Tag Archives: immunosuppressant

By Dr. Pan Meng

Pemphigus is a group of organ-specific autoimmune disorders, including pemphigus vulgaris (PV), pemphigus foliaceus (PF) and paraneoplastic pemphigus (PNP). PV is the most common disease and represents this kind of potentially life-threatening disease. It is characterized by development of blisters and erosions on skin and mucous membranes, termed acantholysis.

In China, the number of the patients with PF and PNP are lower than that of PV, perhaps because of the limitation of diagnostic methods. We only diagnose these disorders by clinical symptoms, histopathology and immuno-fluorescense. In our hospital, from 1989 to present, we have detected 32 patients with pemphigus. Among them, 28 patients were diagnosed as PV and 4 patients were PF. We found PV often occurs in middle-aged people. In two older patients, potential tumors were accompanying. Now, with the development of immunology and molecular biology, the different autoantigen in every patient can be detected. Therefore, we can redetect the patients by ELISA.

Although pemphigus is a rare disease and its incidence in China is about 0.5-3.2 per one hundred thousand people, its impact on patients is devastating. In the past, the mortality of this disease was very high and many patients died within one to two years after diagnosis. At present, with the discovery and development of glucocorticoids, for example, prednisone, patients survive. But an important problem has emerged — the side effects of this drug. After a period of taking the drug, many patients suffer from infection, higher blood pressure, diabetes and osteoporosis. Some patients died, not from the disease itself, but from the side effects of prednisone.

Therefore, how do we treat patients correctly and how do we decrease the mortality rate? We have found the combination of glucocorticoids and immunosuppressives is the best method. In the acute stage, glucocorticoids are used to control the symptoms. Then, immunosuppressives are added to avoid the rebounding when the dosage of prednisone is decreased. The most common immunosuppressives are Azathioprine, Methotrexate and Cyclophosphamide.

Also, many Chinese traditional medicines play an important role, not only in the treatment of this disease, but in alleviating the side effects of the drugs. In the theory of Chinese Medicine, the excessive heart-fire and spleen wetness-evil are the main factors of pemphigus. When they spread to the skin, pemphigus will happen. So the rule in Chinese medicine in the acute stage is to clear away heat, eliminate wetness-evil and detoxify. In the chronic stage, it is to invigorate the spleen.

In the acute stage, blisters and erosions develop on the skin and mucous membrane. Patients show red tongue with thin white fur and string-like pulse on examination by the practitioner. With the differentiation of symptoms and signs, evils of wetness stagnating within the body and the heat-evil attacking the blood were confirmed. The principal includes four parts: clear away heat, eliminate wetness, detoxify and cool the blood. The names of the main herbal medicines used: (1) Clear away heat: Long Dan Cao, Huang Chen, Bai Mao Geng, Shang Shi Gao, Zhi Mu, Da Qing Ye, Bai Hua She She Cao, etc.; (2) Eliminate wetness: Ku Sheng, Che Qian Cao, Fu Ling Pi, Sheng Yi Mi, etc.; (3) Detoxify: Liu Yi San, DA Qing Ye, Lian Qiao, etc.; (4) Cool the blood: Sheng Di, Dan Pi, Chi Shao. The typical prescription is Long Dan Cao 10g, Huang Chen 10g, Bai Mao Geng 15g, Sheng Di 15g, Sheng Shi Gao 20g, Zhi Mu 10g, Liu Yi San 30g, Fu Ling Pi 10g, Sheng Yi Mi 30g, Di Fu Zi 20g, Bai Hua She She Cao 30g. It is concocted in water for oral doses, and can also be used on the lesion directly.

In the chronic stage, lesions become dry and erosions are cured. Patients feel itching on the skin. The signs of the tongue, the fur and the pulse become better than before. The main treatment is adding some other herbal medicine to alleviate itching, for example, Di Fu Zi, Bai Xian Pi, She Chuang Zi, etc. The typical prescription is Long Dan Cao 15g, Huang Chen 10g, Bai Mao Geng 20g, Sheng Di 15g, Liu Yi San 30g, Da Qing Ye 30g, Dan Pi 15g, Dong Gua Pi 20g, Ze Xie 15g, Zhu Ling 30g, Fu Ling Pi 30g, Sheng Mi Ren 30g, Ku Sheng 15g, Di Fu Zi 25g, Bai Hua She She Cao 30g, Chuan Cao Xian 15g, Bai Xian Pi 20g, Sheng Bai Shu 10g, Ma Chi Jian 30g.

We must point out that the treatment of Chinese tranditional medicine is an accessorial treatment in this severe disease. Its function is to reduce the dosage of the drugs and to facilitate the decrease of the drugs, further to decrease the side effects of the drugs. Besides these herbal medicines, many Chinese medicines also can be used to increase the immune system of the patients. For example, Lei Gong Teng, An Beng Feng, Lu Qui, and so on.

The goal of therapy is not to continue all medical treatment, but to improve the patients' quality of life. I hope traditional Chinese medicine will be of some benefit in achieving this goal.

by Thierry Olivry, DrVet, PhD, DipACVD, DipECVD,
Associate Professor of Dermatology, Department of Clinical Sciences,
College of Veterinary Medicine, NC State University,
Raleigh, North Carolina,
and Adjunct Clinical Associate Professor of Dermatology, Department of Dermatology,
School of Medicine, University of North Carolina,
Chapel Hill, North Carolina

Autoimmune blistering skin diseases first were identified in companion animals twenty five years ago, with the description of two dogs affected with pemphigus vulgaris (PV). Two years later, the first cases of pemphigus foliaceus (PF) were recognized in canine patients. These two diseases represent the main forms of animal pemphigus being diagnosed by veterinarians.

Surprisingly, whereas the main form of pemphigus affecting human individuals is pemphigus vulgaris (PV), this entity is extremely rare in dogs with less than 50 cases being reported in veterinary medical journals. This deep pemphigus variant also has been recognized, albeit very sporadically, in rare cats and horses.

By David A. Sirois, D.M.D., Ph.D.
Department of Oral Medicine

Pemphigus vulgaris is a chronic autoimmune disease affecting the mucosa and skin and resulting in epithelial acantholysis, bullae formation, and chronic ulceration.1 Skin lesions of pemphigus vulgaris present clinically with typical bullae formation and ulceration. However, oral mucosal manifestations are less characteristic, typically occurring as multiple, chronic mucosal erosions or superficial ulcerations of various sizes and rarely presenting with intact bullae.2 Although pemphigus vulgaris is widely considered a skin disease, several reports of cases and case series have described it frequently as the initial, and occasionally the exclusive, site of involvement.2, 3 Thus, the unfamiliar features of oral pemphigus vulgaris could result in longer diagnostic and treatment delays than cutaneous pemphigus, which could adversely affect treatment response and prognosis.4, 5 The present study explored the natural history and diagnostic pattern of pemphigus vulgaris among 99 patients, with specific interest in the differences between oral and cutaneous pemphigus.

By Sergei A. Grando, MD, PhD, DSci
Professor of Dermatology
University of California Davis

The Need for Alternative Therapies for Pemphigus. In autoimmune pemphigus, systemic glucocorticosteroid treatment is life saving but may cause severe side effects. Pemphigus patients therefore need drugs that will provide safer treatment of their disease by replacing systemic use of glucocorticoid hormones such as Prednisone. Development of non-hormonal treatment is hampered by a lack of clear understanding of the mechanisms leading to pemphigus lesions. Pemphigus can be associated with myasthenia gravis, and in both diseases the autoantibodies to acetylcholine receptors are produced, suggesting a common mechanism of disease development.

By Edward Tenner M.D.
Hoffman Estates, Il.

Each type of pemphigus and relate diseases has differing kinds and differing percentages of ocular involvement. Also, the treatments for these diseases have many ocular side effects. Therefore it is very important that an Ophthalmologist examines the eyes of patients with pemphigus . This is especially true at the beginning of symptoms and treatments so any eye problem can be promptly handled.

By Sergei A. Grando, M.D., Ph.D., D.Sci.
Professor of Dermatology
University of California Davis
NPF Advisory Board Member

The goal of my research is to develop a safer and more rational treatment for pemphigus. I am deeply concerned that we, as physicians caring for patients with pemphigus, have to accept the risk of severe side effects related to the use of long term, high dose corticosteroid therapy.

Despite recent progress in developing nonhormonal therapy for other autoimmune conditions, the treatment of pemphigus remains largely dependent on corticosteroid hormones. The lack of progress in developing new therapies for pemphigus is ironic because we thought we understood the basic mechanisms responsible for the development of this disease. But, perhaps our understanding was wrong and possibly this misunderstanding has hampered advancement in treatment.

 

By Grant J. Anhalt, M.D. and Hossein Nousari, M.D.
Johns Hopkins University, School of Medicine

In February 1997, the FDA approved a new drug, mycophenolate mofetil (MFM, also known as Cellcept) with an approved indication for use in immunosuppression of patients that have received renal transplants, to prevent graft rejection. MFM is actually a new variant of a drug that has been studied for about 20 years. The active metabolite, Mycophenolic acid (MPA) had been used in the past for the treatment of severe recalcitrant psoriasis.

Although MPA was shown to be a useful drug, it was withdrawn due to a high incidence of side effects, primarily infections such as herpes zoster ("shingles") and gastrointestinal side effects such as nausea and stomach discomfort. MFM is the reformulated product that does not have these same drawbacks, and has better bioavailability than MFA.

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

 

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%