Psoriasis is a chronic autoimmune disease affecting over 2% of the worldwide population. From an ... more Psoriasis is a chronic autoimmune disease affecting over 2% of the worldwide population. From an anatomopathological point of view, psoriasis is characterized by immune cells infiltration, epidermal hyperproliferation, and abnormal keratinocyte differentiation. Understanding the pathogenesis of psoriasis will allow clinicians to manage this complex disease. Under these conditions, the application of effective treatments requires a thorough knowledge of all the pathogenetic mechanisms that lead to psoriasis. Numerous immunopathological pathways play crucial roles in the development of new therapies, such as biological therapies, which have been a breakthrough in psoriasis's treatment. Pharmacogenetics is an essential factor in the patient's response to treatment. One important pathway targeted by modern treatments is the interleukin (IL)-23/T-helper (Th)17 axis. Like IL-17 inhibitors, IL-23 blockers are a very effective therapy for this autoimmune disease. It is considered that micro-ribonucleic acids (microRNAs) are the starting point for any autoimmune disease. Studying certain microRNA (miR) involved in the inflammatory pathway in psoriasis can find direct targets to future treatments that can even be more specific than actual biological therapies. As such, miR-210 has proven to be up-regulated in psoriasis, also leading to the up-regulation of the Th1/Th17 axis. On the other hand, miR-187 was found to be down-regulated, influencing the outcome of psoriasis by increasing the proliferation of IL-6 stimulated keratinocytes and consecutively generating epidermal thickening. In this review, we are aiming to do an up-to-date briefing of psoriasis histopathology and pharmacogenetic factors that are considered for the accurate evaluation of treatment response.
Lichen planus pemphigoides (LPP) and bullous lichen planus (BLP) are rare dermatoses, which are c... more Lichen planus pemphigoides (LPP) and bullous lichen planus (BLP) are rare dermatoses, which are characterised by blisters and lichenoid lesions. Their clinical presentation is heterogenous, displaying overlapping features or mimicking other dermatological diseases. Therefore, diagnosis can often be challenging, requiring a thorough dermatological examination along with distinctive histological and immunopathological characteristics. Lichenoid degeneration of the basal epidermis exposes various antigens of the dermal-epidermal junction in LPP, resulting in the breakdown of immune tolerance, hence, the production of autoantibodies against type XVII collagen. Conversely, no pathogenic autoantibodies are detected in BLP. However, some cases of mucosal lichen planus might display immunopathological features suggestive of autoimmune blistering diseases. Therefore, a better understanding of the pathophysiology of these two distinct dermatoses is imperative. The aim of this review was to provide a summary of the current knowledge on the clinical hallmarks, diagnosis and available therapeutic options in LPP and BLP.
Figure S1. Comparative analysis of serum reactivity with the extracellular matrix and native lami... more Figure S1. Comparative analysis of serum reactivity with the extracellular matrix and native laminin 332 by ELISA in control patients. Box plots represent optical density measurements of serum reactivity from patients with pemphigus vulgaris (PV, n = 20), epidermolysis bullosa acquisita (EBA, n = 20) and dermatits herpetiformis (DH, n = 20) as well as from healthy donors (n = 4) measured in parallel on native laminin 332 and laminin-rich extracellular matrix of keratinocytes. (PNG 20 kb)
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2022
Incontinentia pigmenti ist eine seltene X‐chromosomal dominant vererbte Systemerkrankung, die vor... more Incontinentia pigmenti ist eine seltene X‐chromosomal dominant vererbte Systemerkrankung, die vor allem die Haut, aber auch andere neuroektodermale Gewebe wie Zähne, Haare, Augen und das zentrale Nervensystem betrifft.
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2021
Incontinentia pigmenti is a rare X‐linked dominantly inherited systemic disease affecting primari... more Incontinentia pigmenti is a rare X‐linked dominantly inherited systemic disease affecting primarily the skin but also other neuroectodermal tissues such as teeth, hair, eyes, and the central nervous system.
Autoimmune blistering diseases are a heterogenous group of dermatological disorders characterized... more Autoimmune blistering diseases are a heterogenous group of dermatological disorders characterized by blisters and erosions of the skin and/or mucous membranes induced by autoantibodies against structural proteins of the desmosome or the dermal-epidermal adhesion complex including the hemidesmosome. They consist of the two major disease groups, pemphigus and pemphigoid diseases (PPDs). The diagnosis is based on clinical findings, histopathology, direct immunofluorescence, and detection of circulating autoantibodies. The pathogenesis is not fully elucidated, prognostic factors are lacking, and to date, there is no cure for PPDs. MicroRNAs (miRNAs) represent small, non-coding RNAs that play a pivotal role in the posttranscriptional regulation of gene expression. Their dysfunction was highlighted to play a significant role in the pathogenesis of various diseases. Even though a link between miRNAs and autoimmune blistering diseases had been suggested, the research of their involvement in the pathogenesis of PPDs is still in its infancy. miRNAs hold promise for uncovering new layers in the pathogenesis of PPDs, in order to improve diagnosis and also to develop potential therapeutic options. In the current article, we provide an overview regarding current knowledge of miRNAs in terms of complex pathogenesis of PPDs, and, also, their potential role as biomarkers, predictive factors and therapeutic targets.
pathogens before the first culture. Talan et al. [1] examined 50 patients with dog bites and 57 w... more pathogens before the first culture. Talan et al. [1] examined 50 patients with dog bites and 57 with cat bites, and the cultures yielded a median of five bacterial species; of the 107 cases reported, Bacteroides species were detected in 31 cases, but Bacteroides pyogenes was not present. Bacteroides pyogenes is an anaerobic Gram-negative bacillus, first isolated from pigs [2] and later detected in the oral flora of dogs and cats [3, 4]. The first reported case of human infection with Bacteroides pyogenes was bacteraemia due to a cat bite [5]. To the best of our knowledge, to date, only one other study of Bacteroides pyogenes infection due to an animal bite has been reported. Lau et al. also described four dog-bite and three cat-bite cases [6], and of the eight dog/cat-bite cases in these two reports, seven were treated with penicillin, and one was treated with penicillin and ciprofloxacin. In our case, as Bacteroides pyogenes was sensitive to penicillin and new quinolone, the use of sitafloxacin proved effective. Notably, five of eight previously described cases required multiple (a maximum four times) surgical treatments (incision or debridement) [5, 6]. In our case, three incisions were made. Bacteroides pyogenes associated with dog/cat bites may be recalcitrant and warrant additional surgical treatments after the primary treatment. Therefore, careful observation during the management of dog/cat bites is imperative. Recently, MALDI-TOF MS has gained popularity for the identification of microorganisms. In this technique, a single isolated bacterial or fungal colony is smeared onto a metal plate, conjugated with a chemical reagent matrix and dried, followed by MALDI-TOF MS analysis to generate protein fingerprint signatures. Finally, the microorganisms are identified by comparing fingerprint spectra with reference spectra in a database. Several studies have revealed that MALDI-TOF MS is a precise and high-throughput method for identifying microorganisms [7, 8]. Although the results of MALDI-TOF MS and 16S ribosomal RNA sequencing often correlate well for various microorganisms, discrepancies are sometimes reported [9, 10]. Lau et al. demonstrated a perfect identification match for MALDITOF MS and 16S ribosomal RNA sequencing in their seven Bacteroides pyogenes-infected cases [6]. Thus, the identification of Bacteroides pyogenes in our case is likely to be accurate. In conclusion, Bacteroides pyogenes can potentially cause recalcitrant infection after dog/cat bites. Careful observation, surgical treatment, and appropriate antibiotics are vital for managing these infections. In the future, MALDI-TOF MS usage will facilitate detection of Bacteroides pyogenesassociated infectious disease in daily clinical practice.
Background: Bullous pemphigoid is a subepidermal blistering skin disease, associated with autoant... more Background: Bullous pemphigoid is a subepidermal blistering skin disease, associated with autoantibodies to hemidesmosomal proteins, complement activation at the dermal-epidermal junction, and dermal granulocyte infiltration. Clinical and experimental laboratory findings support conflicting hypotheses regarding the role of complement activation for the skin blistering induced by pemphigoid autoantibodies. In-depth studies on the pathogenic relevance of autoimmune complement activation in patients are largely lacking. Therefore, the aim of this study was to investigate the pathogenic relevance of complement activation in patients with bullous pemphigoid. Complement activation by autoantibodies in vivo as measured by the intensity of complement C3 deposits in the patients' skin and ex vivo by the complement-fixation assay in serum was correlated with the clinical disease activity, evaluated by Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Bullous Pemphigoid Disease Area Index (BPDAI), as well as, with further immunopathological findings in patients with bullous pemphigoid. Results: Complement-activation capacity of autoantibodies ex vivo, but not deposition of complement in the perilesional skin of patients, correlates with the extent of skin disease (measured by ABSIS and BPDAI) and with levels of autoantibodies. Conclusions: Our study provides for the first time evidence in patients for a pathogenic role of complement activation in bullous pemphigoid and should greatly facilitate the development of novel diagnostic tools and of more specific therapies for complement-dependent autoimmune injury.
Mucous membrane pemphigoid is a group of chronic subepithelial autoimmune blistering diseases tha... more Mucous membrane pemphigoid is a group of chronic subepithelial autoimmune blistering diseases that mainly affect mucous membranes. Laminin 332-specific autoantibodies are present in approximately 1/3 of the patients, being associated with an increased risk of malignancy. Because of the severe complications, an early recognition of the disease allowing a timely therapy is essential. The gold standard methods for detection of laminin 332-specific autoantibodies, including the immunoprecipitation and immunoblotting are non-quantitative, laborious and restricted to a few specialized laboratories worldwide. In addition, the use of radioimmunoassays, although highly sensitive and specific, are laborious, expensive and tightly regulated. Therefore, there is a stringent need for a quantitative immunoassay for the routine detection of laminin 332-specific autoantibodies more broadly available to diagnostic laboratories. The aim of this study was to compare different antigenic substrates, inc...
The aim of this study was to evaluate the clinical importance of autoantibodies in pemphigus vulg... more The aim of this study was to evaluate the clinical importance of autoantibodies in pemphigus vulgaris patients who developed steroid-induced diabetes mellitus (SID) because of the glucocorticoid therapy of pemphigus.A total of 137 patients with pemphigus vulgaris were studied. Patients with SID and pemphigus were compared with those that had only pemphigus. The variables recorded were: age at diagnosis, sex, body mass index, presence of diabetes mellitus (DM), cumulative cortisone dose, treatment duration, value of anti-desmoglein 1 and 3, and anti-glutamic acid decarboxylase autoantibodies.A total of 31 patients (22.62%) that developed steroid-induced DM were identified. Anti-glutamic acid decarboxylase autoantibodies were positive in 20.75% of patients with pemphigus vulgaris and in 25.75% of patients with pemphigus vulgaris and SID.The overall anti-glutamic acid decarboxylase autoantibodies prevalence in pemphigus patients was high, and the risk of developing DM in patients with ...
The Australasian journal of dermatology, Jan 8, 2018
We describe a new mutation in exon 4 of IKBKG, encoding nuclear factor-kappa B in a patient with ... more We describe a new mutation in exon 4 of IKBKG, encoding nuclear factor-kappa B in a patient with incontinentia pigmenti. The patient had a severe cholestatic liver disease with features of a ciliopathy and underwent liver transplantation. We cannot establish a link between incontinentia pigmenti, a very rare disease, and hepatic ciliopathy, but we suggest that hepatic evaluation should be considered in patients with incontinentia pigmenti.
Old age seems to be the greatest risk factor for celiac disease. Strict adherence to a gluten-fre... more Old age seems to be the greatest risk factor for celiac disease. Strict adherence to a gluten-free diet is difficult for these patients. We present the clinical reassessment in the case of a third age patient, with celiac disease under gluten-free diet and multiple related diseases.
Cutaneous mastocytosis is a disease characterized by the infiltration and proliferation of mast c... more Cutaneous mastocytosis is a disease characterized by the infiltration and proliferation of mast cells in the skin. In children, the most common form of presentation is urticaria pigmentosa, while the diffuse cutaneous bullous mastocytosis is one of the rarest subtypes seen. The aim of this paper is to present a case of diffuse bullous mastocytosis with detection of IgM deposits at dermo-epidermal junction using direct immunofluorescence (DIF) microscopy. The diagnosis of diffuse bullous mastocytosis is a challenge, and DIF microscopy is necessary in order to exclude an autoimmune bullous disorder. However, IgM deposits at dermo-epidermal junction can be nonspecific, being found in a variety of skin disorders. A 6-month-old girl presented with bullous lesions and erosions on the scalp and the trunk. During hospitalization, further bullous lesions appeared, along with generalized erythrodermia. Skin biopsy revealed aspects of urticaria pigmentosa. Taking into account the clinical findings, the case was enclosed as bullous mastocytosis. Treatment included the avoidance of trigger factors, and administration of antihistamines along with a short-term course of systemic steroids. The evolution was favorable, with remission of the existing lesions and without occurrence of new ones.
Autoimmune bullous skin diseases are characterized by autoantibody production against structural ... more Autoimmune bullous skin diseases are characterized by autoantibody production against structural proteins of the skin and/or mucous membranes. The accurate diagnosis requires clinical evaluation, histologic and immunopathologic findings. The aim of our study was to evaluate the sensitivity of clinical, histologic and immunologic findings for the diagnosis of pemphigus, bullous pemphigoid and dermatitis herpetiformis. In this study, we prospectively investigated 70 patients with pemphigus, 59 patients with bullous pemphigoid and 12 patients with dermatitis herpetiformis. The sensitivity of clinical and histological diagnosis for pemphigus, bullous pemphigoid and dermatitis hepetiformis was 52.8%, 52.5% 41.6% and 78% 50.8%, 50%, respectively. Comparing the performance of the clinical and histological diagnosis with ELISA, the sensitivity of ELISA was higher. We conclude that clinical assessment and routine histologic evaluation must be complemented by direct/indirect immunofluorescenc...
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease affecting mainly the eld... more Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease affecting mainly the elderly. The subtype of the disease induced by physical agents represents a rare and, therefore, insufficiently characterized form. In the present study, we aimed to contribute to a better understanding of the pathogenetic mechanisms involved in the onset of BP induced by different trigger factors. We have retrospectively analyzed nine cases of BP. All patients were characterized based on clinical, epidemiological and immunological parameters. For each case, the trigger factor involved was specified. In addition to our retrospective analysis, a comprehensive review of the 59 published cases was conducted, regarding the involvement of trigger factor in BP, and clinical, epidemiological and immunological data were collected. In the local study, conducted on nine patients diagnosed with BP, various trigger factors were identified: contrast substance injection, surgical procedure, mechanical trauma, insect bite, thermal burn, radiotherapy and ultraviolet exposure associated with pre-existing psoriasis. The autoantibodies from all patients were shown to activate granulocytes and induce dermal-epidermal split. Different hypotheses regarding the pathogenetic mechanism involving the trigger factors have been discussed. In regard of the pathogenetic mechanism, we believe that the most reliable hypothesis is that BP patients already have low titers of anti-basement membrane autoantibodies which activate the granulocytes. However, more studies are needed for a better understanding of the pathogenetic mechanism of the intervention of trigger factors.
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2012
The Melkersson-Rosenthal syndrome (MRS) is a very rare clinical entity and its classical form is ... more The Melkersson-Rosenthal syndrome (MRS) is a very rare clinical entity and its classical form is being characterized by the following triad: facial nerve palsy, swelling of the lips and fissured tongue. However, the monosymptomatic form is more common and the typical manifestation is facial edema and/or enlargement of the lips. We report a case of monosymptomatic MRS with a positive biopsy of granulomatous cheilitis. In the daily practice as a pediatrician, it is not usual to diagnose a patient as having MRS. We consider that this is partly because of misdiagnosis. We therefore believe that this case report will supply additional information, in the scope of recurrent facial paralysis and orofacial edema in both children and adults.
Last consensus in celiac disease in 2008 conducted under the aegis of the European Society of Ped... more Last consensus in celiac disease in 2008 conducted under the aegis of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition jointly with North American Society of Pediatric Gastroenterology, Hepatology and Nutrition reveals the following: "celiac disease is a chronic immune-mediated enteropathy characterized by sensitization to gluten. That can affect any organ or system, with a wide range of clinical manifestations of variable severity". Thus, in recent years, clinical picture of celiac disease has changed the old paradigm--bowel disease with villous atrophy and malnutrition, being replaced with the new paradigm--multi-organ autoimmune disease, affecting many organs and systems throughout but with more less specific symptoms, which undiagnosed leads to delayed diagnosis, at a late-onset disease and long-term major complications as the risk of cancer. According to this consensus "the serological diagnosis of celiac disease is based on high sensi...
Psoriasis is a chronic autoimmune disease affecting over 2% of the worldwide population. From an ... more Psoriasis is a chronic autoimmune disease affecting over 2% of the worldwide population. From an anatomopathological point of view, psoriasis is characterized by immune cells infiltration, epidermal hyperproliferation, and abnormal keratinocyte differentiation. Understanding the pathogenesis of psoriasis will allow clinicians to manage this complex disease. Under these conditions, the application of effective treatments requires a thorough knowledge of all the pathogenetic mechanisms that lead to psoriasis. Numerous immunopathological pathways play crucial roles in the development of new therapies, such as biological therapies, which have been a breakthrough in psoriasis's treatment. Pharmacogenetics is an essential factor in the patient's response to treatment. One important pathway targeted by modern treatments is the interleukin (IL)-23/T-helper (Th)17 axis. Like IL-17 inhibitors, IL-23 blockers are a very effective therapy for this autoimmune disease. It is considered that micro-ribonucleic acids (microRNAs) are the starting point for any autoimmune disease. Studying certain microRNA (miR) involved in the inflammatory pathway in psoriasis can find direct targets to future treatments that can even be more specific than actual biological therapies. As such, miR-210 has proven to be up-regulated in psoriasis, also leading to the up-regulation of the Th1/Th17 axis. On the other hand, miR-187 was found to be down-regulated, influencing the outcome of psoriasis by increasing the proliferation of IL-6 stimulated keratinocytes and consecutively generating epidermal thickening. In this review, we are aiming to do an up-to-date briefing of psoriasis histopathology and pharmacogenetic factors that are considered for the accurate evaluation of treatment response.
Lichen planus pemphigoides (LPP) and bullous lichen planus (BLP) are rare dermatoses, which are c... more Lichen planus pemphigoides (LPP) and bullous lichen planus (BLP) are rare dermatoses, which are characterised by blisters and lichenoid lesions. Their clinical presentation is heterogenous, displaying overlapping features or mimicking other dermatological diseases. Therefore, diagnosis can often be challenging, requiring a thorough dermatological examination along with distinctive histological and immunopathological characteristics. Lichenoid degeneration of the basal epidermis exposes various antigens of the dermal-epidermal junction in LPP, resulting in the breakdown of immune tolerance, hence, the production of autoantibodies against type XVII collagen. Conversely, no pathogenic autoantibodies are detected in BLP. However, some cases of mucosal lichen planus might display immunopathological features suggestive of autoimmune blistering diseases. Therefore, a better understanding of the pathophysiology of these two distinct dermatoses is imperative. The aim of this review was to provide a summary of the current knowledge on the clinical hallmarks, diagnosis and available therapeutic options in LPP and BLP.
Figure S1. Comparative analysis of serum reactivity with the extracellular matrix and native lami... more Figure S1. Comparative analysis of serum reactivity with the extracellular matrix and native laminin 332 by ELISA in control patients. Box plots represent optical density measurements of serum reactivity from patients with pemphigus vulgaris (PV, n = 20), epidermolysis bullosa acquisita (EBA, n = 20) and dermatits herpetiformis (DH, n = 20) as well as from healthy donors (n = 4) measured in parallel on native laminin 332 and laminin-rich extracellular matrix of keratinocytes. (PNG 20 kb)
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2022
Incontinentia pigmenti ist eine seltene X‐chromosomal dominant vererbte Systemerkrankung, die vor... more Incontinentia pigmenti ist eine seltene X‐chromosomal dominant vererbte Systemerkrankung, die vor allem die Haut, aber auch andere neuroektodermale Gewebe wie Zähne, Haare, Augen und das zentrale Nervensystem betrifft.
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, 2021
Incontinentia pigmenti is a rare X‐linked dominantly inherited systemic disease affecting primari... more Incontinentia pigmenti is a rare X‐linked dominantly inherited systemic disease affecting primarily the skin but also other neuroectodermal tissues such as teeth, hair, eyes, and the central nervous system.
Autoimmune blistering diseases are a heterogenous group of dermatological disorders characterized... more Autoimmune blistering diseases are a heterogenous group of dermatological disorders characterized by blisters and erosions of the skin and/or mucous membranes induced by autoantibodies against structural proteins of the desmosome or the dermal-epidermal adhesion complex including the hemidesmosome. They consist of the two major disease groups, pemphigus and pemphigoid diseases (PPDs). The diagnosis is based on clinical findings, histopathology, direct immunofluorescence, and detection of circulating autoantibodies. The pathogenesis is not fully elucidated, prognostic factors are lacking, and to date, there is no cure for PPDs. MicroRNAs (miRNAs) represent small, non-coding RNAs that play a pivotal role in the posttranscriptional regulation of gene expression. Their dysfunction was highlighted to play a significant role in the pathogenesis of various diseases. Even though a link between miRNAs and autoimmune blistering diseases had been suggested, the research of their involvement in the pathogenesis of PPDs is still in its infancy. miRNAs hold promise for uncovering new layers in the pathogenesis of PPDs, in order to improve diagnosis and also to develop potential therapeutic options. In the current article, we provide an overview regarding current knowledge of miRNAs in terms of complex pathogenesis of PPDs, and, also, their potential role as biomarkers, predictive factors and therapeutic targets.
pathogens before the first culture. Talan et al. [1] examined 50 patients with dog bites and 57 w... more pathogens before the first culture. Talan et al. [1] examined 50 patients with dog bites and 57 with cat bites, and the cultures yielded a median of five bacterial species; of the 107 cases reported, Bacteroides species were detected in 31 cases, but Bacteroides pyogenes was not present. Bacteroides pyogenes is an anaerobic Gram-negative bacillus, first isolated from pigs [2] and later detected in the oral flora of dogs and cats [3, 4]. The first reported case of human infection with Bacteroides pyogenes was bacteraemia due to a cat bite [5]. To the best of our knowledge, to date, only one other study of Bacteroides pyogenes infection due to an animal bite has been reported. Lau et al. also described four dog-bite and three cat-bite cases [6], and of the eight dog/cat-bite cases in these two reports, seven were treated with penicillin, and one was treated with penicillin and ciprofloxacin. In our case, as Bacteroides pyogenes was sensitive to penicillin and new quinolone, the use of sitafloxacin proved effective. Notably, five of eight previously described cases required multiple (a maximum four times) surgical treatments (incision or debridement) [5, 6]. In our case, three incisions were made. Bacteroides pyogenes associated with dog/cat bites may be recalcitrant and warrant additional surgical treatments after the primary treatment. Therefore, careful observation during the management of dog/cat bites is imperative. Recently, MALDI-TOF MS has gained popularity for the identification of microorganisms. In this technique, a single isolated bacterial or fungal colony is smeared onto a metal plate, conjugated with a chemical reagent matrix and dried, followed by MALDI-TOF MS analysis to generate protein fingerprint signatures. Finally, the microorganisms are identified by comparing fingerprint spectra with reference spectra in a database. Several studies have revealed that MALDI-TOF MS is a precise and high-throughput method for identifying microorganisms [7, 8]. Although the results of MALDI-TOF MS and 16S ribosomal RNA sequencing often correlate well for various microorganisms, discrepancies are sometimes reported [9, 10]. Lau et al. demonstrated a perfect identification match for MALDITOF MS and 16S ribosomal RNA sequencing in their seven Bacteroides pyogenes-infected cases [6]. Thus, the identification of Bacteroides pyogenes in our case is likely to be accurate. In conclusion, Bacteroides pyogenes can potentially cause recalcitrant infection after dog/cat bites. Careful observation, surgical treatment, and appropriate antibiotics are vital for managing these infections. In the future, MALDI-TOF MS usage will facilitate detection of Bacteroides pyogenesassociated infectious disease in daily clinical practice.
Background: Bullous pemphigoid is a subepidermal blistering skin disease, associated with autoant... more Background: Bullous pemphigoid is a subepidermal blistering skin disease, associated with autoantibodies to hemidesmosomal proteins, complement activation at the dermal-epidermal junction, and dermal granulocyte infiltration. Clinical and experimental laboratory findings support conflicting hypotheses regarding the role of complement activation for the skin blistering induced by pemphigoid autoantibodies. In-depth studies on the pathogenic relevance of autoimmune complement activation in patients are largely lacking. Therefore, the aim of this study was to investigate the pathogenic relevance of complement activation in patients with bullous pemphigoid. Complement activation by autoantibodies in vivo as measured by the intensity of complement C3 deposits in the patients' skin and ex vivo by the complement-fixation assay in serum was correlated with the clinical disease activity, evaluated by Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Bullous Pemphigoid Disease Area Index (BPDAI), as well as, with further immunopathological findings in patients with bullous pemphigoid. Results: Complement-activation capacity of autoantibodies ex vivo, but not deposition of complement in the perilesional skin of patients, correlates with the extent of skin disease (measured by ABSIS and BPDAI) and with levels of autoantibodies. Conclusions: Our study provides for the first time evidence in patients for a pathogenic role of complement activation in bullous pemphigoid and should greatly facilitate the development of novel diagnostic tools and of more specific therapies for complement-dependent autoimmune injury.
Mucous membrane pemphigoid is a group of chronic subepithelial autoimmune blistering diseases tha... more Mucous membrane pemphigoid is a group of chronic subepithelial autoimmune blistering diseases that mainly affect mucous membranes. Laminin 332-specific autoantibodies are present in approximately 1/3 of the patients, being associated with an increased risk of malignancy. Because of the severe complications, an early recognition of the disease allowing a timely therapy is essential. The gold standard methods for detection of laminin 332-specific autoantibodies, including the immunoprecipitation and immunoblotting are non-quantitative, laborious and restricted to a few specialized laboratories worldwide. In addition, the use of radioimmunoassays, although highly sensitive and specific, are laborious, expensive and tightly regulated. Therefore, there is a stringent need for a quantitative immunoassay for the routine detection of laminin 332-specific autoantibodies more broadly available to diagnostic laboratories. The aim of this study was to compare different antigenic substrates, inc...
The aim of this study was to evaluate the clinical importance of autoantibodies in pemphigus vulg... more The aim of this study was to evaluate the clinical importance of autoantibodies in pemphigus vulgaris patients who developed steroid-induced diabetes mellitus (SID) because of the glucocorticoid therapy of pemphigus.A total of 137 patients with pemphigus vulgaris were studied. Patients with SID and pemphigus were compared with those that had only pemphigus. The variables recorded were: age at diagnosis, sex, body mass index, presence of diabetes mellitus (DM), cumulative cortisone dose, treatment duration, value of anti-desmoglein 1 and 3, and anti-glutamic acid decarboxylase autoantibodies.A total of 31 patients (22.62%) that developed steroid-induced DM were identified. Anti-glutamic acid decarboxylase autoantibodies were positive in 20.75% of patients with pemphigus vulgaris and in 25.75% of patients with pemphigus vulgaris and SID.The overall anti-glutamic acid decarboxylase autoantibodies prevalence in pemphigus patients was high, and the risk of developing DM in patients with ...
The Australasian journal of dermatology, Jan 8, 2018
We describe a new mutation in exon 4 of IKBKG, encoding nuclear factor-kappa B in a patient with ... more We describe a new mutation in exon 4 of IKBKG, encoding nuclear factor-kappa B in a patient with incontinentia pigmenti. The patient had a severe cholestatic liver disease with features of a ciliopathy and underwent liver transplantation. We cannot establish a link between incontinentia pigmenti, a very rare disease, and hepatic ciliopathy, but we suggest that hepatic evaluation should be considered in patients with incontinentia pigmenti.
Old age seems to be the greatest risk factor for celiac disease. Strict adherence to a gluten-fre... more Old age seems to be the greatest risk factor for celiac disease. Strict adherence to a gluten-free diet is difficult for these patients. We present the clinical reassessment in the case of a third age patient, with celiac disease under gluten-free diet and multiple related diseases.
Cutaneous mastocytosis is a disease characterized by the infiltration and proliferation of mast c... more Cutaneous mastocytosis is a disease characterized by the infiltration and proliferation of mast cells in the skin. In children, the most common form of presentation is urticaria pigmentosa, while the diffuse cutaneous bullous mastocytosis is one of the rarest subtypes seen. The aim of this paper is to present a case of diffuse bullous mastocytosis with detection of IgM deposits at dermo-epidermal junction using direct immunofluorescence (DIF) microscopy. The diagnosis of diffuse bullous mastocytosis is a challenge, and DIF microscopy is necessary in order to exclude an autoimmune bullous disorder. However, IgM deposits at dermo-epidermal junction can be nonspecific, being found in a variety of skin disorders. A 6-month-old girl presented with bullous lesions and erosions on the scalp and the trunk. During hospitalization, further bullous lesions appeared, along with generalized erythrodermia. Skin biopsy revealed aspects of urticaria pigmentosa. Taking into account the clinical findings, the case was enclosed as bullous mastocytosis. Treatment included the avoidance of trigger factors, and administration of antihistamines along with a short-term course of systemic steroids. The evolution was favorable, with remission of the existing lesions and without occurrence of new ones.
Autoimmune bullous skin diseases are characterized by autoantibody production against structural ... more Autoimmune bullous skin diseases are characterized by autoantibody production against structural proteins of the skin and/or mucous membranes. The accurate diagnosis requires clinical evaluation, histologic and immunopathologic findings. The aim of our study was to evaluate the sensitivity of clinical, histologic and immunologic findings for the diagnosis of pemphigus, bullous pemphigoid and dermatitis herpetiformis. In this study, we prospectively investigated 70 patients with pemphigus, 59 patients with bullous pemphigoid and 12 patients with dermatitis herpetiformis. The sensitivity of clinical and histological diagnosis for pemphigus, bullous pemphigoid and dermatitis hepetiformis was 52.8%, 52.5% 41.6% and 78% 50.8%, 50%, respectively. Comparing the performance of the clinical and histological diagnosis with ELISA, the sensitivity of ELISA was higher. We conclude that clinical assessment and routine histologic evaluation must be complemented by direct/indirect immunofluorescenc...
Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease affecting mainly the eld... more Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease affecting mainly the elderly. The subtype of the disease induced by physical agents represents a rare and, therefore, insufficiently characterized form. In the present study, we aimed to contribute to a better understanding of the pathogenetic mechanisms involved in the onset of BP induced by different trigger factors. We have retrospectively analyzed nine cases of BP. All patients were characterized based on clinical, epidemiological and immunological parameters. For each case, the trigger factor involved was specified. In addition to our retrospective analysis, a comprehensive review of the 59 published cases was conducted, regarding the involvement of trigger factor in BP, and clinical, epidemiological and immunological data were collected. In the local study, conducted on nine patients diagnosed with BP, various trigger factors were identified: contrast substance injection, surgical procedure, mechanical trauma, insect bite, thermal burn, radiotherapy and ultraviolet exposure associated with pre-existing psoriasis. The autoantibodies from all patients were shown to activate granulocytes and induce dermal-epidermal split. Different hypotheses regarding the pathogenetic mechanism involving the trigger factors have been discussed. In regard of the pathogenetic mechanism, we believe that the most reliable hypothesis is that BP patients already have low titers of anti-basement membrane autoantibodies which activate the granulocytes. However, more studies are needed for a better understanding of the pathogenetic mechanism of the intervention of trigger factors.
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2012
The Melkersson-Rosenthal syndrome (MRS) is a very rare clinical entity and its classical form is ... more The Melkersson-Rosenthal syndrome (MRS) is a very rare clinical entity and its classical form is being characterized by the following triad: facial nerve palsy, swelling of the lips and fissured tongue. However, the monosymptomatic form is more common and the typical manifestation is facial edema and/or enlargement of the lips. We report a case of monosymptomatic MRS with a positive biopsy of granulomatous cheilitis. In the daily practice as a pediatrician, it is not usual to diagnose a patient as having MRS. We consider that this is partly because of misdiagnosis. We therefore believe that this case report will supply additional information, in the scope of recurrent facial paralysis and orofacial edema in both children and adults.
Last consensus in celiac disease in 2008 conducted under the aegis of the European Society of Ped... more Last consensus in celiac disease in 2008 conducted under the aegis of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition jointly with North American Society of Pediatric Gastroenterology, Hepatology and Nutrition reveals the following: "celiac disease is a chronic immune-mediated enteropathy characterized by sensitization to gluten. That can affect any organ or system, with a wide range of clinical manifestations of variable severity". Thus, in recent years, clinical picture of celiac disease has changed the old paradigm--bowel disease with villous atrophy and malnutrition, being replaced with the new paradigm--multi-organ autoimmune disease, affecting many organs and systems throughout but with more less specific symptoms, which undiagnosed leads to delayed diagnosis, at a late-onset disease and long-term major complications as the risk of cancer. According to this consensus "the serological diagnosis of celiac disease is based on high sensi...
Uploads
Papers by Adrian Baican