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A Case of Bullous Pemphigoid Exacerbated by Irradiation After Breast Conservative Radiotherapy
Abstract
We present a case, considered to be a form of the Koebner phenomenon, of bullous pemphigoid that was exacerbated mainly within
the irradiated field after breast conservative radiotherapy. In May 2009, a 60-year-old woman was diagnosed with bullous pemphigoid,
which was treated with steroid therapy. The following month, she was diagnosed with breast cancer (invasive ductal carcinoma,
pT1cN0M0). After breast conservative surgery in December 2009, conservative radiotherapy to the right breast was performed
(50 Gy in 25 fractions). Portal skin showed no serious change (up to grade 1 skin erythema) and no bullous neogenesis during
conservative radiotherapy. However, 2 months after conservative radiotherapy, new blisters became exacerbated mainly within
the irradiated field but also in the area outside the irradiated field. Increasing the dosage of oral steroid and minocycline
resulted in relief of bullous pemphigoid, although patchy skin pigmentation remained especially in the irradiated skin.
... Physical factors, including UV radiation, radiotherapy, and irradiation, can alter the basal membrane and expose modified antigens, leading to the stimulation of autoantibody formation, complement activation, and blister formation [6]. UV radiation and/or radiotherapy decrease T-cell immune reactivity and lead to the development of antibodies targeted against the proteins [4]. ...
... First, disruption of the skin due to trauma might increase the expression of the basement membrane zone antigens, leading to the initiation of an inflammatory process with lower titers of circulating antibodies. Due to the increased storage of circulating autoantibodies, besides inflammatory cell recruitment (particularly granulocytes), tissue damage can improve vascular permeability [4,6]. By attaching to granulocytes, autoantibodies stimulate the complement system and initiate a loop of inflammatory stimuli [4]. ...
Bullous pemphigoid (BP) is described as a subepidermal blistering disorder, which is commonly reported among the elderly, particularly those older than 60 years of age. In this report, we present the case of a 41-year-old female patient with BP lesions that were initially detected at the site of Hijama therapy with a subsequent generalized spread. Punch biopsy from the lesions and perilesional direct immunofluorescence (DIF) demonstrated features of BP. The anti-BP180 level was 178 RU/mL, and the anti-BP230 level was negative. BP antigens at the site of Hijama caused an antibody response, which led to widespread blistering over the trunk due to epitope spreading. In a comprehensive review of the literature, a total of 22 BP patients with lesions due to physical trauma were studied, and clinical, immunological, and epidemiological information was gathered. This article is the first report on the occurrence of BP induced by Hijama therapy.
... There are numerous case reports on ABD and breast cancer including predominantly BP [20,[81][82][83][84][85] and PV [86,87] with well-documented BP-lesion induction with radiotherapy. ...
... It may be possible, that the distortion of cell cohesion in neoplastic cells leads to exposing normally hidden antigens or new epitopes are recognized by the immunocompetent cells. There are reports mentioning overlapped breast cancer and BP [20,84] as well as reports describing the evoking of autoimmune blistering dermatosis after breast radiotherapy [216][217][218], that may change antigenicity of the malignant cells. ...
... Similarly, a number of vaccinations have been postulated to induce or unmask subclinical BP by triggering a non-specific immune response in individuals with an immunologic predisposition (28). Several case reports have described BP to be induced or exacerbated by exposure to ultraviolet light in the form of radiation therapy, psoralen with ultraviolet A (PUVA) or UVB therapy, and from local trauma from thermal or electrical burns, however none of these potential triggers have been explored in a case control study (29)(30)(31)(32)(33)(34)(35)(36)(37)(38). ...
Background
Previous case–control studies have suggested that environmental factors including exposure to pesticides and organic materials, diet and medications have an important role in the pathogenesis of pemphigus vulgaris. These studies lacked geographical population controls and had less than three controls per case.
Objective
To identify environmental and occupational risk factors associated with the development of pemphigus vulgaris (PV) and bullous pemphigoid (BP).
Method
Cases were patients with PV (n = 25) and BP (n = 29) recruited from 2009 to 2017. Controls for PV (n = 72) and BP (n = 84) were recruited from the general population via electoral commission matching, matched for age, sex, residential location, and ethnicity. Data about demographics, environmental exposures and occupational exposures, was collected using a structured questionnaire. Conditional logistic regression analysis was undertaken using SPSS software to identify significant variables.
Results
Significant factors associated with PV included the daily consumption of leeks (odds ratio (OR) 3.6; p = 0.025), mustard oil (OR = 4.4; p = 0.049), tomatoes (OR = 4.735; p = 0.032), multivitamins (OR 3.6; p = 0.009), alcohol (0.039), and calcium supplements (OR = 44, p < 0.001). Other associated factors included the number of lifetime sunburns (p = 0.019), high levels of mental stress (p < 0.001), and the use of lime household cleaning products (p < 0.001), Significant factors associated with BP included the daily consumption of green or herbal tea (OR = 3.7; p = 0.004), fish oil (OR = 5.7; p < 0.001), calcium supplements (OR = 6.1; p < 0.001), multivitamins (OR = 2.6; p = 0.043), and glucosamine (OR = 3.0; p = 0.046). The use of lime household cleaning products (p < 0.001) and high levels of mental stress (p = 0.007) were also associated with BP.
Conclusion
Dietary factors containing thiol groups such as leeks, tomatoes, and mustard oil may be potential triggers for PV. High levels of mental stress, the use of supplementary medications such as calcium and multivitamins, and chemical cleaning products containing lime may be associated with an increased risk of developing both PV and BP. Lifestyle changes should be part of routine management for these patients.
... They hypothesized that the daily dose to the skin is a key factor in the development of Koebner phenomenon. Several studies have reported a radiation-induced Koebner phenomenon following radiotherapy in patients with psoriasis who received whole-breast radiotherapy at 50 Gy (2 Gy per fraction) after breast-conserving surgery or postmastectomy radiotherapy to the chest wall at 46 Gy (2.3 Gy per fraction).9 Wu et al.10 described an instance of a skin flare in a 62-year-old woman with a history of active psoriasis who received sequential bilateral hypofractionated whole-breast radiotherapy. ...
We present three cases of patients with breast cancer and psoriasis who received radiotherapy following breast-conserving surgery. One patient developed an extensive flare-up of psoriasis during chemotherapy. After discontinuing chemotherapy, she received conventional radiotherapy to the ipsilateral whole breast, axillary, and supraclavicular lymph nodes with 50.4 Gy in 28 fractions and boosted with 10 Gy in five fractions to the tumor bed. Two patients received hypofractionated whole-breast radiotherapy at a total dose of 40.05–42.4 Gy in 15–16 fractions. In all three cases, there was no flare-up of psoriatic events at least 6 months after the completion of radiotherapy. We hypothesized that there is a close relationship between psoriatic events and the extent of trauma rather than the daily dose of the fraction. Therefore, we confirmed that the effect of radiotherapy on psoriatic events is minimal if the radiation field size does not exceed that of the whole breast.
... In described cases, BP usually appears for the first time after exposure to the incriminated factor. The exacerbation of a previously diagnosed BP has been reported [138,139], while recurrence has rarely been described [31,140]. In the majority of BP patients (60-86%) associated to physical factors, the clinical diagnosis was confirmed by a positive DIF [109]. ...
Bullous pemphigoid (BP) is the most frequent autoimmune subepidermal blistering disease provoked by autoantibodies directed against two hemidesmosomal proteins: BP180 and BP230. Its pathogenesis depends on the interaction between predisposing factors, such as human leukocyte antigen (HLA) genes, comorbidities, aging, and trigger factors. Several trigger factors, such as drugs, thermal or electrical burns, surgical procedures, trauma, ultraviolet irradiation, radiotherapy, chemical preparations, transplants, and infections may induce or exacerbate BP disease. Identification of predisposing and trigger factors can increase the understanding of BP pathogenesis. Furthermore, an accurate anamnesis focused on the recognition of a possible trigger factor can improve prognosis by promptly removing it.
... The clinical signs of pemphigoid include bullae and rash, with or without itching. The outbreak occurs usually within 1 year after radiation treatment [2]. Pemphigoid cannot be diagnosed with clinical symptoms alone, and differential diagnoses including drug eruption, erythema multiforme, and acute viral infections such as varicella-zoster must be excluded using viral marker study, biopsy, and culture [3]. ...
Among the possible complications of radiation therapy, acute and chronic side effects on the skin can be induced by percutaneous radiotherapy in the target site. Common skin lesions include radiation dermatitis, which can be treated by topical application of dressing and ointment. Pemphigoid disease, which displays similar clinical features as other skin diseases such as recurrent cancer and herpes zoster, rarely occurs in the site of radiotherapy; therefore, care must be taken during diagnosis for a timely treatment. The present report is a case of pemphigoid disease that had developed in a patient with endometrioid/clear cell carcinoma after radiation therapy, and the time between onset and radiotherapy was more than 6 months.
... Physical factors, such as radiotherapy [118][119][120][121], UV light [122] and photodynamic therapy [123], can also be related to the onset of localized or generalized BP. These factors may change the antigenicity of the basement membrane and stimulate the formation of autoantibodies. ...
Bullous skin diseases are a group of dermatoses characterized by blisters and bullae in the skin and mucous membranes. The etiology and pathogenesis of bullous skin diseases are not completely clear. The most common are pemphigus and bullous pemphigoid (BP). Autoantibodies play critical roles in their pathogenesis. Abnormalities in the adhesion between keratinocytes in patients with pemphigus leads to acantholysis and formation of intra-epidermal blisters. Anti-desmoglein autoantibodies are present both in the circulation and skin lesions of patients with pemphigus. The deficient adhesion of keratinocytes to the basement membrane in BP patients gives rise to subepidermal blisters. Autoantibodies against the components of hemidesmosome can be detected in BP patients. Many novel therapeutics based on knowledge of the pathogenesis have emerged in recent years.
... 53 Most blistering diseases begin with eruptions in the irradiated field (Fig. 6) and may later spread farther. 54 This condition has largely been described in women who have been treated for breast cancer 55 ; the mean age is 75 years. An interesting fact is that onset is often a year after radiotherapy ended, although some reactions have developed during or immediately after therapy. ...
Radiotherapy for cancer is used increasingly. Because skin cells undergo rapid turnover, the ionizing radiation of radiotherapy has collateral effects that are often expressed in inflammatory reactions. Some of these reactions–radiodermatitis and recall phenomenon, for example–are very familiar to dermatologists. Other, less common radiotherapy-associated skin conditions are often underdiagnosed but must also be recognized.
... Generalized BP, BP strictly confined to the irradiated area, as well as pre-existing BP exacerbated by irradiation have all been reported. [6][7][8][9] Radiotherapy may lead to structural alteration of the basement membrane zone and auto-antibody induction. In addition, matrix metallopeptidase-9 and vascular endothelial growth factor levels may also have an association with radiotherapy treatment. ...
Bullous pemphigoid (BP) is a blistering disorder due to autoantibodies to the epidermal basement membrane zone. The triggering factor could be localized damage to the skin by physical or chemical agents. We report a case of a 68-year-old woman with a three year history of oral lesions of BP following radiotherapy for carcinoma of the hypopharynx, and a three month history of BP over lymphedematous sites on the right hand and right lower limb. Localized BP induced by radiotherapy or lymphedema is rare; both factors working simultaneously in the same patient is even rarer.
The Koebner phenomenon, also known as isomorphic reaction, refers to the development of secondary lesions with the same clinical manifestations and histopathological characteristics as the primary lesions in normal skin after trauma or other stimuli. The triggering factors of Koebner phenomenon include physical trauma, chemical stimulation, mechanical stress, iatrogenic stimulation, and pathogenic infection. Vitiligo, psoriasis and lichen planus are considered true Koebner phenomenon. Recent studies have shown that immunological disorders, oxidative stress, defective melanocyte adhesion, and growth factor deficiency are the main pathological mechanisms of vitiligo Koebner phenomenon. In psoriasis, triggers may drive skin inflammation to induce a psoriatic phenotype through multiple signaling pathways, and thereby cause Koebner phenomenon in susceptible individuals. Significantly, keratinocytes mediate the occurrence of Koebner phenomenon in psoriasis through mechano‐induced signaling pathways after sensing mechanical signals, and explains the high frequency of psoriasis lesions on the extensor side of the elbow and knee joints. On the other hand, TRPA1‐driven mechano‐transduction, autoimmunity and actinic damage are the underlying mechanisms of Koebner phenomenon in lichen planus. In this review, we have summarized the current understanding of the characteristics and pathogenesis of Koebner phenomenon.
Over the years, the occurrences of different types of skin disorders arising from radiation sites have been observed and studied. Examples include autoimmune blistering diseases such as pemphigus, pemphigoid, and interface or inflammatory reaction patterns such as lichen planus, lupus erythematosus, and Steven‐Johnson Syndrome. The phenomenon whereby a new skin disorder arises from a previously healed or irradiated site is called an isotopic response, described as a type of Koebner phenomenon. Ionizing radiation itself can profoundly affect the skin. Both early and late changes can present, which typify the progression of changes following irradiation of the skin. Herein, we report a rare case of labetalol‐associated lichen planus pemphigoides that occurred at the site treated with radiation for a soft tissue malignancy after 19 years as a result of an isotopic response. The rash was well‐controlled after therapy and kept a four‐year remission. The same skin reaction recurred after the re‐introduction of labetalol four years later. This article is protected by copyright. All rights reserved.
The association of bullous pemphigoid (BP) with solid malignancies (SM) is a matter of controversy, as previous studies produced inconclusive findings. The aim of this study was to assess the risk of SM among patients with BP and to evaluate whether a history of SM predisposes individuals to develop subsequent BP. A population‐based cohort study was performed comparing BP patients (n = 3924) with age‐, sex‐ and race‐matched control subjects (n = 19 280) with regard to incident cases of SM. Adjusted hazard ratios (HR) and adjusted odds ratios (OR) were estimated by Cox regression and logistic regression, respectively. The incidence of SM was 13.4 (95% confidence interval [CI], 11.6–15.3) and 14.3 (95% CI, 13.5–15.1) per 1000 person‐years among patients with BP and controls, respectively. BP was not associated with an increased risk of SM (adjusted HR, 0.90; 95% CI, 0.77–1.05). Additionally, a history of SM was not related to the risk of subsequent BP (adjusted OR, 1.00; 95% CI, 0.90–1.10). In a stratified analysis, patients with BP had an increased risk of uterine cancer (adjusted HR, 2.56; 95% CI, 1.39–4.72) unlike the 18 remaining analyzed types of SM. Relative to BP patients without SM, those with BP and SM were older, had a male predominance, a higher prevalence of smoking, a higher burden of comorbidities and comparable survival rates. Although patients with BP do not experience an overall increased risk of developing SM, they are more likely to have uterine cancer. Our findings argue against routine extended cancer screening for patients with incident BP, but raise the awareness of uterine cancer among females with BP.
Radiation therapy is a mainstay for the treatment of primary malignancies and metastatic disease and is associated with several dermatological adverse events that are underreported in the literature. The objective of this paper was to review the literature regarding cutaneous manifestations associated with radiation therapy in order to promote awareness of the cutaneous radiation therapy-associated adverse effects. This extensive literature review was performed using the Pubmed and Embase databases. Studies were reviewed for relevance and critical evidence pertaining to cutaneous manifestations of radiation therapy. The most commonly reported cutaneous sequelae associated with radiation therapy include radiation dermatitis, non-melanoma skin cancer, radiation-associated angiosarcoma, morphea, bullous pemphigoid, lymphangioma circumscriptum, and pseudosclerodermatous panniculitis. For many of these conditions, only case reports or case series exist and there is an absence of large-scale cohort studies. Despite these limitations, this review describes the wide range of dermatological adverse events associated with radiation therapy.
Bullous pemphigoid is the most common autoimmune bullous disease. It usually appears as a very itchy rash of urticarial or eczematous appearance, with subsequent appearance of vesicles and tense blisters on previously inflamed skin. The basis of its pathogenesis consists of the production of autoantibodies that attacks several components of the hemidesmosomes which are located in the basal membrane of the dermoepidermal junction. Localized bullous pemphigoid is a rare clinical variant of bullous pemphigoid. It normally appears in the lower extremities and it’s rarer on palms or on the breast. Several causes have been described, such as physical trauma, ultraviolet radiation, and, in the case of localized bullous pemphigoid on the breast, radiotherapy or ductal carcinoma, although it is not always possible to find an underlying cause.
Bullous pemphigoid (BP) is the most common autoimmune bullous disorder which is characterized by autoantibodies against hemidesmosomal proteins of the skin and mucous membranes. Collagen XVII and dystonin-e have been identified as target antigens. BP affects mostly the elderly. The incidence of the disease is increasing gradually and is associated with high morbidity and mortality. Clinically, BP is characterized by an intensely pruritic eruption with widespread bullous lesions. The clinical diagnosis can be challenging in the setting of atypical presentations. Diagnosis of BP relies on the integration of clinical, histological, immunopathological, and serological findings. The treatment is mainly based on topical and/or systemic glucocorticoids, but anti-inflammatory antibiotics and steroid sparing adjuvants are useful alternatives. Localised and mild BP can be treated with topical corticosteroids alone.
Radiotherapy for cancer is used increasingly. Because skin cells undergo rapid turnover, the ionizing radiation of radiotherapy has collateral effects that are often expressed in inflammatory reactions. Some of these reactions-radiodermatitis and recall phenomenon, for example-are very familiar to dermatologists. Other, less common radiotherapy-associated skin conditions are often underdiagnosed but must also be recognized.
Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.
Radiotherapy has been a common and well-known treatment for several cancers and benign dermatoses. An overview of the characteristics of acute and chronic cutaneous effects of radiotherapy and its treatment is presented. A current overview of benign dermatoses after radiotherapy, presently only dispersedly published in the literature, is given with the mean age of occurrence, dose of radiotherapy, and their latency time calculated for those described more than 8 times. Benign dermatoses occurring most often after radiotherapy (>20 times described), ie, morphea, bullous pemphigoid, pemphigus vulgaris, and acneiform eruptions are discussed in more detail. Finally, dermatoses with a specific distribution related to the irradiated area are highlighted. This review provides an overview of cutaneous side effects of radiotherapy, especially of the benign dermatoses, as a supplement to the clinical knowledge of dermatologists, oncologists, and wound care specialists.
Pemphigus and pemphigoid are the prototypical immunobullous diseases. Although it has been well established that they are caused by deposition of autoreactive antibodies directed against adherence proteins within the skin, the specific genetic and environmental factors leading to development of these diseases continue to be an area of investigation. Herein, we discuss several of the potential environmental triggers that may induce patients to develop immunobullous diseases including medications, viral infections, UV exposure or other radiation injury and dietary factors. In addition, the potential genetic and immunologic mechanisms contributing to the pathogenesis of pemphigus and pemphigoid will be reviewed. The multifactorial nature of these diseases contributes to their complexity and highlights the importance of a detailed personal and family history when caring for these patients.
Bullous Pemphigoid may occur in extremely variegated manners, misleading even experienced dermatologists. Indeed the type and/or distribution of lesions may be unusual. Furthermore, there may be an atypical demographic profile of patients, a different clinical course and a different responsiveness to therapy. Up to 20% of cases the onset is characterized by a non-bullous phase, lasting weeks, months or in particular cases remaining the only manifestation of the disease. During this early phase lesions are generally pruritc erythematous, eczematous or urticarial; however, lesions ma also resemble polycyclic, targetoid, nodular or lichenoid lesions. These atypical lesions may also coexist with typical bullae. Other atypical presentations include a vesicular eruption and erythroderma. Manifestations in children differ from adult forms, presenting an exclusive genital involvement in 50% of cases or a preponderant involvement of the face, the palms and soles. Rarely bullous pemphiogid is confined to certain body areas, due to particular triggering factors or to a lower disease activity. Therefore, the need to formulate universally recognized diagnostic criteria is increasingly evident, especially for atypical bullous pemphigoid. Direct immunofluorescence of perilesional skin and detection of circulating autoantibodies are mandatory in the diagnosis, especially when the clinical presentation is doubtful.
Copyright © 2015 Elsevier B.V. All rights reserved.
: Organ transplant recipients are at high risk to develop secondary cutaneous neoplasms because of immunosuppression. However, little is known about secondary neoplasms developing within a skin area exposed to radiation therapy in these patients. We report a case of a 45-year-old man with history of kidney transplantation in 2005 and rectal adenocarcinoma in 2006 for which he underwent 2 cycles of chemotherapy and a cycle of radiotherapy. In February 2010, he presented with clustered erythematous-violaceous plaques and nodules of 2-month duration, located on the left buttock in the area previously exposed to radiations. Histological examination revealed a poorly demarcated dermal and subcutaneous proliferation of spindle and partly pleomorphic cells, associated with irregularly shaped vessels that dissected through dermal collagen. Immunohistochemistry showed expression of CD31 and podoplanin. Although a moderate expression of the c-Myc protein was found by immunostaining, no amplification of c-myc gene was detected by fluorescence in situ hybridization. Human herpes virus 8 was positive both on immunohistochemistry and PCR. Based on clinicopathologic findings a diagnosis of iatrogenic Kaposi sarcoma localized in the area treated with radiotherapy was made. Clinical and histopathological features of vascular neoplasms may be overlapping, and correct diagnosis may be difficult, particularly in organ transplant recipients. Only the combination of all available information, including histopathological, immunohistochemical, fluorescence in situ hybridization, and PCR data, permit to achieve a correct diagnosis in particularly difficult setting.
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.
Two patients were admitted to our hospital with tense blisters on an erythematous base, typical for bullous pemphigoid. In both patients an infestation with Sarcoptes scabiei was diagnosed by dermatoscopy as well as histological examination. In one patient the clinical diagnosis of bullous pemphigoid could be confirmed by immunofluorescence microscopy, histopathology and a clinical relapse of bullous pemphigoid without scabies infestation. In the other patient no evidence for an autoantibody-mediated autoimmune blistering disease was found. We postulate that bullous scabies could develop after long persistency of the parasites leading to a specific immune response with activation of T helper type 2 (Th2) cells causing high levels of the cytokine interleukin 5 and then consecutively eosinophilia. Secretion of proteolytic enzymes near the basal membrane zone might explain the development of intraepidermal, often suprabasal blisters. In contrast, in the first patient the scabies infestation might have triggered a flare up of the underlying autoimmune disease. Comparison of our two patients demonstrates two entities: bullous pemphigoid triggered by scabies as a Koebner phenomenon and a bullous subtype of scabies mimicking bullous pemphigoid. Therefore both, scabies infestation triggering bullous pemphigoid and bullous pemphigoid-like scabies should be included in the differential diagnosis of vesicles, tense blisters and erythema, especially at an early clinical stage.
Bullous pemphigoid (BP) is the most common autoimmune blistering disease. BP patients have autoantibodies against type XVII collagen (COL17, also called BP180 or BPAG2), a type II transmembrane protein that spans the lamina lucida and projects into the lamina densa of the epidermal basement membrane. The non-collagenous 16A domain of COL17 is considered to contain pathogenic epitopes of BP. The transfer of immunoglobulin (Ig)G from BP patients fails to cause blisters on mouse skin probably due to differences between humans and mice in the amino acid sequence of NC16A pathogenic epitope of COL17. Passive transfer of rabbit IgG antibodies against the murine homolog of human COL17 NC16A triggers immune reactions to COL17 in mice, including complement activation, mast cell degranulation and neutrophilic infiltration, resulting in dermal-epidermal separation. Recent studies using COL17-humanized mice that express human COL17 but lack murine COL17 were the first to demonstrate the pathogenicity of anti-COL17 human BP IgG autoantibodies in vivo. These new findings provide a greater understanding of BP pathomechanisms and facilitate the development of novel specific and efficient therapeutic strategies for BP.
To evaluate the significance of the association of malignancy with autoimmune blistering diseases, we studied the incidence of internal malignancies in pemphigus and bullous pemphigoid based upon 496 cases of pemphigus and 1113 cases of bullous pemphigoid in Japan. Results showed that (1) an association between internal malignancies and pemphigus was observed in 25 out of 496 cases (5.0%), while that with bullous pemphigoid was seen in 64 out of 1113 cases (5.8%). Such association ratios were significantly higher than that of the controls aged over 70 years old (0.61%); (2) The average ages of pemphigus/bullous pemphigoid with malignancy were 64.7 and 69.2 years, respectively. The association ratio of malignancy with pemphigus increased by age, while that with pemphigoid was not correlated with aging; (3) Lung cancer was most common in pemphigus and gastric cancer in bullous pemphigoid; (4) There were no significant differences in the titers of circulating antibody, the presence or extent of mucous involvement or annular erythema between bullous pemphigoid patients with malignancy and without malignancy. Our results indicated that detailed examination for internal malignancy is essential for those patients with pemphigus or bullous pemphigoid.
Two patients were admitted to our hospital with tense blisters on an erythematous base, typical for bullous pemphigoid. In both patients an infestation with Sarcoptes scabiei was diagnosed by dermatoscopy as well as histological examination. In one patient the clinical diagnosis of bullous pemphigoid could be confirmed by immunofluorescence microscopy, histopathology and a clinical relapse of bullous pemphigoid without scabies infestation. In the other patient no evidence for an autoantibody-mediated autoimmune blistering disease was found. We postulate that bullous scabies could develop after long persistency of the parasites leading to a specific immune response with activation of T helper type 2 (Th2) cells causing high levels of the cytokine interleukin 5 and then consecutively eosinophilia. Secretion of proteolytic enzymes near the basal membrane zone might explain the development of intraepidermal, often suprabasal blisters. In contrast, in the first patient the scabies infestation might have triggered a flare up of the underlying autoimmune disease. Comparison of our two patients demonstrates two entities: bullous pemphigoid triggered by scabies as a Koebner phenomenon and a bullous subtype of scabies mimicking bullous pemphigoid. Therefore both, scabies infestation triggering bullous pemphigoid and bullous pemphigoid-like scabies should be included in the differential diagnosis of vesicles, tense blisters and erythema, especially at an early clinical stage.
First described in 1877 as the appearance of psoriatic lesions in the uninvolved skin of psoriatic patients as a consequence of trauma, the Koebner phenomenon has since been described in numerous diseases. Other authors have tried to implicate either infections or parasitic causes as the pathogenesis of this phenomenon. Subsequent research by many authors have contributed to our poor understanding of this reaction in the hope of understanding the pathogensis of psoriasis. We present a review of the literature covering the following topics as they relate to the Koebner phenomenon: diseases that koebnerize and their possible causes, predisposing and provoking factors, type, site, depth and degree of trauma, the all or none phenomenon, time lag, site preference, medications, inhibition of koebnerization and reverse koebnerization.
Skin side effects following XRT take place more often in patients with skin disorders. In this study six patients with psoriatic lesions were evaluated. The total/daily XRT dose to the tumor site was 50-70/1.8-2.0 Gy. No debilitating effect of XRT was observed in both the psoriatic lesions and in the surrounding normal skin.
The report of two patients who developed Bullous pemphigoid (BP) during radiotherapy (RT) of breast cancer is presented. The possible mechanisms and the risk factors were taken into concern during the development of BP. A patient diagnosed with breast cancer underwent breast sparing surgery. Gradually she developed a rash on both inner sides of her arms, which was imparted as an allergic reaction to her medication. Later irradiation for the right breast and periclavicular region was applied. As a result erythematosquamous conflating plaques with excoriations and blister formation confined to the radiation field developed after the 10th fraction. Later a skin biopsy specimen confirmed the diagnosis of BP. It can be concluded that both the patients developed a grade 1 radiation dermatitis independent of the BP and onset of BP. BP may therefore be considered as an early side effect of RT.
Percutaneous radiotherapy (RT) may cause a range of acute and late side effects of the skin within the irradiated area. In rare cases radiotherapy can cause bullous pemphigoid (BP). BP is reported to occur mainly within irradiated fields following radiation treatment. Exceptionally, BP may arise during RT. It is unclear which mechanism exactly triggers BP following megavoltage irradiation and whether there is a potential association with hormonal anticancer treatment.
A systematic literature based review was performed. Publications reporting histologically confirmed BP and a treatment with RT were retrieved based on a standardized query using electronic databases. A standardized quality assessment was applied.
Out of 306 potentially relevant publications 21 were identified to be relevant and included in this review. An association between RT and BP was reported in 27 patients. The majority developed BP after RT and a median dose of 50 Gy. Four patients developed BP during RT after a minimal dose of 20 Gy.
BP induced by RT was observed predominantly in patients with breast cancer. In all reported cases, there is a clear relationship with RT. Therefore, BP may be considered as RT-induced side effect. RT can induce a BP following a minimal dose of 20 Gy. New biological agents may play a role in the future treatment of BP.
A case of bullous pemphigoid exacerbated by radiotherapy
- S Anzai
- D Ueo
- S Fujiwara
Anzai S, Ueo D, Fujiwara S. A case of bullous pemphigoid exacerbated
by radiotherapy. Vis Dermatol 2009;8:32-3 (in Japanese).