Stefano Caccavale

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.

Bullous pemphigoid: associations and management guidelines: facts and controversies.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).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

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.

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.

Categorization of and comments on isomorphic and isotopic skin reactions

Locus minoris resistentiae (lmr) can be defined as a site of the body that offers lesser resistance than the rest of the body to the onset of disease. The well-known Köbner phenomenon is itself a clear example of lmr in dermatology. The new term locus maioris resistentiae (LMR), a site of the body that offers greater resistance than the rest of the body to the onset of disease, defines the opposite condition. Renbök phenomenon (reverse Köbners isomorphic response) typically represents an example of LMR.

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 [...]

Uncommon superficial angiomyxoma of the vulva complicated with condyloma acuminatum and Staphylococcus hominis infection: a mere example of gynecological immunocompromised district

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The immunocompromised cutaneous district and the necessity of a new classification of its disparate causes

Locus minoris resistentiae can be defined as a site of the body that offers lesser resistance than the rest of the body to the onset of disease. There are many reports of privileged localization of cutaneous lesions on injured skin which represents a typical condition of locus minoris resistentiae. Köbner phenomenon, namely the appearance of new lesions pertaining to a previously present skin disorder at the sites of trauma or other insult, is itself a clear example of locus minoris resistentiae in dermatology. The possible causes of the phenomenon are many and multifarious.[1]

Reactive angioendotheliomatosis following implantation of a knee metallic device: an instance of immunocompromised district

they are not appreciably stored within tissues. Rather, the particles’ small size enables them to be easily filtered by the kidneys without tubular resorption. Given normal renal function, indigo carmine is cleared from the circulation and seen in the bladder within 5–7 minutes. The side effects of indigo carmine dye are largely cardiovascular and most commonly involve hypertension and a reflex bradycardia with decreased stroke volume, leading to decreased cardiac output. Rarely, dysrhythmias, cardiac arrest, and anaphylaxis have also been reported. Uncommonly, indigo carmine dye can extravasate from the peripheral line into the skin and cause a dramatic but asymptomatic blue discoloration. The three prior instances of indigo carmine extravasation were also noticed upon the completion of surgery. As in the present case, the previously reported patients did not experience any symptoms and, other than the discoloration and edema of the affected arm, showed unremarkable findings on examination. In all cases, the discoloration resolved within 24–48 hours without any cutaneous or cardiovascular sequelae. Although indigo carmine dye extravasation into the skin is a benign, transient condition, its presentation is dramatic and can induce significant anxiety in both patients and clinicians who are unfamiliar with this complication. Dermatologists consulted for such rashes can reassure patients and the healthcare team that the discoloration will resolve completely without resultant tissue damage or permanent discoloration. Jacqueline N. Chu, BA Jozef Lazar, MD Joanna Badger, MD Department of Dermatology Stanford University School of Medicine Stanford CA, USA E-mail: jnchu@stanford.edu