Monthly Archives: January 2013

Puppy-Love-puppies-9460996-1600-1200Pemphigus in Dogs

Pemphigus is the general designation for a group of autoimmune skin diseases involving ulceration and crusting of the skin, as well as the formation of fluid-filled sacs and cysts (vesicles), and pus filled lesions (pustules). Some types of pemphigus can also affect the skin tissue of the gums. An autoimmune disease is characterized by the presence of autoantibodies that are produced by the system, but which act against the body’s healthy cells and tissues — just as white blood cells act against infection. In effect, the body is attacking itself. The severity of the disease depends on how deeply the autoantibody deposits into the skin layers. The hallmark sign of pemphigus is a condition called acantholysis, where the skin cells separate and break down because of tissue-bound antibody deposits in the space between cells.

There are four types of pemphigus that affect dogs: pemphigus foliaceus, pemphigus erythematosus, pemphigus vulgaris, and pemphigus vegetans.

In the disease pemphigus foliaceus, the autoantibodies are deposited in the outermost layers of the epidermis, and blisters form on otherwise healthy skin. Pemphigus erythematosus is fairly common, and is a lot like pemphigus foliaceus, but less afflictive. Pemphigus vulgaris, on the other hand, has deeper, and more severe, ulcers because the autoantibody is deposited deep in the skin. Pemphigus vegetans, which affects only dogs, is the rarest form of pemphigus, and seems to be a gentler version of pemphigus vulgaris, with somewhat milder ulcers.

full article can be found here:

To evaluate the significance of the association of malignancy with autoimmune blistering diseases, we studied the incidence of internal malignancies in pemphigus and bullous pemphigoid based upon 496 cases of pemphigus and 1113 cases of bullous pemphigoid in Japan. Results showed that (1) an association between internal malignancies and pemphigus was observed in 25 out of 496 cases (5.0%), while that with bullous pemphigoid was seen in 64 out of 1113 cases (5.8%). Such association ratios were significantly higher than that of the controls aged over 70 years old (0.61%); (2) The average ages of pemphigus/bullous pemphigoid with malignancy were 64.7 and 69.2 years, respectively. The association ratio of malignancy with pemphigus increased by age, while that with pemphigoid was not correlated with aging;

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(3) Lung cancer was most common in pemphigus and gastric cancer in bullous pemphigoid; (4) There were no significant differences in the titers of circulating antibody, the presence or extent of mucous involvement or annular erythema between bullous pemphigoid patients with malignancy and without malignancy. Our results indicated that detailed examination for internal malignancy is essential for those patients with pemphigus or bullous pemphigoid.

Abstract from:

In BP lesional skin, immunohistochemistry and confocal microscopy were performed for CD4+, CD25+, forkhead/winged helix transcription factor (FOXP3)+, transforming growth factor (TGF)-β+ and interleukin (IL)-10+ cells. In addition, the number of CD4+CD25++FOXP3+ Tregs in peripheral blood was assessed by flow cytometry, and the levels of TGF-β and IL-10 were determined in serum samples by enzyme-linked immunosorbent assay before and after steroid therapy. Controls included patients with psoriasis, atopic dermatitis (AD) and healthy donors.

The frequency of FOXP3+ cells was significantly reduced in skin lesions from patients with BP (P < 0.001) compared with psoriasis and AD. Moreover, the number of IL-10+ cells was lower in BP than in psoriasis (P < 0.001) and AD (P = 0.002), while no differences were observed in the number of TGF-β+ cells. CD4+CD25++FOXP3+

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Treg in the peripheral blood of patients with BP was significantly reduced compared with healthy controls (P < 0.001), and augmented significantly after steroid therapy (P = 0.001). Finally, TGF-β and IL-10 serum levels were similar in patients with BP compared with healthy controls. However, after therapy, BP patients showed significantly higher IL-10 serum levels than before therapy (P = 0.01).

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Antiga, E., Quaglino, P., Volpi, W., Pierini, I., Del Bianco, E., Bianchi, B., Novelli, M., Savoia, P., Bernengo, M.G., Fabbri, P. and Caproni, M. (2013), Regulatory T cells in skin lesions and blood of patients with bullous pemphigoid. Journal of the European Academy of Dermatology and Venereology. doi: 10.1111/jdv.12091

“I have been in remission now for over 1 year (YES!!!). That is complete remission with no symtpoms and no meds. I was diagnosed in 2004 and rode the roller coaster of varying doses of prednisone coupled with Cellcept at first and then Imuran. After many ups and downs, 4 years of meds, and a very slow taper of prednisone, I was able to go off of all meds and have been doing great for the past year. My treatment was with Dr. Anhalt, who I am extremely grateful to for his knowledge and compassion.

I have never done IVIG or Rituxan although these therapies were discussed as options had I not finally started doing well on the meds I was on. I do have to say, however, that I have never taken zinc or niacinamide, so I cannot owe my remission to that.

I think that it is wonderful that we have alternative therapies such as Rituxan and IVIG. My understanding is that most of the time, these treatments are used for those patients who do not respond well to traditional therapies. I know there are people in {the discussion)} group who have had tough battles and have not responded well to prednisone and immunosuppressive therapies. I think that is when these other treatments come into play.

I think using supplements can be very wonderful and if it works for some, then that is great. I don’t think, however, it’s always enough for everyone. And, I think with this disease, the treatment and journey is different for us all.”

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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.

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