Gold sodium thiomalate treatment of pemphigus

Penneys, N. S.

doi:10.1001/archderm.108.1.56

Cited by 16 publications

(2 citation statements)

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“…IVIg [274], rituximab [275] and daclizumab [276]. Anti-inflammatory drugs: gold [277], dapsone [278], doxycycline [279], tetracycline [280], minocycline [281], tranilast [282], and thalidomide [283]. Extracorporeal autoantibody eliminations: plasmapheresis [284], plasma exchange [285], hemocarbofiltration [243], and protein A immunoadsorption [286].…”

Section: Treatment Of Pemphigusmentioning

confidence: 99%

Pemphigus autoimmunity: Hypotheses and realities

2011

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The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients.

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Section: Treatment Of Pemphigusmentioning

confidence: 99%

Pemphigus autoimmunity: Hypotheses and realities

2011

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“…Further elucidation of the mechanisms underlying the therapeutic activity of GS and other drugs that have been or are successfully used to treat pemphigus may shed light on the pharmacologic mechanisms mediating pemphigus IgG^induced acantholysis. Nonsteroidal treatments of pemphigus reported to date include the following drugs (in chronological order): quinine and strychnine (reviewed in Kartamyshev, 1949), organic arsenic compounds (Oppenheim, 1927), suramin (also known as germanin or nephuride) (Veiel, 1931), vitamin D (Ludy and DeValin, 1932), methotrexate (Lever and Goldberg, 1969), azathioprine (Wol¡ and Schreiner, 1969), cyclophosophamide (Krain et al, 1972), gold (Penneys et al, 1973), dapsone (Haim and Friedman-Birnbaum, 1978), heparin (Mashkilleyson, 1985), cyclosporine (Balda and Rosenzweig, 1986), quercetin and doxycyline (Grando, 1988), aprotinin and e-aminocaproic acid (Grando, 1992), nicotinamide and tetracycline (Cha⁄ns et al, 1993), minocycline (Sawai et al, 1995), p-aminomethylbenzoic acid (Dobrev et al, 1996), mycophenolate mofetil (Enk and Knop, 1997), and tranilast (Miyamoto and Takahashi, 1997). Surprisingly, a single mechanism of action common for GS and many of the above listed nonsteroid drugs is cholinergic activity ( Table 2).…”

Section: Cholinergic Side Effects Of Drugs Used To Treat Pemphigusmentioning

confidence: 99%

New Approaches to the Treatment of Pemphigus

Grando

2004

Journal of Investigative Dermatology Symposium Proceedings

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In pemphigus vulgaris, treatment with systemic glucocorticosteroids is life saving; it may, however, cause severe side effects, including death. A patient with pemphigus vulgaris and myasthenia gravis was treated for approximately five years with the cholinomimetic Mestinon (pyridostigmine bromide), Imuran (azathioprine), and a topical corticosteroid gel before the need to introduce systemic glucocorticosteroids. Because activation of keratinocyte acetylcholine receptors also has been shown to abolish pemphigus IgG-induced acantholysis in cultured keratinocyte monolayers, a clinical trial of Mestinon was initiated in patients with active pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic autoimmune multiorgan syndrome (also known as paraneoplastic pemphigus). First results indicate that nonsteroidal treatment of pemphigus is possible. Mestinon may be used to slow down progression of the disease and to treat mild cases with chronic lesions on limited areas. Stimulation of the keratinocyte- acetylcholine axis may lead to a therapeutic effect through any of the following mechanisms: (1) stimulating keratinocyte cell-to-cell attachment; (2) accelerating reepithelialization; and (3) competing with the disease-causing pemphigus antibodies, preventing them from attachment to keratinocytes. Glucocorticosteroids and various types of steroid-sparing drugs used to treat pemphigus exhibit cholinergic side effects, including effects on expression and function of keratinocyte adhesion molecules, that are very similar to those produced by the cholinomimetic drugs. Further elucidation of the mechanisms underlying therapeutic efficacy of antiacantholytics may shed light on the immunopharmacological mechanisms of pemphigus antibody-induced acantholysis.

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Inflammatory Dermatoses

2011

British Association of Dermatologists' Management Guidelines

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Gold sodium thiomalate treatment of pemphigus

Cited by 16 publications

References 0 publications

Pemphigus autoimmunity: Hypotheses and realities

Pemphigus autoimmunity: Hypotheses and realities

New Approaches to the Treatment of Pemphigus

Inflammatory Dermatoses

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