BACKGROUND: Bullous pemphigoid (BP) is a rare autoimmune blistering disease predominantly affecting the elderly population. OBJECTIVES: The present study aims to identify clinical factors that may influence outcomes of BP, including skin phenotype, serology, mucosal involvement, pruritus, and triggers. METHODS: A retrospective analysis was conducted on 70 cases with BP registered from January 2019 to December 2022. The Bullous Pemphigoid Disease Activity Index (BPDAI) score was used to assess disease intensity. The BPDAI-Pruritus score and a modified Brest questionnaire were used to document pruritus. Anti-BP180 and anti-BP230 autoantibodies were regularly recorded. Peripheral blood eosinophil counts were documented during flare-up and remission phases of BP. RESULTS. Of the cases, 81.4% were identified with bullous BP, 12.9% with nonbullous BP and 5.7% with localized BP. Oral involvement was documented in 17.1% of cases. Increased peripheral eosinophilia was prominent in the nonbullous phenotype and returned to normal level during remission in both phenotypes. CONCLUSION: The outcomes of BP depended on the disease phenotype and trigger types. Bullous BP showed more intense disease activity, while nonbullous BP demonstrated more intense pruritus. BP associated with diabetes mellitus (DM) or psoriasis manifested as a more severe disease, predominantly with the bullous phenotype and pruritus, compared to cases without comorbidities. New triggers, including SARS-CoV-2 infection and vaccination, were documented (Tab. 6, Ref. 43). Text in PDF www.elis.sk

OBJECTIVES:The aim of the study was to analyse the diagnostic performance of the basophil activation test (BAT), to compare the diagnostic reliability of BATs performed with different types of allergens, which are available in Slovakia and to verify the correlation between the symptom severity and the sensitivity and specificity of the BAT in 114 patients with suspected hymenoptera venom allergy (HVA).BACKGROUND:Diagnosis of the HVA and the identification of the appropriate venom for immunotherapy are in Slovakia based on detailed patient'medical history, skin tests and detection of sIgE. In unclear cases, where the clinical decision regarding the relevant insect species for immunotherapy is difficult, the cellular tests are recommended in several countries, such as Sweden, Spain, Germany, Denmark and Italy. In Slovakia, BAT is not adapted as s part of routine diagnostic work-up.METHODS:The identification of the culprit hymenoptera species among 114 patients was based on detailed history, skin tests and detection of sIgE. Obtained results were compared with the results acquired by the BAT.RESULTS:The sensitivity of the BAT was 80.8 % and the specificity was 87.8 %. The sensitivity of the BAT was higher when using Soluprick SQ Allergens, but the specificity was higher with BŰHLMANN CAST Allergens. In the study no correlation between the symptom severity and the sensitivity and specificity of the BAT was observed.CONCLUSIONS:The results show that the BAT can be recommended in the identification of the appropriate venom for immunotherapy, the only specific treatment that is currently available for patients with HVA. Allergen source is one of critical factors in diagnostic reliability of the BAT (Tab. 4, Ref. 29) Keywords: hymenoptera venom allergy, allergy diagnosis, basophil activation test, sensitivity, specificity.

Background: Interleukin 17 is involved in the pathogenesis of psoriasis, a chronic debilitating disease. Objectives: To evaluate the safety/tolerability, immunogenicity, pharmacokinetics/pharmacodynamics, and efficacy of M1095, an antieinterleukin 17A/F nanobody, in moderate-to-severe plaque psoriasis. Methods: This multicenter, double-blind, placebo-controlled dose escalation phase 1 study randomized 44 patients 4: 1 to treatment with subcutaneous M1095 (30, 60, 120, or 240 mg) or placebo biweekly for 6 weeks, in 4 ascending dose cohorts. Results: The most frequent treatment-emergent adverse events with M1095 were pruritus (n = 4) and headache (n = 3); 2 patients withdrew owing to adverse events (injection site reaction and elevated liver enzyme levels). The terminal half-life of M1095 was 11 to 12 days. The area under the curve/maximum concentration was dose proportional. Of 10 M1095-treated patients positive for antidrug antibodies, 5 showed treatment-emergent antidrug antibody responses. There was no effect on M1095 exposure. Marked decreases in psoriasis inflammatory markers were observed with M1095. By day 85, 100% and 56% of patients receiving M1095, 240 mg, achieved psoriasis area and severity index 90 and 100, respectively. Improvements in static Physician's Global Assessment and affected body surface area were also seen. Limitations: Interpretation of efficacy data is limited by the small sample size. Conclusion: Multiple subcutaneous doses of M1095 showed a favorable safety profile with dose-dependent improvements in psoriasis.

The goal of the treatment of autoimmune bullous disease is to reduce the production of pathogenic autoantibodies or increase elimination of pathogenic autoantibodies from serum of the patients. Immunosuppressive therapy reduces the production of autoantibodies. The therapy protocol is divided into three phases. The first is a control phase with the highest dose of immunosuppressive drugs suppressing activity of disease, followed with a consolidation phase, when the bulk of lesions is healed. The last phase is a maintenance phase when immunosuppressive medication is gradually tapered to the lowest level that suppresses the appearance of new lesions. In complete remission off therapy, the patient reached complete clinical remission and does not use any immunosuppressive medication. In complete remission on therapy, the patient uses a minimal immunosuppressive therapy. The first-line treatment is corticosteroids in pemphigus and pemphigoid groups. Adjuvant immunosuppressive drugs are combined with systemic corticosteroids and display a corticosteroid sparing effect. First-line immunosuppressive adjuvants comprise azathioprine, mycophenolate mofetil and mycophenolic acid. Rituximab, intravenous immunoglobulin G, immunoadsorption, cyclophosphamide, dapsone, and methotrexate are regarded as the second-line adjuvants. In dermatitis herpetiformis, a gluten free diet eliminates the clinical symptoms. Dapsone is regarded to be a valid therapeutic option in management of dermatitis herpetiformis.

OBJECTIVE:The aim of the study was to evaluate the epidemiological trends in the incidence rates of mother-to-child transmission of syphilis, syphilis in women of reproductive age and pregnant women in the antenatal care program over the period 1991-2014, in order to find a basis for preventive measures.MATERIAL AND METHOD:Case series data of confirmed syphilis was used to evaluate the incidence rates over the period 1991-2014 in Slovakia.RESULTS:During the monitored period, 101 cases of mother-to-child transmitted syphilis were detected. The rate increased in 1996, corresponding to 33.3 per 100,000 live births and discovered discordance in antenatal care program. The rates of syphilis in women of reproductive age showed increased rate in 2001, corresponding to 10.44 per 100 000 population. Pregnant women reported the highest rate in 2000, corresponding to 3.24 per 1,000 pregnant women population. Syphilis notification rates in all three groups showed increased trend in the first decade following with decreased trend in the second decade. The high decrease in rate notification among pregnant women in 2011 (0.37) decreasing up to 0.11 in 2014 was followed with decreasing of mother-to-child transmission.CONCLUSION:Mother-to-child transmission of syphilis poses a public health problem and requires comprehensive surveillance in all countries. These data result in the requirement of effective improvement of antenatal care program in pregnant women. The last years 2011-2014 showed improvement in antenatal care program corresponding with decrease rate of mother-to-child transmission of syphilis.

BackgroundPemphigus vulgaris (PV) is a rare autoimmune disease that involves the skin and mucosa. The etiology of PV is multifactorial and includes genetic, environmental, hormonal, and immunological factors.ObjectivesThe purpose of this study was to examine the relationships between human leukocyte antigen (HLA) class II alleles associated with PV and variations in the disease phenotype.MethodsForty-four PV patients were diagnosed and analyzed at the Bullous Disorders Unit in cooperation with the Institute of Immunology, Faculty of Medicine, Comenius University, Bratislava, Slovakia. HLA class II alleles previously found to be associated with PV (DRB1*04:02, DRB1*04:04, DRB1*14:54, DRB1*14:04, DRB1*14:05, DQB1*03:02 and DQB1*05:03) were analyzed according to disease severity, PV type, and gender distribution.ResultsCorrelations emerged between PV severity scores and HLA alleles. The DRB1*04:02 and DQB1*03:02 alleles were associated with severe PV (P=0.001); DRB1*04:02 was associated with the mucocutaneous type (P=0.024), and DQB1*03:02 was found more frequently in female than in male patients (P=0.016). Analyses of the other alleles did not reveal significant associations with the clinical parameters evaluated.ConclusionsThe HLA DRB1* and DQB1* alleles influence susceptibility to PV and may contribute to PV severity and type. These results suggest that genetic background may contribute to disease outcome by affecting the disease course and efficacy of treatment because some of the alleles were found significantly more frequently in patients with severe disease.

Background Pemphigus vulgaris (PV) is a rare, life-threatening, autoimmune bullous disease with unpredictable progression and prognosis.Objectives This study aimed to analyze long-term outcomes in patients with PV, focusing on factors that may influence the prognosis of the disease, including the phenotype of PV, age at onset, multiplicity of mucosal involvement, relapse and remission rates, and survival functions.Methods A retrospective analysis was conducted in 44 patients who were diagnosed and monitored from 1993 to 2012. Statistical analyses were conducted using the Mann-Whitney test and Kruskal-Wallis test. Survival data were analyzed using Kaplan-Meier and log rank tests. Fisher's exact test was used to assess statistical significance at P < 0.05.Results A total of 79.5% of patients were identified as having mucocutaneous PV. The female : male gender ratio was 1.58; in severe PV, this increased to 2.8. The difference between the genders in age at onset was statistically significant (P = 0.05). Furthermore, multiple mucosal involvements in the oral cavity and at other sites were associated with severe mucocutaneous PV. Multiple relapses occurred more frequently in patients with severe PV than in those with mild PV (P = 0.001). The remission survival of females was longer than that of males (P = 0.003).Conclusions Poor prognosis factors include the severe mucocutaneous type of PV, especially in female patients, and multiple mucosal involvements in the oral cavity and other mucosal sites. Female patients were younger than male patients and were more often observed to have severe mucocutaneous PV and to have a higher median period of remission survival than male patients.

BACKGROUND:Intravenous immunoglobulin (IVIG) is a biological agent composed of polyclonal antibodies prepared from a large cohort of human plasma pools. IVIG is increasingly used for the treatment of various antibody-mediated diseases, including pemphigus vulgaris (PV).OBJECTIVE:The aim of the study was to evaluate the benefit and safety profiles of high dose IVIG therapy in PV patients determined by clinical remission, corticosteroid-sparing and immunomodulatory effects, and adverse events at 12 months' follow up.METHODS:Ten PV patients underwent 3-8 monthly cycles of IVIG therapy at a dose of 2 g/kg per cycle. The pemphigus disease area index (PDAI) score, direct immunofluorescence (DIF), indirect immunofluorescence (IIF), and corticosteroid dosage were evaluated before IVIG therapy, after each cycle, and at 6 and 12 months' follow up.RESULTS:The baseline PDAI score was 75.70 ± 21.0 and baseline prednisone dosage was 201.60 ± 71.7 mg/day. The PDAI score reduction of 98% was achieved at 12 months' follow up and a corticosteroid dose reduction of 90% corresponded to clinical improvement. The decrease in both values was statistically significant (P = 0.002, respectively). At 12 months' follow up, seven patients were shown to be negative on IIF, of whom three proved to be negative on DIF. Adverse events were mild and transient and did not require the cessation of IVIG therapy.CONCLUSION:IVIG induced long-term clinical remission, while displaying a corticocorticosteroid-sparing effect and evoking a long-standing immunomodulatory effect in PV patients. The safety profile of IVIG therapy was assessed as good.

OBJECTIVESThe aim of this study was to evaluate the epidemiological situation of syphilis in the Slovak Republic in the period of the past two decades.BACKGROUNDIn last decade, the incidence of syphilis has decreased in European countries by 13%. However, several countries reported an increase in the trend of syphilis.METHODSCases of syphilis reported to the National Health Information Center in the Slovak Republic were statistically evaluated.RESULTSIn the first decade syphilis possessed an increase rate 262.5% and 127.6% in five subsequent year intervals, and then the rate fluctuated and showed minimal decrease in the last three years. The highest rate 7.3 per 100,000 population documented in 2009. The peak in the Bratislava region reached 36.36 in 2000. Epidemic was documented in marginalized group in East region. Early syphilis was the most frequent stage observed in both decades but late and no specified cases increased in the last period. The M/F rate was up to 1.7, the most frequently recorded age category was 15-24 years.CONCLUSIONThese results indicate a requirement for developing a comprehensive control and educational program in the overall population, particularly in marginalized groups, and improving case management by health providers (Fig. 3, Ref. 20).

INTRODUCTIONSeborrheic keratoses are very common benign epidermal tumors. Despite the high frequency, the pathogenesis is still unknown. They are extremely rare in the genital area. The participation of human papilloma viruses (HPVs) in pathogenesis of seborrheic keratoses is being discussed.AIMSThe aims of this case report are to inform about extremely rare lesion in genital area in a young man and evaluate the association of HPVs in the development of seborrheic keratoses.METHODSWe used histopathological examination to establish the correct diagnosis, which revealed signs of seborrheic keratosis. The real-time polymerase chain reaction method confirmed low-risk HPV 6 from the lesions.MAIN OUTCOME MEASURESHPVs may play a role in pathogenesis of seborrheic keratoses.RESULTSThe patient was successfully treated with shave excision under spinal anesthesia. Six-month follow-up was without any recurrence. We suggest that HPVs can be considered as etiologic factor in creation of seborrheic keratosis.CONCLUSIONSSeborrheic keratoses are very common on sun-exposed skin, but they are rare in the genital area, such as on the shaft of penis. This localization may lead to misdiagnosis. Seborrheic keratoses in genital area might negatively influence the sexual life of the patient. Containing HPV 6 low-risk virus, they never lead to malignant transformation.

Background Dimethyl fumarate (DMF) is an effective inhibitor of mold growth. In very low concentrations, DMF is a potent sensitizer that can cause severe allergic contact dermatitis (ACD). It has been identified as the agent responsible for furniture contact dermatitis in Europe. The aim of this study was to evaluate patients in Slovakia with footwear ACD associated with DMF, with regard to clinical manifestations, patch test results, and results of chemical analysis of their footwear. Methods Nine patients with suspected footwear contact dermatitis underwent patch testing with the following allergens: samples of their own footwear, commercial DMF, the European baseline, shoe screening, textile and leather dye screening, and industrial biocides series. The results were recorded according to international guidelines. The content of DMF in footwear and anti-mold sachets was analyzed using gas chromatography and mass spectrometry. Results Acute ACD was observed in nine Caucasian female patients. All patients developed delayed sensitization, as demonstrated by positive patch testing using textile footwear lining. Seven patients were patch tested with 0.1% DMF, and all seven were positive. Chemical analysis of available footwear showed that DMF was present in very high concentrations (25-80mg/Kg). Conclusions Dimethyl fumarate is a new footwear allergen and was responsible for severe ACD in our patients. To avoid an increase in the number of cases, the already approved European preventive measures should be accepted and commonly employed.

The current work describes an association between pemphigus vulgaris (PV) and class II HLA alleles in the Slovak population, the first such study in Slovakia on the high-resolution level'. This work takes into account the new HLA allele nomenclature, officially adopted in 2010. In particular, we have focused on the associations between PV and DRB1*14:54 and DRB1*14:01. This case-control study was performed in a cohort of 43 PV Caucasian patients and 113 Caucasian control subjects from Slovakia. HLA typing was performed using PCR-SSP (polymerase chain reaction with sequence-specific primers). We found significantly positive associations between PV and the HLA alleles DRB1*04:02, DRB1*04:04, DRB1*14:54, DRB1*14:04, DRB1*14:05, DQB1*03:02 and DQB1*05:03. In contrast, HLA-DQB1*06, DRB1*07 and DRB1*13 were negatively associated with PV. Importantly, 93% of PV patients possessed at least one of two HLA haplotypes, DRB1*04-DQB1*03 or HLA-DRB1*14-DQB1*05. We confirmed the previously reported associations between HLA class II alleles and PV and described a new association between PV and DRB1*14:54. This allele was first described in 2005, and there has been only one report of its association with PV to date.

The current work describes an association between pemphigus vulgaris (PV) and class II HLA alleles in the Slovak population, the first such study in Slovakia on the ‘high‐resolution level’. This work takes into account the new HLA allele nomenclature, officially adopted in 2010. In particular, we have focused on the associations between PV and DRB1*14:54 and DRB1*14:01. This case–control study was performed in a cohort of 43 PV Caucasian patients and 113 Caucasian control subjects from Slovakia. HLA typing was performed using PCR‐SSP (polymerase chain reaction with sequence‐specific primers). We found significantly positive associations between PV and the HLA alleles DRB1*04:02, DRB1*04:04, DRB1*14:54, DRB1*14:04, DRB1*14:05, DQB1*03:02 and DQB1*05:03. In contrast, HLA‐DQB1*06, DRB1*07 and DRB1*13 were negatively associated with PV. Importantly, 93% of PV patients possessed at least one of two HLA haplotypes, DRB1*04–DQB1*03 or HLA‐DRB1*14–DQB1*05. We confirmed the previously reported associations between HLA class II alleles and PV and described a new association between PV and DRB1*14:54. This allele was first described in 2005, and there has been only one report of its association with PV to date.

Skin squamous cell carcinomas (SCCs) are arguably the second most common carcinoma of the skin and are responsible for the majority of non-melanoma skin cancer deaths. Gynecologist treated a Caucasian 56-years old female patient for genital wart with podophyllotoxin cream. She did not achieve complete response and therefore she has interrupted the therapy and the collaboration with the gynecologist. At the time of evaluation the lesion had a size of man's palm in anogenital region and showed characteristic features of neoplasm. The regional lymph nodes have produced infiltrated painful bubo. PCR analysis for HPV proved negative. Histopathology revealed well-differentiated squamous cell keratinizing carcinoma from the tumor as well as from the regional lymph node packet. Staging computed tomography scans proved negative and pelvis scans disclosed regional lymphadenopathy underlying the tumor. Palliative radiation therapy (by linear accelerator) was administered for the oversized tumor to the total TD 50.0Gy. The patient died 6 months after diagnostic assessment from cardio-respiratory failure. Staging computed tomography before her death did not disclose distinct metastases in her inner organs. Well-differentiated squamous cell keratinizing carcinoma could be growing endophytically affecting the underlying adipose tissue and musculature, with spreading into the regional lymph nodes. The rate of metastases into inner organs seems to vary according to the aggressiveness and metastatic behavior of each SCC. The case report calls for attention to the importance of collaboration among various specialists assisting in the diagnosis and management of skin neoplasm (Fig. 5, Ref. 12). Full Text in PDF www.elis.sk.

BackroundPemphigus vulgaris is a rare chronic autoimmune disease of skin and mucous membranes, with several cytokines participating in its development. The role of their gene polymorphisms in susceptibility to the disease is, however, not fully understood.ObjectiveThe aim of our case-control study was to investigate whether some of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine genes (IL-1 alpha, IL-1 beta, IL-1RI, IL-1Ra, IL-4R alpha, IL-12, IFN-gamma, TGF-beta 1, TNF-alpha, IL-2, IL-4, IL-6 and IL-10) are associated with pemphigus vulgaris in the Slovak population.MethodsDNA samples were obtained from 34 pemphigus vulgaris patients and 140 healthy controls of Slovak origin. Cytokine gene SNPs were determined using the polymerase chain reaction with sequence-specific primers (PCR-SSP) method.ResultsWe found a weak association between pemphigus vulgaris and polymorphic variants in TNF-alpha and IL-10 genes only, with haplotypes TNF-alpha-308G/-238G and IL-10 -1082A/-819C/-592C being significantly overrepresented in pemphigus vulgaris patients (TNF-alpha GG: 94.12% vs. 82.86%, P = 0.0216; IL-10 ACC: 44.12% vs. 30.00%, P = 0.0309).ConclusionsOur preliminary results suggest that certain TNF-alpha and IL-10 gene polymorphisms might contribute to genetic susceptibility to pemphigus vulgaris; however, their overall impact on disease development will be rather limited.

BACKGROUND:Norwegian or crusted scabies is considered a rare affection and presumably represents an abnormal host immune response to Sarcoptes scabiei. As the condition mimics a range of dermatoses, it can be easily misdiagnosed and mismanaged.CASE REPORT:A 85-year-old woman suffering from bullous pemphigoid was referred for evaluation with presumptive diagnosis of an adverse drug reaction to hydrochlorothiazide or lacipil. Systemic corticosteroid therapy as the mainstay in the control of the bullous skin disorder was increased, but the skin condition worsened. ELISA for the detection of antibodies against the drugs suspected of causing hypersensitivity was negative. Histological examination disclosed inflammatory cells in the upper dermis and parasites. Direct microscopy of the scraped material revealed numerous parasites of the Sarcoptes scabiei type. The patient was treated with topical keratolytics following traditional scabicides for twice as long in comparison with the standard protocol.CONCLUSION:Norwegian scabies may be misdiagnosed and mismanaged in immunosuppressed patients. The diagnosis of scabies should always be considered in immunosuppressed patients with pruritus.

BACKGROUND:Pemphigus vulgaris (PV) is a rare, chronic life-threatening autoimmune blistering disease of the skin and mucous membranes.METHODS:A retrospective analysis of 31 patients with the diagnosis of pemphigus vulgaris, admitted for hospitalization from January 1996 to December 2006. Descriptive statistics has been used for data evaluation.RESULTS:The average age at onset was 49.0 +/- 16.2 years, with female to male ratio 1.4/1. Diagnosis was confirmed histologically and by a direct immunofluorescence. Mucocutaneous form of PV was observed in 25 patients (80.%), mucous form in 3 patients (9.7%), cutaneuos form in 3 patients (9.7%). Factors preceding the onset of PV were most often viral (38.7%) and bacterial (35.5%) infections, dental focuses (25.8%), stress (16.1%), and contact with chemical substances (16.1%). 6 patients (19.4%) did not indicate any triggering factor. Corticosteroids alone were given to 18 patients, combined with azatioprin or cyclosporin to 13 patients, and 1 patient was treated with intravenous immunoglobulin. Adverse events were mostly osteopenia/osteoporosis (41.9%), hyperlipoproteinemia (41.9%), cataract (32.3%) and Cushing's syndrome (32.3%). Cutaneous and mucous infections were most often caused by Staphylococcus aureus and Candida albicans, respectively. 3 patients died (9.7%), and in 3 patients (9.7%) in a long term remission, the immunosuppressive treatment was discontinued.CONCLUSION:Pemphigus vulgaris is still a life-threatening disease. Although corticosteroids dramatically improved the mortality, and are still considered the first-choice therapy, significant morbidity of the disease and the corticosteroid treatment still exists. The combination of corticosteroids with corticosteroid-sparing agents delays the onset of adverse events (Fig. 2, Ref. 33).

Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disease, accounting for about 2-3% of all leukemias in adults. The skin lesions were described in about 10-12% of patients. Vasculitis in lymphoproliferative disease is relatively uncommon and may predate the diagnosis of lymphoproliferative disease. A 54-year old female with one month history of general symptoms and sudden onset of maculopapular exanthema on the skin, suffered from anemia, leukopenia and thrombocytopenia. Examination of the skin biopsy revealed lymphocytic vasculitis. Immunophenotyping of the skin biopsy revealed cell population with CD45RO, and small groups with CD20, partly DBA44 positivity. Bone marrow trepanobiopsy showed 50% infiltration with medium-sized lymphoid cells with clear cytoplasm and immunophenotypic coexpression of CD20 and DBA-44 antigens. The diagnosis of HCL was confirmed by flow cytometry of the bone marrow and of the peripheral blood cells that revealed pathological cell population with expression of CD11c, CD19, CD25, CD103. The patient was successfully treated with a single dose of cladribrine. The patient with acute vasculitis should be screened and monitored for possible lymphoproliferative diseases. Skin manifestation of acute vasculitis accompanied with hairy cells may be the first manifestation of HCL. Purine nucleoside analogue cladribrine is considered as the first line of therapy for HCL and induces a total response in more than 80% of cases with HCL.