Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR) as Systemic Inflammatory Predictors in the Diagnosis of Bullous Pemphigoid and Pemphigus Vulgaris

Introduction: Autoimmune blistering skin disorders such as Bullous Pemphigoid and Pemphigus Vulgaris present diagnostic challenges. The Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), are inflammatory markers used to assess the body’s immune-inflammatory response. Objectives: The study aims to evaluate the significance of hematologic markers, specifically the Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), as diagnostic predictors of bullous pemphigoid (BP) and pemphigus vulgaris (PV). Methods: A retrospective study of 64 patients (36 with BP and 28 with PV). Patient clinical data: age, gender, complete blood count, autoimmune antibody levels (Dsg1, 3 and BP180, 230), IgE and C-reactive protein, and history of hypertension, diabetes, brain infarction, and coronary heart disease. The data was analyzed using SPSS. Results: The study involved 36 (56.3%) diagnosed with bullous pemphigoid (BP) and 28 (43.75%) with pemphigus vulgaris (PV). The average age in BP was 71 ± 8 and 52 ± 13 in PV. Laboratory findings showed high levels of Dsg1, Dsg3, neutrophil count, and lymphocyte count in PV, while high levels of eosinophils with a significant increase in C-reactive protein (CRP) in BP. Blood biomarkers, including NLR, PLR, SII, MPV, CRP, and IgE, proved an overall of 84.4% in disease prediction. Dsg1, Dsg3, BP180, and BP230 showed an overall of 88.1%. No significant relationship was noted between NLR, SII, and patients with comorbidities. Conclusion: The study highlights the diagnostic potential of SII and NLR in addition to hematologic markers in BP and PV, emphasizing their role in early diagnosis and therapeutic interventions, requiring further validation in larger patient cohorts.

Rituximab Therapy for Persistent, Severe and Extensive Idiopathic Bullous Pemphigoid

Background: Idiopathic Bullous Pemphigoid (IBP) is a rare blistering autoimmune disease. Its morbidity and mortality have remained high owing to complications of extensive skin involvement as well as its conventional steroid therapy. We reviewed the medical literature and found indicators of an autoimmune etiology for its pathogenesis triggering genetically predisposed patients. Objective: to evaluate, prospectively, the role of Rituximab (R) therapy in its persistent, severe and extensive form. Patients and methods: A total of 12 patients, with disease duration of 6 ± 1 months, were treated with yearly R infusions (1 g followed by 1 g 2 weeks later). Results: Significant clinical improvement was achieved as documented by decrease in total score of Bullous Pemphigoid Disease Area Index from 60 ± 3 to 6 ± 2 that persisted for 26 ± 11 months of follow up. Moreover, IBP autoantibodies (anti-BP 180 and anti-320 IgG) levels fell from to 91 ± 3 and 81 ± 2 to 8 ± 2 and 9 ± 2, respectively. Conclusions: R is a safe and effective treatment for severe IBP and such response further confirms its autoimmune pathogenesis.

Bullous Pemphigoid Induced by Doxycycline: Case Report and Literature Review

Bullous pemphigoid (BP) is the most prevalent autoimmune sub-epidermal blistering disease that affects mainly the elderly and could lead to serious morbidity. It has numerous risk factors and triggers, including an aging population with several comorbidities and drug exposure. In the published paper, we reported a case about a 32 years old male patient with unknown medical conditions who presented with erythematous patches and plaques on the scalp, face, and trunk with scattered blisters two weeks after initiating doxycycline treatment for folliculitis. The exact pathogenesis of the drug-reaction in drug- associated bullous pemphigoid (DABP) remains controversial. In conclusion, it is crucial for clinicians to be aware of DABP when prescribing doxycycline. The purpose of this case report is to raise awareness of the possible association between bullous pemphigoid and doxycycline.

Urticarial Bullous Pemphigoid: A New Case Report

Background: Bullous pemphigoid (BP) is the most common autoimmune bullous disease and it primarily affects the elderly population. It typically presents with tense bullae and severe pruritus. Non-bullous pemphigoid is a subtype of BP characterized by lacking the typical bullae formation with different presentations including erythematous, eczematous, urticarial, polycyclic, targetoid, nodular, lichenoid, vesicular and erythrodermic. Aim: to document a new case presentation of urticarial BP who was treated for several years as chronic urticarial and chronic eczema. Case Report: A 56-year-old male patient presented with a history of recurrent severely pruritic urticarial wheals for 4 years duration involving the lower abdomen, lower back, upper and lower extremities associated with excoriations, keratosis, and post-inflammatory hyperpigmentations on resolved sites, diagnosed as urticarial BP on histopathology & direct immunofluorescence study (DIF) and was improved on systemic doxycycline therapy. Conclusion: BP can be presented with atypical manifestation. Urticarial BP is a rare variant of non-bullous pemphigoid that should be taken into consideration in the differential diagnosis of an atypical urticarial wheal not responding to conventional therapy.

Bullous pemphigoid associated with acquired hemophilia A: A case report

BACKGROUND Acquired hemophilia A (AHA) is a rare and potentially severe bleeding disordercaused by circulating autoantibodies against factor Ⅷ (FⅧ). In approximately50% of the patients, the condition is associated with autoimmune diseases,cancers, medication use, pregnancy, and the post-partum period. Bullous pemphigoid(BP) is a chronic autoimmune subepidermal blistering disease associatedwith tissue-bound and circulating autoantibodies against BP antigens 180 (BP180)and 230 (BP230). AHA-associated BP has a high mortality rate;hence, the understandingof this disease must improve.CASE SUMMARY A 69-year-old man presented with erythema, blisters, blood blisters, and crustsaccompanied by severe pruritus for more than 20 days, and ecchymosis andswelling on his left upper arm for 3 days. Pathological examination revealed asubepidermal blister that contained eosinophils. Laboratory tests showed that theBP180 autoantibody levels had increased, isolated activated partial thromboplastintime was notably prolonged (115.6 s), and coagulation FⅧ activity wasextremely low (< 1.0%). Furthermore, the FⅧ inhibitor titer had greatlyincreased (59.2 Bethesda units). Therefore, the patient was diagnosed as having BP associated with AHA, prescribed 0.05% topical halometasone cream, and transferred to a higher-level hospitalfor effective treatment;however, he died after 2 days.CONCLUSION AHA associated BP is rare, dangerous, and has a high mortality rate. Therefore, its timely diagnosis and effectivetreatment are necessary.

Topical use of ozone effectively alleviates the acute symptoms and quality of life of patients with moderate to severe bullous pemphigoid: a randomized controlled trial

Objective:To evaluate the adjuvant treatment of acute stage symptoms and quality of life of patients with bullous pemphigoid(BP)with ozone.Methods:We included 74 patients with moderate and severe BP hospitalized from July 2018 to December 2020.The participants were randomly divided into the control group and the ozone group,with 37 patients in each group(n=37).The control group used tap water to wash the whole body,and mupirocin ointment was used for the erosions.The ozone group used ozone water to wash the whole body,and the erosion place was coated with ozone oil.The bullous pemphigoid disease area index(BPDAI)score of BP disease was used to observe the clinical symptoms and skin lesions of the two groups before and on day 3,7,and 14 after treatment.Pruritus and sleep were observed before and on day 3,7,and 14 after treatment.The Dermatology Life Quality Index(DLQI)was used to observe the quality of life before and after treatment and the adverse reactions were recorded.Results:The total BPDAI score and erythema score in the ozone group were significantly different from those in the control group on day 3,7,and 14 after treatment(P<0.050).The scab drying time and erosion drying time of ozone group were shorter than that of control group(P<0.001).There were statistically significant differences between the ozone group and the control group in pruritus score and sleep score on day 3,7,and 14 after treatment(P<0.001).There was statistically significant difference in skin disease quality of life between the two groups 14 days after treatment(P<0.001).No significant adverse reactions and complications were observed in both groups.Conclusions:Ozone external use can rapidly improve the acute stage of edema erythema,erosion,and itching of BP,improve the quality of life of patients,is an effective treatment method,and wor thy of clinical promotion.

Expression of MMP-2 and MMP-13 in Bullous Pemphigoid

Objective:To investigate the expression and significance of matrix metalloproteinase-2(MMP-2)and matrix metalloproteinase-13(MMP-13)in bullous pemphigoid(BP)skin lesions.Methods:Immunohistochemical SP method was used to detect the expression of MMP-2 and MMP-13 in 32 BP skin lesions,and compared with 15 normal skin tissues.Results:The expression of MMP-2 in the case group was significantly increased(38.56±10.06)compared to the normal control group(21.20±5.98);the expression of MMP-13 in the case group was significantly augmented(18.62±5.90)compared to the normal control group(11.47±8.484).The expressions of MMP-2 and MMP-13 in the skin lesions of patients with bullous pemphigoid were statistically different from those of normal people(both P<0.05).Compared with the expression of MMP-2 and MMP-13 in bullous pemphigoid,the expression of MMP-2 and MMP-13 was moderately correlated(correlation coefficient was 0.523).Conclusion:The expression of MMP-2 and MMP-13 is significantly increased in bullous pemphigoid skin lesions,suggesting that they may play an important role in the pathogenesis of BP.There is a certain correlation between the expression of MMP-2 and MMP-13,suggesting that the high expression of MMP-13 may play a role in the mechanism that further leads to the high expression of MMP-2.

Rare bullous pemphigoid during PD-1 inhibitor therapy:a case report

Immunotherapy is an important treatment modality in cancer,but it can also cause adverse reactions,with skin toxicity being the most common.The increasing number of immune checkpoint inhibitors being used in the clinic will inevitably cause an increase in the rate of adverse skin reactions that markedly affect the patient's quality of life.A 58-year-old patient with intrahepatic cholangiocareinoma developed bullous pemphigoid(BP)nearly a year after using immune checkpoint inhibitors,which is different from what has been reported inthe literature within two weeks of treatment.Pathologically,the skin biopsy diagnosis was epidermal hyperplasia and focal sub-epidermal pustule formation,consistent with drug-induced dermatitis.The patient was treated with methylprednisolone,minocyeline,colchicine,nicotinamide,triamcinolone,and traditional Chinese medicine decoction.No new blisters developed after 1 week of treatment.The medication was gradually discontinued,and BP did not recur.Clinicians should carefully consider the risk-benefit ratio when using PD-1 inhibitors,particularly concerning rash severity.Further studies are needed to investigate the relationship between adverse skin reactions and drug efficacy.

Ocular cicatricial pemphigoid:diagnosis and systemic management

Ocular cicatricial pemphigoid(OCP)is a subcategory of mucous membrane pemphigoid(MMP)where the conjunctiva is the main site of inflammation.It is a chronic and autoimmune disease characterized by acute and chronic conjunctivitis that can progress to severe conjunctival cicatrization,corneal opacification,ocular surface keratinization,and eyelid abnormalities.OCP can lead to structural damage that can result in visual impairment,visual loss,and blindness,and can have a significant impact in a patient’s quality of life.Patients may manifest with varying symptoms,degrees of severity and may have different rates of progression.Early diagnosis and appropriate systemic immunosuppression are of utmost importance for prompt and adequate disease control.Various systemic immunomodulatory therapies(IMTs),including anti-metabolites,alkylating,and biologic agents have been utilized to achieve inflammation control and remission.Careful monitoring of disease progression is important to assess response and to modify and escalate therapy if needed.Treatment to alleviate symptoms of dry eye disease and address trichiasis and other eyelid abnormalities is recommended as well.A multidisciplinary approach to optimize clinical care is recommended in the management of patients with OCP.This review will address the immunopathogenesis,clinical features,keys to diagnosis and staging of patients with OCP.It will highlight the current immunomodulators utilized for disease management and proposed stepladder strategies.This review will discuss the updated roles of combination therapy,novel use of biologics as well as the recent use of adrenocorticotropic hormone(ACTH)analog in severe recalcitrant cases.

Preliminary Application of High-Frequency Ultrasound in the Differentiation of Pemphigus and Bullous Pemphigoid:An Observational Study

Objective:Ultrasonography is a diagnostic imaging technique used to visualize subcutaneous body structures for identification of possible pathologies.In this study,we aimed to explore the clinical significance of high-frequency ultrasound in differentiating the location of blisters between pemphigus and bullous pemphigoid.Methods:Eighteen patients were recruited in Department of Dermatology,Zhongda Hospital from 2020 to 2021 and divided into a pemphigus group(n=8)and a bullous pemphigoid group(n=10)according to the diagnostic criteria for each.Ultrasonographic images were collected using a 50-MHz high-frequency ultrasound system.The indexes of ultrasonic evaluation were the layer(epidermis or dermis),size,shape,internal echo,and boundary of the blister.Categorical variables are expressed as n(%),and differences were compared using Fisher’s exact test.Results:The ultrasonographic images in the pemphigus group showed an intraepidermal semi-arc or irregular anechoic or hypoechoic areas.The inferior borders were situated above the characteristic thin linear hyperechoic bands of the epidermis.A linear hypoechoic band was present at the dermoepidermal junction in some cases.In the ultrasonographic images of the bullous pemphigoid group,the linear hyperechoic bands of the epidermis were continuous and intact.An oval fluid anechoic area(subepidermal blister)was present immediately below the bands.The location of the blisters in the ultrasonographic images was significantly different between the 2 groups(P<0.001).Conclusion:High-frequency ultrasound can be used as an auxiliary means to differentiate the location of blisters between pemphigus and bullous pemphigoid.

Airway management of a patient with linear immunoglobulin A bullous dermatosis:A case report

BACKGROUND There is limited literature on managing the airway of patients with linear immunoglobulin A(IgA)bullous dermatosis,a rare mucocutaneous disorder that leads to the development of friable bullae.Careful clinical decision making is necessary when there is a risk of bleeding into the airway,and a multidisciplinary team approach may lead to decreased patient morbidity during these high-risk scenarios,especially when confronted with an unusual cause for bleeding.CASE SUMMARY A 45-year-old African American female presented to our ambulatory surgical center for right corneal transplantation due to corneal perforation after blunt trauma in the setting of cicatricial conjunctivitis and diffuse corneal neovascularization from linear IgA bullous dermatosis.The diagnosis of IgA dermatosis was recent,and the patient had been lost to follow-up.The severity of the disease and extent of airway involvement was unknown at the time of the surgery.Significant airway bleeding was noticed upon intubation and the otorhinolaryngology team had to be called to the operating room.The patient required transfer to the intensive care unit where a multidisciplinary team was involved in her case.The patient was extubated on postoperative day 4.CONCLUSION A multidisciplinary approach to treating this disease is the best course of action before a surgical procedure.In our case,key communication between the surgery,anesthesia,and dermatology teams led to the quick and safe treatment of our patient’s disease.Ambulatory surgery should not be considered for these cases unless they are in full remission and there is no mucous membrane involvement.

Bilateral malignant glaucoma with bullous keratopathy:A case report

BACKGROUND Malignant glaucoma,caused by aqueous misdirection,is a challenging postsurgical complication presented with normal/high intraocular pressure and shallowing of the central and peripheral anterior chambers.Its incidence is about 0.6%-4.0%.It can be secondary to filtering surgeries,laser iridotomy,and cataract surgery.Short axial length and a history of angle closure glaucoma are its main risk factors.Here,we report a bilateral malignant glaucoma with bullous keratopathy in the patient’s left eye.CASE SUMMARY We present a case of bilateral malignant glaucoma.The cause of malignant glaucoma for each eye of this patient was different.Hence,the management strategy and selection of surgical methods were also different.However,the normal anterior chamber was ultimately maintained,and maximum visual function was preserved.Even though the left eye received multiple surgeries and corneal endothelial decompensation occurred,the formation of a retroendothelial fibrous membrane partially compensated for the function of the corneal endothelium.CONCLUSION The formation of a retroendothelial fibrous membrane partially compensated for the function of the corneal endothelium.

Pseudopemphigoid as caused by topical drugs and pemphigus disease

Pseudopemphigoid can cause a chronic cicatricial conjunctivitis that is clinically identical to the manifestations seen in mucous membrane pemphigoid, a disorder with a common clinical phenotype and multiple autoimmune links. For the purpose of this review, we will describe pseudopemphigoid as caused by topical drugs, the most common etiology with ocular manifestations, and as caused by the pemphigus disease, a more rare etiology. Specifically, we will discuss the ophthalmological features of drug-induced cicatricial conjunctivitis, pemphigus vulgaris, and paraneoplastic pemphigus. Other etiologies of pseudopemphigoid exist that will not be described in this review including autoimmune or inflammatory conditions such as lichen planus, sarcoidosis, granulomatosis with polyangiitis(Wegener's granulomatosis), erythema multiforme(minor, major, and Stevens-Johnson syndrome), bullous pemphigoid, skin-dominated linear IgA bullous dermatosis, and skin-dominated epidermolysis bullosa acquisita. Prompt diagnosis of the underlying etiology in pseudopemphigoid is paramount to the patient's outcome as certain diseases are associated with a more severe clinical course, increased ocular involvement, and differential response to treatment. A completehistory and ocular examination may find early cicatricial changes in the conjunctiva that are important to note and evaluate to avoid progression to more severe disease manifestations. When such cicatricial changes are noted, proper diagnostic techniques are needed to help elucidate a diagnosis. Lastly, collaboration between ophthalmologists and subspecialists such as dermatologists, pathologists, immunologists, and others involved in the care of the patient is needed to ensure optimal management of disease.

Nivolumab-induced severe bullous pemphigoid in a patient with renal cancer:a case report and literature review

With the widespread use of immunotherapy in numerous solid tumours,immunotherapy-related adverse events(irAEs)have started to emerge and bring new challenges for clinicians to manage.Among established irAEs,dermatologic toxicity is one of the most common toxicities;it is often mild but can be severe and potentially life-threatening,such as bullous pemphigoid.Here,we report a case of nivolumab-mediated severe,extensive,refractory bullous pemphigoid involving both skin and oral mucosa in a patient with metastatic renal cancer.We also summarise a list of selected case reports of immunotherapy-induced bullous pemphigoid by literature review.We highlight various presentations,investigations and managements of this type of skin irAEs.Meantime,we would like to discuss the correlation of skin irAEs incidence rate with immunotherapy drug benefit and resistance.

Esophagitis dissecans superficialis and autoimmune bullous dermatoses: A review

Esophagitis dissecans superficialis(EDS)is a rare and severe endoscopic finding characterized by sloughing of large fragments of esophageal mucosal lining.Although EDS has been reported in association with serious illnesses and certain medications,the pathophysiological association of autoimmune bullous dermatoses with EDS has gained remarkable attention.Among these dermatoses,pemphigus vulgaris and pemphigoid frequently present with various types of esophageal involvement including EDS.We review the pathophysiology and clinical features of this involvement with the presentation of our experiences.The importance of endoscopic evaluation of this entity is discussed.

Clinical features and in vivo confocal microscopy assessment in 12 patients with ocular cicatricial pemphigoid

AIM： To describe the clinical features and microstructural characteristics assessed by in vivo confocal microscopy（IVCM） in patients with ocular cicatricial pemphigoid（OCP）.· METHODS： A descriptive, uncontrolled case series study. Patients diagnosed with OCP were examined by clinical history, slit-lamp biomicroscopy features and IVCM images. The results of direct immunofluorescence（DIF） biopsies and indirect immunofluorescence（IIF） were also recorded. Local and systemic immunosuppressive therapy were administered and adjusted according to response.·RESULTS： A total of 12 consecutive OCP patients（7male, 5 female; mean age 60.42 ±10.39y） were recruited.All patients exhibited bilateral progressive conjunctival scarring and recurrent chronic conjunctivitis was the most frequent clinical pattern. The mean duration of symptoms prior to diagnosis of OCP was 2.95 ±2.85y（range： 5mo to 10y）. The Foster classification varied from stage I to IV and 20 eyes（83%） were within or greater than Foster stage Ⅲ on presentation. Two of the 12patients（17%） demonstrated positive DIF; 3 of the 12（25%） patients reported positive IIF. The mean duration of the follow-up period was 20.17 ±11.88mo（range： 6 to48mo）. IVCM showed variable degrees of abnormality in the conjuctiva-cornea and conjuctival scarring was detected in all the involved eyes. Corneal stromal cell activation and dendritic cell infiltration presented asocular surface inflammation, ocular surface keratinization along with the destroyed Vogt palisades was noted in eyes with potential limbal stem cell deficiency. After treatment, remission of ocular surface inflammation was achieved in all the patients, 18 eyes（75%） remained stable, 6 eyes（25%） had recurrent conjunctivitis and cicatrization in 2 eyes（8%） was progressing.· CONCLUSION： As an autoimmune disease, OCP manifests as variable degrees of clinical and laboratory abnormalities with both local and systemic immunosuppressive treatment playing important roles in disease therapy. IVCM can be as a valuable non-invasive technique to assess ocular surface changes in a cellular level with a potential value for providing diagnostic evidence and monitoring therapeutic effects during follow-up.

Recent advancement on autoantigens, autoantibodies and inflammatory cells in subepidermal autoimmune bullous diseases

Subepidermal autoimmune bullous diseases （SABD） are some autoimmune skin diseases that can present in a variety of forms and can be a challenging disease to treat. An overview of the different forms of SABD are discussed including bullous pemphigoid （BP）, epidermolysis bullosa acquisita （EBA）, cicatricial pemphigoid （CP）, bullous systemic lupus erythematosus （BSLE）, and Anti-p200 pemphigoid. Emphasis on recent advancement is presented. In recent years, improved knowledge of the mechanisms of intercellular and cell-matrix adhesion has led to better understanding of the blistering process in some SABD. Defects of such structures cause the subepidermal bullous diseases and have also led to the discovery of new diseases （e.g. anti-p200-pemphigoid）. Recent studies have outlined the important role of autoantibodies, mast cell lymphocytes and their cytokines in pathogenesis of SABD.

Identification of human herpesvirus-8 in Kaposi＆#39;s sarcoma with bullous pemphigoid

Kaposi＆#39;s sarcoma （KS） is a rare,malignant vascular.tumor of the skin,mucosa,and viscera with an increased incidence in human immunodeficiency virus （HIV）-positive patients.According to the clinical characteristics and the affected population,four clinical types of KS have been described successively：classic,endemic to Africa,acquired immunodeficiency syndrome （AIDS）-associated,and immunosuppression associated type.Bullous pemphigoid （BP） is an acquired autoimmune bullous skin disease that frequently occurs in the elderly and is characterized by intraepidermal blisters and immunoglobulin G （IgG） deposits on the basement membrane.A few cases of KS have occurred in immunosuppressed patients with BP.Here,we report a Chinese female patient diagnosed with immunosuppression associated KS that was induced by the short-term use of immunosuppressive agents for BP.We also present a review of the literature on immunosuppressed KS with BP and discuss the potential role of human herpesvirus-8 （HHV-8） in the pathogenic mechanism.

Cicatricial Pemphigoid in Accompany with Rheumatoid Arthritis:a Case Report

CICATRICIAL pemphigoid （CP, also known as benign mucous membrane pemphigoid） is a rare chronic autoimmune subepithelial blister- ing disease, with an incidence of 1 per million,characterized by erosive lesions of mucous membranes and skin that result in scarring. Rheumatoid arthritis （RA） is a symmetric inflammatory arthritis that mainly affects the small joints of hands and feet, with a prevalence of 0.3% in China.3 In this case report we described the diagnosis of and treatment for a patient developing CP 18 years after the onset of RA, a combination rarely encountered or reported so far.

Appearance of prominent milia as secondary lesions during recovery of refractory bullous pemphigoid:a case report

Introduction Bullous pemphigoid (BP) is an autoimmune blistering disease that affects patients of advanced age. BP is characterized clinically by tense bullae on the extremities and trunk, histopathologically by subepi-dermal blisters with eosinophilic infiltration, and immunologically by autoantibodies to BP180 and BP230. Direct immunofluorescence of perilesional skin shows depositions of IgG and C3 in the basement membrane zone(1)BP rarely shows prominent milia formation, which is a hallmark of epidermolysis bullosa acquisita. We herein describe a 53-year-old man with refractory BP showing numerous milia during recovery.