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Pemphigus vegetans (P Veg), the rarest form of pemphigus, is thought to be a variant of pemphigus vulgaris (PV). Classically, two subtypes of P Veg are recognized: (1) Neumann P Veg, which usually begins as PV with vesicles and bullae that rupture to form hypertrophic granulating erosions, then evolving into vegetating exuding masses; (2) Hallopeau P Veg, initially characterized by pustular lesions that, after rupturing, merge and gradually evolve into vegetating erosions with a centrifugal expansion. The disease typically affects the big folds (axillary, inframammary, inguinocrural, intergluteal), where semiocclusion, maceration, and mixed infections continuously incite exudation and granulation tissue formation (wet P Veg). In nonintertriginous locations, the vegetating buttons can dry out to change into warty, fissured, painful, seborrheic keratosis-like lesions (dry P Veg). Histologic examination indicates hyperplastic epidermis with intramalpighian leukocyte microabscesses and indistinct traits of suprabasal acantholysis. Immunofluorescence findings are similar to those of PV. Diagnosis is straightforward when PV lesions coexist. Difficulties can arise in cases with nonflexural location. Cytology (Tzanck test), histology, immunofluorescence, and ELISA search for anti-desmoglein antibodies are the diagnostic laboratory tools. Systemic treatment is similar to that for PV, high-dose steroids being the first choice therapy. Immunosuppressive agents and etretinate may allow a steroid-sparing effect. Topical treatment is aimed at countering the granulation tissue formation by means of several strategies (sublesional steroid injection, application of medicated gauzes in the involved flexures, chemical cautery or surgical excision of vegetating lesions)., (Copyright © 2015. Published by Elsevier Inc.)

Virus infections and autoimmunity have long been linked. As to pemphigus, many studies have been directed to prove or rule out the possibility of viral induction. Herpesviruses have often been related to the onset or reactivation of pemphigus. The association may be (i) casual, (ii) due to the iatrogenic immunosuppression facilitating opportunistic viral infections or (iii) based on a pathogenic link between the viral presence and the host's dysregulated immune response leading to autoimmunity. Japanese researchers, using real-time polymerase chain reaction, lately detected herpes simplex virus DNA in the saliva from pemphigus patients at the earliest stage of the disease and with no signs or history of herpetic infection, thus confirming the possible existence of cases of pemphigus induced by herpesviruses. These selected cases could be included into the innovative concept of 'paraviral eruptions', where an inciting role for induction may be played by the concomitant intake of certain drugs.

Pemphigus, a prototypical organ-specific human autoimmune disease, may be associated with other immunity-related disorders, viral infections, and different types of tumors. Coexistence with immune diseases is fairly frequent and, for some of them (eg, myasthenia gravis, Basedow's disease, rheumatoid arthritis, or lupus erythematosus), common pathogenic mechanisms can be considered. The association with viral infections (mainly herpesvirus infections) raises the question of whether the virus triggers the outbreak of the disease or simply complicates its clinical course. Neoplastic proliferations coexisting with pemphigus have a different histogenesis and the pathogenic link may vary according to the associated tumor (thymoma, lymphoma, carcinoma, or sarcoma). A subset of pemphigus-neoplasia association is represented by Anhalt's paraneoplastic pemphigus, with peculiar clinical, histologic, and immunologic features characterizing it. Coexistence of pemphigus with Kaposi's sarcoma, albeit not frequent, offers an intriguing speculative interest. The cornerstone of management in pemphigus is the combination of systemic corticosteroids and immunosuppressants. The conventional treatment used in most cases is based on oral administration of deflazacort and azathioprine. In selected cases, mycophenolate mofetil is preferred to azathioprine. Severe forms of pemphigus require intravenous pulse therapy with dexamethasone (or methylprednisolone) and cyclophosphamide. In the recent years, the use of high-dose intravenous immunoglobulin therapy has gained several consents. Rituximab, a monoclonal anti-CD 20 antibody, which affects both the humoral and cell-mediated responses, has proved to give a good clinical response, often paralleled by decrease of pathogenic autoantibodies. The combination with intravenous immunoglobulin offers the double advantage of better clinical results and a reduced incidence of infection. Interventional treatments, such as plasmapheresis and extracorporeal immunoadsorption, are aimed at patients with life-threatening forms of pemphigus and high levels of circulating autoantibodies, a circumstance where the medical therapy alone risks failing. Second-line treatments include gold salts (which we do not favor because of the acantholytic potential inherent in thiol structure) and the association of oral tetracyclines with nicotinamide, which is rather safe. Local treatments, supplementary to the systemic therapy, are aimed at preventing infections and stimulating reepithelialization of eroded areas. Innovative topical treatments are epidermal growth factor, nicotinamide gel, pimecrolimus, and a proteomics-derived desmoglein peptide. Pemphigus patients should be warned against over-indulging in unnecessary drug intake, prolonged exposure to ultraviolet rays, intense emotional stress, and too spiced or too hot foods. Cigarette smoking is not contraindicated in pemphigus patients because of the nicotine anti-acantholytic properties., (Copyright © 2013. Published by Elsevier Inc.)

Pemphigus includes a group of autoimmune bullous diseases with intraepithelial lesions involving the skin and Malpighian mucous membranes. Pemphigus vulgaris (PV), the most frequent and representative form of the group, is a prototypical organ-specific human autoimmune disorder with a poor prognosis in the absence of medical treatment. The pathomechanism of PV hinges on autoantibodies damaging cell-cell cohesion and leading to cell-cell detachment (acantholysis) of the epidermis and Malpighian mucosae (mainly oral mucosa). A controversy exists about which subset of autoantibodies is primarily pathogenic: the desmoglein-reactive antibodies or those directed against the acetylcholine receptors of the keratinocyte membrane. The onset and course of PV depend on a variable interaction between predisposing and inducing factors. Genetic predisposition has a complex polygenic basis, involving multiple genetic loci; however, the genetic background alone ("the soil"), although essential, is not by itself sufficient to initiate the autoimmune mechanism, as proven by the reports of PV in only one of two monozygotic twins and in only two of three siblings with an identical PV-prone haplotype. The intervention of inducing or triggering environmental factors ("the seed") seems to be crucial to set off the disease. The precipitating factors are many and various, most of them directly originating from the environment (eg, drug intake, viral infections, physical agents, contact allergens, diet), others being endogenous (eg, emotional stress, hormonal disorders) but somehow linked with the subject's lifestyle. As to certain drugs, their potential of provoking acantholysis may be implemented by their interfering with the keratinocyte membrane biochemistry (biochemical acantholysis) and/or with the immune balance (immunologic acantholysis). Viral infections, especially the herpetic ones, may trigger the outbreak of PV or simply complicate its clinical course. The precipitating effect might be due to interferons and other cytokines released by the host as a consequence of the viral attack, which overactivate the immune response. Inductions of PV by physical agents (ultraviolet or ionizing radiation, thermal or electrical burns, surgery and cosmetic procedures), contact allergens (in particular, organophosphate pesticides), dietary factors (eg, garlic, leek, onion, black pepper, red chili pepper, red wine, tea), and emotional stress are rare, but well-documented events. The possible intervention of the environment in the outbreak of PV has been overlooked in the past, but nowadays clinicians perceive it more frequently. The assumption that genetic factors alone are not sufficient to cause the outbreak of the disease, inevitably instills the idea that PV may not occur spontaneously, but always results from an interaction between an individual predisposing genetic background and environmental precipitating factors, often concealed or apparently harmless., (Copyright © 2013. Published by Elsevier Inc.)

Pemphigus is an autoimmune disease that results from the interaction between predisposing genetic factors and exogenous agents, mainly drugs and viruses. Herein we report the case of a 66-year-old woman referred to our department for the onset of painful oral erosions and bullous lesions on the torso. Clinical, laboratory and histopathological investigations led to the diagnosis of pemphigus vulgaris. Two weeks before the outbreak of the lesions, the patient had suffered from a viral pharyngitis, subsequently diagnosed as herpangina, and had been taking an oral cephalosporin (cefixime) for 1 week to prevent possible bacterial complications. A relationship between the onset of pemphigus and coxsackievirus infection or cefixime administration or both was supposed. The case may represent a peculiar paraviral eruption, where a predisposing pemphigus-prone genetic background paved the way for the acantholytic autoimmune disorder as a consequence of the combined effect of the coxsackievirus infection and the cephalosporin treatment., (Copyright 2008 S. Karger AG, Basel.)

Pemphigus is a chronic, autoimmune disease involving the skin and Malpighian mucous membranes. Pemphigus leads to progressive blistering and subsequent erosions. This article describes the etiology and treatment of pemphigus.

The current knowledge on Pemphigus vulgaris (PV) pathophysiology suggests that blister formation relies on both PV IgG and non-IgG serum factors activity. PV autoimmunity seems to develop against both desmoglein 1/3 and acetylcholine receptors leading to transduction of signals to the cell mediated by phosphorilation events. Serum factors other than IgG also participate to PV acantholysis through apoptotic or cytokine-mediated mechanisms. Apart from the role played by each actor within the acantholysis, however, the current scenario arises important methodological issues. For example, the use of PV IgG or monoclonal anti-Dsg3 antibodies to experimentally reproduce the disease appears inadequate, as it does not take into account the role of non-IgG factors. On the basis of the above observations and those from our laboratories, here we propose that using whole sera from PV patients with active disease represents the most faithful manner to mimic the disease.

A possible mechanism for phenol-induced pemphigus lesions in genetically predisposed individuals is proposed that accounts for in vitro observations and cases of biochemical acantholysis, as well as the in vivo acantholysis in pemphigus induced by phenols. The mechanism involves the induction of interleukin-1a and tumor necrosis factor-a release by keratinocytes. These cytokines in turn have been shown to be involved in the regulation and synthesis of complement and proteases like plasminogen activator, which have been implicated in the pathogenesis of acantholysis in pemphigus vulgaris.

Pemphigus vulgaris (PV) is a rare autoimmune bullous dermatosis with a high mortality rate if untreated. The disease results from autoimmunity to normal components of keratinocyte cell membrane (desmogleins 3 and 1) belonging to the cadherin supergene family. Standard therapy for PV is based on a combined administration of high-dosed glucocorticoids and immunosuppressive drugs. In patients with severe, life-threatening, or recalcitrant PV, stronger therapeutic options should be considered, such as 'pulse-therapy' with discontinuous intravenous infusion of megadoses of immunosuppressive drugs over a short-time, plasmapheresis, and extracorporeal immunoadsorption of pathogenic autoantibodies using the extracellular domain of the PV main antigen (desmoglein 3) produced by baculovirus or, more recently, a tryptophan-linked polyvinyl alcohol adsorber.

The apoptotic cell has recently been shown to play a central role in tolerizing B cells and T cells to both tissue-specific and ubiquitously expressed self-antigens, and to possibly drive the autoimmune response in systemic lupus erythematosus, an autoimmune disease which bears many similarities to pemphigus. We now propose a similar mechanism in the induction of pemphigus, namely, that a dysregulation in apoptosis expressed as an impairment of normal programmed cell death of epidermal keratinocytes and/or deficient and inadequate clearance of apoptotic material (specifically, desmoglein) may render it antigenic with the consequent production of autoantibodies. The fact that some thiol-containing compounds which are well-known inducers of acantholysis in vitro and pemphigus in vivo were shown to inhibit apoptosis might support our hypothesis.

Background: Captopril is an angiotensin-converting enzyme inhibitor with sulphydryl groups in its chemical structure. It is commonly used as an antihypertensive drug. The occurrence of pemphigus vulgaris has repeatedly been reported in patients receiving captopril. The capacity of captopril and pemphigus serum to induce acantholysis, in vivo or in vitro, has been demonstrated experimentally., Objectives: To show that captopril and pemphigus serum, acting by a biochemical and immunological mechanism, respectively, trigger apoptosis., Methods: Human keratinocyte cells were treated with 15 mmol L-1 captopril or with pemphigus serum. DNA was extracted and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling method was used to detect apoptosis., Results: DNA fragmentation occurred after 72 h of treatment. Increased expression of p53, c-myc and inducible nitric oxide (NO) synthase (iNOS) mRNA were observed by polymerase chain reaction (PCR) in the treated cells compared with the untreated ones. The increase in iNOS gene expression was associated with overproduction of NO. Moreover, the addition of 1 mmol L-1N-monomethyl-L-arginine, a structural analogue of arginine, reduced nitrite levels by about 70% in cells treated with captopril or pemphigus serum. Western blot analysis revealed an overexpression of heat shock protein 70 (hsp70) in cells treated with captopril or pemphigus serum. Finally, total inhibition of the keratinocyte transglutaminase gene was shown by PCR analysis in the same samples, compared with control cells., Conclusions: These data demonstrate the involvement of apoptosis in keratinocytes treated with captopril or pemphigus serum, with induction of the iNOS gene and hsp70 in the cascade of events leading to programmed cell death.

Background: Pemphigus is a chronic auto-immune blistering disease with four main variants, i.e. pemphigus vulgaris (PV), foliaceus (PF), erythematosus (PE) and vegetans. The common histological feature of this disease is acantholysis., Objective: The aim of this study was to compare levels of some cytokines in blister fluid and sera of patients with pemphigus, using as control blister fluid of patients with bullous pemphigoid (BP) and bullous contact dermatitis (BCD)., Methods: Using an immuno-enzymatic assay (ELISA), we tested 16 sera and 6 blister fluids of patients with various forms of pemphigus (13 with PV, 1 with PF, 2 with PE), the sera of 16 healthy control subjects, 5 blister fluids of patients with BP and 5 blister fluids of patients with BCD, for the presence of some cytokines (IL-10, IL-8 and IFN-gamma). Intercellular antibodies were searched for and titred; desmoglein 1 and 3 antibody levels were independently evaluated to compare them with the severity of both cutaneous and oral involvement., Results: The levels of IL-10 in the sera of patients with pemphigus were below the detection limits. IL-8 was significantly increased only in 4 samples of sera from pemphigus patients compared with controls, while IFN-gamma was detected at low levels in almost all patients compared with sera of controls. The cytokine levels in blister fluid of patients with pemphigus were significantly higher than in the sera. There was a difference between the expression of cytokines in blister fluid of control patients with BP and BCD compared with those of pemphigus patients., Conclusion: This report discusses the anti-inflammatory role played by IL-10 in the chronic form of pemphigus and the hypothesis of a possible role of IL-8 in neutrophil and lymphocyte-monocyte recruitment., (Copyright 2002 S. Karger AG, Basel)

Background: There have been reports suggesting the involvement of environmental factors in the disease process of pemphigus. Factors suggested include exposure to pesticides or certain drugs., Objective: To analyze the association of pemphigus with environmental exposure to various agents, including smoking, recreational and occupational insults, drugs, and food., Design and Setting: In-person interviews of pemphigus patients and control subjects were conducted by trained medical investigators using a structured questionnaire. Questions included occupational, behavioral, medical, and qualitative food frequency details. The multicenter study was conducted at outpatient services of teaching hospitals in Bulgaria, Brazil, India, Israel, Italy, Spain, and the USA., Participants: A total of 126 pemphigus patients (55 men, 71 women; age, 54 +/- 17 years) and 173 healthy controls (87 men, 86 women; age 50 +/- 19 years) were interviewed in the period between October 1, 1999 and March 31, 2000. The diagnosis of pemphigus was based on clinical, histologic, immunohistologic, and immunohistochemical criteria. The disease duration was 2-27 years (8.4 +/- 7.2 years). Individuals with skin diseases other than pemphigus were selected as control subjects., Main Outcome Measure: Information on drugs, foods, and occupational, environmental, constitutional, and other possible risk factors was analyzed by t-tests and chi-squared tests as applicable. A multivariate logistic regression model was applied to the data to study simultaneously the independent relationship between each risk factor and pemphigus vulgaris., Results: The risk for pemphigus vulgaris was lower for ex-smokers and current smokers than for patients who had never smoked. Exposure to pesticides and occupational exposure to metal vapor were associated with an increased risk of pemphigus. Pemphigus patients had more pregnancies than controls. There were differences in environmental factors between countries, with exposure to gardening materials and pesticides being highest among patients from Bulgaria, followed by Israel. Disease characteristics also exhibited differences between countries. Bulgarian patients less frequently had oral mucous membrane lesions: 66% compared to 92% for Israeli patients and 83% for Italians. The distribution of the disease in skin and mucous membranes was similar among patients from all countries. Exclusive skin involvement was seen in 50% of patients, mucous membranes alone in 23% of patients, and both skin and mucous membranes in 27% of patients., Conclusions: The beneficial effect of smoking on pemphigus might be explained by its effect on the immune system. In addition, smoking has an antiestrogenic effect, while pesticides have an estrogenic effect. The lower numbers of smokers among patients, the higher exposure rates to pesticides, and the higher number of female patients who had been pregnant may point to the contribution of estrogens to the disease process. It remains to be determined whether measures, such as avoiding exposure to pesticides or metal vapor, may be beneficial in the clinical context. As the present study was a survey, more definitive studies should be conducted to validate the results.

The onset and course of pemphigus are often the result of an interaction between predisposing genetic factors and environmental triggering agents. The latter are heterogeneous, numerous and increasing, ranging from drug intake (the commonest cause of pemphigus induction) to the exposure to physical agents (heat, UV and ionizing rays, surgical and cosmetic procedures), viral infections (especially by herpesvirus), contact dermatitis, certain diet ingredients and even emotional stress. Alerting physicians and pemphigus patients to the effects that unsuspected precipitating factors may have on the progression of the disease is an important task. In fact, avoiding or limiting deleterious habits (e.g. overindulging in unnecessary drugs) and suggesting alternative ways (e.g. substituting potentially pemphigus-inducing drugs with others considered harmless in this respect) may be a useful precaution in the management of pemphigus patients, since it can improve the efficacy of conventional treatments, reduce the risks of relapses and sometimes result in a cure., (Copyright 2001 S. Karger AG, Basel)

Pemphigus is an autoimmune disease where both endogenous (genetic) and exogenous (environmental) factors play a part. Viral infections, in particular herpesvirus infections, have been identified as a possible triggering factor for pemphigus. In this study, using the polymerase chain reaction, we studied peripheral blood mononuclear cells (PBMC) and skin biopsies from patients with pemphigus, and in some of these were able to demonstrate the presence of DNA sequences of herpes simplex virus 1/2 (50% in PBMC and 71% in skin biopsies), Epstein-Barr virus (15% in PBMC and 5% in skin biopsies) and human herpesvirus 6 (20% in PBMC only). However, the inability to detect herpesvirus DNA consistently in these cases suggests that viral infection may only be an occasional factor triggering the outbreak or exacerbation of the disease. The possible role of interferons and interleukins in the pathogenesis of virus-induced pemphigus is discussed.

Similar lesion topography which resembled an inverted fir tree in two patients with nifedipine-related pemphigus vulgaris is described. The possible relation of the lesion pattern to the offending drug is discussed.

Pemphigus refers to a group of autoimmune blistering skin diseases, mainly identified as pemphigus vulgaris and pemphigus foliaceus, both characterized by the presence of autoantibodies against keratinocyte adhesion molecules, leading to loss of cell-cell adhesion with consequent blister formation. Pemphigus vulgaris is reported to be associated with human leukocyte antigen DR4 and/or DR6 whereas no data are available on pemphigus foliaceus, except for the endemic Brazilian form (fogo selvagem), which is reported to be associated with DR1 and DR4. We here report human leukocyte antigen molecular typing on a total of 87 patients, 61 with pemphigus vulgaris and 26 with pemphigus foliaceus, versus 128 healthy matched controls. Generic typing showed an increase of DRB1*04 and DRB1*14 and a decrease of DRB1*07 in both pemphigus vulgaris and pemphigus foliaceus patients. Molecular subtyping of DR4+ and DR14+ subjects showed a highly significant association between the DRB1*1401 and both pemphigus vulgaris (p < 0.0001) and pemphigus foliaceus patients (p < 0.0001) together with a significant increase of the linked DQB1*0503 (pemphigus vulgaris p < 0.0001; pemphigus foliaceus p < 0.0001). Moreover, whereas the association between DRB1*0402 and pemphigus vulgaris (p < 0.0001) has been confirmed, no significant association between a specific allele of the DR4 group and pemphigus foliaceus, has been found. Therefore, at least in Italian patients, pemphigus vulgaris and pemphigus foliaceus share DRB1*1401 and DQB1*0503, as susceptible human leukocyte antigen alleles, whereas DRB1*0402 is only found associated with pemphigus vulgaris. The observation that both diseases, pemphigus vulgaris and pemphigus foliaceus, carry the same susceptible human leukocyte antigen alleles has been interpreted as a common genetic background predisposing to pemphigus as, like in other autoimmune disorders, it is not sufficient to explain the onset of the disease on the basis of the sole aforementioned alleles. Other linked genes and/or environmental factors should play a facilitating role in the outbreak of pemphigus, either pemphigus vulgaris or pemphigus foliaceus.

Background: A variety of drugs have been implicated in the onset and exacerbation of pemphigus and bullous pemphigoid. The demonstration of biochemical acantholysis in skin explants to various drugs in the absence of autoantibodies, in which the tested drugs evoke a biochemical reaction that leads to desmosomal function loss, may be a valuable adjunct to patient management by confirming the suspicion of drug-related pemphigus or bullous pemphigoid., Objective: To determine whether a skin explant model might serve as a possible in vitro correlate of drug-induced pemphigus and pemphigoid-like effects related to the calcium channel blocker nifedipine., Methods: Normal human breast skin obtained from nonpemphigus and nonpemphigoid patients undergoing mastectomy was cultured with nifedipine at final concentrations of 2, 4, and 8 mM. The drug effect on skin explants evidenced by morphologic changes was evaluated by microscopy by three observers., Results: Five out of seven explants cultured with nifedipine at concentrations ranging from 2 to 8 mM exhibited obvious morphologic changes of two types: intraepithelial (or pemphigus-type) splittings and subepithelial (or pemphigoid-type) splittings. Two explants showed no acantholysis and no subepithelial splittings. Control cultures without polyethylene glycol 200 (PEG) showed no changes. Skin control samples cultured in medium supplemented with 10% PEG displayed vacuolar degeneration throughout the entire epidermis, but no sign of cell-cell dyshesion or dermo-epidermal detachment., Conclusions: A type of skin susceptibility to nifedipine may be genetically determined, with some nifedipine-treated patients developing an acantholytic reaction and others a subepidermal bullous eruption.

The extension of the blisters of pemphigus to the esophagus is relatively uncommon, especially in patients treated with corticosteroids who appear to be in clinical remission. The aim of this study was to evaluate the esophagus in eight patients affected by oral pemphigus in various stages of the disease. Upper gastrointestinal endoscopy revealed esophageal involvement in five patients (two men and three women); three had blisters or erosions in the upper esophagus, whereas two showed red longitudinal lines along the entire organ. Direct immunofluorescence was positive in all eight patients. It is suggested that endoscopic examination of esophageal mucosa is an objective criterion by which to judge the success of therapy of pemphigus vulgaris.

Eighteen patients, ten affected by pemphigus vulgaris and four affected by herpes simplex of the oral mucosa, together with four healthy patients as controls, were investigated by cytologic examination of Papanicolaou stained smears obtained by scraping the oral mucosa. In all cases additional smears were immunostained with the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique using monoclonal antibodies against human heavy IgG chains and lambda light chains. The results have shown that, for a cytological diagnosis of pemphigus, this technique can be used as an easy substitute for the immunofluorescence test and does not require any specialized training or equipment. The findings are clearly detectable by light microscopy and allow, together with the immunostaining, an adequate visualization of cell morphology.

An experimental investigation has lately shown that certain allyl compounds of garlic are able to provoke acantholysis in normal human skin cultured in vitro. The acantholytic effect has been more prominent in the samples from DR4+ donor. We here report a case of superficial pemphigus which appeared spontaneously in a DR4,14+, 49-year-old man and which ran a course that proved to be affected by dietary factors, in particular by the consumption of garlic. In the absence of a conventional treatment and on a garlic-free diet only, the disease ceased for several months. Soon after an unintentional dietary test with a strongly and presumable garlic-spiced fish meal, the pemphigus recurred. Nutritional factors should be added to the ever-growing list of exogenous factors capable of inducing or perpetuating pemphigus in genetically predisposed individuals.

Background: Today it is generally accepted that every drug that possesses an active thiol group in its molecule is capable of inducing pemphigus in vivo and provoking acantholysis in vitro. We therefore suggested that plants, in particular those belonging to the Allium group, that contain several active compounds with stable disulfide and thiol groups in their molecule may cause the same., Objective: To verify this hypothesis by investigating the in vitro acantholytic effect of three compounds of garlic., Methods: Skin samples from donors were cultured in the presence of three compounds of garlic (i.e. allylmercaptan, allylmethylsulfide and allylsulfide) for 3 days. The skin samples were then processed for microscopic control for acantholysis., Results: Results indicate that, indeed, the three garlic compounds tested are capable of inducing acantholysis in vitro. Focal and diffuse acantholysis was observed in the specimens from 4 out of 7 donors cultured in the presence of 6 and 9 mM of each of the allyl compounds for 3 days. Interestingly, tissues from a DR4+ donor proved to be more acantholysis prone than others, showing large blistering due to diffuse acantholysis, thus indicating that individual susceptibility plays a crucial role also in vitro., Conclusion: Garlic compounds with stable disulfide and thiol groups in their molecule are capable of inducing acantholysis in vitro. These findings lend further support to the theory that 'harmless' nutritional factors are capable of inducing acantholysis in vitro and possibly also in vivo. In view of these findings, it is suggested that nutritional factors should be added to the ever-growing list of exogenous factors capable of inducing pemphigus.

Pemphigus lesions appeared in a 58-year-old man who was taking captopril for his hypertension. Drug withdrawal resulted in complete remission of the eruption. The subsequent use of enalapril as an antihypertensive agent caused a recurrence of pemphigus lesions along with onset of itching and dermographism. Intercellular antibodies were not found. Discontinuance of enalapril therapy had no effect on the clinical course. Steroid treatment was needed to resolve the eruption. Recently repeated immunofluorescent studies disclosed intercellular IgG antibodies in the serum at a low titer. Pemphigus induction could be initially related to the thiol acantholytic property of captopril. Subsequent production of intercellular antibodies and drug-activation of the kinin system could be responsible for relapsing.

A 31-year-old woman with three pemphigus-prone antigens in her HLA haplotype (B7, DR4, DQw7) developed the disease soon after taking a pyrazolone derivative, viz. feprazone. The pemphigus lesions persisted despite withdrawal of the drug and worsened appreciably when she used ceftriaxone (a new cephalosporin with three sulphur atoms) for a bout of acute pharyngitis. Thiol groups formed from the metabolic breakdown of ceftriaxone are thought to have promoted acantholysis via a biochemical route. Genetic predisposition alone ('the soil') may be essential, though not per se sufficient for outbreak of pemphigus; the intervention of exogenous, heterogeneous factors ('the seed') often seems decisive in triggering full-blown disease.

A case of an abortive form of pemphigus probably induced by protracted penicillin treatment is reported. Because of a positive patch test with penicillamine and the finding of such an amino acid in patient's plasma, the authors are induced to believe that the trigger factor could really have been penicillamine formed by the metabolic breakdown of the penicillin molecule.

The authors are convinced that the intercellular antibodies of pemphigus are pathogenic. Consequently periodic plasmapheresis in two patients with pemphigus has been performed to remove the antibodies from the circulation. After larger plasma-exchanges there was a decrease of the antibody titre and a parallel improvement of the clinical condition.

We present the results of our experiments with in vitro tissue cultures of normal human skin, carried out in order to clarify the mechanism(s) by which D(-) penicillamine provokes pemphigus. Various concentrations of D(-) penicillamine were added to the culture medium and produced acantholytic splitting, closely similar to control lesions produced by pemphigus serum, whereas no lesions occurred in controls cultured without the drug. This suggests to us that the pemphigus of D(-)penicillamine is due to biochemical mechanisms and is not mediated by antibodies. Integrating our data with those of previous clinical and experimental studies on idiopathic pemphigus vulgaris leads us to think that the pemphigus antigen(s) might be present in certain structures of the cell membrane of epithelial cells, which are linked with the initial phases of keratin differentiation.

7 patients with pemphigus unresponsive to and/or with side effects from conventional therapy were treated by plasma exchange using three different procedures. Results were good and confirmed that plasmapheresis may actually be an alternative or adjunctive method of treating problem cases of pemphigus. The current drawbacks related to plasma exchange might be overcome in the future by dialysis of the patients' own plasma through suitable immunoadsorbent matrixes.

A 3 1/2-year-old haemophilic child, repeatedly transfused with blood products, developed pemphigus foliaceus with presence in serum of both intercellular and anti-cytomegalovirus antibodies at high titre. The locus A26, which seems to be a genetic marker of pemphigus, was detected in his haplotype. Cytomegalovirus infection of transfusional origin is suspected to have triggered the outbreak of pemphigus.

The reports of induced pemphigus have multiplied over the last 10 years. Several heterogeneous factors, such as drugs (penicillamine, pyritinol, captopril, rifampicin, etc.), physical agents (burns, UV, and ionizing radiation) and viruses, can play an inducing role. Usually, the disease is preceded by prodromal, non-specific lesions. The full-blown stage shows features of pemphigus foliaceus, erythematosus or herpetiformis. Histologically, acantholytic splits mostly occur at the highest malpighian layers. Intercellular antibodies and frequently concomitant other auto-antibodies are found in the serum, the titre of the former usually being low and unrelated to the severity or course of the disease. The biological progress is variable and ranges from rapidly and definitively healing cases (induced pemphigus proper) to others which, in spite of the elimination of the inducing factor, self perpetuate just like true pemphigus (triggered pemphigus). Pathogenic hypotheses are based on the act that some inducing factors can alter the antigen distribution on keratinocyte membranes and/or interfere with immune surveillance by impairing T-suppressor cells.

A study was undertaken to verify the reliability of the Tzanck test, performed both by traditional cytomorphology and by a direct immunofluorescence technique, for the diagnosis of oral pemphigus vulgaris. Cytologic smears were obtained from oral erosions of 129 patients with various bullous diseases of the oral mucosa, clinically suspected of being oral pemphigus, as well as from 30 healthy subjects. The 40 cases with subsequent histologic proof of oral pemphigus were cytologically diagnosed as such, based on the significant cytomorphologic findings of acantholytic cells or on the pericellular deposition of IgG (which persisted after cytocentrifugation) in epithelial cells, as studied by direct immunofluorescence. Cytomorphology gave positive results in 37 patients with pemphigus and in one patient with a final diagnosis of herpetic stomatitis and gave negative results in all other cases. Immunocytology gave positive results in all patients with pemphigus and negative results in all other cases. The findings indicate that cytomorphologic studies may be useful in screening suspected cases of oral pemphigus vulgaris while the immunocytologic test may provide a reliable definitive diagnosis.