Pemphigus vulgaris. Combined treatment with intravenous corticosteroid pulse therapy, plasmapheresis, and azathioprine

Fine, Jo‐David; Appell, Melanie; Green, Linda K.; Sams, W. Mitchell

doi:10.1001/archderm.124.2.236

Cited by 30 publications

(17 citation statements)

References 13 publications

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“…Subsequent in vivo experiments demonstrated that administration of methylprednisolone significantly decreased the extent of acantholysis in the epidermis of 3-5-day-old nude mice injected with PV IgG [214]. This was in keeping with the clinical observations that blistering in pemphigus patients stops within 24-48 hrs after initiation of a high dose, “pulse” therapy with methylprednisolone or dexamethasone [293-296], while the major decline in autoantibody titers occurs 3-4 weeks after initiation of glucocorticoid therapy [297]. It is well known that pemphigus therapy improves disease earlier than decreasing the antibody titers [298].…”

Section: Treatment Of Pemphigusmentioning

confidence: 63%

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: 63%

Pemphigus autoimmunity: Hypotheses and realities

2011

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“…6,7 Since then, plasma exchange has been described as an effective adjuvant therapy in PV patients in controlling disease activity by reducing serum levels of autoantibodies. 4,[8][9][10][11][12][13][14][15][16] Turner et al 17 treated seven patients with severe or resistant pemphigus vulgaris with a series of five plasma exchanges over an average of 8 days with administration of immunosuppressive drugs immediately after plasmapheresis. Remission or partial remission was induced in six patients.…”

Section: Discussionmentioning

confidence: 99%

The role of therapeutic plasma exchange in pemphigus vulgaris

Sagi

Baum

Gendelman

et al. 2010

Journal of the European Academy of Dermatology and Venereology

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“…Although the antiacantholytic effect of glucocorticosteroids is attributed to immunosuppression, high doses of glucocorticosteroids can directly block PV IgG-induced acantholysis in vitro 1,2 and rapidly (within 48 hours) stop blistering in patients with pemphigus without altering the titer of autoantibodies or blocking antibody binding to keratinocytes ("pulse therapy"). [3][4][5] Patients develop autoantibodies to keratinocyte cholinergic receptors regulating cell adhesion. 6 Activation of these receptors mimics antiacantholytic effects of glucocorticosteroids in vitro.…”

Section: Discussionmentioning

confidence: 99%