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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.)

The term isotopic response was coined in 1995(1) to describe the occurrence of a new skin disorder at the site of another, unrelated, and already healed skin disease. That publication paved the way to recognition of this phenomenon by the medical community worldwide with multiple reports describing it under a variety of conditions. The term isotopic response, however, turned out to be unsuitable for a Medline search, because it generated hundreds of references linked with radioactive isotopes. To facilitate Medline searches for this dermatologic phenomenon by avoiding unnecessarily time-consuming sifting through so many unrelated references, it was suggested that the name Wolf be added. The name Wolf's isotopic response has since been generally accepted and even included in Stedman's Illustrated Dictionary of Dermatology Eponyms. Although the concept of the isotopic response was conceived as being analogous to Köbner's isomorphic response, and despite the similarities between the two terms, the similarities are only "skin deep," and there is a major difference between the two. Isomorphic response means "the same morphology" (as that of the existing disease) and describes the appearance of the same disease at another location. The term isotopic response describes the appearance of an altogether different disease at the site of an already healed skin disease. We describe this entity and present representative clinical examples. Some problems in the definition of Wolf's isotopic response are provided, with special emphasis on its overlapping with Köbner's isomorphic response. The description of Wolf's isotopic response, which is analogous but not identical to the isomorphic response described some 120 years ago by Köbner, illustrates the contribution of morphologic findings and original ideas in keeping up with the ongoing progress in the field of dermatology., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Lymphedematous areas are sites of regional immune destabilization depicting a typical example of an immunocompromised cutaneous district (ICD). This study evaluates the expression of some components of the skin innate immunity on lymphedematous limbs with the aim to clarify some facets of the ICD. Patients selected underwent two skin biopsies: One was obtained from the limb affected by lymphedema, another from the contralateral healthy limb. Expression of some components of the skin innate immunity was analyzed by reverse transcription-polymerase chain reaction. Stronger gene expression of Toll-like receptor 2 (TLR-2), human β-defensin 2 (HBD-2), desmoglein 1, desmoglein 3, matrix metallopeptidase 9 (MMP-9), and interleukin 10 (IL-10) was found in keratinocytes derived from the affected limb compared with that of keratinocytes derived from contralateral healthy limb. Downregulation of survivin and vasoactive intestinal polypeptide (VIP) gene expression was found in the affected limbs. No induction of IL-1α and tumor necrosis factor α (TNF-α) was detectable in keratinocyte cultures obtained from both lymphedematous and normal limbs. Different phases and components of skin innate immunity turned out to be altered in the lymphedematous sites. Molecular alterations were similar in all patients recruited in the study. These changes might favor the local appearance or progression of opportunistic diseases such as tumors, infections, and immune-mediated skin disorders., (Copyright © 2014. Published by Elsevier Inc.)

Herpes simplex viruses (HSV-1/HSV-2) and varicella-zoster virus (VZV) have several characteristics in common. Both are epidermoneurotropic, cause skin eruptions accompanied by sensory symptoms (itch, pain), damage peripheral sensory nerve fibers and cutaneous nerve endings, and interfere with neuromediator release, which can alter local mechanisms of immune control. For this reason, herpes-infected areas may become a preferential location for the subsequent onset of immunity-related skin disorders (infections, tumors, and dysimmune reactions), an event first reported by a neurologist and focused on by two brothers, a dermatologist and a pediatrician. The phenomenon therefore named Wolf's post-herpetic isotopic response (PHIR) refers to the occurrence of a new skin disorder at the site of a previous and already healed herpetic eruption (herpes zoster in most cases). Until now, we have been able to gather 189 well-documented cases of PHIR (all reported in the reference section), but our list is far from being complete. Some of the most emblematic cases are briefly described here. In some circumstances, the opposite of PHIR occurs, with diffuse skin disorders or eruptions that selectively spare herpes-infected areas (Wolf's post-herpetic isotopic nonresponse). Experimental investigations with patch testing have been performed in seven patients who were sensitized to nickel and had had herpes zoster in the past years. The tests were carried out bilaterally on the affected dermatomes and on the unaffected contralateral ones. The uneven immune responses we obtained have shown that the immune behavior of an herpes zoster-affected dermatome can be different from that of the corresponding contralateral dermatome, thus supporting the existence of immune dysregulation in herpes-infected areas., (Copyright © 2014. Published by Elsevier Inc.)

Besides the systemic immune deficiency, a sectorial default in immune control may occur in immunocompetent subjects. This regional immune defect can appear and remain confined to differently damaged skin areas, lately labeled immunocompromised districts (ICDs). An ICD is a skin area more vulnerable than the rest of the body for genetic or acquired reasons. Its vulnerability mainly consists in a local dysregulation of the immune control, which often facilitates (but sometimes hinders) the local onset of immunity-related eruptions or skin disorders. The factors responsible for localized immune dysregulation are multifarious, being represented by chronic lymphatic stasis, herpetic infections, ionizing or ultraviolet (UV) radiations, burns, all sorts of trauma (especially amputation), tattooing, intradermal vaccinations, and others of disparate nature (eg, paralytic stroke, poliomyelitis). Whatever the cause, in time an ICD may become a vulnerable site, prone to developing opportunistic infections, tumors, or dysimmune reactions (often of granulomatous type), strictly confined to the district itself; however, the opposite may also occur with systemic immune disorders or malignancies that selectively spare the district. In any case, the immunologic behavior of an ICD is different from that of the rest of the body. The pathomechanisms involved in this sectorial immune destabilization may reside in locally hampered lymph drainage that hinders the normal trafficking of immunocompetent cells (eg, chronic lymphedema, posttraumatic lymph stasis) or in a damage to sensory nerve fibers that release immunity-related peptides (eg, herpetic infections, carpal tunnel syndrome), or in both conditions (eg, amputation stump, radiation dermatitis). The ICD is a conceptual entity with no definite shape or dimension. It may take an extremely variable form and extent depending on the causative agent, ranging from a minimal area (eg, intradermal vaccination) or a small area (eg, herpes simplex infection), through a wide area (eg, radiotherapy), a bandlike segment (eg, skin mosaicism, herpes zoster infection), or an acral area (eg, carpal tunnel syndrome), up to a whole limb (eg, Stewart-Treves syndrome) or even an entire half body (eg, brain stroke). Varied newly coined terminology can be used to indicate the specific cause each time that it is responsible for a regional immune dysregulation. The advantage of the umbrella term ICD is that it encompasses all the possible causes involved in a local immune destabilization. An ICD may have a congenital or a postnatal origin, and interesting similarities between the two forms exist. An ICD may also take place in patients with a preexisting systemic immune deficiency, thus creating a more vulnerable site in an already vulnerable patient. Identifying a cutaneous ICD in a given patient is an important standpoint for both diagnostic and prevention purposes. This can be proven by the educative clinical examples that are reported here., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The history of contact dermatitis (CD) is inseparable from the history of the patch test, and the patch test is inseparable from the pioneer in the field, Josef Jadassohn (1860-1936). Despite the fact that we have been diagnosing, treating, and investigating the condition for more than 100 years, there are still many unsolved questions and controversies, which show no signs of coming to an end in the foreseeable future. This contribution reviews and highlights some of the disagreements and discrepancies associated with CD. For example: • What is the real sensitizer in balsam of Peru, one of the most common allergens, and what, if any, is the value of a low-balsam diet? • Is benzalkonium chloride, which has well-known and undisputed irritant properties, a contact allergen as well? • Is cocamidopropyl betaine (CABP) a common contact allergen and what is the actual sensitizer in CABP allergy the molecule itself, or impurities, or intermediaries in its synthesis? • How can the significant differences in the prevalence of sensitization of formaldehyde (FA, a common cause of contact allergy) between the United States (8%-9%) and Europe (2%-3%) be explained? • What is the relationship between formaldehyde releasers (FRs) allergy and an FA allergy? Should we recommend that FA-allergic patients also avoid FRs, and, if so, to what extent? • What is the true frequency of lanolin allergy? This issue remains enigmatic despite the expenditure of thousands of dollars and the innumerable hours spent investigating this subject. • What is the basis behind the so-called "lanolin paradox"? This label was coined in 1996 and is still a matter of controversy. • Is there such a thing as systemic CD from nickel, and, if so, to what extent? Is there a cross-reactivity or concomitant sensitization between nickel and cobalt?These are some of the controversial problems discussed. We have selected the ones that we consider to be of special interest and importance to the practicing dermatologist., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Kaposi's sarcoma (KS), an angioproliferative disorder, has a viral etiology and a multifactorial pathogenesis hinged on an immune dysfunction. The disease is multifocal, with a course ranging from indolent, with only skin manifestations to fulminant, with extensive visceral involvement. In the current view, all forms of KS have a common etiology in human herpesvirus (HHV)-8 infection, and the differences among them are due to the involvement of various cofactors. In fact, HHV-8 infection can be considered a necessary but not sufficient condition for the development of KS, because further factors (genetic, immunologic, and environmental) are required. The role of cofactors can be attributed to their ability to interact with HHV-8, to affect the immune system, or to act as vasoactive agents. In this contribution, a survey of the current state of knowledge on many and various factors involved in KS pathogenesis is carried out, in particular by highlighting the facts and controversies about the role of some drugs (quinine analogues and angiotensin-converting enzyme inhibitors) in the onset of the disease. Based on these assessments, it is possible to hypothesize that the role of cofactors in KS pathogenesis can move toward an effect either favoring or inhibiting the onset of the disease, depending on the presence of other agents modulating the pathogenesis itself, such as genetic predisposition, environmental factors, drug intake, or lymph flow disorders. It is possible that the same agents may act as either stimulating or inhibiting cofactors according to the patient's genetic background and variable interactions. Treatment guidelines for each form of KS are outlined, because a unique standard therapy for all of them cannot be considered due to KS heterogeneity. In most cases, therapeutic options, both local and systemic, should be tailored to the patient's peculiar clinical conditions., (Copyright © 2013. Published by Elsevier Inc.)

There are currently five types of recognized phacomatosis pigmentovascularis plus one more, phacomatosis pigmentokeratotica, making six types altogether. Should we stop here and consider the classification as being complete? Or, do we leave room to add more types or, alternatively, lump the ones we have together and shorten the list? We present our reasons for adding one or two new types of phacomatoses to the current classification, in full recognition that it is already complicated and somewhat cumbersome. We consider that the benefits of doing so outweigh any additional strain on the already complicated classification. We expect that this might not sit well with some of our colleagues, but we are prepared to do battle., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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.)

The term pemphigoids includes a group of autoimmune bullous diseases characterized by subepidermal blistering. Bullous pemphigoid (BP) is not only the most common disorder within the pemphigoid group, but also represents the most frequent autoimmune blistering disease in general. The onset and course of BP depend on a variable interaction between predisposing and inducing factors. HLA genes are the most significant genetic predisposition factor to autoimmunity mechanisms. Many studies show an association between HLA-DQβ1*0301 and distinct clinical pemphigoid variants. Imbalance between autoreactive T helper (Th) and T regulatory cells, toll-like receptor activation, and Th17/IL-17 pathway are the three possible autoimmunity triggers underlying BP. The pathomechanism of BP hinges on an autoantibody response toward structural components of the hemidesmosome (BP180 and BP230). The binding of autoantibodies leads to complement activation, recruitment of inflammatory cells, and release of proteolytic enzymes. The inflammatory cascade also may be directly triggered by activation of Th17 cells with no intervention of autoantibodies. The intervention of inducing factors in BP can be identified in no more than 15% of patients. Facilitating factors in genetically predisposed individuals are various (drug intake, physical agents, and viral infections). Drugs may act as triggers by either modifying the immune response or altering the antigenic properties of the epidermal basement membrane. Cases of induction of BP by physical agents (eg, radiation therapy, ultraviolet radiation, thermal or electrical burns, surgical procedures, transplants) are rare, but well-documented events. A contributing role in inducing BP has been suggested for infections, in particular human herpes virus (HHV) infections (cytomegalovirus, Epstein-Barr virus, and HHV-6), but also hepatitis B and C viruses, Helicobacter pylori, and Toxoplasma gondii. Unlike pemphigus, no dietary triggers have been suspected of being involved in the induction of BP. In all patients who have a diagnosis of BP, an environmental agent as a potential cause should always be considered, because the prompt discontinuation of it might result in rapid improvement or even cure of the disease., (Copyright © 2013. Published by Elsevier Inc.)

The German dermatologist, Josef Jadassohn (1863-1936), first presented the results of his innovative patch-testing technique in 1895. The safety and efficacy of this diagnostic tool has stood the test of time and is still the gold standard for the diagnosis of allergic contact dermatitis (ACD). Since its discovery, much effort has been put into standardization and optimization of allergens, vehicles, and concentrations of patch-test materials; in procedures of its application; and in reading and scoring of test reactions--all contributing to the development of an accurate, reliable, and safe test with a high reproducibility of its results. Even this seemingly carved-in-stone practice, which has been used for nearly 120 years, has been questioned and challenged, engendering debates, disagreements, and controversies, which show no signs of coming to an end. Almost every step of the procedure has provoked discussions and controversies:, (Copyright © 2013 Elsevier Inc. All rights reserved.)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor following the discovery that the text overlaps significantly with sections of several articles that are cited in the reference section, including the following: Culton DA, Diaz LA. Treatment of subepidermal immunobullous diseases. Clin Dermatol 2012;30:95–102. Meurer M. Immunosuppressive therapy for autoimmune bullous diseases. Clin Dermatol 2012;30:78–83. Ljubojevic S, Lipozencic J. Autoimmune bullous diseases associations. Clin Dermatol 2012;30:17–33. Sehgal VN, Verma. Leflunomide: dermatologic perspective. J Dermatolog Treat 2013;24:89–95. Gürcan HM, Ahmed AR. Analysis of current data on the use of methotrexate in the treatment of pemphigus and pemphigoid. Br J Dermatol 2009;16:723–31. Chen YJ, Wu CY, Lin MW, et al. Comorbidity profiles among patients with bullous pemphigoid: a nationwide population-based study. Br J Dermatol 2011;165:593–9, (Copyright © 2013. Published by Elsevier Inc.)

The most important function of the skin is the formation of a barrier between the "inside" and the "outside" of the organism, which prevents invasion of pathogens and fends off chemical assaults as well as the unregulated loss of water and solutes. The physical barrier is mainly localized in the stratum corneum, which consists of protein-enriched cells and lipid-enriched intercellular domains. Any modifications in epidermal differentiation and lipid composition results in altered barrier function, a central event in various skin alterations and diseases. This contribution presents a brief description of the structure of the skin, paying attention to the most important components responsible for skin barrier function., (Copyright © 2012. Published by Elsevier Inc.)

Almost 2 decades ago, Williams and Elias suggested a unifying concept for the pathogenesis of disorders of cornification, according to which the integrity of the epidermal barrier and its effective function is an important factor in the regulation of epidermal DNA synthesis. Interference with the barrier integrity or function will result in epidermal hyperplasia and may be the primary event leading to hyperproliferative skin diseases, such as psoriasis. We have analyzed alterations to several structures of the epidermal barrier that might be responsible for barrier dysfunction and thus lead to hyperproliferation of the epidermis in an attempt to repair the barrier and, as a result, might be inducers of psoriasis. There are several convincing reports indicating that inhibiting of epidermal transglutaminase may lead to epidermal hyperproliferation and that this stimulus might trigger psoriasis among genetically predisposed patients. Disturbance of epidermal barrier function caused by derangement of lipid or cholesterol or ceramide synthesis leads to increased DNA synthesis and epidermal hyperplasia and as a result might be an inducer of psoriasis. We could find little evidence to show that defective defense of the epidermis or an abnormal response of it to bacteria plays a role in the pathogenesis of psoriasis. Accumulating data indicate that there is an association of psoriasis and mutations of genes within the epidermal differentiation complex, which are crucial for the development, maturation, cornification, cross-linking, and terminal differentiation of the epidermis, called psoriasis susceptibility locus 4., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Genetic, developmental, and immune defects can make certain anatomic areas of the body more prone than others to harbor skin lesions. Cutaneous areas with skin barrier dysfunction (eg, atopic dermatitis) are the clearest example of vulnerable sites where opportunistic diseases, mainly infections (eg, herpes simplex), can easily occur. Somatic mosaicism, by giving rise to mutated cell clones with a bandlike arrangement, may form tissue segments prone to developing congenital or acquired skin disorders. Cutaneous districts that have been infected by herpes viruses become sites permissive for a subsequent onset of heterogeneous skin disorders, mainly tumors, further infections, and disimmune reactions (Wolf isotopic response). Regional lymphedema, by impairing lymph circulation and consequently the local immune control, favors the location of immunity-related lesions in the involved district. A vast series of skin injuries, such as ionizing or ultraviolet radiation, burns, traumas, and even vaccinations, can render the affected areas vulnerable to subsequent cutaneous disorders. Lack of immune control, ensuing from locally altered neuroimmune interaction, may be the basic defect responsible for the opportunistic location of skin lesions in herpes-infected, lymphedematous, or otherwise damaged areas, together featuring the novel concept of "immunocompromised district.", (Copyright © 2011 Elsevier Inc. All rights reserved.)

Although most skin diseases can be diagnosed with simple visual inspection, laboratory investigations are necessary in several clinical circumstances. This contribution highlights the usefulness of routine diagnostic procedures that are often overlooked and the innovative methods of molecular biology, which are expensive and require an experienced staff. Among the classic diagnostic investigations are (1) the use of Wood's light in many dermatologic disorders (eg, vitiligo, pityriasis versicolor, erythrasma, porphyrias), (2) cytodiagnosis of Tzanck in dermatologic practice (eg, herpetic infections, molluscum contagiosum, leishmaniasis, pemphigus vulgaris, basal cell carcinoma, erythroplasia of Queyrat, Hailey-Hailey disease), and (3) microscopic examination for fungal and bacterial skin infections as well as for mite infestation using potassium hydroxide, simple saline, and Gram stain. Modern molecular biotechnologies encompassing gene-specific polymerase chain reaction and its variants have a substantial affect in selected cases of viral (especially herpes simplex virus), bacterial, fungal, and protozoan (Leishmania) skin infections., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The term "isotopic response" was coined by Wolf et al in 1995 to describe the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. When this term was found to be unsuitable for Medline searches because it generated hundreds of references that were linked with radioactive isotopes, it was changed to "Wolf's isotopic response" and eventually included as such in Stedman's Illustrated Dictionary of Dermatology Eponyms. Our search of the literature yielded 176 cases of Wolf's isotopic response. We describe this entity and present representative clinical examples. Some problems in the definition of Wolf's isotopic response are provided with special emphasis on its overlapping with the Koebner isomorphic response, a similar, but different, phenomenon. Also addressed are a number of issues associated with another term, "isotopic nonresponse," which had been introduced in analogy to the "isomorphic nonresponse" for describing the absence of an eruption at the site of another unrelated and already healed skin disease, or the sparing of the sites of another unrelated and already healed skin disease. In the spirit of the present issue, this contribution discusses only the clinical morphology and not the etiology, pathomechanism, or molecular biology of Wolf's isotopic response., (Copyright © 2011 Elsevier Inc. All rights reserved.)

During the last decades, the conventional therapy for autoimmune blistering diseases has been high-dose, long-term systemic corticosteroid and immunosuppressive agents or adjuvant drugs. Long-term, high-dose steroid therapy can result in serious adverse effects. The rationale for using adjuvant drugs is that concerns reducing the need for corticosteroids, and hence, their side effects, or it may result in better control of the disease, or both. Immunosuppressive agents are not free of adverse effects, however. Prolonged immune suppression may account for high rates of morbidity, disability, and possible death. There is no consensus about the first-choice adjuvant drug for the management of blistering autoimmune diseases. This contribution evaluates six adjuvant drugs-cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil, intravenous immunoglobulin, and rituximab-and discusses the choice of a "winning drug" that is effective and safe., (Copyright 2010. Published by Elsevier Inc.)

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.