epidermal-growth-factor and Pemphigus

A range of interventions has been described for the treatment of pemphigus; however, the optimal therapeutic strategy has not been established.. We sought to evaluate the safety and efficacy of interventions for pemphigus vulgaris and pemphigus foliaceus.. We undertook a systematic review and meta-analysis according to the methodology of the Cochrane Collaboration. We selected randomized controlled trials including participants with the diagnosis of pemphigus vulgaris or pemphigus foliaceus confirmed with clinical, histopathological, and immunofluorescence criteria. All interventions were considered. Primary outcomes studied were remission and mortality. Secondary outcomes included disease control, relapse, pemphigus severity score, time to disease control, cumulative glucocorticoid dose, serum antibody titers, adverse events, and quality of life.. Eleven studies with a total of 404 participants were identified. Interventions assessed included prednisolone dose regimen, pulsed dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor, and traditional Chinese medicine. We found some interventions to be superior for certain outcomes, although we were unable to conclude which treatments are superior overall.. Many interventions for pemphigus have not been evaluated in controlled trials. All studies were insufficiently powered to establish definitive results.. There is inadequate evidence available at present to ascertain the optimal therapy for pemphigus vulgaris and pemphigus foliaceus. Further randomized controlled trials are required.

Topics: Azathioprine; Cyclophosphamide; Epidermal Growth Factor; Glucocorticoids; Humans; Immunosuppressive Agents; Mycophenolic Acid; Pemphigus; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome

Pemphigus is a rare autoimmune bullous disorder. Numerous treatment regimens have been proposed in the literature.. To assess the efficacy and tolerance of treatment regimens proposed in pemphigus vulgaris (PV) and pemphigus foliaceus (PF), from a systematic review of the literature.. Randomized control trials have been identified using the PubMed and Embase databases up to April 2009. Uncontrolled prospective and retrospective studies have also been analyzed.. Eleven randomized control trials having included a total number of 421 patients (377 PV, 44 PF) have been analyzed. Most studies had a limited statistical power due to the rather low number of cases included. Results from ten different treatment regimens have been analyzed: different dosages of prednisone and prednisolone, pulse intravenous dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate mofetil, plasmapheresis, topical applications of epidermal growth factor (EGF), and intravenous immune globulins (IVIG). Inclusion criteria were: (i) consecutive patients in nine studies, (ii) patients who did not respond to low doses of corticosteroids in one study, and (iii) patients with relapsing type of pemphigus in one study. None of these studies allowed identifying the best effective and well tolerated regimen. Mycophenolate mofetil was more effective than azathioprine for disease control (from one study; n=40; OR=0.72; 95% CI=0.52-0.99). However, no difference in the rate of clinical remission was evidenced between these drugs. Azathioprine and cyclophosphamide seem to have a corticosteroid sparing effect.. Data from the literature did not allow identifying the best therapeutic regimen, mainly because of the lack of statistical power of most studies. The usefulness of immunosuppressant added to systemic corticosteroids as the first line of treatment is not clearly established.

Topics: Adrenal Cortex Hormones; Combined Modality Therapy; Drug Therapy, Combination; Epidermal Growth Factor; Gold Compounds; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Meta-Analysis as Topic; Multicenter Studies as Topic; Niacinamide; Paraneoplastic Syndromes; Pemphigus; Plasma Exchange; Prospective Studies; Randomized Controlled Trials as Topic; Recurrence; Retrospective Studies; Tetracycline

Treatment modalities in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are many and varied, although level 1 evidence supporting their use is limited. To date, only 2 systematic reviews exist to support the use of different treatment modalities to control this group of conditions. Overall, within the literature, the quality of trials comparing treatment modalities is poor. Cohort sizes are small, methodologies are varied, and standardized outcome measurements are lacking. The authors aim to present a comprehensive view of the level 1 evidence that exists for common treatment modalities used in PV and PF.

Topics: Azathioprine; Cyclophosphamide; Cyclosporine; Dapsone; Dermatologic Agents; Epidermal Growth Factor; Evidence-Based Medicine; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Medicine, Chinese Traditional; Mycophenolic Acid; Pemphigus; Pentoxifylline; Plasmapheresis; Randomized Controlled Trials as Topic; Sulfasalazine; Tacrolimus

Pemphigus vulgaris (PV) is a severe blistering disease involving the skin and mucous membranes. The most common causes of death in these patients are adverse effects of drugs, and infection. Skin lesions are one of the important sources of infection. Thus, any local treatment that could reduce healing time of lesions and consequently reduce the total dosage of drugs needed to treat is favourable.. To evaluate the efficacy of epidermal growth factor (EGF) in reducing healing time of lesions in patients with pemphigus vulgaris.. In this randomized, double-blind, within-patient, left/right, controlled trial, 20 hospitalized patients with pathologial and immunohistologial (direct and indirect immunoflourecence) proven pemphigus vulgaris (PV) were chosen. In addition, all patients had at least one appropriate pemphigus lesion on each side of the body that had not healed after 2-week systemic therapy and sterile saline washing. EGF (10 microg/g) in 0.1% silver sulfadiazine cream vs. 0.1% silver sulfadiazine cream alone was applied randomly on one side of the body.. Kaplan-Meier survival analysis suggested that median time to heal with application of EGF plus silver sulfadiazine cream was 9 days, in comparison with 15 days for silver sulfadiazine cream alone (log-rank test, P=0.0003). No intervention-related adverse effect was observed during the study.. EGF can significantly reduce healing time of skin lesions in patients with pemphigus vulgaris, at least when this cream base is applied (Cochrane skin group identifier: CSG20).

Topics: Adult; Aged; Double-Blind Method; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Pemphigus; Wound Healing

Pemphigus vulgaris (PV) is an autoimmune blistering disease characterized by the presence of IgG autoantibodies against Dsg3. Our aim was to investigate the molecular events implicated in the development and localization of apoptosis and acantholysis in PV. We used a passive transfer mouse model together with immunohistochemical (IHC) techniques and the TUNEL assay, with quantification analysis in the basal layer of the epidermis. The activated signalling molecules analysed and apoptotic cells detected showed an identical localization. Herein, we found for the first time in vivo an increased expression of activated HER receptor isoforms in the basal layer in PV lesions. Besides, we observed the almost total lack of activated Akt compared with a higher level of activated mTOR within the basal cells of the epidermis. Our observations strongly support that the restriction of acantholysis to the basal layer may be due, at least in part, to the selective and increased presence of activated HER receptor isoforms in these cells. After phosphorylation of HER receptor isoforms, intracellular signalling pathways are activated in the basal layer. In addition, the imbalance in Akt/mTOR that takes place in the basal cells may provide intracellular signals necessary for the development of apoptosis and acantholysis.

Topics: Acantholysis; Animals; Apoptosis; Betacellulin; Carrier Proteins; Disease Models, Animal; Enzyme Activation; Epidermal Growth Factor; Epidermis; ErbB Receptors; Erlotinib Hydrochloride; Humans; Immunoglobulin G; Intercellular Signaling Peptides and Proteins; Intradermal Tests; Isoenzymes; Mice; Mice, Inbred C57BL; Pemphigus; Phosphotransferases (Alcohol Group Acceptor); Proto-Oncogene Proteins c-akt; Pyrazoles; Pyrimidines; Quinazolines; Sirolimus; src-Family Kinases; TOR Serine-Threonine Kinases; Transforming Growth Factor alpha

A murine monoclonal antibody (ECS-1) was prepared from BALB/c mice immunized with trypsinized cultured human foreskin keratinocytes. The antibody showed a pattern suggestive of intercellular staining on the nucleated layers of normal human epidermis, adult palm, mouse lip epidermis, and cultured human keratinocytes. ECS-1 stained human fetal skin by 9 weeks estimated gestational age. ECS-1 reacted with a 35 kD protein extracted from neonatal foreskin epidermis and cultured human keratinocytes. The protein required Nonidet P-40 or sodium dodecyl sulfate and mercaptoethanol for solubilization. ECS-1 induced epidermal cell detachment which was enhanced by complement. ECS-1 shares characteristics with human pemphigus antibodies.

Topics: Animals; Antibodies, Monoclonal; Epidermal Growth Factor; Female; Fluorescent Antibody Technique; Humans; Mice; Mice, Inbred BALB C; Pemphigus