Tag Archives: acantholysis

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Human epidermis shows a non-neuronal cholinergic system including keratinocyte (kc) acetylcholine (Ach) axis which is composed by enzymes and two families of Ach receptors (muscarinic and nicotinic receptors). The activity of these two receptors can regulate the interkeratinocytes and kcs-extracellular matrix adhesion modifying the regulation of intercellular adhesion molecules like cadherins and integrins. Some authors demonstrate that acantholysis in pemphigus depends not only on anti desmogleins antibodies (abs) (mostly IgG) but even on other abs directed against kc membrane antigens (e.g. anti Ach receptors Abs). In the early phase of pemphigus pathogenesis, anti Ach receptors Abs block Ach signaling essential for cell shape and intercellular adhesion and increase the phosphorylation of adhesion molecules. Combined with the action of abs antidesmogleins, anti Ach receptors Abs cause the acantholytic phenomenon. In vitro experiments show that high doses of Ach in acantholytic kcs can rapidly reverse this pathologic event. In vivo experiments using neonatal mice model of Pemphigus have demonstrated that cholinergic agonists reduce these lesions. Therapy with pyridostigmine bromide and Nicotinamide per os or pilocarpine used topically, drugs that present cholinomimetic effects, has

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lead to encouraging results in patients affected by Pemphigus disease. Cholinergic agents could have a strategic role in the therapy of pemphigus since they could be responsible for the early stage of acantholytic diseases.

Full article available at: http://www.ingentaconnect.com/content/ben/aiaamc/2012/00000011/00000003/art00008

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Background  Pemphigus foliaceus (PF) is a chronic cutaneous autoimmune blistering disease that is characterized by superficial blistering of the skin, and according to the current perspective is caused by autoantibodies directed against desmoglein 1 (Dsg1).

Objectives  To examine early acantholysis in skin of PF patients at an ultrastructural level.

Methods  Two Nikolsky negative (N-), five Nikolsky positive (N+) and two lesional skin biopsies of immunoserological defined PF patients were studied by light and electron microscopy.

Results  We found no abnormalities in N- PF skin, whereas all N+ skin biopsies displayed intercellular widening between desmosomes, a decreased number of desmosomes, and hypoplastic desmosomes in the lower epidermal layers. Acantholysis was present in two of five N+ biopsies, but only in the upper epidermal layers. The lesional skin biopsies displayed acantholysis in the higher epidermal layers. Hypoplastic desmosomes were partially (pseudo-half-desmosomes) or completely torn off from the opposing cell.

Conclusion  We propose the following mechanism for acantholysis in PF: initially PF IgG causes a depletion of non-junctional Dsg1, leading to intercellular widening between desmosomes starting in the lower layers and spreading upwards. Depletion of non-junctional Dsg1 impairs the assembly of desmosomes, resulting in hypoplastic and a decreased number of desmosomes. In addition antibodies might promote disassembly of desmosomes. In the upper layers of the epidermis, where Dsg3 is not expressed and cannot compensate for Dsg1 loss, ongoing depletion of Dsg1 will finally result in a total disappearance of desmosomes and subsequent acantholysis.

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2133.2012.11173.x/abstract

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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.