A comparative analysis of tuberculosis in vitro screening in pemphigus patients selected for treatment with rituximab.

INTRODUCTION: Patients qualified for the Polish government programme of treating severe pemphigus diseases with rituximab (RTX) available in 2018-2019 had to meet numerous criteria, including no active infectious disease. AIM: The clinical usefulness of tuberculosis screening with the QuantiFERON-TB Gold Plus (QFT-Plus) in native pemphigus patients selected for RTX treatment was statistically evaluated. MATERIAL AND METHODS: Eighteen pemphigus patients were examined with QFT-Plus prior to the intended RTX therapy. Ninety hospital employees examined with QFT-Plus due to contact with a cleaning worker who was diagnosed with active pulmonary tuberculosis were the control group. RESULTS: Six of 18 pemphigus patients had a positive QFT-Plus test result, one indefinite result and one initially indefinite and then negative. In the control group, 26 of 90 employees had a positive test result and none had an indefinite result. Statistical analysis by Fisher's exact test showed no statistically significant difference in QFT-Plus positive results between the groups (p = 0.5577). Only in 1 patient with recurrent mucocutaneous pemphigus vulgaris previously treated with traditional immunosuppression, lung changes were detected by computed tomography. No employee had any changes in the chest radiograph. CONCLUSIONS: Prior immunosuppression and autoimmunity might be the cause of indefinite test results, but they do not seem to increase positive results. In the native population, the QFT-Plus screening reveals a significant population exposure to M. tuberculosis infection independent of pemphigus autoimmunity, and such screening can be a starting point for identifying patients requiring anti-tuberculosis drug prophylaxis before combined RTX-glucocorticosteroid treatment.

Contemporary treatment patterns in plaque psoriasis and psoriatic arthritis.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease affecting about 2% of the general population. Although there are many treatment options, and new medications have been introduced, the disease is considered not curable, and it may seriously affect patients' quality of life. AIM: The authors present contemporary treatment patterns used by dermatologists in Poland to manage plaque psoriasis and psoriatic arthritis, particularly regarding systemic treatment. The authors also aimed to analyse how these treatment patterns are influenced by the guidelines of the Polish Dermatological Society. MATERIAL AND METHODS: The author's questionnaire, consisting of 13 questions was used. It included demographic and professional characteristics of questioned dermatologists, as well as the assessment of the attitudes towards management of plaque psoriasis and psoriatic arthritis. RESULTS: A total of 132 dermatologists completed the questionnaire. Most of the specialists worked in out-patient clinics and private practices. The most commonly used topicals for psoriasis included: glucocorticosteroids, a combination of glucocorticosteroid and vitamin D analogue and salicylic acid. Regarding the treatment of psoriatic arthritis, most of the specialists declared using systemic therapy and a combination of systemic therapy and phototherapy. The majority of the respondents were particularly concerned with possible side effects or difficulties in qualifying and monitoring the patients, and less frequently on the cost of the therapy. CONCLUSIONS: Observations suggest that 60% of physicians have some reservation to initiate systemic treatment in outpatient clinics, and they admit that they lack additional training. On the other hand, it seems also that the organization of systemic treatment in psoriasis may generate these difficulties and thus necessitate additional effort. Another factor could be the budget - not only regarding healthcare professionals, but also the patient, sometimes financing various investigations from private resources.

Acute-phase response and its biomarkers in acute and chronic urticaria.

INTRODUCTION: Since urticaria is a persisting inflammatory disease it is important to establish the prognostic factors for the duration and severity of the disease. AIM: To evaluate serum concentrations of selected acute-phase proteins (APP) in patients with various forms of urticaria as compared to healthy volunteers and also to analyze these concentrations in different types of urticaria. Additionally, to evaluate the correlation between serum levels of selected APP and disease activity. MATERIAL AND METHODS: Serum concentrations of C-reactive protein (CRP), α1-acid glycoprotein (AGP), α1-antichymotrypsin (ACT), α1-antitrypsin (AT), ceruloplasmin (Cp), transferrin (Tf), α2-macroglobulin (α2M) and haptoglobin (Hp) were measured. Quantitative measurement was conducted using the rocket immunoelectrophoresis. Disease activity was assessed with the use of total symptom score. RESULTS: Analysis of serum APP concentrations revealed statistically higher serum concentrations of CRP, AGP and ACT in the entire group of patients with urticaria in comparison with the control group. In the entire group of patients with urticaria, CRP, AGP, ACT, Cp and Hp correlated positively with disease activity, intensity of pruritus and the number and size of urticarial wheals. Statistically lower serum concentrations of CRP, ACT, Cp and Hp were detected in the group of patients with acute urticaria (AU) and angioedema together, compared to the patients suffering from AU only. CONCLUSIONS: Patients with symptoms of various forms of urticaria present a distinct profile of serum APP concentrations. A significant correlation observed between CRP, AGP, ACT, Cp, Hp and clinical activity score points to the potential role of APP as markers of the urticarial activity.

Clinical evaluation of a multiparametric ELISA as a rapid tool for routinely diagnosing IgG-mediated autoimmune blistering dermatoses in ethnic Slavs.

BACKGROUND: Technical innovation of autoimmune blistering dermatoses (ABDs) diagnosis aimed at multiplex approach. Two multiparametric ELISA tests are commercially available for ABDs serology. The aim was to compare diagnostic accuracy of multiparametric and monospecific ELISAs and to examine the diagnostic value/agreement of multivariant ELISA in compliance with traditional diagnostic setup for ABDs. METHODS: In total, 128 sera from suspected ABDs patients were studied (27 sera in order to compare ELISAs). Multivariant ELISA (detection of IgG against desmoglein 1 and 3 - DSG1/3; BP180, BP230, envoplakin, type VII collagen), monovariant ELISA, and statistical analysis were performed. RESULTS: With the use of sera from patients with suspected ABDs, the multiparametric ELISA yield an agreement of 84% with traditional stepwise diagnostics. Multivariant ELISA with BP180 and BP230 showed 87.5% and 80% sensitivity, 87.5% and 91% specificity, 87.5% reliability as well as 87.5% and 80% positive predictive value, 87.5% and 91% negative predictive value, respectively, in relation to monospecific ELISA. Multivariant ELISA with DSG1 and DSG3 showed 50% and 80% sensitivity, 100% and 80% specificity, 85% and 80% reliability as well as 100% and 57% positive predictive value, 82% and 92% negative predictive value, respectively, in relation to monospecific ELISA. A better rate of agreement was observed among ELISA systems with BP180 and BP230, than with ELISA systems with DSG1 and DSG3. CONCLUSION: Multivariant ELISA test combined with clinical examinations and DIF is recommended as a minimal approach to diagnosing ABDs in ethnic Slavs.

A comparative study of expression of Fc receptors in relation to the autoantibody-mediated immune response and neutrophil elastase expression in autoimmune blistering dermatoses.

Here we investigated the cutaneous CD32A and CD89 expression in relation to the neutrophil elastase (NE) expression and serum level of anti-desmoglein 1 and 3 (DSG1/DSG3) IgG in pemphigus, anti-BP180/BP230 IgG in bullous pemphigoid (BP), anti-gliadin nonapeptides (npG), tissue (tTG), and epidermal transglutaminases (eTG) IgA in dermatitis herpetiformis (DH). The examined material consisted of skin/mucosal tissues and sera. In total, 87 patients were studied. Immunohistochemistry on paraffin-embedded sections with quantitative digital morphometry was used to measure the intensity of CD32A/CD89/NE expressions. Levels of anti-DSG1/DSG3 IgG, anti-BP180/BP230 IgG, and anti-npG/tTG/eTG IgA were evaluated with ELISAs. CD32A was abundantly expressed in cutaneous lesions in pemphigus and BP. We found no statistically significant correlation between the CD32A/CD89 and NE expression intensities in pemphigus, BP, and DH. There was a significant correlation between CD89 expression and anti-npG IgA in DH. Our results revealed a lack of correlation between CD32A expressions and anti-DSG1/DSG3 IgG levels in pemphigus, anti-BP180/BP230 IgG in BP as well as CD89 expression and anti-tTG/eTG IgA in DH. CD89 seems to be linked with gluten intolerance in DH rather than with proteolytic destruction of dermal-epidermal junction. CD32A appears to play an important role in mediating skin injury in pemphigus and BP, but probably independently from specific autoantibodies.

Reviewing putative industrial triggering in pemphigus: cluster of pemphigus in the area near the wastewater treatment plant.

A range of pemphigus is relatively rare potentially fatal group of autoimmune blistering dermatoses. Usually, there is no apparent triggering, while in some predisposed patients there are alleged environmental/industrial inducing factors. In a short time period (4 years), we diagnosed 3 novel cases of pemphigus (1 pemphigus vulgaris, 1 pemphigus foliaceus and 1 shift from pemphigus foliaceus into pemphigus vulgaris) at a clinical and laboratory level (ELISA, immunofluorescence studies). We discuss a possible common inducing mechanism as these patients inhabit one estate of the Poznan suburbia (Kozieglowy, population < 12,000), Greater Poland district, Poland, and review literature data on alleged pemphigus triggers. To the best of our knowledge, this is the first report exploring the putative association between pemphigus diseases and wastewater treatment plant waterborne or volatile by-products in the vicinity of such a facility.

Analysis of the autoimmune response against BP180 and BP230 in ethnic Poles with neurodegenerative disorders and bullous pemphigoid.

Recent studies postulated the association between bullous pemphigoid (BP) and neurodegenerative disorders (ND). The autoantibodies to BP180 and/or BP230 may be present not only in BP, but also in ND as neuronal isoforms of these proteins are identified in the central nervous system. However, there are only scant data about the precise pathogenetic mechanisms interlinking ND and BP as well as the immunologic profile in these patients. The aim is to analyze the serological immunopathological profiles (anti-BP180 IgG, anti-BP230 IgG) in BP patients with and without ND in order to identify the specific autoantibody(ies) and corresponding antigens responsible for ND development in BP patients. Altogether, 82 ethnic Poles with BP and their medical records were examined (62 BP-ND; 20 BP+ND). Levels of serum anti-BP180/BP230 IgG in BP patients were evaluated with ELISAs. The statistical analyses involved Pearson chi-squared test, Mann-Whitney U-test and ranking of autoantibodies. The prevalence of ND among BP patients was 24.4%. There were no statistically significant differences in autoantigens profiles (anti-BP180/anti-BP230 IgG) between BP+ND and BP-ND groups. There was no relationship between ND development and anti-BP180/anti-BP230 IgG level (p = 0.5933, p = 0.4701, respectively). The autoantibodies levels of BP+ND and BP-ND patients show insignificant differences suggesting that also in ethnic Poles a hypothetical pathogenetic association of BP and ND, but not only an aging-related epidemiological one, appears to be independent of a particular BP antigen. Nevertheless, it cannot be excluded that phenomena of epitopes spreading, immune cross-reaction and conformational changes in BP180/BP230 may underlie BP development in ND patients.

Accuracy of molecular diagnostics in pemphigus and bullous pemphigoid: comparison of commercial and modified mosaic indirect immunofluorescence tests as well as enzyme-linked immunosorbent assays.

INTRODUCTION: Pemphigus and bullous pemphigoid (BP) are identified by autoantibodies (abs) against desmoglein 1, 3 (DSG1/3) and BP180/BP230, respectively. A novel mosaic to indirect immunofluorescence (IIF) using purified BP180 recombinant proteins spotted on slide and transfected cells expressing BP230, DSG1, DSG3 is available. The commercial (IgG detection) and modified (IgG4 detection) mosaic for indirect immunofluorescence (IIFc - IIF commercial, IIFm - IIF modified) and IgG ELISAs were evaluated in pemphigus and bullous pemphigoid (BP) molecular diagnostics. AIM: To compare diagnostic accuracy of commercial (IgG detection) and modified (IgG4 detection) mosaic IIF assay and to examine the diagnostic value of ELISAs in relation to mosaic IIF in routine laboratory diagnostics of pemphigus and BP. MATERIAL AND METHODS: Sera from 37 BP and 19 pemphigus patients were studied. Associations between tests were assessed using Fisher's exact test. RESULTS: There are associations between the positive/negative samples detected by IIFc with desmoglein1 (DSG1)/desmoglein3 (DSG3)/BP230 transfected cells and ELISAs and no association between anti-BP180 IgG detection by IIFc and ELISA. IIFm with DSG1 and DSG3 showed both 100% sensitivity and 100% and 78% specificity, respectively, and 100% and 83% positive predictive value in relation to IIFc. IIFm with BP230 had 87% specificity, 55% sensitivity, whereas IIFm with BP180 had a 100% sensitivity and 13% specificity in relation to IIFc. CONCLUSIONS: The IIFc with DSG1/DSG3/BP230 transfected cells, excluding BP180 spots, is an alternative method to ELISA in pemphigus/BP diagnostics. IgG4 antibodies, both pathogenically and diagnostically important, are inconsistently detectable with IIFm.

Neurodegenerative disorders, bullous pemphigoid and psoriasis: a comparative study in ethnic Poles indicates that Parkinson's disease is more relevant to bullous pemphigoid.

INTRODUCTION: Bullous pemphigoid (BP) is an autoimmune blistering dermatosis of the elderly with autoimmunity to hemidesmosomal proteins, BP180 and BP230, which are expressed also in neuronal tissue. AIM: The aim here was to retrospectively compare the prevalence of neurodegenerative disorders (ND), particularly Parkinson's disease (PD), unspecified conditions manifesting as dementia and stroke, in two groups of ethnic Poles, with BP and with psoriasis (Ps), in order to obtain data whether BP is more prone to coexist with ND than Ps in the elderly. Psoriasis was chosen in this comparative study as it was considered to be a paradigm of cutaneous disease with systemic manifestations. MATERIAL AND METHODS: The available medical records of 96 BP patients and 149 Ps patients over 70 years of age were analyzed for the presence of ND. RESULTS: There were no statistically significant differences in prevalence of ND without specifying the type and ND types analyzed between BP and Ps groups, except for a higher prevalence of PD in the BP group. CONCLUSIONS: Thus, regarding population aging and increasing incidence and prevalence of BP corresponding with that phenomenon in various ethnicities, it appears justified to expand studies of a possible immunopathogenic relationship, appearing to be PD-related, between BP and ND.

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.

The first non-African case of Trichophyton rubrum var. raubitschekii or a urease-positive Trichophyton rubrum in Central Europe?

We report a case of a 34-year-old Polish Caucasian male who was diagnosed with tinea manuum caused by Trichophyton rubrum var. raubitschekii. It would be the first described case of a dermatophytosis caused by this fungus in Poland and one of a few cases in Central Europe described so far. Admittedly, it would be the first case in Central Europe with no evidence pointing to African origin. The clinical condition improved after administering itraconazole (daily dose 100 mg orally) supplemented with a topical treatment, while the patient was totally cured after 2 months. The histopathological examination turned out to be highly useful in the diagnostic process. The genetic analysis of the urease gene pointed to a urease-positive T. rubrum rather than T. rubrum var. raubitschekii.