Rituximab in the Management of Autoimmune Bullous Diseases: A Treatment-Resistant Case Series from a Single Central European Referral Center.

Background and Objectives: Rituximab (RTX) has been the predominant treatment for autoimmune bullous diseases (AIBDs). The objective of this research was to assess the advantages and safety characteristics of RTX treatment in individuals with AIBD. This assessment focused on clinical remission and a reduction in glucocorticosteroid usage, its effect on the titers of autoantibodies targeting desmoglein-1 (DSG-1) and desmoglein-3 (DSG-3), and adverse occurrences during a 12-month follow-up period in a dermatology department within a Central European university context. Materials and Methods: Our case series involved eleven patients, including eight patients with pemphigus vulgaris, two with pemphigus foliaceus, and one with epidermolysis bullosa acquisita. They received a 1 g dose of rituximab, repeated over a two-week interval. Results: The reduction in a prednisone-equivalent dosage after 2, 6, and 12 months following the second RTX infusion was 65.05%, 73.99%, and 76.93%, in that order. The titers of antibodies against DSG-1 exhibited reductions of 43.29%, 75.86%, and 54.02% at 2, 6, and 12 months, respectively. By contrast, the antibody concentrations targeting DSG-3 displayed a decrease of 27.88%, 14.48%, and 5.09% at the corresponding time points. Over the course of the 12-month monitoring period, 18.18% of patients experienced disease relapse, while the remaining individuals achieved either complete or partial remission with minimal or no therapy. Adverse effects were noted in 36.36% of the patient population; they were mild, and no serious adverse effects were reported. Conclusions: RTX represents an efficacious and well-tolerated therapeutic option for the management of AIBD and merits consideration in cases of refractory AIBD. However, further research is imperative to delineate the most optimal dosage, dosing frequency, and total quantity of maintenance infusions required. Additionally, there is a compelling need for studies that explore the impact of RTX on individuals with AIBD who do not exhibit a significant reduction in anti-desmoglein autoantibody levels.

Involvement of palms and soles in patients with autoimmune bullous diseases: a comparative analysis of a diagnostically relevant localization.

Introduction: The involvement of palms and soles is variable among disease entities belonging to autoimmune bullous diseases (AIBD). We present our own clinical-laboratory experience concerning presentations of skin lesions on palms and soles in the pemphigus diseases group, pemphigoid diseases group, epidermolysis bullosa acquisita (EBA), and lichen planus pemphigoides (LPP) and discuss the pertinent literature. Methods: Lesions on palms and soles were assessed retrospectively on the basis of just photographic archives from the beginning of 2014 to March 2023. We comparatively evaluated 462 Slavic patients with AIBD. Results: Palmoplantar involvement was observed in only 21 patients with AIBD (12 females and 9 males). There was no statistically significant difference between palmoplantar involvement in the pemphigus diseases group compared to the pemphigoid diseases group and no statistically significant difference between the pemphigus diseases group compared to the subepithelial AIBD. Discussion: Nevertheless, particularly in LPP and EBA, and occasionally in pemphigus diseases and pemphigoid diseases groups of AIBD, localization on palms and soles may be diagnostically important at the clinical level.

Stem cells in plastic surgery and aesthetic medicine.

Stem cells (SCs) have multiple applications in today's medicine including aesthetic dermatology and plastic surgery. The purpose of this paper is to review some clinical use of mesenchymal SCs. The main focus was put on adipose tissue-derived stem cells (ADSCs) as these cells are easy to harvest and because of their properties showed great potential in many studies, where they proved to accelerate wound healing, reduce scars, cause hair regrowth, or rejuvenate skin. Furthermore, when added to lipofilling procedures, such as breast augmentation they enhance fat graft survival and provide satisfying results. Currently, many different strategies for using SCs in treatments are developed with great efficacy, however, there are still many limitations and concerns regarding their clinical use.

The Role of Cosmetology in an Effective Treatment of Rosacea: A Narrative Review.

Rosacea is a chronic inflammatory facial skin disease usually occurring in middle-aged patients. It manifests itself as an inflammatory condition with perivascular infiltrate, dilated blood vessels, lymphoedema, hyperplasia of sebaceous glands, and disorders of connective tissue structures brought on by fibrosis. Rosacea is characterized by multifactorial inflammatory mechanisms, and therefore it requires an interdisciplinary approach including adequate skin care, topical and/or systemic therapy, and physical modalities to successfully treat the various symptoms and disease subtypes. However, data regarding the possible role of cosmetologists in rosacea remains scanty and equivocal. The objectives of cosmetology therapy include restoration and regeneration, anti-inflammatory effects, the strengthening of blood vessels and regulation of their permeability, and the regulation of keratinization. Vascular abnormalities can be targeted with specific light and laser devices. Therefore, the present paper aims to review the latest advances and summarize different aspects concerning skin care in rosacea. Particular attention has been paid to the co-operation of cosmetologists with other specialists in order to bring about the interdisciplinary management of rosacea. It is also important to keep in mind that it is usually necessary to combine various methods of treatment, as this approach is more effective than monotherapy for attaining satisfactory cosmetic results in rosacea patients.

Lasers' Q-switched treatment in skin and subcutaneous lesions - review.

The numerous medical fields like dermatology, ophthalmology and surgery widely use laser therapy including Q-switched lasers. This review aims to provide information on the application and effectiveness of Q-switched lasers in dermal and vascular lesions. Q-switched lasers play a crucial part in the athlete's foot treatment and onychomycosis both in mono- and polytherapy. Laser therapy remains the gold standard for tattoo removal. Additionally, laser therapy shows high effectiveness in melasma, telangiectasias and photoaging therapy. The ability to adjust precise laser parameters like length or beam energy provides tight control of the treated area, significantly reducing the risk of adverse effects.

Treatment-naïve pemphigus patients showing IgG tissue deposits have serum IgG antibodies against desmoglein 1 detected more often than those against desmoglein 3: a monocentre laboratory experience.

Introduction: Pemphigus is a heterogeneous group of autoimmune acantholytic diseases. Aim: To check whether there is a relationship between detecting IgG deposits in the direct immunofluorescence (DIF) and finding IgG antibodies against particular desmoglein (DSG) isoforms in ELISA techniques in patients with pemphigus. Material and methods: Single-step DIF for revealing the deposits of IgA, IgM, IgG, IgG1, IgG4 and C3, and monoanalyte ELISAs or the multiplex ELISA were used for diagnosis. The Z test for two independent proportions was used for the statistical analysis. Results: We evaluated 19 consecutive treatment-naïve pemphigus patients, who exhibited IgG deposits, accompanied by other types of immunoreactants in various combinations, in DIF. Serum IgG antibodies against DSG1 were detected in 18 patients, whereas serum IgG antibodies against DSG3 were found in 10 patients. The statistical analysis showed that the proportion of anti-DSG1 antibody-positive individuals (18 of 19, 94.74%) was statistically significantly higher than the proportion of anti-DSG3 antibody-positive ones (10 of 19, 52.63%) (p = 0.0099). Conclusions: IgG deposition in the pemphigus pattern seems to be related to the presence of serum IgG antibodies against DSG1 rather than against DSG3. DSG1 may bind IgG more efficiently than DSG3 since DSG1 has a longer cytoplasmic region compared to that of DSG3.

Clinical significance of umbilical region involvement in pemphigus vulgaris in a series of 81 ethnic Poles: a comparative analysis of the distribution of lesions in two infrequent locations.

Introduction: Autoimmune bullous diseases are potentially life-threatening dermatoses which present with cutaneous and/or mucosal blisters, diagnosed on the basis of clinical manifestations, direct immunofluorescence of perilesional tissue, and serum testing for circulating autoantibodies. Sometimes, lesions in the navel can lead to the diagnosis of a bullous disease. Aim: To assess the frequency of occurrence of pemphigus lesions located in the navel area and nail apparatus in pemphigus vulgaris (PV) in ethnic Poles. Material and methods: Eighty one patients (31 males and 50 females, mean age 59 years) with dermatoses of the PV group diagnosed in 2002-2020 were retrospectively analysed using their photographic files. Statistical analysis was performed using the difference test between two proportions to check the difference between the percentage of PV patients with navel area involvement and nail apparatus involvement. Results: There was no statistically significant difference between PV patients with nail apparatus involvement (12.3%) and navel area involvement (14.8%) (p = 0.4632). Only females had lesions in the navel area in our series of PV patients. Conclusions: It is speculated that the causal relationship may exist between the female reproductive system and the pattern of expression of PV lesions around the umbilicus. The awareness that PV can infrequently affect the umbilical region and the nail apparatus should help in some cases to establish the diagnosis of PV. The periumbilical involvement can facilitate the performance of DIF in individuals with lesions in less accessible areas.

Frontal Fibrosing Alopecia - a review and a practical guide for clinicians.

Despite a significant increase in reported cases of frontal fibrosing alopecia (FFA) in literature, discussion about the possible role of environmental factors, instruction for diagnosis and guideline for treatment, are limited. The review aims to provide a detailed synthesis of this condition that could be used by clinicians in their practise. Whether single-centre or multi-centre, studies of more than 60 cases less than 5 years old were mainly taken into consideration. Results obtained were that FFA affects mainly postmenopausal Caucasian women; the most common comorbidities are hyperlipidaemia, arterial hypertension, osteoporosis, hypothyroidism, depression, alongside dermatological disorders such as atopic dermatitis, rosacea, seborrheic dermatitis and androgenetic alopecia. Autoimmune, genetic, hormonal (e.g. estrogen deficiency, pregnancy, lactation, HRT and raloxifene) and environmental (e.g. daily use of facial sunscreens and less frequent use of hair dyes and shampoo) hypotheses were proposed for pathogenesis, as well as association with various predisposing factors (patient's health-social profile, disease's history and comorbidities). Clinical presentation of FFA can be divided into 3 specific patterns, each with a different prognosis. Diagnosis is usually made clinically with the use of trichoscopy; however, scalp biopsy remains the gold standard. The condition is regarded as a variant of lichen planopilaris (LPP) due to the similarity of the prominent histopathological findings, but the clinical image is distinct and therapeutic options vary. 5α-reductase inhibitors, intralesional steroids, and hydroxychloroquine provide the highest level of evidence for the treatment of FFA. The conclusion is that a better understanding of the disease is crucial for proper disease management.

A Probing of the Issue of Detecting IgG, IgG4 and IgA Antibodies to Laminin 332 Epitopes in Mucous Membrane Pemphigoid: A Clinical-Laboratory Experience of a Single Central European University Dermatology Department.

Purpose: Mucous membrane pemphigoid (MMP) is a very rare autoimmune bullous disease, affecting predominantly the mucosae and characterized by autoantibodies to the epithelial basement membrane components. Laminin 332 (Ln-332) is one of the most probable antigens with association with malignancy. The laboratory diagnosis of Ln-332-mediated autoimmunity is troublesome. The aim here was to comparatively examine IgG, IgG4, and IgA autoantibodies specific to α3, ß3 or γ2 subunits of Ln-322 in MMP patients using the BIOCHIP mosaic-based indirect immunofluorescence technique (IIF). Patients and Methods: Sera from 15 MMP patients were studied. BIOCHIP mosaic-based Ln-332 IIF, direct immunofluorescence, ELISA tests for anti-BP180/BP20 IgG antibodies and statistical analyses were performed. Results: Of all the 15 sera examined for IgG4 antibodies, only 1 (6.67%) reacted with the α3 chain, 0 with the ß3 chain, and 0 with the γ2 chain. No positive reactivity was seen with the IgG and IgA antibodies. BIOCHIP mosaic-based IIF with Ln-332 showed 100% sensitivity, 8% specificity, 21% positive predictive value, and 100% negative predictive value in relation to the diagnostic gold standard of DIF. The concomitant malignancies were revealed in three cases. Conclusion: The detection of antibodies to Ln-332 chains is occasional in Polish MMP sufferers. Still, the evaluation of IgG4 antibodies in MMP can reduce the false-negative results.

Sacral Dimple, Conjunctiva, and Nipple as Less Obvious Pemphigus Vulgaris Locations around Natural Body Orifices: A Report of Three Cases.

In this paper, we present our own clinical-laboratory experience concerning three less obvious presentations of pemphigus vulgaris (PV) and discuss the pertinent literature. The involvement of the sacral dimple reported here for the first time, as well as the nipple and the eyes, could initially be misleading clinically. These less stereotypical localizations may occur due to the transition of different epithelia, each with varying levels of cadherin (desmoglein, desmocollin) and thus altered sensitivity to mechanical stress. The role of dermatologists who have experience in treating autoimmune blistering dermatoses is fundamental for identifying promptly the initial and exacerbating PV lesions in such unusual locations.

Issues occupying our minds: Nomenclature of autoimmune blistering diseases requires updating, pemphigus vulgaris propensity to affect areas adjacent to natural body orifices unifies seemingly diverse clinical features of this disease.

In this conceptual analysis, we present our concepts on two issues regarding autoimmune bullous diseases (AIBD), namely (i) current nomenclature of AIBD requires updating by incorporating molecular data and (ii) pemphigus vulgaris (PV) "likes" areas adjacent to natural body orifices. The problem of inadequacy of the currently used nomenclature was noticed recently by Zillikens, who proposed to form a group with the task of updating it. The early efforts by Dmochowski to update this nomenclature happened to be a daunting task. Nevertheless, the ideal nomenclature should retain the bulk of clinical data, which generations of dermatologists are accustomed to, including triggers if known, and incorporate molecular data revealing targets of autoimmune response and immunoglobulin isotypes involved. The natural body orifices affected by PV were previously described in numerous publications. However, these openings are described separately in these publications. Here, Dmochowski comes up with an intellectual concept that this propensity of PV unifies seemingly diverse clinical features of this disease.

Case Report: Infantile Bullous Pemphigoid: Triggering by COVID-19 Is Speculative.

Bullous pemphigoid (BP) is a cutaneous disease triggered by numerous stimuli, where genetic milieu-influenced autoimmunity to hemidesmosomal proteins, namely, BP180 and/or BP230 initiate an inflammation leading to dermal-epidermal junction (DEJ) enzymatic pathological remodelling. Here, to the best of our knowledge, we present the first case of an infantile BP apparently triggered by COVID-19. BP should be included in differential diagnosis of infantile rashes showing blisters or vesicles or both as well as their prodromal and evolutionary lesions. Possible triggers, such as coronavirus disease 2019 (COVID-19), of BP in infancy should be identified and properly dealt with.

Conceptualization and validation of an innovative direct immunofluorescence technique utilizing fluorescein conjugate against IgG + IgG4 for routinely diagnosing autoimmune bullous dermatoses.

INTRODUCTION: Autoimmune bullous diseases (ABDs) are potentially life-threatening mucocutaneous illnesses that require diagnosis with direct immunofluorescence (DIF). In this study we compared the diagnostic accuracy of traditional DIF (DIFt; separate immunoglobulin (Ig) G, IgG1, IgG4, IgA, IgM and C3 deposits detection) and modified DIF (DIFm; simultaneous IgG + IgG4 deposits detection instead of separate IgG and IgG4 deposits detection) in routine diagnostics of ABDs. MATERIAL AND METHODS: Eighteen patients with ABDs (7 with pemphigus dermatoses and 11 with subepithelial ABDs) were evaluated with DIFt and DIFm. RESULTS: The agreement of detectability of IgG immunoreactants was obtained in 16 ABD cases (88.89%), as positive results in both DIFt and DIFm were obtained in 13 cases and negative results in both DIFt and DIFm were obtained in 3 cases. One ABD case (Brunsting-Perry pemphigoid) (5.56%) was negative in DIFm with a positive DIFt result (IgG1 deposits). One ABD case (bullous pemphigoid) (5.56%) had only C3 deposits in DIFt with a positive DIFm reading (IgG + IgG4 deposits). A statistically significant relationship (p = 0.0186) between DIFm and DIFt results was revealed using Fisher's exact test. CONCLUSIONS: Both DIFt and DIFm are useful methods to detect deposition of IgG immunoreactants, but it seems that the innovative DIFm method slightly increases the detectability of IgG/IgG4 immunoreactants in relation to DIFt. The introduction of DIFm into routine laboratory diagnostics of ABDs seems to be justified, as it enables the abandonment of separate FITC conjugates for IgG and IgG4, which is important for cost-effectiveness.

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.

Evaluation of a Bi-Analyte Immunoblot as a Useful Tool for Diagnosing Dermatitis Herpetiformis.

Immune responses to tissue transglutaminase (tTG) and nonapeptides of gliadin (npG) are associated with dermatitis herpetiformis (DH), a gluten-related dermatosis. Recently, a bi-analyte immunoblot (b-aIB) was introduced to detect IgA antibodies in response to tTG and npG. We compared the utility of ELISA and b-aIB with tTG in serological diagnoses of DH and their agreement with direct immunofluorescence (DIF). In total, 55 sera (27 DIF-positive DH patients, 4 DIF-negative DH patients and 24 healthy controls) were examined. ELISA for anti-tTG IgA, b-aIB for anti-npG and anti-tTG IgA, and statistical analysis were performed. The b-aIB with tTG showed 78% sensitivity, 100% specificity, 100% positive predictive value, and 82% negative predictive value in relation to ELISA. A better rate of agreement (Cohen's kappa values) in IgA detection was observed in the pair tTG ELISA and b-aIB with npG (0.85) than in pairs tTG ELISA and b-aIB with tTG (0.78) or b-aIB with tTG and b-aIB with npG (0.78). No degree of agreement was found between serological tests and DIF. Both serological tests may be used to detect the anti-tTG IgA in DH patients. Still, DH diagnosing requires careful consideration of clinical data as well as results of tissue imaging (crucial DIF) and immunoserological techniques detecting DH-type features.

Serological Evidence of Borrelia burgdorferi in Patients with Morphea from West-Central Poland: An Original Paper and Review of Literature.

Morphea (localized scleroderma) is an inflammatory connective tissue disease. Borrelia burgdorferi, as a causative factor, has been discussed controversially. The aim of this original study was to evaluate the frequency of IgM and IgG classes of anti-Borrelia antibodies in groups of morphea and psoriasis patients using the traditional ELISA method. Blood samples of 82 patients with morphea and 112 patients with psoriasis vulgaris were examined for the presence of IgM and IgG classes of anti-Borrelia antibodies (ELISA). IgM and IgG classes of anti-Borrelia antibodies were detected in 4% of blood samples taken from morphea patients, while 4.5% of blood samples from patients with psoriasis vulgaris. There is one major limitation in this study that could be addressed in future research. First, the study focused on the determination of IgM and IgG classes of anti-Borrelia antibodies as a risk factor for morphea, but other infectious agents also require further testing, such as Hepatitis B, Hepatitis C, and other viral or bacterial infections. The results of this study showed no significant relationship between Borrelia infection and morphea. Detection of IgM and IgG classes of anti-Borrelia antibodies is not recommended for routine diagnostics of patients with morphea at this time.

[Evaluation of the results of the prevention program "Protect your voice" implemented by The Greater Poland Center of Occupational Medicine of Poznan]. / Ocena wyników programu profilaktycznego "Chron swój glos" przeprowadzonego przez Wielkopolskie Centrum Medycyny Pracy w Poznaniu.

BACKGROUND: The aim of the study was to evaluate the rationale for training in voice emission and voice prophylaxis among teachers and to assess the effects of voice disorders rehabilitation in the selected group of teachers participating in the program "Protect your voice." MATERIAL AND METHODS: An anonymous survey was conducted among 463 teachers participating in the training part of the program. The effectivness of rehabilitation of teachers with occupational voice disorders was evaluated among 51 subjects (average age: 43 years) taking part in diagnostic and rehabilitation part of the program. Phonation voice exercises with speech therapist and physiotherapy (iontophoresis, inhalations and elektrostimulation) were administered. Evaluation of rehabilitation was based on phoniatric examination, including videostroboscopy and statistical calculations. RESULTS: The survey showed that among teachers there is high demand (98%) for training in proper voice emission, hygiene and prevention of voice. The effectiveness of rehabilitation has been confirmed by the observed improvements in phonatory activities of larynx, proper breathing during phonation (p = 0.0000), the voice quality (p = 0.0022), prolonged phonation time (an average of 1.39 s), increased number of people who correctly activated resonators (p = 0.0000) and increased number of people with phonation without excesive muscle tension of the neck. CONCLUSIONS: The results indicate that among all the professionally active teachers, there is a need for regular training of proper voice emission and vocal hygiene and then conduct individually phonation and breathing exercises, supported by the physiotherapy. This should be an effective method of voice disorders prevention in teachers. Med Pr 2017;68(5):593-603.

Cowpox virus infection in a child after contact with a domestic cat: a case report.

Human cowpox represents a seldom diagnosed zoonosis but this diagnosis should be considered more frequently as the number of cases has increased in recent years. We describe a case of cowpox in an 11-yearold boy following regular direct daily contact with a domestic cat. The 11-year-old patient, an otherwise healthy boy, demonstrated skin ulceration located at his chin, with enlargement of regional lymph nodes and fever reaching 39°C. The diagnosis of cowpox was made on the basis of PCR involving DNA isolated from a scab covering the skin lesion. Application of PCR involving DNA isolated from the scab covering the lesion with parallel use of OPXV-specific (ORF F4L) and CPXV-specific (ORF B9R) oligonucleotide primer sequences is recommended for rapid laboratory confirmation of the diagnosis.

Current applications of high-frequency ultrasonography in dermatology.

The era of ultrasounds in dermatology started in 1979, when pioneering use of 15 MHz by Alexander and Miller in measuring the skin thickness was introduced. Since then, some new applications of high-frequency ultrasonography (HF-USG) have emerged providing the clinicians with an extra hand in their everyday practice. The main advantages of HF-USG include the possibility of real-time imaging, measurements of morphological and physiological aspects of the skin, safety associated with the use of non-ionizing media as well as the lack of contraindications to its performance. Currently the main clinical use of HF-USG in dermatology regards preoperative assessment of the depth of invasion in melanomas and basal cell carcinomas. The ultrasound image analysis allows noninvasive follow-up of inflammatory skin diseases, like atopic dermatitis, psoriasis and may be used for monitoring effectiveness of therapy in skin lymphomas and sclerotic skin diseases.