. However, it must be recognized that the autoantibodies are under feedback inhibition control. If one simply removes the end-product, the B cells that produce the antibody are actually stimulated to produce more and a rebound flare with worsening of the disease will occur several weeks after plasmapheresis has been discontinued. Therefore, it is best to reserve plasmapheresis as an adjunct to therapy and to use it in conjunction with an alkylating agent. After the plasmapheresis has been discontinued, the loss of circulating anitbody from the serum causes a preferential stimulation of the B cells producing the autoantibody. As they proliferate, they are preferentially destroyed by the cyclophosphamide. The patients who are treated with this combination of plasmapheresis and an alkylating agent sometimes go into prolonged disease-free remissions after 1 or 2 years of therapy.

Cyclosporin (Sandimmune) has been used with benefit in some cases of PV, but it is not generally accepted to be particularly effective. The high incidence of pephrotoxicity also limit its usefulness.

Finally, treatment should always be adjusted according to the disease activity that is clinically apparent, without being unduly influenced by autoantibody titers as estimated by indirect immunofluorescence. The anitbody titers generally are high when the disease is active and are low or undetectable when the disease is in remission. If a patient is in apparent clinical remission but has persistent low titers, that should not prevent planned reduction of drug dosages. The indirect immunofluorescent titer is most useful during maintenance if a patient develops a flare of disease activity. In this circumstance, a low or negative anitbody titer would be reassuring that the flare may be self-limited and may not require increased drug dosages. On the contrary, a high titer raises more concern and prompts earlier intervention.

Pemphigus Foliaceus

Most cases of pemphigus foliaceus can be controlled by oral corticosteroids alone. A starting dose of 0.5 to 1.0 mg per kg per day, with a slow taper over a period of six months and the use of an alternative-day steroid regimen, is usually effective. Topical or intralesional steroids are somewhat effective in limited cases of pemphigus foliaceus. The list of drugs that are useful as a second or steroid sparing agents is identical to that in PV, with ;the possible addition of anitmalarials such as hydroxychloroquine (Plaquenil), 200 mg twice daily. The necessity of using an immunosuppressive agent, such as cyclophosphamide, azathioprine, or other agents such as gold or methotrexate in management of this disease is less frequent than in PV. Efficacy and toxicities of these therapies have already been outlined.

[LIGA girl]

This article comes with an assurance that it is written by a medical or research professional ....  I think it goves a good overview of autoimmunity and some different aproaches that are non medical. It also expplains clearly why there is a link between cancer and taking immuno suppressants.


Pemphigus: An Ayurvedic Approach

by Jay Glaser, MD, 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.

A Sanskrit expression from Charaka Samhita, the oldest textbook of medicine, states, yatha pinde tatha brahmande, i.e. œas is the individual physiology, so is the universe.� This means that the body is an expression of an underlying field of intelligence, the same intelligence that also governs the functioning of larger structures such as galaxies, ecosystems and societies. In the wake of recent horrific events, we have all wondered if there is any intelligence at all at work in a human society. Quantum mechanics and chaos theory both insist, œYes! But like biology, it is an intelligence that operates with probabilities and uncertainty.� This also means that social systems have their own physiology.

The ancient Ayurvedic texts call this intelligence Veda, and describe it as a blueprint for the physiology, indeed for the cosmos. Veda functions as a constitution of the universe, describing the laws of nature at work as unmanifest, unexpressed intelligence that expresses itself into a human, a virus or a star. The verses of Veda and the Vedic literature also have a discrete structure, an architecture defined by the relationships between the syllables, words, chapters and rhythms.

If Veda indeed provides the blueprint for nature including for humankind, one would expect that human physiology and anatomy reflects the architecture and functioning of Veda. Tony Nader, MD, PhD, a Harvard-trained neuroscientist investigated whether the structure of Veda could be found in the human neuroanatomy. Dr. Nader analyzed all 40 areas of Veda and the Vedic literature and discovered that each Vedic text has an almost identical corresponding structure in the human anatomy. For example, Rg Veda, the primordial Vedic text which gives rise to all others, is composed of 192 groups of verses. Similarly, the human autonomic nervous system governing our vital functions consists of 192 nerves.

This recent insight from neuroscience provides one of the strongest confirmations of the existence of an underlying blueprint for creation and that every human individual is cosmic. This correspondence also validates the biblical understanding that man is made in the image of the divine.

Agnivesha, a medical student who lived thousands of years ago, poses in the ancient Ayurvedic medical text a question about immunity that is still pertinent today. œWhy is it that some people eat all the right things and they still get disease and infections, while some people never eat well and they seem to never fall sick?� His professor, Atreya, gives an answer that prophesies our modern understanding. œPredisposition to disease also depends on how and when the food is eaten, the environment of the individual, as well as on genetics.�

Immune disorders, like problems with security systems or militias, can be categorized as either 1) weak immunity or 2) strong immunity, but lacking organization and leadership. AIDS is an example of the former because the immune cells are both scarce and weak. Pemphigus and other autoimmune disorders and allergies are examples of the latter. In allergic conditions, a strong immune system aims its formidable weapons at a non-threatening foreign irritant, the proverbial cannon against the mosquito.

Autoimmune disorders are the most interesting to a student of social policy and domestic security because they represent an imbalance between adequate internal vigilance and tolerance of individuality. Autoimmune diseases are caused by activation of immune cells for no apparent reason such as an infection. The immune response is directed against one's own tissues, perhaps tissues that, to a T cell, look a lot like an invader. This includes not only pemphigus, but common disorders such as hypothyroidism, rheumatoid arthritis, psoriasis, juvenile diabetes and probably multiple sclerosis, as well as more uncommon problems such as lupus, spondylitis and inflammatory bowel disease.

Immune cells are not designed simply to discriminate self from foreign, but to attack in an environment of inflammation triggered by chemical signals. Autoimmune disease usually implies both a genetic predisposition and the presence of triggers such as viruses or bacteria, drugs, a woman's natural estrogen or even stress. It seems that Atreya was right: genes and one's environment are just as important as a good diet.

Pemphigus and other immune disorders of the skin may be more common than immune disorders involving other organs simply because the skin, our largest organ, is responsible with the toughest immune task in the body: keeping the interior sterile in the face of an unsterile hostile environment. The intelligence to accomplish this difficult task, according to Ayurveda, comes from the source of intelligence in Veda, whose first biological expression is our DNA.

The standard medical approach is to subdue the immune system using harmful steroids and other risky immune suppressants otherwise used for preventing transplant rejection. Continuing our analogy, this is comparable to so weakening the FBI and other domestic security agencies, simply because they lacked perfect discrimination between the innocent citizenry and subversives, that it endangers the whole society.

It has long been known that stress aggravates allergic disorders like asthma, eczema and hives. What experienced ER doc hasn't seen kids with severe wheezing at home, who are fine as soon as they enter the hospital, knowing that they wouldn't suffocate? Now several studies have shown that stress can also be a trigger for autoimmune disorders, including Grave's disease, lupus, colitis, and rheumatoid arthritis. Our forebears fleeing a saber-tooth tiger had a good chance of being wounded, and needed an immune system that would be mobilized and stimulated from the chase alone. Today the tiger and its like are extinct, but we go about our business with our nervous systems in high gear as if these dangers were present, creating neuropeptides and stress hormones in the brain that circulate through our bodies to turn our immune systems on inappropriately. Serenity, on the other hand, allows proliferating cells to be quiescent.

So intimately are the nervous and immune systems connected that a new science called psychoneuroimmunology has arisen that may make this connection not only legitimate but also practical. Brains and immune cells both have memories and intellects, and even share some common cells. Most importantly, a nervous system free of anxiety and depression creates a neurochemistry that signals the immune system to deactivate. Countries at peace, like Switzerland and Costa Rica, marshal small, inconspicuous armies.

The western approach to pemphigus and other autoimmune disorders is to take corticosteroids and other powerful immunosuppressants. The Ayurvedic approach to autoimmunity is to put the immune system to rest rather than to suppress it. Transcendental Meditation has been shown to improve the inflammatory response of gingivitis and to lower cortisol and increase DHEA, exactly the opposite of the stress response. Several Ayurvedic herbs, including guggulu, have powerful anti-inflammatory effects and have been shown effective in rheumatoid arthritis, the autoimmune disorder that wreaks the most widespread suffering.

When I was in medical school, we thought that the body naturally eliminates clones of cells that attack one's self, leaving intact only the T and B cells which react against foreign antigens such as bacteria. Now we understand that a low level of autoreactivity is natural and even critical to normal immune function. Apparently, tissues that provoke an immune response help naïve immune cells to differentiate and survive. In addition, since our bodies create cancer cells every day, a hint of autoreactivity may be one of the ways the immune system is recruited to eliminate these abnormal cells, which don't look quite like œself.�

It seems that the healthiest condition for the body is akin to a benign yet testy society that is perpetually challenging the domestic security agencies to keep them on their toes. In these challenging times, may we have the humility to take a few lessons from Nature in establishing our new world order. Perhaps we can take a few lessons from the ancient sages of Ayurveda in overcoming pemphigus.

[LIGA girl]

This article is specific to pemphigus, but may have applications to other autoimmune skin diseases. It gives a broad overview of possible triggers for the autoimmune response for pemphigus:

PEMPHIGUS
An Acronym for a Disease with Multiple Causes

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:
PE       PEsticides
M       Malignancy
P       Pharmaceuticals
H       Hormones
I       Infectious agents
G       Gastronomy
U       UV radiation
S       Stress

Pesticides

Gardening materials and pesticides are a major group of agents implicated in the development of the disease. The medical literature documents numerous cases provoked by pesticides all over the world. Organochlorine pesticides, and organophosphates, a new generation of pesticides, have been tied to the disease.

How pesticides work on the skin is unclear. It is speculated that the immune system is activated via contact or systemic exposure, resulting in the generation of autoantibodies targeting desmosomal antigens. Interestingly, in most of the reported cases the patients had a first-time, long-duration exposure to the offending substance, and developed the disease only after a massive additional exposure, resembling the induction and elicitation phases of allergic contact dermatitis.

Malignancy

Pemphigus has been associated with malignant processes, mainly hematolymphoproliferative diseases such as Hodgkin's lymphoma, chronic lymphocytic leukemia, Castelman's disease, and others. These constitute a specific clinicopathological variant called paraneoplastic pemphigus. A few reports on cases of pemphigus associated with malignant diseases that did not meet the above criteria raised the possibility of simple co-existence. In both events, the physician should perform a malignancy-directed work-up on a pemphigus patient.

Pharmaceuticals

Drugs reported to induce pemphigus are divided into three main groups according to their chemical structure: drugs containing a sulfhydryl radical such as penicillamine; phenols such as rifampin, levodopa and aspirin; and nonthiol nonphenol drugs, such as calcium channel blockers, angiotensin converting enzyme inhibitors, NSAIDS, dipyrone, and glibenclamide.

Again, speculated mechanisms are chemical insult and immune system activation by a complicated mechanism involving diverse molecules (autoantibodies, cytokines). Calcium channel blockers are emphasized in view of the fact that the calcium ion is critical to maintaining an intact epithelium.

Hormones

Pregnancy is closely related to autoimmune diseases and thus to immunoblistering diseases, an association seen in the aggravation of pemphigus vulgaris during pregnancy, and pregnancy- or postnatally-induced herpes gestationis and neonatal pemphigus. These diseases are attributed to the passage of pathogenic autoantibodies via the placenta that target different placental antigens or skin antigens in the newborn. The role of sex hormones, mainly estrogen, in the pathogenesis of pemphigus has not yet been established.

Infection

Different infectious agents and immunizations can induce or exacerbate pemhigus, mainly by activating the cellular immune system. The most frequently incriminated infectious agents are the viruses of the herpetoviridae family, namely herpes simplex, EBV, CMV, and even HH8.

Despite the confusing clinical similarities of viral diseases and pemphigus, and because of the different outcomes of the two conditions, it is important to diagnose viral infection in a pemphigus patient and initiate early antiviral therapy, often as an adjunct to immunosuppressive therapy. Viral isolation remains the most reliable laboratory means for viral diagnosis, followed by molecular biology techniques, which are more sensitive but less reliable and indicated only in cases in which the results of the former are not conclusive.

In addition, bacteria such as coagulase positive staph aureus are capable of inducing pemphigus. Gram negative bacteria and even Actinomyces have been cultured in patients before the pemphigus becomes manifest, and were therefore described as its possible triggers.

Gastronomy

Although rarely mentioned in the literature, recent studies indicate that certain foods can induce or trigger pemphigus. Some nutritional components are chemically similar to known causative drugs, and may act in the same way. The following chemicals and related foodstuffs have been associated with pemphigus:

PHENOLS
Fruits: mango, bananas, potatoes, tomatoes
Nuts: pistachio, cashew
Pinenes: baked goods, smoked and grilled food, candy, chewing gum, ice cream, black pepper
Cow's milk
Food additives: aspartame, sodium benzoate, tartrazine, vanillin, eugenol, caffeic acid, cinnamic acid, vitamis C and E

TANNINS
Nuts: Kola, betal, walnuts
Fruits: cassava, cranberry, raspberry, blackberry, cherry, banana, apple, pear, grape skins, peach avocado
Drinks: tea, mate, fruit juice, beer, wine, liquors, water, coffee, guarana
Food additives: vanillin
Spices: ajowan, coriander, cumin, black pepper, red chilies, rosemary, garlic, ginger

THIOLS
Vegetables: garlic, onion, shallot, chive, leek
Assuming that foods containing thiol, phenol, and polyphenolic compounds may contribute to pemphigus, avoidance of certain foods may lead to remission.

Ultraviolet radiation

Pemphigus is considered a photosensitive disease, especially the superficial variant pemphigus erythematosus. Ultraviolet radiation, either occupation- or leisure-related, can induce or exacerbate the clinical manifestation. Whether the phototoxic reaction is a simple one or entails specific immune system stimulation remains to be determined.

Physical factors such as x- ray radiotherapy, burns, major surgery and cosmetic procedures have also been reported capable of inducing pemphigus.

Stress

The well-known connection between the immune and nervous systems raises the possibility that a psychoneural disorder can influence the onset and course of autoimmune disease. Several studies and case reports point to the possible contribution of emotional stress as a precipitating factor in pemphigus. Hence, avoiding emotional stress may be therapeutic in pemphigus patients, hastening the healing process and reducing or stopping the use of immunosuppressive drugs.

In summary, while the myriad causes of pemphigus complicate the differential diagnosis and course of the disease, it also points to the numerous factors that can help in its diagnosis and treatment. These factors have been documented in the studies cited here. The acronym is suggested to give clinicians a tool to pinpoint possible causes and prevent flare-ups in every newly diagnosed pemphigus patient.

[LIGA girl]

This article is again focussing on Pemphigus, but may have wider applications. It looks at predictors for remission ..... written in 2000

Remissions in Pemphigus

by
   

Jean-Claude Bystryn, M.D.
Professor of Dermatology
Director of Immunofluorescence Laboratory
The Ronald O. Perelman
Department of Dermatology
New York University Medical Center

Pemphigus vulgaris (PV) can enter into remissions in which all manifestations of the disease disappear and all therapy can be discontinued. How often, and when this occurs is unclear. Review of all major studies of PV conducted during the past four decades describes remissions as occurring in less than one-third of patients.1 However, a problem with these studies is that the incidence of remissions is usually provided at only a single time point. Thus, it is unclear how long it takes for remissions to appear, how long they last and what happens when therapy is discontinued. Further complicating interpretations of the results is that the meaning of remission is often unclear. The criteria used by different investigators to define this event differ and/or are not provided. The practical outcome of this incomplete information is uncertainty about the management of pemphigus. It is unclear whether treatment simply suppresses the manifestations of the disease and must be continued permanently, or whether complete and durable remissions can be induced that permit therapy to be safely discontinued.

To answer these questions we examined the induction of remissions in 40 patients with pemphigus vulgaris who were followed for a prolonged period (on the average of 7.7 years) by the same investigator. The results of the study have recently been published in the Journal of the American Academy of Dermatology.2

A strict set of entry criteria was used to include patients in the study, to minimize the effects of patient selection bias on the results. These included: a) diagnosis of PV confirmed by clinical, histologic and immunofluorescence criteria; b) first seen shortly (<3 months) after the diagnosis of pemphigus, to exclude bias from early death; c) seen continuously by the same investigator during the course of their illness; and d) a minimum of two years of follow-up information from onset of disease. All patients were treated conventionally with steroids, with or without adjuvants, using guidelines that have previously been published.3 All patients were followed and evaluated using defined criteria for disease activity and remissions, to ensure a consistent evaluation of clinical outcome. Scores were recorded for the most severe phase of the disease during the first year of treatment, yearly on the anniversary of diagnosis, and at last follow-up. Complete remission was defined as a period greater than one month during which the patient was on no systemic therapy and lesion-free. Partial remission was defined as a period greater than one month during which the patient was lesion-free and on no more than 15 mg./day of prednisone or its equivalent; or on only 100 mg./day or less of cyclophosphamide or azathioprine; or only on gold or dapsone. Duration of remission was classified as short if at least one month but less than 6 months, and as long if 6 months or longer. Time to partial or complete remission was calculated from date of diagnosis to onset of partial or complete remission. The results show that pemphigus improved with time in almost all patients. Improvement was particularly rapid during the first two years of therapy, with the severity score declining 64% from an average of 5.3 during the most severe phase of the illness to 1.9 two years after diagnosis (see Figure 1). Severity continued to decline, albeit more slowly, during the ensuing years. Five years after diagnosis the average severity score was only 1.4, indicating the disease was inactive or treated with <15 mg./day of Prednisone in most patients.

Remissions were found to be much more common than previously reported. This is probably because the incidence of remissions increases with time, and we studied patients for prolonged periods. Remissions that were complete and long-lasting (no evidence of disease and no systemic therapy for at least 6 months) occurred in 25%, 50% and 75% of patients 2, 5 and 10 years after diagnosis. These remissions were durable, lasting on the average over 4 years. Actual duration is probably longer, since most patients in remission were still in remission at last follow-up. The bulk of the remaining patients were in partial remissions or had mild disease controlled on 15 mg./day or less of Prednisone or with only an adjuvant (see Fig 1).3
Study results.

The course of pemphigus in different patients as evidenced by induction of remissions and flare in disease activity was variable, but followed one of 4 patterns. In pattern 1, the disease responded rapidly to treatment and went into a remission that was complete and long lasting. This occurred in 17% of the patients. There was no flare in disease activity when treatment was stopped. The average time to complete remission was 15 months and the remissions were maintained to last follow-up for an average of over 4 years. In pattern 2, seen in 37% of patients, response to therapy was slower and intermittent but complete and long-lasting remissions were also eventually induced in all patients. Pemphigus in these patients fluctuated between periods of partial or complete remissions of various length, which were punctuated by flares in disease activity as the intensity of therapy was decreased. Relapses were usually less severe than initial disease activity. With continued therapy, all patients eventually had long-lasting, complete remissions that persisted for longer than 6 months following termination of all systemic therapy. The average time to the first complete long-lasting remission was 35 months. In the third pattern, seen in 35% of patients, disease activity also fluctuated but no long-lasting complete remissions were induced during the course of this study. This may be because these patients were on the average followed for a shorter period of time.

However, disease activity in most of these patients eventually became mild and could be controlled by low doses of Prednisone (15mg/day or less), or with only an adjuvant. There was no mortality in patients whose disease followed these three patterns. In pattern 4, seen in 10% of patients, the disease was resistant to therapy and never went into a remission of any type. Mortality in this small group was high, occurring in two of four patients.

Two factors were identified as predictive of the course of pemphigus. One was initial severity and extent of disease. Patients with mild or moderate disease at diagnosis were twice as likely to enter a long-lasting complete remission as those with severe disease. The other was early response to treatment. Patients who responded rapidly to treatment were over twice as likely to enter a long and complete remission as those with a slower response.

These results indicate that the outlook of pemphigus is more favorable than currently believed. The disease can be converted into an inactive state in the majority of patients. Most patients will eventually enter a complete and durable remission that permits systemic therapy to be safely discontinued without an exacerbation in disease severity. The remaining patients will usually have only mild disease controllable with low doses of Prednisone or an adjuvant. The practical implication of these observations is that the ultimate goal of treatment in pemphigus vulgaris is to discontinue all treatment.
References

1. Bystryn J-C, Steinman NM. The adjuvant therapy of pemphigus - an update. Arch Dermatol 1996; 1 32:203-212.

2. Herbst A, Bystryn JC. Patterns of remission in pemphigus vulgarism. J Am Acad Dermatol 2000; 42:422-7.

3. Bystryn J-C. Therapy of pemphigus. Semin Dermatol 1988;7:186-194.

August 2000

[bunnie]

[

[LIGA girl]

Link to an articel on the judas enzyme ... provided by Andi on another thread...

http://www.innovations-report.de/html/berichte/biowissenschaften_chemie/bericht-74690.html

[LIGA girl]

A little more on the Judas enzyme ....

http://www.ntnu.no/gemini/2002-06e/43.htm

[LIGA girl]

This link has some good definitions of autoimmune diseases and if you look around the site there is some info on autoimmune skin diseases as well.....


http://autoimmunity.pathology.jhmi.edu/whatis_disease.cfm#circumstantial

[LIGA girl]

There is more discussion taking place on autoimmune diseases of the skin at

http://www.skincell.org/yabbse/index.php/topic,21129.740.html

the Linear IGA thread ..... please feel free to have a look or to join in.

Vicki 

[CalamityJane]

A little more on the Judas enzyme ....

http://www.ntnu.no/gemini/2002-06e/43.htm

Hi Vicki:  I emailed the doctor today at the institution.  It's a great theory, and I'm glad the mice/rats all recovered from their psoriasis.  However, what I have (and you have, methinks, isn't psoriasis).  All this though adds enormously to our knowledge and research!

[LIGA girl]

Yes, I agree that I certainly dont have psoriasis, thankfully, and that this new brekthrough wont help me directly, but I think that if any of us have an autoimmune disease and a treatment is being developed to treat any other autoimmune disease, there is a chance that further developments in that area may help us, especially when they are looking at the whole autoimmune process. The bit that interested me in that link is the following ....


"If the blockers are patented, rights in them can either be sold to a pharmaceutical company able to develop a drug, or a spin-off firm from the research environment may develop the concept further," says Professor Berit Johansen.
She explains that knowledge about the enzyme phospholipase A2 and the method of blocking unwanted activity in the cells most probably can be applied to the treatment of other diseases.
"This new knowledge is of more general interest, not least in relation to chronic diseases such as allergies, asthma, rheumatism, chronic enteric diseases, and cardiovascular diseases. A symptom common to all these diseases is a physical inflammatory reaction."

Vicki

[LIGA girl]

Jane

PS from my last posting ... if you hear back from them can you let us know what they say, please? It will be interesting to find where they are up to with their research ....