Monika Bowszyc-Dmochowska

Autoimmunity-driven enzymatic remodeling of the dermal-epidermal junction in bullous pemphigoid and dermatitis herpetiformis.

Pathogenesis of blister formation in bullous pemphigoid (BP) and dermatitis herpetiformis (DH) is associated with destruction of numerous components of the dermal–epidermal junction. Proteolytic enzymes (PE) are involved in a multitude of physiological reactions and may have impact on the epidermal–dermal integrity. Involvement of various PE in inflammation and blister formation in BP and DH is intensively investigated using both morphologic and functional approaches, particularly in BP. The development into the full-blown stage in BP and DH may be caused by an impairment of the human Fc receptor regulatory system that may cause the inefficiently controlled activation of inflammatory cells and subsequent secretion of various proteases.

Bullous pemphigoid and neurodegenerative diseases: a study in a setting of a Central European university dermatology department

Bullous pemphigoid (BP) is an autoimmune blistering dermatosis of the elderly mediated by IgG and IgE antibodies to skin hemidesmosomal proteins, BP180 and/or BP230, that occur physiologically also in neuronal tissue. It was reported that BP is associated with neurodegenerative diseases (ND). We performed a retrospective study in a setting of a Central European university dermatology department on prevalence of ND in 94 BP patients. 26 out of 94 BP patients had at least one ND. ND included: Parkinson’s disease, dementia, stroke, hear loss, tinnitus, blindness, vertigo, neurosyphilis, systemic sclerosis, and epilepsy. Since population aging is conceivably responsible for the rising number of BP cases as a result of immunosenescence-related phenomena, the plausible BP-specific immunopathogenetic relationship between BP and ND deserves to be further experimentally explored.

Basal cell carcinoma – diagnosis

Basal cell carcinoma is the most common skin cancer in the Caucasian population. The cancer arises in sun exposed areas of the skin. The incidence of morbidity is high and it is still growing. The metastatic rate is low, but the enlarging tumor may cause severe tissue disfigurement and a poor cosmetic outcome. The diagnosis is usually clinical but there are many subtypes of this carcinoma and correct diagnosis is the clue to appropriate treatment of the lesion. The main problem in basal cell carcinoma management is the high recurrence rate.

A retrospective study of antihypertensives in pemphigus: a still unchartered odyssey particularly between thiols, amides and phenols.

Introduction Autoimmune pemphigus diseases comprise several entities with serious prognoses, including the pemphigus vulgaris (PV) group and pemphigus foliaceus (PF) group. Antihypertensives are suspected to be one of the factors triggering/sustaining pemphigus. Here, the data of pemphigus patients regarding arterial hypertension (AH) and taking potentially noxious drugs were statistically analyzed in a setting of a Polish university dermatology department. Material and methods Medical histories of pemphigus patients (40 admissions of 24 female patients – 13 PV, 11 PF; and 102 admissions of 38 male patients – 24 PV, 14 PF), diagnosed at both immunopathological and biochemical-molecular levels, were studied. Results Ten of 16 (62.50%) AH-positive PV patients received known PV triggers/sustainers 11 times (1–3 per patient). Fourteen of 15 (93.33%) AH-positive PF patients received known PF triggers/sustainers 21 times (1–3 per patient). No differences in numbers of patients taking potentially culprit drugs were shown between PV and PF (Fishers exact test: p = 0.0829; Yates’ χ2 test: p = 0.1048). The most frequently used culprit drugs were ramipril in PV and enalapril in PF. On average, each PV/PF AH-positive patient received 3.161 different antihypertensives in his/her history of admissions (2.155 antihypertensives per admission). Conclusions Drug triggering should be suspected in every case of newly diagnosed or exacerbated pemphigus, as eliminating possible PV/PF triggers/sustainers may alleviate the clinical symptoms and enable the decrease of dose/range of immunosuppressants regardless of pemphigus form. Eliminating possible drug PV/PF triggers/sustainers may alleviate the clinical symptoms and enable the decrease of dose/range of immunosuppressants regardless of pemphigus form.

Mucosal-dominant pemphigus vulgaris in a captopril-taking woman with angioedema

We describe a 39-year-old woman with an apparent captopril-induced, contact mucosal-dominant pemphigus vulgaris and angioedema, who took captopril during a bout of arterial hypertension. This exposure suggests that captopril and pathophysiology of angioedema stimulated the development of pemphigus vulgaris, which was diagnosed using the novel, indirect immunofluorescence BIOCHIP mosaic, with the modification to detect serum IgG4 autoantibodies. We discuss the patient, who experienced a chain of events leading to the active stage of pemphigus vulgaris, and review concepts of pemphigus vulgaris inducible by drugs and pathological immunity.

Discordant expression of desmoglein 2 and 3 at the mRNA and protein levels in nodular and superficial basal cell carcinoma revealed by immunohistochemistry and fluorescent in situ hybridization.

Basal cell carcinoma (BCC) is the most common human cancer. It is thought that skewed expression of desmogleins (Dsgs) in BCC may promote tumourigenesis.

Evaluation of an Avidin-Biotin-Peroxidase Method with a Monoclonal Antibody to Type IV Collagen in the Differential Diagnosis of Bullous Pemphigoid and Epidermolysis Bullosa Acquisita

There are reports in which an immunohistochemical technique with a monoclonal antibody to type IV collagen has been employed for differentiating between bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA). The aim of this study was to determine whether this method could be used routinely. Biopsies (paraffin‐embedded lesional skin containing a blister) from currently diagnosed patients with clinical features suggesting BP or EBA were examined by an avidin‐biotin‐peroxidase (ABC) technique. Sera were tested by indirect immunofluorescence on salt‐split skin (IF) and immunoblotting (IB). In all cases which exhibited clear type IV collagen staining, the results of the ABC technique agreed with results of both IF and IB. In one confirmed EBA case, it was impossible to unequivocally localize type IV collagen, because it stained very faintly. Taking into consideration the results of our study, data indicating that the level of blistering might not coincide with the localization of immunoreactants in EBA cases and the possibility of an enzymatic destruction of lamina densa, we conclude that the ABC method is unsuitable for differentiation between BP and EBA.

Cutaneous expressions of interleukin-6 and neutrophil elastase as well as levels of serum IgA antibodies to gliadin nonapeptides, tissue transglutaminase and epidermal transglutaminase: implications for both autoimmunity and autoinflammation involvement in dermatitis herpetiformis

Introduction Dermatitis herpetiformis (DH) seems to be a chronic immune-mediated inflammatory disease of partially known origin. In light of its known biological functions and its involvement in tissue pathology in other disease states, particularly in nickel-induced allergic contact dermatitis coexisting with DH, it would appear that the central and peripheral response by neutrophils and their mediators (e.g. neutrophil elastase – NE) in DH may be partially mediated by interleukin-6 (IL-6). The aim of the study was to assess the role of IL -6 in DH lesions by examining the relationships between IL -6/NE cutaneous expression and levels of serum anti-nonapeptides of gliadin (npG) IgA, anti-tissue transglutaminase (tTG) immunoglobulin A (IgA), anti-epidermal transglutaminase (eTG) IgA in DH. Material and methods In total, 24 DH patients having IgA cutaneous deposition were studied. Immunohistochemistry on paraffin-embedded sections with quantitative digital morphometry was used to measure the intensity of IL -6 and NE cutaneous expressions. Levels of serum anti-npG IgA, anti-tTG IgA and anti-eTG IgA were evaluated with ELISA. Results We found no statistically significant correlation between the NE and IL -6 expression intensities. Our results revealed also a lack of correlations between NE/IL -6 expressions and levels of anti-npG IgA, anti-tTG IgA, anti-eTG IgA in DH. However, the IL -6 expression level was significantly lower than that of NE. Conclusions The lack of correlations suggested no substantial interactions between IL -6, NE, IgA/npG, IgA/tTG or IgA/eTG in DH. Presented results might indicate the heterogenetic nature of DH pathogenesis suggesting further that both autoimmune and autoinflammatory phenomena may be involved in DH cutaneous pathology.

Association between Levels of IgA Antibodies to Tissue Transglutaminase and Gliadin-Related Nonapeptides in Dermatitis Herpetiformis

Dermatitis herpetiformis (DH) is an autoimmunity-driven inflammatory blistering dermatosis associated with a gluten-dependent enteropathy. Tissue transglutaminase (tTG) and nonapeptides of gliadin (npG) are considered in its pathomechanism/diagnostics. Here, the diagnostic accuracy of anti-tTG/anti-npG IgA ELISAs in Slavic DH patients with active skin rash was assessed through creating receiver operating characteristic (ROC) curves, determining cutoff values, and calculating correlations between levels of anti-tTG/anti-npG IgA in DH, IgA/neutrophil-mediated non-DH patients and healthy persons. Altogether, sera from 80 Slavic individuals were examined. There were negligible differences between cutoff points obtained by the ELISAs manufacturer and those in this study. There were statistically significant correlations between levels of anti-tTG/anti-npG IgA in both DH group and the group of IgA/neutrophil-mediated non-DH dermatoses. There was no such correlation in healthy controls. It seems that IgA autoantibodies to tTG and npG in the IgA/neutrophil-mediated DH are produced in the coordinated way implying their causal relationship.

Generalized lichen nitidus: a case report and review of the literature

Lichen nitidus, first described by Pinkus in 1907, is a rare skin disease of unknown aetiology [1, 2]. It is clinically characterized by the presence of multiple discrete papules that are tiny, shiny, and of varied colours. Most commonly, the lesions are localized on the neck, trunk, forearms, abdomen and the genitalia. However, infrequently cases with generalized skin involvement have been reported, mostly affecting children. Herein, we present a generalized form of lichen nitidus in a middle-aged woman, which has been successfully treated with aci-tretin. A 34-year-old woman was referred to the outpatient clinic of the Department of Dermatology due to the skin lesions, which have been observed for 2 years. Dermato-logical examination revealed thousand of shiny, polygonal, 1–2 mm sized papules located on the trunk, upper and lower limbs including palms (Figures 1 A–C). The papules did not show any tendency to coalesce (Figure 1 C). The face, neck, soles, and the genitalia were not affected. In the oral cavity, there were signs of whitening of the mucosa. Onychorrhexis was observed within the nails. The patient did not suffer from any concomitant disease. She did not use any drugs. Two skin biopsy samples from the thumb and trunk were taken for histopathological examination in order to confirm the clinical diagnosis (H + E) (Figure 2). Topical treatment with mild potent glucocorticoste-roids was initiated, but they proved to be ineffective. For this reason, a systemic treatment with methylpred-nisolone at an initial dose of 16 mg/day was introduced. A significant improvement after 2 months of therapy was observed, however the symptoms recurred while tapering the dose. As soon as histopathological confirmation of lichen nitidus in our department was made, acitretin at an initial dose of 50 mg/day was administered with good tolerance. The reduction of the skin lesions within 3–4 months was observed. At present, the patient takes the drug at a dose of 10 mg/day (6 months) showing marked improvement (she presents lesions only on her palms) and is being followed in the outpatient clinic. A typical clinical pattern of lichen nitidus is characterized by the presence of numerous shiny papules which may appear in a variety of shades, from fleshy pink to dark brown, whereas within dark skin they appear as light spots [3, 4]. The papules are 1–2 mm in diameter. Skin lesions are usually not accompanied by any additional symptoms with a sporadic exception of mild pruritus. …