Subepidermal Blister Research Articles

183 Dystrophic epidermolysis bullosa pruriginosa: a new case series of a rare phenotype unveils skewed Th2 immunity

Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of hereditary epidermolysis bullosa, with a poorly understood pathogenesis and no satisfactory treatment. Our objective was to assess the clinical, biological features and genetic basis, to better characterize this rare genodermatosis. We conducted a retrospective study, reviewing the clinical presentation, genetic diagnosis, biological analyses and management of patients with DEB-Pr seen between 2010 and 2020. Seven patients were included, average age of 50.1 years. Pruriginous lichenified papules or nodules appeared at 27.6 years on average on pretibial areas and forearms, associated with milia and toenails dystrophy. All patients received multiple therapies but none could sustainably reduce pruritus. Immunohistopathological analysis of lesion skin revealed subepidermal blister with fibrosis, milia and mast cell infiltration. Serum TNFα, IL1β and IL6 levels were elevated in 2/6 patients. Total serum IgE levels were increased in 7/7 patients. Immunophenotyping of circulating T-cells revealed an increased Th2 subset in 4/4 patients, with reduced Th1 and Th17 subpopulations. Genetic analysis of COL7A1 identified 8 distinct causative mutations, 6 of which were new. Intra-familial clinical variability was documented in 5/7 patients and was associated with the co-inheritance of a recessive COL7A1 mutation or an FLG2 mutation in 2 families. Our study confirms the stereotyped presentation of DEB-Pr with large intra-familial variability in disease expression. Mast cell infiltration, elevated IgE and increased Th2 subset without atopy strongly support a role of Th2-mediated immunity in DEB-Pr, and further argue for new targeted therapeutic options such as dupilumab.

S2631 Porphyria Cutanea Tarda, Type 2, in a Man With a Novel UROD Mutation

Introduction: Porphyria cutanea tarda (PCT) is usually caused by acquired defects in uroporphyrinogen decarboxylase (UROD) activity in the liver. 20% of cases occur in patients who have a genetically determined partial decrease in UROD activity. We describe a case of a man with a novel UROD mutation causing PCT type 2. Case Description/Methods: A 77-year-old man was evaluated for 6 months of painful blistering over his dorsal hands, forearms and head [Fig 1a]. His medical history was notable for hypertension, melanoma, and stroke. He reported heavy alcohol and tobacco use. He had no family history of porphyria. He worked for years at a manufacturing facility, with exposure to various industrial chemicals. More recently, he had exposure to weed killers, carburetor cleaners, and wood varnish. Exam revealed tense bullae with milia and hyperpigmented macules on dorsal hands and forearms. Biopsies revealed a subepidermal blister containing a small number of neutrophils with fibrin and evidence of festooning of the vessels consistent with porphyria. Labs revealed AST 63 U/L, ALT 64 U/L, alkaline phosphatase 54 U/L, and total bilirubin 0.8 mg/dL. Iron profile was unremarkable, and antibodies against HIV and hepatitis A, B and C were negative. Total plasma porphyrins were elevated to 13.4 mcg/dL. Fractionated urine, stool and plasma porphyrin levels were obtained [Table 1]. Urinary uro- and hepta-carboxyl porphyrins were markedly elevated, consistent with PCT. The patient was advised to start hydroxychloroquine 100 mg 3 times weekly and to avoid alcohol, tobacco use and sun exposure. Genetic testing revealed a novel mutation of UROD gene (c.224 G >C; p. Arg 75 Pro) with red blood cell UROD activity decreased by 50%. He returned to clinic 3 and 7 months after the index visit. He had stopped alcohol use, but continued smoking cigarettes. His hands were improved [Fig 1b]. Repeat urinary porphyrins showed improvement [Table 1]. The mutation in UROD is predicted to have a major effect on protein structure and function [Fig 1c]. Discussion: Inherited partial deficiency in UROD is not sufficient to cause clinically manifest PCT. Other factors that increase oxidative stress are also required. This patient has a mutation in the UROD gene not heretofore described in PCT type 2, but that we show markedly affects the structure and activity of the protein product. Nonetheless, the patient did not develop clinically manifest PCT until age 77, emphasizing the importance of acquired factors in disease pathogenesis.Figure 1.: A. Dorsal right hand at presentation B. Dorsal right hand at 7 month follow-up C. Structure of URO-D showing the substrate (yellow) in the active site located at the C-terminal end of the beta-sheets (magenta) that form the core of the TIM-barrel structure. The location of arginine 75 (Arg 75) is shown in green. Arg 75 is the penultimate residue in one of the eight corresponding alpha-helices that surround the central core. Arg 75 forms two hydrogen bonds with glutamic acid 45 (Glu 45) of the preceding helix in the structure. This hydrogen bonding network supports the overall tertiary fold of the protein in this otherwise solvent-exposed region of the protein. The UROD mutation of the patient (Arg 75 Pro) disrupts the helix with premature termination and more importantly eliminates the hydrogen bonding network.Table 1-A.: Results of Selected Laboratory Studies.Table 1-B.: Results of Selected Laboratory Studies.

The Frequency and Causes of Subepidermal Gaps or Blisters and the Compliance Rate Between Clinical Diagnosis and Pathology Reports from 2015 to 2019

Background: Skin diseases are the fourth most common cause of human illness, and blisters with different clinical manifestations make a diagnostic challenge. Objectives: This study aimed to evaluate the frequency and causes of subepidermal gaps or blisters, as well as the compliance rate between the initial and final clinical diagnoses based on pathology reports. Methods: In this cross-sectional study, pathology reports of subepidermal blisters or gaps were evaluated in the patients referred to the Razi Laboratory of Rasht from 2015 to 2019. The samples were examined by a pathologist after hematoxylin and eosin staining. The reports included demographic information, clinical differential diagnoses, final diagnosis, direct immunofluorescence findings, and salt split results. Finally, the compliance rate of clinical diagnosis with pathology reports was determined. Results: A total of 183 pathology reports were evaluated, 170 of which contained the final diagnosis. Females were more frequently affected by the disease, and pemphigoid bolus and lichen planus were the most prevalent final diagnoses. The compliance rate between the initial and final diagnoses was 94%. About 37.2% of the reports lacked direct immunofluorescence (DIF) and salt split, and only 42.6% of the samples had undergone DIF examination, while 20.2% had both DIF and salt split. There was no significant association between the compliance rate of the final diagnosis with age, sex, and undergoing diagnostic tests. Conclusions: A high incidence of subepidermal gaps or blisters was seen in middle-aged individuals and females. The compliance rate of the initial clinical diagnosis with the final diagnosis based on pathological reports was high. Our findings emphasize the importance of histopathological examination and the complementary role of direct immunofluorescence and salt split in diagnosis.

Bullous Pemphigoid- A Rare Case report

Introduction: The most severe autoimmune subepidermal blistering condition of the skin and mucous membranes is bullous pemphigoid (BP). In Europe, it is estimated to affect 1 in every 4,000 people. Currently incidence range between 2-22/1,000,000 worldwide. It primarily affects the elderly and is diagnosed using clinical, histologic, and immunologic criteria. Clinically, it appears as diffuse eczematous, pruritic, urticaria-like lesions with the later emergence of tense bullae or blistering lesions filled with clear fluid.
 Case Presentation: Here, we report a case of a 50- years old female patient with a complaint of itchy lesions with wounds all over the body present with an 8-month of history. A subepidermal blister with eosinophils and neutrophils infiltration was discovered on histopathological evaluation. Salt-split indirect immunofluorescence revealed linear deposition of IgG at the dermo-epidermal junction. On further investigation, using diagnostic and Interventional aids a final diagnosis of Bullous pemphigoid.

Bullous eruption as a cutaneous manifestation of eosinophilic granulomatosis with polyangiitis

AbstractCutaneous manifestations are variable in patients with eosinophilic granulomatosis with polyangiitis (EGPA). We report a case where bullous eruption was a presenting manifestation of EGPA. A 55‐year‐old Chinese man with a background of adult‐onset asthma and chronic sinusitis was admitted for a 3‐week history of lower limb weakness and a large bulla on his right calf with surrounding erythema. Skin biopsy showed a subepidermal blister with significant dermal eosinophilia, without vasculitis. The patient was diagnosed with EGPA with systemic involvement on the basis of a thorough medical history, eosinophilia, cardiac magnetic resonance imaging showing acute myocarditis, and nerve biopsy with eosinophilic vasculitic neuropathy. He responded well to corticosteroids and rituximab. Nonvasculitic bullous eruptions are rarely described as manifestations of EGPA. Prompt recognition of this entity is crucial for its early diagnosis.

26685 Transient bullous dermolysis of the newborn: An extremely rare entity presenting in two brothers

A five-day-old male infant presented with an erosion on his foot followed by further erosions and blisters of the tongue several weeks later. The patient’s older brother had a similar, but more severe presentation at birth with numerous bullae and erosions on the head, ears, back, and thumb. Their mother denied a family history of blistering disorders. The lesions resolved within one year of age with residual scarring and hyperpigmentation. Punch biopsy of lesional skin from the left foot revealed a cell-poor subepidermal blister.

State-of-the-art review of human autoimmune blistering diseases (AIBD).

Autoimmune blistering diseases (AIBDs) are a heterogenous group of skin conditions, broadly classified into two categories depending on the location of blister formation: intraepidermal blistering in the pemphigus group and subepidermal blistering in the pemphigoid group. Although AIBDs occur in both humans and animals, the arsenal of data for human AIBDs far exceeds those of their animal counterpart. Therefore, the main purpose of this review is to highlight existing knowledge, and recent advances in the diagnosis and management of AIBDs in humans - to serve as a road map for veterinary dermatologists. AREAS COVERED: Recent findings include complement-independent pathways in the pathogenesis of bullous pemphigoid, as well as the role of desmoglein and desmocollin autoantibodies in inducing acantholysis. Systemic glucocorticoids are the mainstay of treatment for AIBDs in humans, yet their long-term use is associated with severe adverse effects and complications, thereby limiting their use. Therefore, researchers have been exploring new and safer alternative therapeutic options for human AIBDs such as anti-CD20 monoclonal antibodies (Rituximab), Bruton's tyrosine kinase inhibitors (BTKi) and neonatal Fc receptor (FcRn) blockers. EXPERT OPINION: Randomised controlled trial (RCT) level evidence show that Rituximab and short-course GC regimes are more effective and safer than traditional GC treatment for human AIBDs. FcRn blockers such as SYNT001 have shown positive results in preliminary phase 2 clinical trials for treatment of human pemphigus; further trials are required. Rilzabrutinib (PRN1008), an orally administered BTKi, has recently completed phase 2 trials in pemphigus and is in a phase 3 RCT in humans.

Extension of separation along the follicular epithelium and follicular basement membrane in pemphigus and bullous pemphigoid.

The outer root sheath of hair follicle and the interfollicular epidermis are continuous and basically similar in many aspects. The expression of various basement membrane (BM) components in the upper portion of the hair follicle is similar to that of the interfollicular BM. The extension of acantholysis into the adnexal structures was highlighted in the pemphigus group of diseases. On the other hand, extension of separation down the hair follicle BM has not been studied in subepidermal autoimmune bullous dermatoses. The aim of the present work was to study the extension of separation along follicular epithelium and follicular BM in pemphigus and bullous pemphigoid. This retrospective study was conducted on pemphigus and bullous pemphigoid cases. For each case, 4-μm-thick sections stained with hematoxylin and eosin were examined for the presence of hair follicles and the extension of separation down follicular epithelium and follicular BM. Positive extension of acantholysis down the follicular epithelium was seen in 23/27 (85.2%) of pemphigus vulgaris (PV) and 7/9 (77.8%) of pemphigus foliaceus (PF) cases with hair follicles. Follicular extension was limited to the infundibulum in PF but down the entire follicular length in PV. As for bullous pemphigoid (BP) cases, 20/26 cases (76.9%) that had hair follicles showed positive extension of the separation down the follicular BM. The cellular infiltrate detected was identical in its nature and density to that of subepidermal blister in all cases. Extension of the separation along follicular epithelium and follicular basement membrane was observed in PV, PF, and BP without significant difference.

Porphyria Cutanea Tarda

A 44-year-old man with human immunodeficiency virus infection, untreated hepatitis C virus infection, and active alcohol abuse presented with bilateral blistering on the dorsal hands of 2 months’ duration (Figure 1). The blisters were pruritic and photoexacerbated and resolved spontaneously with scarring. Examination revealed tense bullae limited to the dorsal hands in various stages of healing, including milia and scarring. Biopsy specimens for histopathologic evaluation and direct immunofluorescence revealed pauci-inflammatory subepidermal clefting and homogeneous deposition along the basement membrane and within walls of superficial dermal vessels with multiple conjugates, consistent with porphyria cutanea tarda (PCT; Figure 2). The patient’s baseline ferritin concentration was found to be higher than 800 ng/dL (to convert to pmol/L, multiply by 0.02247). Serum porphyrins demonstrated increased total porphyrins; fractionation showed increased uroporphyrin, confirming PCT.Figure 2A pauci-inflammatory subepidermal blister on histopathologic examination (hematoxylin and eosin, magnification ×200).View Large Image Figure ViewerDownload Hi-res image Download (PPT) PCT, the most common type of porphyria, is caused by inhibition of hepatic uroporphyrinogen decarboxylase (UROD). Pathogenesis involves cutaneous phototoxicity due to deposition of alternative metabolic products from excess hepatic porphyrinogen accumulation. Approximately 20% of cases are associated with familial UROD mutations,1Badenas C. To-Figueras J. Phillips J.D. Warby C.A. Muñoz C. Herrero C. Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives.Clin Genet. 2009; 75: 346-353Crossref PubMed Scopus (28) Google Scholar,2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar whereas 80% of patients present with acquired PCT with absence of UROD mutations. These patients often have liver damage, frequently from alcohol, hepatitis C, human immunodeficiency virus infection, or hemochromatosis.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar, 3Jalil S. Grady J.J. Lee C. Anderson K.E. Associations among behavior-related susceptibility factors in porphyria cutanea tarda.Clin Gastroenterol Hepatol. 2010; 8 (302.e1): 297-302Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar, 4Gisbert J.P. Garcia-Buey L. Pajares J.M. Moreno-Otero R. Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis.J Hepatol. 2003; 39: 620-627Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar, 5Ellervik C. Birgens H. Tybjærg-Hansen A. Nordestgaard B.G. Hemochromatosis genotypes and risk of 31 disease endpoints: meta-analyses including 66,000 cases and 226,000 controls.Hepatology. 2007; 46: 1071-1080Crossref PubMed Scopus (113) Google Scholar Typical presenting features include bullae and dyspigmentation of sun-exposed areas. First-line treatment is therapeutic phlebotomy of 450 mL every 2 weeks until ferritin concentration is less than 20 to 25 ng/dL.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar Additional management recommendations include broad-spectrum sun protection, alcohol cessation, and hepatitis C treatment. Hydroxychloroquine can be used when phlebotomy is contraindicated.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar Although PCT is readily treated and nonfatal, relapses may follow successful treatment.2Singal A.K. Porphyria cutanea tarda: recent update.Mol Genet Metab. 2019; 128: 271-281Crossref PubMed Scopus (17) Google Scholar Thank you to Dr Scott Tuttle for his contributions to this report.

Bullous Pemphigoid in Children: Clinical Presentation, Pathology and Management

Bullous pemphigoid rarely presents in childhood age group and when it presents it has two age peaks infantile and childhood forms. Key presenting features of childhood BP include subepidermal blistering, eosinophilia and severe itching.The histological features of bullous pemphigoid are the same as those described in adulthood and vary with the age of the lesion.Childhood BP tends to have a generally good prognosis with appropriate therapy Keywords: Bullous Pemphigoid; Autoimmune Disorders; Blistering Diseases

Assessing the Outcomes of Focused Heating of the Skin by a Long-Pulsed 1064 nm Laser with an Integrated Scanner, Infrared Thermal Guidance, and Optical Coherence Tomography.

The skin on the forearm and back of two consenting volunteers was marked and anesthetized with lidocaine with epinephrine. The parameters of a scanner-equipped LP 1064 nm Nd:YAG laser were adjusted to achieve an epidermal/superficial dermal heating of between 50°C and 60°C over a specified time course. Experimental single treatments examined various adjusted parameters including, fluence, pulse overlap, pulse duration, scan size, and pulse rate. A FLIR camera was used to record skin temperature. Outcome measures included skin temperature, post-treatment appearance, and OCT assessment of skin and vascular damage. The clinical response of each treatment was followed daily for 4 weeks. Optimal protocols initially raised the skin temperature to between 55°C and 60°C, which was carefully maintained using subsequent laser passes over a 60-second time course. Immediately post laser, clinical responses included erythema, edema, and blistering. Immediate OCT revealed increased vascularity with intact, dilated blood vessels. Prolonged exposure above 60°C resulted in sub-epidermal blistering and an absence of blood flow in the treatment area with prolonged healing. The LP 1064 nm laser can be used to achieve heat-related tissue injury, though the narrow parameters necessary for the desired endpoint require the assistance of IR thermal regulation to avoid unacceptable outcomes. The use of the laser scanner ensures precise energy delivery over a defined treatment area. Future studies might explore this as a selective hyperthermic method for the treatment of non-melanoma skin cancer. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Granzyme B inhibition reduces disease severity in autoimmune blistering diseases

Pemphigoid diseases refer to a group of severe autoimmune skin blistering diseases characterized by subepidermal blistering and loss of dermal-epidermal adhesion induced by autoantibody and immune cell infiltrate at the dermal-epidermal junction and upper dermis. Here, we explore the role of the immune cell-secreted serine protease, granzyme B, in pemphigoid disease pathogenesis using three independent murine models. In all models, granzyme B knockout or topical pharmacological inhibition significantly reduces total blistering area compared to controls. In vivo and in vitro studies show that granzyme B contributes to blistering by degrading key anchoring proteins in the dermal-epidermal junction that are necessary for dermal-epidermal adhesion. Further, granzyme B mediates IL-8/macrophage inflammatory protein-2 secretion, lesional neutrophil infiltration, and lesional neutrophil elastase activity. Clinically, granzyme B is elevated and abundant in human pemphigoid disease blister fluids and lesional skin. Collectively, granzyme B is a potential therapeutic target in pemphigoid diseases.

Bullous Pemphigoid in a Dog

Background: In dogs, bullous pemphigoid (BP) is a subepithelial autoimmune disease, a rare dermatopathy in the clinical routine. BP is characterized by formation of vesicles and subepidermal blisters that result from dissolution of the dermal-epithelial junction. Clinical signs of BP usually include severe dermatological alterations with a variable prognosis. The aim of this work is to report a case of BP in a dog to contribute information for diagnosis, and to present clinical and pathological aspects that emerge during development of BP.Case: An adult male mongrel dog exhibited hyperemic, exudative, crusty lesions on the lip commissure and periocular areas. Results from laboratory tests were normal. Results from parasitological and mycological tests on skin scrapings were negative. Imprint cytology of the crusts revealed presence of gram-positive cocci bacteria. In the histopathological analysis of punch biopsy material, the epidermis was detached from the dermis, leading to formation of vesicles. There were inflammatory infiltrates containing neutrophils, eosinophils, and high amounts of fibrin, and areas of multifocal orthokeratotic hyperkeratosis. Multifocal infiltrates containing lymphocytes, histiocytes, and plasma cells were observed on the superficial portions of the dermis, which indicated a diagnosis of BP. After the definitive clinical diagnosis, the animal was treated with enrofloxacin (Baytril Flavour®; 5 mg/kg once a day for 10 days), and prednisolone (Prediderm®; 2 mg/kg once a day until further instructions). On the follow-up visit, 15 days later, the clinical picture had improved, and the lesions had decreased. Continuity of the treatment was prescribed, along with a gradual decrease in the corticoid dose. The dose of prednisolone was initially reduced to 1 mg/kg once a day, and later to 0.5 mg/kg until improvement of the clinical status of the patient. Remission of the lesions was observed 13 weeks later.Discussion: The diagnosis of BP was established after identification of the clinical cutaneous lesions and observation of microscopic findings on punch biopsy material obtained from the ocular and lip regions. BP does not exhibit breed or sex predisposition, and affects adult dogs. The clinical signs of BP are characteristic of autoimmune diseases that affect the dermoepidermal junction, and consist of erythematous, ulcerated, crusty, and painful lesions on the nose, dorsal area of the muzzle, and periorbital region. However, these lesions must be differentiated, by histological analysis, from several other conditions with a similar clinical presentation. Diseases that must be considered in the differential diagnosis comprise other variants of the pemphigus complex, lupus erythematosus, drug eruption, erythema multiforme, toxic epidermal necrolysis, epitheliotropic lymphoma, inherited bullous epidermolysis, mucous membrane pemphigoid, and lymphoreticular neoplasia. The clinicopathological findings indicated that the lesions were compatible with BP. The occurrence of necrotic and erythematous lesions is due to production of antibodies accompanied by a strong response of neutrophils, which results in loss of cell adhesion and epidermal necrosis. The presence of detachment of the epidermis from the dermis, inflammation in the superficial portion of the dermis, and infiltrates containing lymphocytes, histiocytes and plasma cells observed at the histopathological examination indicated the occurrence of BP. The skin histopathological examination warranted establishment of a diagnosis and therapeutic success. The lack of recurrence of clinical manifestations 43 weeks after the end of the glucocorticoid treatment demonstrated that the therapeutic approach and the cooperation of the owner are essential for success of the treatment.

During’s herpetiform dermatitis in pediatric dermatology: issues of diagnostics and treatment

This article presents a case of clinical observation of a 5-year-old child with herpetiformis dermatitis (Duhrings). This rare dermatosis is characterized by a chronic relapsing course, the presence of itching polymorphic rashes, typical histological and immunomorphological signs. The diagnosis was made on the basis of the clinical picture, histological and immunohistochemical studies of skin biopsy, as well as the results of HLA typing by PCR. Clinical observation of this case is of interest to practicing physicians-dermatologists due to the rare occurrence of Duhrings herpetiformis in children, the complexity of differential diagnostic search, which requires further generalization of experience using histological, immunohistochemical and molecular genetic research methods. The disease is clearly differentiated from other rashes with the formation of subepidermal blisters according to histological, immunological and gastrointestinal criteria. The prevalence of dermatosis in various populations of the Europian race ranges from 10 to 39 cases per 100,000 population. Duhrings dermatitis herpetiformis can develop at any age (cases of the childhood form of Dhrings dermatitis herpetiformis have been reported), but most often the disease occurs at the age of 4050 years. Dermatitis herpetiformis persists indefinitely with variable severity. In patients with Duhrings dermatitis, associated gluten-sensitive enteropathy is often noted, which in most cases is asymptomatic.

Childhood bullous systemic lupus erythematosus

Background Bullous systemic lupus erythematosus (BSLE) has rarely been described in pediatric lupus population, and the real prevalence of childhood-onset BSLE has not been reported. BSLE is a rare manifestation of systemic lupus erythematosus and is very rare in children. BSLE affects women more often than men, reflecting the female preponderance in systemic lupus erythematosus. It most often manifests in the second through fourth decades of life, but it has also been reported in children and older adults. Patients and methods Herein, we describe a case of a 10-year-old female patient who presented with a 1-year history of recurrent itchy urticated skin eruption, which was followed 2 months later (after the first year) by a generalized blistering eruption with photosensitivity. Results Histopathologic examination revealed a subepidermal blister and papillary-tip neutrophil microabscesses. Immunofluorescence studies showed linear immunoglobulin G (IgG) and IgC deposition along the BMZ with weaker staining of IgA and IgM. Laboratory tests revealed positive ANA, dsDNA, anti-SM antibodies, elevated erythrocyte sedimentation rate, and proteinuria. Conclusion Although the course of BSLE is often remitting, but not in our case, treatment with dapsone is successful in most cases of BSLE.

Porphyria cutanea tarda induced by alcohol abuse: A case report

Porphyrias are group of inherited and acquired disorders resulting from enzyme deficiency in the metabolic pathway of haem biosynthesis. Among all types of porphyria, the most common type is porphyria cutanea tarda in adults, occurring due to deficiency of enzyme uroporphyrinogen decarboxylase in the metabolic pathway ofm heme biosynthesis. A 35‑year old man presented in opd with chief complaints of recurrent episodes of vesicles, blisters, erosions, raw areas on dorsum of hand and face for 2 years. Local examination revealed multiple erosions with adherent crusting, atrophic plaques of healed lesions over the face and multiple hyperpigmented macules with scaring, erosion and raw areas present overe dorsum of the hands. Laboratory findings showed abnormal liver profile and elevated zinc protoporphyrin and coprophyrin levels. Urine revealed coral pink fluorescence under woods lamp. Histology of the skin showed epidermal spongiosis, subepidermal blister with minimal inflammatory cell infilterate in the dermis. Treatment given were sun screen lotions, hydroxy-chloroquine, avoidance of triggering factors and alcohol discontinuation. Patient showed marked improvement in skin lesions. Keywords: Porphyria, Gunther?s disease, Uroporphyrinogen III synthase deficiency.

Epidermolysis bullosa acquisita as an adverse effect from rituximab therapy

Rationale:Rituximab is a monoclonal antibody directed against B cells and is a first-line agent for the treatment of B cell lymphoma and a second-line agent for the treatment of idiopathic thrombocytopenic purpura (ITP). It has also been used for the treatment of several other autoimmune diseases. Epidermolysis bullosa acquisita (EBA) has never been reported as an adverse effect resulted from rituximab therapy.Patient concerns:A 54-year-old female presented with relapse of the ITP for around eight months. She was treated with rituximab. Intramuscular chlorpheniramine and intravenous methylprednisolone and cimetidine were used as premedication before rituximab infusion. The infusion was initially started at 50 mg/h for 1 h followed by 100 mg/h till the end of infusion. The day after rituximab infusion, the patient noticed pruritic blisters on both arms and chest skin. The next day, the lesions increased in severity and extent.Diagnosis:The skin biopsy established the diagnosis of EBA. H&E staining revealed subepidermal blisters infiltrated by inflammatory cells, including eosinophils and lymphocytes. Direct immunofluorescence (DIF) showed linear deposition of IgG and C3 at the dermoepidermal junction. Indirect immunofluorescence with the patient's serum on salt-split skin revealed exclusive dermal binding of circulating IgG antibasement membrane antibodies at a titer of 1:160.Interventions:She was treated with intravenous methylprednisolone and was continued on oral prednisolone.Outcomes:The lesions regressed. Six weeks later, she had a recurrence of similar lesions but in milder form. This episode subsided in 4 to 5 days with topical steroid application.Lessons:Physicians should consider this diagnosis when a patient develops bullous skin eruptions while undergoing Rituximab therapy.

Brunsting-Perry pemphigoid: A retrospective case series of a frequently unrecognized condition

Brunsting-Perry pemphigoid: A retrospective case series of a frequently unrecognized condition

Autoantibodies to BPAG1e Trigger Experimental Bullous Pemphigoid in Mice

Bullous pemphigoid (BP) is an autoimmune blistering disease that targets the hemidesmosomal proteins BP180 and BP230/BPAG1e. Whereas the role of anti-BP180 antibodies has been extensively characterized, the pathogenicity of anti-BPAG1e antibodies remains unclear. The purpose of this study is to elucidate the role of antibodies to BPAG1e in the experimental bullous pemphigoid models. We generated Bpag1 conditional knockout mice, where the knockout of Bpag1 is restricted to keratin 5-expressing epithelial cells. Bpag1 conditional knockout mice were immunized with the C-terminal portion of BPAG1e, and the splenocytes were injected into Rag2-/- mice intravenously. The recipient mice presented with erosion on the feet and tails. Microscopic examination showed subepidermal blisters and a linear deposition of IgG at the dermal-epidermal junction. To assess the potential role of trauma on BP development, we inflicted surface wounds on the dorsum of the Rag2-/- recipient mice after adoptive transfer. The wounded Rag2-/- mice had increased morbidity and severity of BP-like symptoms. Moreover, the depletion of B cells from splenocytes abolished a subepidermal blistering phenotype invivo. These findings demonstrate that antibodies to BPAG1e might play a pathogenic role in causing subepidermal blistering, and external factors, including trauma, might be a trigger for BP development.

Programmed Death-1 Inhibitors-induced Bullous Pemphigoid in 21 Cases

Objective To investigate the clinical features and treatments of programmed death-1(PD-1)inhibitors-induced bullous pemphigoid(BP).Methods The clinicopathological and immunohistological data of patients with PD-1 inhibitors-induced BP from Peking Union Medical Collage Hospital and reported in the literature were retrospectively analyzed.Results Totally 21 cases(15 males and 6 females)were enrolled.The average age was(70.9±9.7)years(56-86 years).The most common primary malignancies were melanoma(38.10%)and lung cancer(33.33%).The average duration from onset of PD-1 inhibitors treatment to diagnosis of BP was(49.1±23.7)weeks.Typical dermatopathological features were sub-epidermal blisters(76.19%)with infiltration of eosinophils(88.24%).Direct immunofluorescence features were linear deposition of complement C3(95%)and IgG(75%)in the basement membrane zone.Anti-BP180-NC16A antibodies were positive in most cases(84.21%).Patients were mainly treated with systemic corticosteroids,whereas biologics such as rituximab and omazumab were also effective.Conclusions The risk of PD-1 inhibitors-induced BP should be recognized by dermatologists and oncologists.Early diagnosis and timely treatment of BP induced by PD-1 inhibitors are important to improve the prognosis.