A recent article summarizes research conducted by dermatologists lead by Dr. Sarah Brenner, M.D., at Tel Aviv University into possible triggers of
pemphigus. The new research sheds some important new light on the possible causes of pemphigus.

The article, "PEMPHIGUS: An Acronym for a Disease With Multiple Etiologies," appeared in June issue of Skin Medicine. In this article, Dr. Brenner offers the acronym P.E.M.P.H.I.G.U.S. as a tool to remember pathogenic (causative)
and course-related factors.

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

Pesticides and gardening materials
"A multi-center study on pemphigus found exposure to gardening materials in 66.7% of patients in Bulgaria and 33.3% in Israel; 39% of the Bulgarian patients and 21.9% of the Israeli patients had been directly exposed to pesticides," says Brenner. The first case of pemphigus tied to pesticides and gardening materials was reported in 1973. Exposure to pesticides over time may affect cell-to-cell adhesion. Some kind of dermatitis may precede the detection of pemphigus antibodies in the blood.

"Interestingly," Brenner says, "In most 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
Paraneoplastic pemphigus is nearly 100% associated with Hodgkin's lymphoma, chronic lymphocytic leukemia, Castleman disease, or other cancers. Deciding which came first, the pemphigus or the cancer is a "chicken or egg" debate.

Pharmaceuticals
Three main groups drugs known to induce pemphigus. First are drugs like penicillamine, Captopril and thiomalate that contain a sulfhydryl (SH) radical (thiol drugs or SH drugs). Seven percent of patients taking penicillamine for at least six months developed pemphigus.

The second group contains phenols, like cefadroxil, aspirin and
pentachlorophenol and compounds that combine phenols and thiols. This group includes drugs like pyritinol and 5-thiopyridoxine.

Third are nonthiol nonphenol drugs, including calcium channel blockers,
angiotensinconverting enzyme inhibitors, nonsteroidal and anti-inflammatory drugs.

"With regard to the calcium channel blockers, calcium was found to play an essential role in maintaining an intact epidermis." Enzymes involved in the process of keratogenesis require free calcium ions for their normal activity; desmogleins, adhesion molecules, are also calcium dependent," said the report.

Hormones
Autoimmune blistering diseases, like pemphigus vulgaris, are exacerbated during pregnancy. Cases of pregnancy, or postnatally-induced herpes
gestationis and neonatal pemphigus have been documented. Some researchers believe hormones, especially estrogen play a role but a recent study disputes this theory.

Infection
Certain infectious diseases and immunizations may cause or worsen pemphigus by activating an immune response. Associate most frequently with pemphigus
are herpes simplex, Epstein-Barr, cytomegalovirus, and human herpes.

"Despite the confusing clinical similarities of viral diseases and
pemphigus, and because of the different critical outcome 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."

"Bacteria such as coagulase positive Staphylococcus aureus are capable of inducing pemphigus. Gram negative bacteria and even actinomyces have been
cultured in patients before overt clinical expression of pemphigus, and were therefore described as its possible triggers and not a coincidental infection in immunosuppressed patients."

Gastronomy
Trigger foods have not often been studied in the past, but research shows that certain foods can induce or trigger pemphigus. The foods suspected contain chemical compounds similar to drugs that are known to cause pemphigus. Garlic, onion and leeks which are part of the Allium food group (which also includes the mustard and caper families) is perhaps the most
studied. All these foods contain thiol. See Pharmaceuticals above.

"Plants with phenols, including the urishiol group that contains mango,
cassava, areca nuts, and cashew nuts, are also implicated. Other phenolic compounds, such as food additives, are also suspected of causing pemphigus."

States Brenner in her report. "The naturally-occurring polyphenolic compound tannin has also been implicated in pemphigus. Experimental models have demonstrated that the acantholytic potential of tannins in vitro was much greater than that of known acantholytic drugs. Foods with tannins include nuts, fruits, drinks, spices, and additives.

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 to be capable of inducing pemphigus."

Stress
Patients have shared anecdotal evidence of stress as a trigger of pemphigus for many years and science is beginning to verify the assertions with clinical research.

The Brenner says, "The first case of pemphigus foliaceous exacerbated by emotional stress was reported in 1965, followed by a report in 1984 of two patients who developed pemphigus vulgaris during severe emotional stress.
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 the steroid dose."

WHY STUDY PEMPHIGUS?

In spite of a very small patient population, pemphigus continues to be
studied in major laboratories around the world. In fact, it is said that
more research is being done on pemphigus than on some of the major diseases
when measured on a "cost per patient" basis.

Why is this true?

The reason may be that pemphigus is easy to study. Science has a mouse model so pemphigus can be easily and relatively cheaply studied in the lab. Also, unlike diseases like multiple sclerosis and arthritis, the success--or lack of success--in a potential treatment can be easily measured: If the treatment works, the lesions fade. If the lesions do not fade, the treatment did not work.

Contrast this to arthritis where it is impossible to accurately measure how much success a treatment has in improving mobility or slowing down the progression of the disease.

But pemphigus is being studied not just because it is easy to study. It is being studied because while they are loath to admit it, scientists feel that if they can unlock the mechanism of one autoimmune disease, they may be able
to unlock others, possibly many others--maybe all autoimmune diseases.

And autoimmune disease strikes one in five persons in America and the rate is probably universal worldwide. There is a great deal of suffering and lost productivity connected to autoimmune disease. And the researcher who works
out the key to unlocking the mechanism will earn a place in history.

And it probably won't hurt financially.

For this reason, I call pemphigus the lynch pin disease and I concur with those scientists who are researching pemphigus, that it is one of the most exciting --and potentially significant--scientific fronts of the 21st century.

I'll keep you posted.

Sal Capo
PV since 1997