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BACKGROUND Severe hypertension (sHTN) is prevalent in 10% of hospitalized patients and treatment guidelines are lacking. As such, patients who develop sHTN might unnecessarily receive antihypertensive medications which could lead to worse outcomes. Our goal was to investigate correlates of spontaneous blood pressure (BP) reduction to help guide future treatment decisions and avoid harm associated with aggressive BP treatment. METHODS This is a retrospective cohort study of hospitalized adults between 2016 and 2020 who developed sHTN, SBP >180 or DBP >110 mm Hg, after admission. Spontaneous BP reduction was defined as a SBP <160 and a DBP <100 mm Hg achieved within 3 h of sHTN in the absence of antihypertensive therapy. Multivariable logistic regression was used to identify correlates of spontaneous BP reduction. RESULTS Of the 12,825 patients who developed sHTN, 44.2% had spontaneous BP reduction. After adjustment, we found that patients most likely to experience a BP drop received steroids before onset of sHTN (Odds ratio [OR]: 1.3 [1.09, 1.56]), had higher potassium levels on admission (OR: 1.2 [1.09, 1.24]) and were more likely to have a history of chronic pulmonary disease (OR: 1.1 [1.01, 1.18]) or cardiac arrythmia (OR: 1.1 [1.01, 1.18]). While numerically different, these differences were not clinically relevant. CONCLUSIONS Our findings indicate that almost half the patients who develop sHTN have spontaneous BP reduction. Conventional clinical and demographic characteristics were not strong predictors of spontaneous BP reduction following sHTN development. More research is needed to confirm our findings and help guide treatment of sHTN. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP) is a common immune-mediated blistering disorder with predominant skin involvement and occasionally oral manifestations. Vesiculobullous lesions of the oral mucosa present with similar clinical features, and hence arriving at a clinical diagnosis is aided by a valuable chairside investigation, exfoliative cytology. Cytology done in the present case ruled out pemphigus because of the absence of Tzanck cells in the smear. Biopsy and direct immunofluorescence further confirmed the diagnosis of BP. Treatment initiated with systemic steroids and immunomodulators, along with oral topical application of triamcinolone acetonide resulted in complete remission in 2 months. This case report highlights the role of cytology in the diagnosis of vesiculobullous lesions and management protocol for BP patients presenting with simultaneous skin and oral lesions. [ABSTRACT FROM AUTHOR]

BackgroundBullous pemphigoid (BP) is the most common autoimmune blistering skin disease in humans, characterized by tense blisters, erosions, urticarial lesions, and itching on normal or erythematous skin. Many autoimmune diseases are considered comorbidities of BP, but clinical case reports of BP complicated by Sjögren’s syndrome are very scarce. Furthermore, cases of central nervous system infection secondary to both autoimmune diseases are even rarer.Case presentationWe report a 74-year-old woman diagnosed with bullous pemphigoid, who showed relief of active lesions after treatment with methylprednisolone and dupilumab injections. However, she was admitted for pulmonary infection during which she was diagnosed with Sjögren’s syndrome (SS). Subsequently, the patient developed altered consciousness, indicating a central nervous system infection. Adjustment of steroid dosage and aggressive antimicrobial therapy led to alleviation of symptoms.ConclusionThe coexistence of autoimmune subepidermal blistering diseases and SS is rare. The role of SS in the pathogenesis of skin lesions is unclear, and the relationship between these blistering diseases and SS remains elusive. Further research is needed to determine whether there are common pathological mechanisms between the two conditions.

Abstract is missing (Short communication)

Abstract is missing (Short communication)

Bullous pemphigoid (BP) is the most common autoimmune bullous disease: it most commonly affects individuals over 70 years old and impacts severely on their quality of life. BP represents a paradigm for an organ-specific autoimmune disease and is characterized by circulating IgG autoantibodies to hemidesmosomal components: BP180 and BP230. While the crucial role of these autoantibodies in triggering BP inflammatory cascade is fully acknowledged, many ancillary etiological mechanisms need to be elucidated yet. Cutaneous melanoma is due to a malignant transformation of skin melanocytes, that produce and distribute pigments to surrounding keratinocytes. Melanoma is the most fatal skin cancer because of its increasing incidence and its propensity to metastasize. Several data such as: i) reported cases of concomitant melanoma and BP; ii) results from association studies; iii) BP onset following immune check-point inhibitors therapy; iv) expression of BP antigens in transformed melanocytes; and vi) circulating autoantibodies to BP antigens in melanoma patients suggest an intriguing, although unproven, possible association between melanoma and BP. However, a possible causative link is still debated and the putative pathogenetic mechanism underlying this association is unclear. This review aims to describe and discuss the possible relationship between BP and melanoma and give an overview of the speculations for or against this association. Of note, if demonstrated, this association could unwrap considerations of clinical relevance that represent new research frontiers.

Introduction: Bullous pemphigoid (BP) is an autoimmune disease involving the sub-epidermal layer. Eosinophilia may play a role in the pathogenesis of BP. Objectives: We aimed to investigate the correlation between dermal or peripheral eosinophilia with clinical presentations in patients with BP. Methods: This cross-sectional study was conducted on 108 BP patients from January 2010 to September 2019. Clinical data were recovered. Skin biopsies were re-evaluated, and the Bullous Pemphigoid Disease Area Index (BPDAI) severity score was calculated. Finally, the relationship between clinical features of BP and dermal or peripheral eosinophilia was analyzed. Results: A total number of 108 patients were included in this study. Thirty-five were excluded due to our exclusion criteria. Finally, data from 73 patients were analyzed. 57.5% of the population was female. There was a significant direct correlation (r= 0.33) between BPDAI severity score and tissue eosinophilia (p= 0.03). No significant relationship was found between BPDAI severity score and peripheral eosinophilia (P= 0.52). There were significant positive correlations between tissue eosinophilia with absolute serum eosinophil count (P= 0.002; r= 0.49) and percentage (P< 0.0001; r= 0.89). Conclusion: This study revealed significant relationships between tissue eosinophilia and BP severity. These findings could be useful in clinical practice. The possible role of eosinophils in BP clinical features should be considered as a promising help for better diagnosis and treatment.

ROS are involved in the pathogenesis of bullous pemphigoid (BP), but this involvement has not been fully elucidated. In this study, to further elucidate the pathogenic role of ROS in BP, we examined the results of the diacron-reactive oxygen metabolite test and the biological antioxidant potential test for 16 patients with BP who visited our hospital before being treated with systemic corticosteroids. In the patients with BP, the average diacron-reactive oxygen metabolite levels, expressed in Carratelli units, were significantly reduced at 1 month of treatment (from 335.6 ± 40.3 Carratelli units to 224.7 ± 61.6 Carratelli units, P < .001). Bullous Pemphigoid Disease Area Index (erosions/blisters) scores correlated with diacron-reactive oxygen metabolite levels (r = 0.51), suggesting that those levels reflect the disease severity. We also performed staining of 3,5-dibromotyrosine in skin tissues. The 3,5-dibromotyrosine is expected to be a marker of tissue damage related to inflammation and allergies. The 3,5-dibromotyrosine was stained in infiltrated cells around the dermis, throughout the blister fluid, and at the basement membrane within the blister. It is considered that tissue destruction caused by the myeloperoxidase released from neutrophils and by eosinophil peroxidase released from eosinophils is involved in blister formation. The results suggest that ROS play a role in BP.

This article discusses the occurrence of new-onset inflammatory facial dermatoses and the exacerbation of pre-existing dermatoses due to prolonged mask wearing during the COVID-19 pandemic. The authors present two cases of pemphigus vulgaris (PV) where patients developed a well-defined triangular crusty nose after regularly wearing masks. PV is a rare autoimmune mucocutaneous bullous disorder characterized by intraepidermal blisters. The article highlights the importance of considering PV as a potential diagnosis in cases of localized skin damage triggered by mask wearing and emphasizes the need for close clinical monitoring. [Extracted from the article]

This article discusses a case report of a patient with severe epidermolysis bullosa acquisita (EBA), a rare autoimmune disease characterized by auto-antibodies against type-VII collagen. The patient had previously tried various treatments without success, but achieved sustained clinical remission (CR) for 5 years after receiving rituximab infusions. Rituximab, a monoclonal antibody targeting B lymphocytes, has shown promise in inducing long-term remission for patients unresponsive to conventional therapies. The article highlights the patient's improvement in symptoms, decrease in disease activity scores, and improved quality of life following rituximab treatment. This case adds to the existing evidence for rituximab as an effective treatment for severe EBA. [Extracted from the article]

This article discusses a case of recalcitrant erosive palms and soles eccrine syringofibroadenoma successfully treated with radiotherapy. The patient, a 73-year-old Caucasian woman, had nonhealing lesions on her palms and soles for the past 3 years. Despite initial misdiagnosis and unsuccessful treatments, radiotherapy was initiated and resulted in gradual improvement and re-epithelialization of the lesions. Eccrine syringofibroadenoma is a rare and benign skin adnexal tumor that typically affects the extremities, and alternative treatments for refractory cases include surgery, radiotherapy, and other therapies. [Extracted from the article]

This article discusses the role of COVID-19 vaccines in the development and recurrence of pemphigus and bullous pemphigoid, which are autoimmune-mediated dermatologic conditions characterized by blistering. The study analyzed data from the Vaccine Adverse Events Reporting System (VAERS) and found that there were cases of pemphigus and bullous pemphigoid following COVID-19 vaccination. Most cases occurred after the second dose of the vaccine, and the Pfizer and Moderna vaccines were associated with higher rates of these conditions. However, the study has limitations, such as reliance on self-reporting data and missing variables. Further research with larger patient cohorts is needed to evaluate the relationship between COVID-19 vaccines and these dermatologic conditions. [Extracted from the article]

This article discusses a case of acute photoallergic contact dermatitis caused by diclofenac, which initially presented as bullous pemphigoid. The patient, a non-atopic man, developed a severe rash on his right shoulder and knee after using a diclofenac-based gel. Skin biopsies confirmed the diagnosis of photoallergic contact dermatitis. The patient was also found to have multiple contact allergies to other substances. The article highlights the potential for photocontact allergy to diclofenac and the importance of conducting patch tests to identify allergens. [Extracted from the article]

This article, published in Experimental Dermatology, explores the levels of interleukin 38 (IL-38) in patients with pemphigus vulgaris (PV), an autoimmune bullous disease. The study found that patients with PV had significantly lower serum levels of IL-38 compared to healthy controls. Immunohistochemical staining also revealed reduced expression of IL-38 in the epidermal layers of PV patients' skin. These findings suggest that IL-38 may play a role in modulating inflammatory responses and could have implications for understanding autoimmune and inflammatory conditions. However, further research with larger sample sizes is needed to confirm these preliminary findings. [Extracted from the article]

This article discusses the use of ultra-low-dose rituximab as an alternative treatment for autoimmune dermatological conditions. The authors conducted a study on three patients with different autoimmune skin diseases and found that a regimen of 100mg of rituximab once a week for four weeks resulted in significant improvement without any adverse events. The authors suggest that this low-dose regimen could be a cost-efficient and effective treatment option, especially in countries where rituximab is expensive and not easily accessible. However, more studies are needed to determine the efficacy, safety, and duration of remission for this treatment. [Extracted from the article]

This article discusses a case of successful treatment of pemphigus foliaceus (PF), a rare autoimmune blistering dermatosis, with upadacitinib. The patient had been suffering from the disease for 8 years with recurrent severe relapses. Previous treatments with corticosteroids and immunosuppressive drugs had failed to control the disease. However, treatment with upadacitinib resulted in the resolution of skin lesions and a significant improvement in the patient's quality of life. The mechanisms by which upadacitinib exerts its effect in PF are still unknown, but it is believed to inhibit the proliferation and differentiation of T and B cells. Further studies are needed to determine the safety of upadacitinib in elderly adults with comorbidities. [Extracted from the article]

This article discusses a rare case of co-occurrence of bullous pemphigoid (BP) and mucosal-dominant pemphigus vulgaris (MDPV) in a Japanese man. The patient presented with tense blisters and erosions on the skin and mucosal lesions on the lips, tongue, and buccal mucosa. Initially, the mucosal lesions were attributed to BP, but further analysis revealed that they were caused by pathogenic anti-desmoglein 3 (Dsg3) antibodies. The article emphasizes the importance of confirming the pathogenicity of anti-Dsg antibodies and highlights the usefulness of a bead aggregation assay in monitoring disease activity and selecting appropriate treatments. [Extracted from the article]

This article discusses a case of a 43-year-old woman with a pruritic rash on her neck and back. The patient had a medical history of anorexia nervosa, herpes zoster, and peripheral neuropathy. Physical examination revealed red scaly papules that coalesced in a reticular pattern. The diagnosis was prurigo pigmentosa, a rare inflammatory disorder that is more commonly observed in young adults of Asian descent. The condition is associated with diet, particularly ketosis induced by ketogenic diets or anorexia nervosa. Treatment options include oral antibiotics, such as doxycycline, and dietary modifications. [Extracted from the article]

This article discusses a case of bullous pemphigoid (BP), a rare autoimmune skin disorder, induced by nivolumab therapy for malignant melanoma. The patient initially received corticosteroids and rituximab for treatment, but the BP was recalcitrant. Cyclosporine was then administered, resulting in near-complete resolution of the BP. The article highlights the potential effectiveness of cyclosporine as an alternative treatment for immune checkpoint inhibitor-induced BP that does not respond to standard therapies. The document emphasizes the importance of dermatologists being aware of the cutaneous manifestations of immune-related adverse events and the potential treatment options available. [Extracted from the article]

Linear IgA bullous dermatosis (LABD) is a rare mucocutaneus blistering autoimmune disease caused by IgA autoantibodies. Its clinical manifestation can be indistinguishable from bullous pemphigoid (BP), a similar autoimmune bullous disease caused by IgG and IgE autoantibodies. Although BP has been reported as an adverse cutaneous effect of immunotherapy, LABD has rarely been associated with immunotherapy in the literature. We present the case of a 67-year-old woman with metastatic ovarian cancer receiving anti-PD1 and anti-CTLA4 with new onset pruritic tense bullae to the trunk, hands, elbows (in annular distribution) that occurred after immunotherapy. Skin biopsy showed subepidermal blister with abundant neutrophils on H&E histology, and linear IgA staining at the basement membrane on direct immunofluorescence consistent with the diagnosis of LABD. The condition did not improve on initial prednisone taper, but blisters rapidly resolved a few days after initiation of dapsone therapy. We favor that our patient's LABD is secondary to her immunotherapy. Our case highlights the importance of both H&E histology and direct immunofluorescence in diagnosis of blistering disorders in patients on immunotherapy to help in choosing the most effective treatment option in an attempt to avoid discontinuation of immunotherapy.

We report a 48-year-old woman with bullous pemphigoid (BP) with antibodies against the B3 subunit of laminin 332 after the development of graft-versus-host disease (GVHD). She was diagnosed with recurrent acute lymphoblastic leukemia at 40 years of age and underwent two rounds of allogeneic peripheral blood stem cell transplantations (PBST). Two and a half years after the second PBST, multiple tense blisters appeared on her face, hands, and lower legs. The diagnosis of BP was based on hematoxylin eosin and immunofluorescence staining and immunoblotting analyses. A combination regimen of topical corticosteroids (clobetasol propionate) and tetracycline/niacinamide was administered. Complete clinical resolution was achieved after four weeks of therapy without the use of immunosuppressive drugs. To maintain the graft-versus-tumor effect, topical corticosteroids and immunomodulatory drugs are preferred for BP after hematopoietic stem cell transplantation considering the risk of recurrence of hematologic malignancies. To date, there have been no reports of successful treatment of GVHD-associated BP without immunosuppressive drugs. Chronic GVHD is characterized by the production of autoantibodies. Furthermore, this autoimmune subepidermal blistering disease, BP, may be a manifestation of chronic GVHD. However, the precise mechanism of autoantibody production in chronic GVHD is not yet fully elucidated.

Abstract Background The prognosis of dipeptidyl peptidase‐4 inhibitor‐associated bullous pemphigoid (DPP‐4i‐BP) is variable, with some cases showing spontaneous remission after drug cessation and others showing worsening BP or developing infectious complications, termed infectious immune reconstitution inflammatory syndrome (IRIS), after DPP‐4i cessation. We recently demonstrated that the neutrophil‐to‐lymphocyte ratio measured at baseline and during treatment predicts the eventual development of infectious IRIS. Objectives To identify key molecular immune parameters that correlate with, and potentially shape, subsequent immune responses after DPP‐4i cessation. Methods This retrospective observational study examined DPP‐4i‐BP patients who were treated at our hospital for 4 years. Patients selected for this study were those who developed BP after initiation of DPP‐4i and were followed up at least 90 days after DPP‐4i cessation, if information and the relevant parameters were available from the medical records. The patients were divided into two cohorts: a spontaneous remission group and an exacerbation group showing worsening BP or developing infectious IRIS. Serum cytokine/chemokine levels were determined using a multiplex biometric immunoassay. Results Serum levels of eotaxin and interferon (IFN)‐α/γ before DPP‐4i cessation were significantly higher in the remission group (161.6 [standard error 21.9] pg/mL and 14.4 [4.8]/9.2 [4.6] pg/mL, respectively) than in the exacerbation group (51.1 [standard error 9.8] pg/mL and 1.6 [1.6]/1.0 [0.5] pg/mL, respectively, p

Objective: The gold-standard method for assessment of autoimmune bullous disease is direct/indirect immunofluorescence (IF) examination applied to fresh frozen tissue. Since the sensitivity of IF is greatly reduced in formalin-fixed paraffin-embedded (FFPE) tissues, IF cannot be relied upon in these samples. However, immunohistochemistry with the C4d antibody is a promising marker used as a surrogate for immune complex deposition, in nephropathology practice, and the paraffin IF method is also used as a `salvage` technique when fresh frozen tissue is not available or lacks glomeruli. We aimed to investigate whether it is possible to obtain immunofluorescence data from FFPE tissues diagnosed with bullous pemphigoid (BP) and pemphigus vulgaris (PV) and its relationship with inflammatory parameters in the skin. Material and Methods: Eighty-nine in-house cases with both IgG and C3 positivity by routine immunofluorescence examination were included in the study. Inflammation parameters were evaluated in hematoxylin-eosin sections. Immunofluorescence study with IgG protease digestion and C4d immunohistochemistry were performed. Results: Results of 83 biopsies were obtained by paraffin immunofluorescence with IgG. There were positive reactions in 28 (34%) of these 83 biopsies. Five of the 28 positive results belonged to BP (18%), and 23 were PV (82%). Ten positive results were on lesional skin (36%), and 18 (64%) were on non-lesional skin. In the immunohistochemical study with C4d, 84 biopsy results were obtained. There were positive reactions in 34 (40.4%) of 84 biopsies. Of the 34 positive results, 12 belonged to BP (35.3%) and 22 to PV (64.7%). Again, 22 (64.7%) of 34 positive results belonged to lesional skin, and 12 (35.3%) belonged to non-lesional skin. When both techniques were used together, 44 (54%) of 81 biopsies yielded positive results for at least one of the two studies, while in 37 (46%), both tests showed negative results. Conclusion: The sensitivity of both IgG and C4d was less than in the literature, especially in BP-diagnosed biopsies. Positive samples were mostly PV. In conclusion, obtaining immunofluorescence data in FFPE samples is possible and is independent of the related skin being lesional or not, however, negative results should not be relied upon.

Objective To investigate the expression levels of type 2 inflammatory cytokines, IL-4 and IL-13, in the serum and blister fluid of patients with bullous pemphigoid (BP). Methods The serum or blister fluid was collected from BP patients (49 cases) and healthy individuals (33 cases). ELISA was used to measure the concentrations of IL-4 and IL-13. The expression levels of IL-4 and IL-13 were compared between the BP patients and healthy controls. The correlations of IL-4 and IL-13 with total serum IgE levels, eosinophils, skin erythema score and pruritus severity (NRS) in BP patients were analyzed. Moreover, the associations of BP180 and BP230 IgG antibodies with IL-4, IL-13 and total serum IgE levels, and eosinophils were determined. Results The concentrations of IL-4 and IL-13 in the blister fluid, but not in the serum, were significantly higher in the BP patients than in the healthy controls (P

Background: Direct immunofluorescence (DIF) including salt split skin technique is quintessential in the diagnosis of subepidermal bullous disorders. These techniques are expensive and require technical expertise, limiting their diagnostic utility. The property of periodic-acid–Schiff to stain the basement membrane and the patterns produced by it was observed in a cohort of subepidermal bullous disorders, to see if it offers an alternative cost-effective testing method. Materials and Methods: This was a retrospective, observational study conducted in the department of general pathology, in a tertiary care medical center, over a period of 4 years. Only those cases for which paraffin sections, DIF and direct salt split skin immunofluorescence technique were available were included. The levels of anti-bullous pemphigoid (BP) antibodies were collected where available. Results: Of the 21 cases analyzed, 15 were BP, two each of epidermolysis bullosa acquisita (EBA) and lichen planus pemphigoides (LPP), one each of porphyria cutanea tarda (PCT), and bullous systemic lupus erythematosus (SLE). All the cases of BP, LPP and EBA showed a floor pattern of staining with periodic acid–Schiff (PAS) stain. Roof pattern of staining was observed in bullous SLE and PCT. PAS was found to be useful in diagnosing BP, especially in conjunction with an eosinophil rich bulla and anti-BP antibodies. Conclusion: We found that PAS stain could be an adjunct to hematoxylin and eosin stain when the diagnosis of BP is in doubt. However, larger sample size is needed to study its utility in other subepidermal bullous disorders.

Aim: Bullous pemphigoid induced by secukinumab in treatment of psoriasis is rare.Methods: We report a 49-year-old man with psoriasis who developed bullous pemphigoid during treatment with secukinumab.Results: Scattered tense vesicles with itching appeared all over the body after the fourth treatment. Bullous pemphigoid was confirmed by pathological examination and direct immunofluorescence. The patient was treated with topical corticosteroids, oral nicotinamide and minocycline hydrochloride. The lesions of bullous pemphigoid improved significantly after 7 days of treatment.Conclusions: Bullous pemphigoid is a rare adverse event following administration of secukinumab.

Background: The association between psoriasis vulgaris and bullous pemphigoid (BP) remains largely unknown. Objectives: To investigate whether there is a causal effect between psoriasis vulgaris and BP. Methods: Two-sample bidirectional Mendelian randomization (MR) analyses were conducted using publicly released genome-wide association studies (GWAS) summary statistics. The GWAS summary statistics for BP were downloaded online from FinnGen Biobank Documentation of the R12 release, which includes 219 BP cases and 218,066 controls. The GWAS data for psoriasis vulgaris were extracted from Sakaue et al., which comprises 5072 cases and 478,102 controls. Single-nucleotide polymorphisms (SNPs) associated with exposure were selected as instrumental variables by performing additional quality control steps. The inverse-variance-weighted (IVW) method was used for the primary MR analyses, and the MR-Egger regression, weighted mode method, weighted median method, and simple mode were employed for sensitivity analyses. The MR-Egger intercept test and "leave-one-out" sensitivity analysis were performed to evaluate the horizontal pleiotropy and the potentially influential SNPs, respectively. Results: Genetically determined log odds of psoriasis vulgaris were associated with an increased risk of BP (IVW: odds ratio (OR) = 1.263, 95% confidence interval (CI): 1.013-1.575, P=0.038). Sensitivity analyses by the weighted mode (OR=1.255, 95%CI: 0.973-1.618, P=0.106), MR Egger (OR=1.315, 95%CI: 0.951- 1.817, P=0.126), simple mode (OR=1.414, 95%CI: 0.823-2.429, P=0.234) and weighted median method (OR=1.177, 95%CI: 0.889-1.559, P=0.254) derived directionally consistent relationship between the genetically predicted log odds of psoriasis vulgaris and risks of developing BP. On the contrary, we found that genetically predicted BP had no significant effect on psoriasis vulgaris (IVW: OR=0.996, P= 0.707), indicating the unidirectionality of the relationship. MR-Egger intercept tests showed no evidence of horizontal pleiotropy. No influential SNP driving the results was detected by the leave-one- out sensitivity analysis. Conclusions: Our results suggested that psoriasis vulgaris causally increases the risk of BP, highlighting the need for potential strategies for the prevention and early diagnosis of comorbid BP in patients with psoriasis vulgaris. Further researches into this association and underlying mechanisms are warranted. [ABSTRACT FROM AUTHOR]

Background. Heparin-induced bullous hemorrhagic dermatosis (HBHD) is a rare cutaneous adverse effect of heparin and has unclear clinical features. We explored the clinical features of HBHD to provide evidence for the safe use of heparin. Methods. We collected HBHD-related case reports for a retrospective analysis by searching the Chinese and English databases from inception to December 31, 2022. Results. Seventy-two patients, including 51 males (70.8%), were included, and they had a median age of 71.5 years (range: 21, 94). Low-molecular-weight heparin was used in 62 patients (86.1%), and unfractionated heparin was used in 10 patients (13.9%). The median time for HBHD to appear was 7 days (range: 0.25, 270). Lesions appeared far from the injection site, and the extremities (57 patients, 79.2%) were the most frequently involved site. The blisters were mainly located in the intraepidermal (34 patients, 47.2%), subcorneal (10 patients, 13.9%), and subepidermal (9 patients, 12.5%) regions. Thirty-seven patients (51.4%) had no obvious dermal inflammatory infiltration, and 20 patients (27.8%) had lymphocytic inflammatory infiltration. Sixty-seven patients (93.1%) recovered from their skin lesions after the discontinuation of heparin or despite continuing heparin and at a median treatment time of 14 days (range: 2, 141). Conclusion. HBHD is a rare self-limiting disease that occurs far from the injection site. Clinicians should be aware of BHD during the administration of heparin. Heparin can be discontinued or continued depending on the patient's condition. [ABSTRACT FROM AUTHOR]

Claudin-4 is a key component of tight junctions, which play an important role in the formation of the epidermal barrier by forming a circumferential network in the granular layer that serves as a gatekeeper of the paracellular pathway. The aim of this study is to illustrate claudin-4 immunohistochemical staining patterns of different blistering disorders. We collected 35 cases, including two Hailey–Hailey disease, one Darier disease, three Grover disease, one acantholytic acanthoma, two warty dyskeratoma, 11 pemphigus vulgaris (PV) including six mucosal PV, and two pemphigus foliaceus. For comparison, we included five cases of normal skin, five eczema, and three bullous pemphigoid cases. Claudin-4 demonstrated weak-to-moderate expression in keratinocytes located in the stratum granulosum, keratinocytes surrounding hair follicles, and adnexal glands. Further, claudin-4 exhibited moderate-to-strong membranous staining in disrupted keratinocytes surrounding and within the acantholytic and bullous areas in 16/22 of the acantholytic cases (not seen in the six cases of mucosal PV) and all three bullous pemphigoids. This finding suggests that claudin-4 is upregulated in these conditions, which may be a compensatory response to the disrupted barrier function. This finding could shed light on the molecular mechanisms underlying disrupted barrier function in blistering disorders, independent of the specific underlying disease mechanism. [ABSTRACT FROM AUTHOR]

Nurr1 is a member of the orphan nuclear receptor family NR4A (nuclear receptor subfamily 4 group A) that modulates inflammation in several cell lineages, both positively and negatively. Macrophages are key regulators of inflammatory responses, yet information about the role of Nurr1 in human macrophages is scarce. Here we examined Nurr1 expression and activity in steady state and activated human macrophages. Pro- and anti-inflammatory macrophages were generated in vitro by culture of blood monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Nurr1 expression was predominant in macrophages with the pro-inflammatory phenotype. Nurr1 activation with the agonists 1,1-bis(3ʹ-indolyl)-1-(p -chlorophenyl) methane (C-DIM12) or isoxazolo-pyridinone 7e (IP7e) did not globally modify the polarization status of pro-inflammatory macrophages, but they decreased their production of TNF, IL-1β, IL-6, IL-8, IL-12 p40, CCL2, IFN-β, and reactive oxygen species, with variable potencies. Conversely, Nurr1 deficient macrophages increased the expression of transcripts encoding inflammatory mediators, particularly that of IL6 , IFNB1 , and CCL2. Mechanistically, endogenous Nurr1 interacted with NF-κB p65 in basal conditions and upon lipopolysaccharide (LPS)-mediated activation. C-DIM12 stabilized those complexes in cells exposed to LPS and concurrently decreased NF-κB transcriptional activity and p65 nuclear translocation. Expression of high levels of Nurr1 was associated with a subset of dermal macrophages that display enhanced levels of TNF and lower expression of the anti-inflammatory marker CD163L1 in skin lesions from patients with bullous pemphigoid (BP), a chronic inflammatory autoimmune blistering disorder. These results suggest that Nurr1 expression is linked with the pro-inflammatory phenotype of human macrophages, both in vivo and in vitro , where it may constitute a brake to attenuate the synthesis of inflammatory mediators. [ABSTRACT FROM AUTHOR]

Abastract: Bullous pemphigoid (BP) is a common autoimmune bullous disease affecting mainly the elderly, with rising incidence due to increased life expectancy. This disease is characterized by tense bullous lesions on normal or erythematous skin, accompanied by pruritus. BP pathogenesis involves autoantibodies against hemidesmosomal proteins BP180 and BP230, leading to detachment at the dermo-epidermal junction as well as blister formation. BP is associated with coexisting comorbidities and drug exposure, and its management often requires high doses or chronic use of systemic glucocorticoids, posing risks of adverse effects. This review focuses on novel treatment options for BP, exploring therapies targeting different immune pathways. Rituximab, a CD20 monoclonal antibody, depletes B-lymphocytes and has shown efficacy in severe cases. Dupilumab, targeting interleukin (IL)-4 receptor α and thus blocking IL-4 and IL-13, downregulates type 2 helper (Th2) responses and has demonstrated promising results. Targeting eosinophil-related molecules using bertilimumab and AKST4290 has yielded positive results in clinical trials. Omalizumab, an immunoglobulin (Ig) E antibody, can reduce disease severity and allows corticosteroid tapering in a number of cases. Complement inhibitors such as nomacopan and avdoralimab are being investigated. IL-17 and IL-23 inhibitors such as secukinumab and tildrakizumab have shown potential in a limited number of case reports. Neonatal Fc receptor antagonists such as efgartigimod are under investigation. Additionally, topical therapies and Janus kinase inhibitors are being explored as potential treatments for BP. These novel therapies offer promising alternatives for managing BP, with potential to improve outcomes and reduce high cumulative doses of systemic corticosteroids and related toxicities. Further research, including controlled clinical trials, is needed to establish their efficacy, safety, and optimal dosing regimens for BP management. [ABSTRACT FROM AUTHOR]

Vildagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i) is a widely used type 2 diabetes medication that is associated with an up-to 10-fold increased risk for the development of bullous pemphigoid (BP), an autoimmune skin disease. The mechanism by which vildagliptin promotes the development of BP remains unknown. To elucidate effects of vildagliptin treatment on the mouse cutaneous proteome. We analyzed the cutaneous proteome of nondiabetic mice treated for 12 weeks with vildagliptin using label-free shotgun mass spectrometry (MS), two-dimensional difference gel electrophoresis (2D-DIGE), immunohistochemistry, immunoblotting, and quantitative real-time polymerase chain reaction. Although vildagliptin treatment did not cause any clinical signs or histological changes in the skin, separate MS and 2D-DIGE analyses revealed altered cutaneous expression of several proteins, many of which were related to actin cytoskeleton remodeling. Altogether 18 proteins were increased and 40 were decreased in the vildagliptin-treated mouse skin. Both methods revealed increased levels of beta-actin and C->U-editing enzyme APOBEC2 in vildagliptin-treated mice. However, elevated levels of a specific moesin variant in vildagliptin-treated animals were only detected with 2D-DIGE. Immunohistochemical staining showed altered cutaneous expression of DPP-4, moesin, and galectin-1. The changed proteins detected by MS and 2D-DIGE were linked to actin cytoskeleton remodeling, transport, cell movement and organelle assembly. Vildagliptin treatment alters the cutaneous proteome of nondiabetic mice even without clinical signs in the skin. Cytoskeletal changes in the presence of other triggering factors may provoke a break of immune tolerance and further promote the development of BP. • No clinical signs of adverse effects on vildagliptin-treated mice. • Cutaneous proteomic changes detected in vildagliptin-treated nondiabetic mice. • Vildagliptin exposure elevates proteins that are linked to actin. • Vildagliptin exposure decreases cytoskeleton-interacting proteins. [ABSTRACT FROM AUTHOR]

Introduction: Increased arterial stiffness is a marker of Cardiovascular Disease (CVD), even before clinical signs and symptoms become evident. Hypertension is an established risk factor for CVD. However, recent studies have revealed increased arterial stiffness even among prehypertensives. Photo Pulse Plethysmography (PPG) is an efficient non-invasive, and cost-effective technique to measure arterial stiffness. Studying arterial stiffness using PPG can serve as a surrogate marker of Cardiovascular (CV) risk among prehypertensives. Aim: To compare arterial wall stiffness among prehypertensives and normotensives using PPG. Materials and Methods: This pilot study was conducted at the Sri Ramachandra Institute of Higher Education and Research, Chennai, TamilNadu, India from December 2022 to February 2023. The study population included 10 non diabetic prehypertensives and 10 normotensives, aged between 30-50 years, with normal lipid profiles. The peripheral pulse was recorded using a PPG module and digitised using AUDACITY software. The Arterial Stiffness Index (SI) was calculated and compared between the two groups. The correlation between anthropometry and arterial SI was also determined. Pearson's correlation test was used to assess the association using Statistical Package for Social Sciences (SPSS) version 24.0. Results: The SI was found to be higher in prehypertensives compared to normotensives, and this difference was statistically significant (p-value=0.04). SI showed a positive correlation with increasing Blood Pressure (BP) and anthropometric variables (Body Mass Index [BMI] and Waist-Hip Ratio [WHR]; r=0.2 and r=0.15, respectively); however, no significant relationship was observed among these variables. Conclusion: This study concludes that the SI, an important CV risk marker, shows a significant increase in prehypertensive subjects compared to normotensive subjects. However, SI showed mild positive correlation with BP and other anthropometric measurements, though not statistically significant. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Dysphagia resulting from bulbous pemphigoid is a rare but significant manifestation. A 77‐year‐old with bullous pemphigoid with no neurological history presented with severe oropharyngeal dysphagia, attributable to underlying blistering and edema, as documented on a fiberoptic endoscopic swallow examination. [ABSTRACT FROM AUTHOR]

In recent years, the medical use of cannabinoids has attracted growing attention worldwide. In particular, anti‐inflammatory properties of cannabinoids led to their emergence as potential therapeutic options for autoimmune and inflammatory disorders. Recent studies have also shown that cannabinoid receptors are widely expressed and have endogenous ligands in the skin, suggesting that the skin has its own endocannabinoid system. The aim of this review is to discuss the potential therapeutic effects of cannabinoids in autoimmune and inflammatory skin diseases. Following an overview of cannabinoids and the endocannabinoid system, we describe the cellular and molecular mechanisms of cannabinoids in skin health and disease. We then review the clinical studies of cannabinoids in autoimmune and inflammatory skin diseases including systemic sclerosis (SSc), dermatomyositis (DM), psoriasis (Pso) and atopic dermatitis (AD). A primary literature search was conducted in July 2023, using PubMed and Web of Science. A total of 15 articles were included after excluding reviews, non‐human studies and in vitro studies from 389 non‐duplicated articles. Available evidence suggests that cannabinoids may be beneficial for SSc, DM, Pso and AD. However, further studies, ideally randomized controlled trials, are needed to further evaluate the use of cannabinoids in autoimmune and inflammatory skin diseases. [ABSTRACT FROM AUTHOR]

This document provides concise summaries of several research studies in the fields of dermatology and immunology. The studies explore the role of different immune cells in the development and progression of various skin conditions, such as psoriasis, atopic dermatitis, vitiligo, and allergic contact dermatitis. The findings of these studies offer valuable insights into the underlying mechanisms of these conditions and may contribute to the development of new treatment options. The document emphasizes the importance of understanding the immune system's role in skin diseases and highlights potential therapeutic targets for further investigation. [Extracted from the article]

This document presents the findings of a study on the presence of eosinophils and basophils in patients with bullous pemphigoid (BP) and non-bullous pemphigoid (NBP) skin. The study found that the number of eosinophils and basophils was significantly higher in BP lesional skin compared to BP perilesional skin and NBP skin. The activation of eosinophils and basophils in BP lesional skin was also observed. These findings suggest that eosinophils and basophils play an important role in the pathophysiology of BP and may contribute to the itch experienced by pemphigoid patients. Further research is needed to validate these findings. [Extracted from the article]

Introduction: Several vaccine‐related cutaneous adverse events occurred following the widespread use of vaccines to prevent coronavirus disease 2019 (COVID‐19). This case series reports 25 patients with de novo or accentuated dermatologic conditions after receiving the Sinopharm, Sputnik V, AstraZeneca, or BIV1‐CovIran vaccine in Iran. Methods and Results: Twenty‐five eligible patients with a mean age of 46.80 years were investigated. The cutaneous adverse events included pityriasis rosea, zoster, viral exanthema, urticaria, bullous pemphigoid, pemphigus vulgaris, and acute generalized exanthematous pustulosis. The manifestations appeared 14.45 ± 6.98 and 20.79 ± 22.18 days following injection of the first and second doses of COVID‐19 vaccines, respectively. All patients experienced new cases of cutaneous disease other than two who developed flare‐ups of lichen planus and psoriasis. Conclusion: Several cutaneous reactions, ranging from allergic events to skin diseases, have been reported following the injection of COVID‐19 vaccines. Focal injection‐site reactions are the most common cutaneous adverse events; however, de‐novo skin diseases and a flare‐up of preexisting cutaneous disorders have also been described. Although many cases of COVID‐19 vaccine‐related cutaneous diseases have been published, our zoster/lichen planus and AGEP cases after vaccination are interesting. A more detailed understanding of cutaneous adverse events following COVID‐19 vaccination will facilitate better diagnosis and management. [ABSTRACT FROM AUTHOR]

We present a case of bilateral giant bullous emphysema (GBE) with rapidly progressive dyspnea. The dyspnea was thought to be due to tension bullae caused by the check valve mechanism in COVID‐19 bronchitis. Multiple nodules were also detected on both sides of the lung. As the patient had poor pulmonary reserve for surgical bullectomy, we first performed percutaneous intracavitary drainage. Prior to this procedure, we placed a chest tube in the thoracic cavity to avoid tension pneumothorax. As a result, the patient's remaining lung expanded and respiratory status improved, allowing him to undergo surgical bullectomy. Intraoperatively, needle biopsy of the lung nodule was directly performed, which led to a diagnosis of adenocarcinoma. Despite multiple distant metastases, the patient's general condition improved postoperatively, and chemotherapy was successfully initiated. [ABSTRACT FROM AUTHOR]

Dermatological toxicity is one of the most common immune-related adverse events (irAEs) of treatment with immune checkpoint inhibitors (ICIs). Bullous pemphigoid (BP) is a rare and serious complication of these drugs that can be difficult to establish, as its initial symptoms may be indistinguishable from mild skin lesions. This paper presents the case of a 68-year-old patient who developed BP after receiving one of the ICI therapies, pembrolizumab, for advanced non-small cell lung cancer (NSCLC). After approximately 7 months of therapy, a grade 3 skin toxicity in the Common Terminology Criteria for Adverse Events (CTCAE) occurred in the form of rash and pruritus. Pembrolizumab was then held and prednisone and antihistamines were introduced. When dermal toxicity improved to grade 1, pembrolizumab was resumed and prednisone was kept at a dose of 10 mg. Immunotherapy was discontinued 3 months later, after the recurrence of grade 3 skin toxicity symptoms. When the patient developed blisters filled with clear fluid, dermatologists suspected pembrolizumab-induced bullous pemphigoid. Bullous pemphigoid was subsequently confirmed using a direct immunofluorescence test and histopathological examination. The patient's skin condition improved after the use of steroid therapy and methotrexate, and the cancer process stabilized for over one year. Cancer progression and deterioration of the patient's general condition were observed approximately 4 months after the termination of pembrolizumab therapy. The paper also discusses the key aspects of ICIs-induced BP, especially pembrolizumab-induced BP in the first-line treatment of metastatic NSCLC. Early diagnosis of skin lesions and the initiation of appropriate treatment may lead to better outcomes for patients and prevent disruptions in immunotherapy [ABSTRACT FROM AUTHOR]

BACKGROUND Glaucoma is one of the leading causes of global blindness and is expected to co-occur more frequently with vascular morbidities in the upcoming years, as both are aging-related diseases. Yet, the pathogenesis of glaucoma is not entirely elucidated and the interplay between intraocular pressure, arterial blood pressure (BP) and ocular perfusion pressure is poorly understood. OBJECTIVES This systematic review aims to provide clinicians with the latest literature regarding the management of arterial BP in glaucoma patients. METHODS A systematic search was performed in Medline, Embase, Web of Science and Cochrane Library. Articles written in English assessing the influence of arterial BP and systemic antihypertensive treatment of glaucoma and its management were eligible for inclusion. Additional studies were identified by revising references included in selected articles. RESULTS 80 Articles were included in this systemic review. A bimodal relation between BP and glaucoma progression was found. Both high and low BP increase the risk of glaucoma. Glaucoma progression was, possibly via ocular perfusion pressure variation, strongly associated with nocturnal dipping and high variability in the BP over 24 h. CONCLUSIONS We concluded that systemic BP level associates with glaucomatous damage and provided recommendations for the management and study of arterial BP in glaucoma. Prospective clinical trials are needed to further support these recommendations. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP) is the most common autoimmune blistering disease, which primarily affects the elderly. However, the relationship between BP and malignancy remains controversial in traditional observational studies. The aim of this study, which included only European populations, was to assess the potential causative link between BP and 13 types of malignant tumors in a two‐sample Mendelian randomization (MR) study. BP was not associated with an increased risk of developing 13 types of malignant tumors. This study did not find a causal relationship between BP and malignant tumors. However, further research is warranted to examine the generalizability of this conclusion in non‐European populations. [ABSTRACT FROM AUTHOR]

(1) Background: Linear immunoglobulin A bullous dermatosis (LABD) is a rare autoimmune, subepidermal blistering disease, characterized by linear IgA deposits along the epidermal basement membrane. LABD is idiopathic and is associated with medication and systemic autoimmune diseases. (2) Methods: We investigated the demographic characteristics, disease course, causative agents, and associated diseases in Korean patients with LABD. The Korean Health Insurance Review and Assessment Service database was used to obtain data. We identified 670 LABD cases between 2010 and 2022. (3) Results: The annual incidence of LABD was 1.3 per 100,000 persons, with a higher prevalence in individuals ≥60 years old. The patients were treated with dapsone for 30.7 ± 56.7 days, had 1.3 ± 0.7 hospital visits, and were hospitalized for 19.8 ± 19.7 days. Risk factors, including malignancy, commonly preceded LABD. Antibiotic use, specifically vancomycin and third-generation cephalosporins, was a risk factor. The mean age of LABD diagnosis was 55.9 ± 21.7 years. (4) Conclusion: This is the first published study to assess a nationwide cohort for LABD. The incidence of LABD was higher than that in other studies. Most case reports have linked LABD with the administration of specific antibiotics; however, this study shows there were more associations with other conditions. [ABSTRACT FROM AUTHOR]