Porokeratosis of Mibelli Treated With Topical 2% Lovastatin/2% Cholesterol Ointment.

Porokeratosis is characterized by disruptions in the isoprenoid pathway, leading to the development of cornoid lamella, a unique skin lesion consisting of parakeratotic cells. The condition has a genetic foundation involving mutations affecting cholesterol synthesis, and new treatments aim to address these metabolic disruptions. This study examines a 56-year-old male with porokeratosis of Mibelli (PM) who presented with a non-healing erosion on his finger that persisted for two years. Previous therapies, including corticosteroids, antibiotics, and tacrolimus, proved ineffective. The patient then received a novel treatment with a topical 2% lovastatin/2% cholesterol ointment. After nine months, there was significant clinical improvement; the lesion was markedly reduced in size and appearance. This case underscores the potential of lovastatin/cholesterol ointment as an effective treatment for PM, indicating its promise for broader therapeutic applications.

Dapsone as a Current Option for the Treatment of Autoimmune Bullous Diseases with Autoimmunity to Non-Enzymes: A Retrospective Study from a Single Central European Referral Center.

Background and Objectives: Dapsone (DP) is employed in the management of various skin conditions, including autoimmune bullous diseases to non-enzymes (n-eAIBDs). This study aimed to assess the advantages and safety profile of DP treatment in n-eAIBDs patients. The evaluation focused on clinical remission, reduction in glucocorticosteroid (GCS) usage, and adverse incidents during a 12-month observation in a dermatology department at a Central European university. Materials and Methods: Our retrospective study included forty-one patients who met the inclusion criteria, comprising nineteen with pemphigus vulgaris, nine with pemphigus foliaceus, four with bullous pemphigoid, and nine with mucous membrane pemphigoid, including one patient with Brunsting-Perry pemphigoid. Patients received 25-50 mg/day of DP along with oral GCSs for a year, with a subsequent dose reduction where feasible. Results: The mean decreases in prednisone-equivalent dosages across all groups after 2, 6, and 12 months of DP treatment were 45.66%, 65.77%, and 63.03%, respectively. Throughout the 12-month observation period, 21.62% of patients experienced a relapse, while the remaining patients attained either complete or partial remission with minimal therapy. Adverse incidents were observed in 29.27% of patients; these were mild or moderate, and no severe negative effects were observed. Conclusions: DP is an effective and affordable choice to support the treatment of n-eAIBDs, but it may not be sufficient for long-term management in certain patients with severe n-eAIBDs.

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.

Porokeratoses-A Comprehensive Review on the Genetics and Metabolomics, Imaging Methods and Management of Common Clinical Variants.

Porokeratosis is a heterogeneous group of keratinising disorders characterised by the presence of particular microscopic structural changes, namely the presence of the cornoid lamella. This structure develops as a consequence of a defective isoprenoid pathway, critical for cholesterol synthesis. Commonly recognised variants include disseminated superficial actinic porokeratosis, disseminated superficial porokeratosis, porokeratosis of Mibelli, palmoplantar porokeratosis (including porokeratosis palmaris et plantaris disseminata and punctate porokeratosis), linear porokeratosis, verrucous porokeratosis (also known as genitogluteal porokeratosis), follicular porokeratosis and porokeratoma. Apart from the clinical presentation and epidemiology of each variant listed, this review aims at providing up-to-date information on the precise genetic background, introduces imaging methods facilitating the diagnosis (conventional and ultraviolet-induced fluorescence dermatoscopy, reflectance confocal microscopy and pathology), discusses their oncogenic potential and reviews the literature data on the efficacy of the treatment used, including the drugs directly targeting the isoprenoid-mevalonate pathway.

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.

Pityriasis Versicolor-A Narrative Review on the Diagnosis and Management.

This narrative review presents a comprehensive overview of the diagnosis and management of pityriasis versicolor (PV), a common superficial fungal infection caused by the yeast Malassezia. PV is characterised by scaly hypopigmented or hyperpigmented patches, primarily affecting the upper trunk, neck, and upper arms. Regarding commensal interactions, Malassezia utilises nutrient sources without affecting the human host. In cases of pathogenicity, Malassezia can directly harm the host via virulence factors or toxins, or indirectly by triggering damaging host responses. The diagnosis typically relies on recognising characteristic clinical features. Due to the wide variability in its clinical presentation, recognising the differential diagnosis is critical. In this paper, we discuss the clinical differentials, with their dermatoscopic presentation, but also describe a range of helpful diagnostic techniques (microscopy, conventional and ultraviolet-induced fluorescence dermatoscopy, and confocal microscopy). Topical therapies are the primary treatment for PV, encompassing non-specific antifungal agents like sulphur with salicylic acid, selenium sulphide 2.5%, and zinc pyrithione. Additionally, specific topical antifungal medications with either fungicidal or fungistatic properties may also be incorporated into the topical treatment regimen, such as imidazoles, allylamines, and ciclopirox olamine. Systemic therapies might occasionally be used. Patient education and the promotion of good personal hygiene are pivotal to reduce the risk of recurrence. In recurrent cases, particularly during warmer and more humid periods, prolonged prophylaxis with topical agents should be considered.

Intravenous Immunoglobulin for Autoimmune Bullous Diseases: A Case Series from a Central European Referral Center.

Background and Objectives: Autoimmune bullous diseases (AIBDs) may be treated with intravenous immunoglobulin (IVIG) infusions. This study aimed to evaluate the benefits and safety profiles of high-dose IVIG therapy in AIBD patients, as determined by clinical remission, the glucocorticosteroid-sparing effect, and adverse events at 12 months follow-up in a Central European university dermatology department setting. Materials and Methods: Our case series included 10 patients: five patients with pemphigus vulgaris, one with pemphigus herpetiformis, one with pemphigus foliaceus, one with bullous pemphigoid, two with epidermolysis bullosa acquisita. They underwent 4-12 monthly cycles of IVIG therapy at a dose of 2 g/kg per cycle. Results: The prednisone dosage reduction after 2, 6, and 12 months following the final IVIG course was 65.45%, 70.91%, and 76.37%, respectively. During the 12-month observation period, disease relapse was observed in 20% of patients, while others achieved complete or partial remission without or with minimal therapy. Side effects were seen in 80% of patients; they were transient and did not necessitate discontinuation of IVIG. Conclusions: IVIG demonstrates effectiveness as a treatment with a favorable safety profile. Nevertheless, its high cost remains a significant drawback, particularly in low-income countries. IVIG should be considered, especially in patients opposed to standard therapies or with contraindications to their use.

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.

Immunopathological Assessment of the Oral Mucosa in Dermatitis Herpetiformis.

Dermatitis herpetiformis (Duhring's disease, DH) is a chronic blistering cutaneous condition with pruritic polymorphic lesions, consisting of vesicles, papules or nodules and erythema, found predominantly on the extensor surfaces of the limbs, buttocks, and neck. Diagnosis is based on characteristic clinical and immunopathological findings. Oral manifestations of DH have rarely been described. The aim of the study was to evaluate IgA, IgG, IgM and C3 complement deposits in the oral mucosa in DH patients. Direct immunofluorescence (DIF) was performed on the oral mucosa specimens collected from 10 DH patients. Biopsy was taken in a local anesthesia from perilesional site from the buccal mucosa and then preserved in a standard procedure using polyclonal rabbit IgG, IgA, IgM and C3 antibodies. Granular IgA and C3 deposits were found in 6 patients (60%), and in 3 subjects (30%) the result was indeterminate. Significant fluorescence of the deposits along the basement membrane was observed in 2 patients, moderate fluorescence in 3 patients, and in 4 cases the result was indeterminate. C3 deposits were found in 5 subjects (50%), 3 of them being moderate and 2 indeterminate. No IgM and IgG deposits were detected in the collected buccal mucosa specimens.

Challenges in the Diagnosis of Tertiary Syphilis: Case Report with Literature Review.

Tertiary syphilis is a large diagnostic challenge. It is rarely the case that it affects the skin, bone tissue and the eyes at the same time. The presented case shows that extensive symptomatology of syphilis poses a challenge in making a proper diagnosis in patients whose history does not suspect STDs. The study aims to present the case of a young woman hospitalized with a suspected autoimmune disease, diagnosed with symptomatic late syphilis with involvement of the skin, bones and eyes.

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.

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.

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.

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.

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.