Is the combination of tetracycline and nicotinamide therapy alone effective in pemphigus?

Alpsoy, Erkan; Yılmaz, Ertan; Başaran, Erdal; Yazar, Şahin; Çetin, Lütfiye

doi:10.1001/archderm.131.11.1339

Cited by 25 publications

(8 citation statements)

References 4 publications

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“…Oral nicotinamide (niacinamide) is often used to treat pemphigus patients [280,281,308,309]. Although the exact mechanism of its therapeutic action in pemphigus remains unknown, the efficacy of 4% nicotinamide gel in the treatment of cutaneous erosions of PV patients in a double-blind, placebo-controlled study [310] suggests that it exerts a pharmacologic effect on target cells.…”

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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“…nicotinic acetylcholine receptor agonist choline (51)(52)(53) and inhibition of the acetylcholine hydrolyzing enzyme acetylcholinesterase (54,55) Used to treat PV patients both systemically and topically (35), producing steroid-sparing effects; usually combined with either tetracycline (32)(33)(34)56) or minocycline (57)…”

Section: ␣7mentioning

confidence: 99%

Mechanisms of Mitochondrial Damage in Keratinocytes by Pemphigus Vulgaris Antibodies

Kalantari-Dehaghi

Chen²,

Deng³

et al. 2013

Journal of Biological Chemistry

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Background: Previous studies suggested that mitochondrial antibodies contribute to pemphigus vulgaris (PV). Results: PV sera elicited mitochondrial damage, and mitochondria-protecting drugs exhibited protective effect in cell culture and mouse skin. Conclusion: PV antibodies altered O 2 respiration, disrupted electron transfer chain, and increased reactive oxygen species. Significance: Results provide the mechanism of therapeutic action and justify the use of mitochondria-protecting drugs in PV.

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“…Tetracycline at a dose of 2 g per day for 1 month reducing to 1 g per day for 4 weeks enabled more rapid tapering of corticosteroids in 13 patients with PV [93]. However the study by Alspoy found that a combination of tetracycline (2 g/d) and nicotinamide (1.5 g/d) for 2 months was not an effective alternative to the classic forms of therapy in 14 patients with pemphigus [92]. Further trials are needed before recommending these agents.…”

Section: Tetracycline Antibiotics and Nicotinamidementioning

confidence: 99%

Pemphigus Vulgaris and Pemphigus Foliaceus

Fernando¹,

Li²,

Schifter³

2013

Skin Biopsy - Diagnosis and Treatment

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four subtypes of desmoglein, which are glycoproteins that belong to a superfamily of cadherin molecules and are essential components of desmosomal intracellular adhesive junctions [8]. The molecular target in PF is desmoglein-1, which is found predominantly in the upper layers of the epidermis of the skin [9] [10]. Two subtypes of PV are described. In mucosal-dominant PV, the molecular target is restricted to desmoglein-3, whereas in mucocutaneous PV, the target is desmoglein-3 and desmoglein-1.[8] Desmoglein-3 is found in mucous membranes and predominantly in the lower layers of the epidermis of the skin and hence explains the absence of mucous membrane involvement in PF. Current evidence suggests that autoantibodies to desmogleins cause the loss of this desmosome from the surface of the keratinocyte and rearrangement of the actin cytoskeleton. This results in an unidentified cascade of signalling events resulting in apoptotic cell death and acantholysis [11]. Autoantibodies to desmoglein-3 and desmoglein-1 are paramount in the pathogenesis of PV and PF. In PV, this is demonstrated by the fact that passive transfer of serum IgG to desmoglein-3 into newborn mice induces blister formation [12]. Interaction between antigen specific T cells and B cells is postulated for the production of antibodies to desmoglein-3 and desmoglein-1. Autoantibody production has been shown, in vitro, to be dependent on mononuclear cells [13]. Further, aberrant T cell recognition of desmoglein-3 and desmoglein-1 is likely involved in the initiation and perpetuation of the B cell response. Additionally, in PV, HLA Class 2 alleles including HLA DRβ1*0402, β1*1401, β1*0503 may be involved in the presentation of desmoglein-3 peptides to autoreactive T cells. However, similar associations are not observed in PF [14]. Further it has been observed that autoantibodies of the Th2-dependent IgG4 subtype are present in active disease but are not detectable in inactive disease or healthy individuals [15]. In active disease, IgG1 and IgG4 recognises epitopes in EC1 (amino acids 50-79, Bos 1) and EC2 (amino acids 200-29, Bos 2) of desmoglein-3. In inactive disease, only autoantibodies of the Th1-dependent IgG1 subtype to EC1 are detectable [15]. These observations suggest that IgG4 against EC2 is the main antibody responsible for acantholysis, but that this process may be facilitated or enhanced by IgG4 against EC1 [14]. A Th2 response predominates in PV. This suggests that Th2 cells are needed to activate B cells to initiate antibody production [16]. Further, in PV and PF, imbalance between Th2 and Th1 cytokines in terms of the elevation of the former against the suppression of the latter is postulated to contribute to pathogenesis [16],[17]. It is possible that Th17 and Treg pathways may also be integral. However, the association between Th cell subsets and disease activity is not well understood. PV autoantibodies also bind large portions of keratinocytes outside desmosomal structures. Autoantibodies against other keratinocyte surface antigens suc...

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Is the combination of tetracycline and nicotinamide therapy alone effective in pemphigus?

Cited by 25 publications

References 4 publications

Pemphigus autoimmunity: Hypotheses and realities

Pemphigus autoimmunity: Hypotheses and realities

Mechanisms of Mitochondrial Damage in Keratinocytes by Pemphigus Vulgaris Antibodies

Pemphigus Vulgaris and Pemphigus Foliaceus

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