Ada Lo Schiavo

Bullous pemphigoid: Etiology, pathogenesis, and inducing factors: Facts and controversies

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.

Pemphigus: Associations and management guidelines: Facts and controversies

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, Basedows 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 Anhalts paraneoplastic pemphigus, with peculiar clinical, histologic, and immunologic features characterizing it. Coexistence of pemphigus with Kaposis 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.

Radiation dermatitis, burns, and recall phenomena: Meaningful instances of immunocompromised district

Ionizing and ultraviolet radiations, as well as burns, can selectively damage and immunologically mark the cutaneous area they act on through direct and indirect mechanisms. After the causal event has disappeared, the affected skin district may appear clinically normal, but its immune behavior is often compromised forever. In fact, irradiated or burned skin areas undergo a destabilization of the immune control, which can lead to either a reduction of immunity (as suggested by the facilitated local occurrence of tumors and infections) or an excess of it (as suggested by the possible local onset of disorders with exaggerated immune response). In other words, these areas become typical immunocompromised districts (ICD). Also, in recall phenomena the damaged skin area usually behaves as an ICD with an exaggerated immune response toward a wide range of drugs (especially chemotherapeutic agents) that prove to be harmless on the undamaged skin surface. The occurrence of any skin disorder on an irradiated, photoexposed, or burned skin area can be defined as an isoradiotopic, isophototopic, or isocaumatopic response, respectively; however, the opposite may also occur when elsewhere generalized cutaneous diseases or eruptions selectively spare irradiated, photoexposed, or burned skin sites (isoradiotopic, isophototopic, and isocaumatopic nonresponse, respectively). The pathomechanisms involved in any secondary disorder occurring on irradiated or burned skin areas may be linked to locally decreased or altered lymph flow (with dysfunction of lymph drainage) on the one hand, and to fibrotic throttling or reduction of peptidergic nerve fibers (with dysfunction of neuroimmune signaling) on the other hand, resulting in a significant dysregulation of the local immune response. Future clinical observations and experimental investigations on radiation dermatitis, sunburns, and thermal or chemical skin injuries should shed new light on the mechanisms regulating regional resistance to infectious agents, local oncogenesis, and district propensity to dysimmune reactions.

The in vitro effect of hydroxychloroquine on skin morphology and transglutaminase

Background Antimalarials are some of the most notorious drugs which may induce psoriasis, with 25% of all reported cases being associated with them. Antimalarials do not induce psoriasis de novo, but trigger subclinical psoriasis. In a previous report, we suggested that antimalarials exert their effect by interfering with the epidermal transglutaminase (TGase) activity.

Discoid lupus erythematosus at a site of previous injury.

A 71‐year‐old man with three patches of discoid lupus erythematosus (DLE) confined to the right preauricular region drew our attention because of the unusual linear arrangement of the lesions. Twenty‐five years previously, the patient had suffered a trauma in the same area from falling off his motorcycle. We believe that, despite the great lapse in time, this injury may have facilitated the onset of DLE in the very same area, through long‐term destabilization of the local neuroimmune network. The case fits the recently coined concept of the immunocompromised district, a cutaneous region with altered immune control, more susceptible to harbouring opportunistic infections, tumours, and immune disorders.

Bullous pemphigoid initially localized around the surgical wound of an arthroprothesis for coxarthrosis

Holi dermatoses: annual spate of skin diseases following the spring festival in India. Indian J Dermatol 2009; 54: 240–242. 3 Ghosh SK, Bandyopadhyay D, Verma SB. Cultural practice and dermatology: the Holi dermatoses. Int J Dermatol 2012; 51: 1385–1387. 4 Ghosh SK, Bandyopadhyay D. Chemical leukoderma induced by colored strings. J Am Acad Dermatol 2009; 61: 909–910. 5 Ghosh SK, Bandyopadhyay D. Chemical leukoderma induced by herbal oils. J CutanMed Surg 2010; 14: 310–313. 6 Ghosh SK, Bandyopadhyay D. Concurrent allergic contact dermatitis of the index fingers and lips from toothpaste: report of three cases. J Cutan Med Surg 2011; 15: 356–357. 7 Ghosh SK, Bandyopadhyay D. Granuloma pyogenicum as a complication of decorative nose-piercing: report of eight cases from eastern India. J Cutan Med Surg 2012; 16: 197–200. 8 Saraswat A, Lahiri K, Chatterjee M, et al. Topical corticosteroid abuse on the face: a prospective, multicenter study of dermatology outpatients. Indian J Dermatol Venereol Leprol 2011; 77: 160–166.

Pemphigus induced by radiotherapy for breast cancer: an instance of immunocompromised district

We read with great interest the report recently published in the European Journal of Dermatology by Thimon et al.[1], which describes an intriguing case of pemphigus vulgaris (PV) induced by radiotherapy for breast cancer [1]. Bullous lesions, strictly localized on the irradiated zone, appeared three weeks after the last cycle of radiotherapy, suggesting induction by ionizing radiation. After two weeks, the bullous eruption spread onto the entire body [1].PV may have a location potentially confined [...]

Granulomatous dysimmune reactions (sarcoidosis, granuloma annulare, and others) on differently injured skin areas

Granulomatous disorders are chronic cell-mediated immune responses histologically characterized by collections of macrophages, epithelioid cells, and multinucleated giant cells. This disease spectrum often has an infectious origin, but sometimes neither an infective agent nor an inciting antigenic stimulus can be identified. The skin may be a preferential target for these disorders, especially in the areas that have been damaged by various forms of skin injury (eg, herpetic infections, trauma, thermal or solar burns, vaccinations, tattoos). These damaged skin sites frame the new concept of an immunocompromised cutaneous district (ICD), which defines a skin area with acquired immune dysregulation that can pave the way for the local onset of opportunistic disorders, such as infections, tumors, and granulomatous disorders. Sarcoidosis, granuloma annulare (GA), and forms of granulomatous vasculitis, such as Churg-Strauss syndrome (CSS) and Wegeners granulomatosis (WG), are the most common granulomatous disorders that occur in an ICD and may share common pathogenic mechanisms. Recent studies have found clinical and pathologic overlapping features across noninfectious granulomas. Although no unifying etiology exists, the development of granulomatous processes in the ICD has often been reported and the literature contains various hypotheses to explain it: (1) overactive immune response in a previously injured region with or without loss of immune tolerance; (2) overall reduced immune response; (3) retention of an exogeneous antigen or foreign body; (4) altered neural signaling; and (5) a combination of all the aforementioned processes. T helper cells, T regulatory cells, and macrophages, as well as a number of antigenic proteins, have been identified as potential contributing factors. In addition, a genetic predisposition and an intact systemic immune system are both instrumental for the persistence of local granuloma formation in the ICD.

Inverse notalgia paresthetica: a strange case of professional disease.

intermarriage. Fitzpatrick’s classification of skin types holds true today and can be used to broadly distinguish between skin types according to their ability or lack of it to burn and tan, and to distinguish among the degrees of lighter and darker skin, and thus seems more relevant than a geographically based descriptor such as Asian. The more accurate term South Asian skin as a descriptor for skin of Fitzpatrick phototypes IV–VI in people living in India has already been suggested and is factually correct not just for the 1.3 billion people of India but for populations of the entire Indian subcontinent, including those of Bangladesh, Pakistan, Sri Lanka, the Maldives, Afghanistan, Tibet, and Nepal. Interestingly, the Indian subcontinent is also referred to as the South Asian subcontinent by many workers for political considerations. Therefore, this letter may also serve as a reminder to use the term South Asian skin for skin of Fitzpatrick types IV, V, and VI in native people living in these locations.

Contact pemphigus: a side‐effect of imiquimod therapy

carcinoma. Akiyama et al. have recognized the development of squamous cell carcinomas on chronic ulcers, scars, and burns, but association with this fungal infection is not completely understood. Associations with melanoma are rare; yet, we found this one previous report of chromoblastomycosis in association with melanoma. With both malignant tumors, we only found a description that appeared on a burn scar. Fonsecaea pedrosoi is the most common etiological agent in chromoblastomycosis, but it rarely affects nails. We did not find cases of onychomycosis caused by F. pedrosoi in the literature.