Bullous Lesions Research Articles

Direct immunofluorescence in bullous disorders: A mini-review

Background: Immunofluorescence microscopy is an invaluable tool for different lesions in dermatopathology. These lesions include bullous lesions, vasculitis, and connective tissue disorders/systemic lupus erythematosus. In this review, we take a look at bullous disorders. Some of these diagnoses are not possible on routine histopathology alone and require immunofluorescence for confirmation. Different diseases can be diagnosed according to the immunoglobulins/complements, sites of deposition (dermo-epidermal / intercellular spaces / dermal), and their patterns (linear, granular). Knowing the exact type of lesion can help guide treatment accordingly.

Eosinophilic dermatosis of haematologic malignancy treated with ibrutinib: A case report

AbstractEosinophilic dermatosis of haematologic malignancy is an infrequent skin disorder characterised by severe pruritus and skin lesions resembling arthropod bites. It primarily affects individuals with underlying haematological conditions, most commonly chronic lymphocytic leukaemia (CLL). While it does not correlate with a worse prognosis for the haematological disease itself, it significantly impacts patients' quality of life due to the distressing pruritus and recurring nature. Clinical presentation typically shows erythematous papules resembling arthropod bites, with less frequent occurrences of urticarial plaques or bullous lesions. Histologically, an intense and polymorphous inflammatory infiltrate is found both in the superficial and deep dermis, marked by an abundance of eosinophils and the absence of atypical cells. Treatment of this disease remains uncertain, with corticosteroids often being the only effective therapy. Here, we present the case of an 80‐year‐old patient with a history of CLL, who experienced a widespread, itchy eruption of papules and plaques over 2 months. Despite various therapeutic attempts, the lesions only responded to high‐dose corticosteroids. Following the initiation of ibrutinib at a daily dose of 420 mg, both the skin lesions and pruritus resolved within 3 months. Ibrutinib, a tyrosine kinase inhibitor, is approved as a first‐line treatment for CLL. However, its potential as a remedy for refractory eosinophilic dermatosis has not been reported thus far.

Utility of Immunofluorescence in Immune-Mediated Vesiculobullous Lesions of Skin

Bullous lesions may be due to various causes, including bullous pemphigoid, pemphigus vulgaris, linear IgA disease, connective tissue disorders, and other rare vesico-bullous skin diseases. Though histopathology can help narrow down possible diagnoses, direct immunofluorescence is required for a definite diagnosis based on positivity patterns of different immunoglobulins. In this study, 47 cases of clinically suspected immune mediated vesiculo-bullous diseases (IMVBD) were confirmed with histopathology. Females were more commonly affected and the age range was from 10 to 93 years. Among these cases, 23 were diagnosed as pemphigus vulgaris, l6 as bullous pemphigoid, 3 each as pemphigus foliaceus and linear IgA disease. DIF, including testing for c1q, was instrumental for the diagnosis of the disease in order for the patient to get appropriate treatment.

Tense blisters and hemorrhagic bullae as the first manifestation of eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) poses a significant diagnostic challenge due to its varied clinical presentation. Here, we present a case of a 59-year-old female with a history of asthma and sinusitis, who manifested with an extremely rare presentation of drastic tense blisters and hemorrhagic bullae alongside purpuric lesions and peripheral neuropathy. Examinations revealed eosinophilia, positive anti-neutrophil cytoplasmic antibody, and characteristic pathological findings with small vessel vasculitis in the purpura. Treatment with glucocorticoids and cyclophosphamide led to rapid improvement in peripheral eosinophilia, skin manifestations and motor neuron deficits. Although rare, our case underscores that bullous skin lesions should be recognized as a potential cutaneous hallmark of EGPA to aid timely diagnosis, since prompt treatment initiation is crucial given the potential irreversible organ damage and poor prognosis of EGPA.

A case of eosinophilic granulomatosis with polyangiitis preceded by allergic bullous lesions.

A 62-year-old man with a history of diabetes mellitus was hospitalised with numbness of lower limbs, bullous lesions of the whole body, kidney dysfunction, presence of eosinophils, and elevated antineutrophil cytoplasmic antibodies to myeloperoxidase and anti-bullous pemphigoid 180 antibodies and was diagnosed with mononeuritis multiplex. Kidney and muscle biopsies showed vasculitis with fibrinoid necrosis, whereas skin biopsies showed only blister formation between the epidermis and dermis; a high eosinophilic infiltrate was present in all three tissues. These findings led to a diagnosis of eosinophilic granulomatosis with polyangiitis combined with allergic bullous lesions. Immunohistological examination indicated cytolytic eosinophils and extracellular traps, suggesting the presence of eosinophil extracellular trap cell death (eosinophil ETosis) in diseased tissue.

Milia within resolving bullous pemphigoid lesions

Milia within resolving bullous pemphigoid lesions

Oral Lichen Planus: A Narrative Review Navigating Etiologies, Clinical Manifestations, Diagnostics, and Therapeutic Approaches.

Background/Objectives: Oral Lichen Planus (OLP) is a common immune-mediated inflammatory disorder affecting the oral mucosa, impacting 0.5% to 2% of the global population, primarily middle-aged women. Immunological dysregulation is a key factor in OLP's pathogenesis, involving CD4+ T helper and CD8+ T cytotoxic cells. The World Health Organization (WHO) classifies OLP as a potentially malignant disorder, with a risk of oral squamous cell carcinoma (OSCC) developing in up to 2% of lesions. This narrative review aims to provide a comprehensive overview of the etiopathogenesis, clinical manifestations, diagnostic criteria, and therapeutic strategies for OLP, informing clinical practice and guiding future research. Methods: A review of the literature from the PubMed and Google Scholar databases was conducted up to December 2023, focusing on studies addressing the etiopathogenesis, diagnosis, clinical manifestations, and treatment of OLP. Results: OLP's pathogenesis is driven by immune dysregulation, with CD4+ and CD8+ cells playing crucial roles. Clinically, OLP presents as reticular, erosive, bullous, and plaque-like lesions. Diagnosis relies on clinical examination, histopathology, and direct immunofluorescence. Recent advancements in diagnostic markers and imaging techniques have improved detection and monitoring. Treatment primarily involves corticosteroids, but novel therapies such as curcumin, retinoids, and laser therapy are increasingly used for their effectiveness and reduced side effects. These treatments show promise in symptom reduction and recurrence prevention, although long-term data are needed. Conclusions: Regular screenings and biopsies are essential due to OLP's likelihood of malignant transformation. This study urges further investigation into long-term results, improved diagnostic techniques, and evidence-based treatment regimens.

Clinical and pathological characterization of Tebentafusp-associated skin toxicity – a cohort study with 33 patients.

BackgroundTebentafusp is a novel treatment for patients with metastatic uveal melanoma and often causes cutaneous side effects. ObjectivesThe aim of this study was to better characterize these heterogenous cutaneous side effects. MethodsThis prospective cohort study evaluated all patients from a tertiary hospital center who were treated with tebentafusp between January 2019 and June 2023 clinically and assessed skin biopsies histologically. ResultsIn total, 33 patients were analysed. Skin toxicity was observed in 78.8% of patients and was classified in five clinical categories: 1) symmetrical erythematous patches (83.8%), 2) hemorrhagic macules (11.8%), 3) urticarial lesions (7.4%), 4) bullous lesions (1.5%) and 5) skin (8.5%) and hair depigmentation (11.4%). Histopathologic features were focal lymphocytic interface dermatitis with epidermal infiltration of CD8-positive lymphocytes. Patients with skin reactions had a significantly longer median overall survival compared to patients without any cutaneous events (34 versus 4 months, p<0.001). LimitationMonocentric study with a limited number of patients. ConclusionTebentafusp frequently induced cutaneous reactions. Pathogenesis is likely due to binding of tebentafusp to stimulated melanocytes in the skin followed by infiltration and activation of lymphocytes. Development of treatment induced skin reactions may be associated with survival benefit.

A Comprehensive Review on the Intricate Interplay between COVID-19 Immunization and the New Onset of Pemphigus Foliaceus.

Autoimmune bullous diseases (AIBDs) are characterized by the formation of vesicles, bullous lesions, and mucosal erosions. The autoantibodies target the cellular anchoring structures from the surface of epidermal keratinocyte named desmosomes, leading to a loss of cellular cohesion named acantholysis. AIBDs are classified into intraepidermal or subepidermal types based on clinical features, histological characteristics, and immunofluorescence patterns. Pemphigus foliaceus (PF) is an acquired, rare, autoimmune skin condition associated with autoantibodies that specifically target desmoglein-1, leading to a clinical presentation characterized by delicate cutaneous blisters, typically sparing the mucous membranes. Several factors, including genetic predisposition, environmental triggers, malignancies, medication use, and vaccination (for influenza, hepatitis B, rabies, tetanus, and more recently, severe acute respiratory syndrome Coronavirus 2 known as SARS-CoV-2), can potentially trigger the onset of pemphigus. With the advent of vaccines playing a pivotal role in combatting the 2019 coronavirus disease (COVID-19), extensive research has been conducted globally to ascertain their efficacy and potential cutaneous adverse effects. While reports of AIBDs post-COVID-19 vaccination exist in the medical literature, instances of PF following vaccination have been less commonly reported worldwide. The disease's pathophysiology is likely attributed to the resemblance between the ribonucleic acid (RNA) antigen present in these vaccines and cellular nuclear matter. The protein produced by the BNT-162b2 messenger ribonucleic acid (mRNA) vaccine includes immunogenic epitopes that could potentially trigger autoimmune phenomena in predisposed individuals through several mechanisms, including molecular mimicry, the activation of pattern recognition receptors, the polyclonal stimulation of B cells, type I interferon production, and autoinflammation. In this review, we present a comprehensive examination of the existing literature regarding the relationship between COVID-19 and PF, delving into their intricate interactions. This exploration improves the understanding of both pemphigus and mRNA vaccine mechanisms, highlighting the importance of close monitoring for PF post-immunization.

Dermotoscope assisted diagnosis of adolescent bullous pilomatricoma: six case reports

BackgroundPilomatricoma (PM) is a cutaneous benign neoplasm derived from the hair matrix. It clinically presents as a solitary and firm nodule overlying normal epidermis and is usually not easy to be noticed at early stage. Nevertheless, when special bullous lesion occurs in a short time or even ulcerates, preoperative diagnosis by a dermatologist is often challenging especially when the pediatric patients refuse biopsy.Case presentationWe present six bullous PM cases and particularly conduct correlation analysis on the dermotoscopy and histopathology detection data. The basic information, medical history, symptoms and lesion morphology results of the patients were also provided. We found that the incidence of bullous PM was higher in females than in males, and most patients were adolescents and the predilection location seem to be consistent in the vaccine injection site. The dermatoscopic features of bullous PM reported were luminous yellow structure below, with gray-blue homogeneous areas and branched capillary. The histological features were consistent with PM, and evident epidermis bullae were above the tumor with extraordinary dilation of lymphangion in the upper dermis. The patients described in this study were Chinese patients in Han population included 4 females and 2 males, coincidentally, they are almost teen-age, respectively are 5,11,17,19,21,22 year-old.ConclusionsThis study reported and analyzed the dermotoscopy and clinical characteristics of bullous PM, dermotoscopy may guide as a rapid and reliable technique in bullous PM diagnosis.

Bullous lesions in the course of the classic form of Kaposi’s sarcoma

Kaposi sarcoma (KS) is a cancer originating from the endothelial cells of blood and lymphatic vessels. It develops multifocally as a result of pathological vascular hyperplasia. There are four forms of the disease: classic, endemic, iatrogenic, and epidemic. The treatment of Kaposi’s sarcoma depends on the clinical form, stage of advancement, and the immunological condition of the patient. The article presents the case of an 82-year-old patient from the Dermatology Department of the Provincial Hospital in Elblag diagnosed with Kaposi’s sarcoma with bullous lesions. Key words: Kaposi’s sarcoma, Dermatology, Oncology

EB Naevi-like Lesion in Infant Bullous Pemphigoid

Epidermolysis Bullosa Naevi (EBN) is a subset of melanocytic nevi with atypical features arising at sites of blistering in patients with congenital EB. It may be clinically misdiagnosed as melanoma and may represent a challenge for the dermatologist. Bullous Pemphigoid (BP) consists of an autoimmune condition presenting with subepidermal blisters, usually affecting the elderly and rarely observed in children The case is reported of an infant who presented with pruritic erythematous bullous lesions, initially appearing over the trunk and legs with progression to arms and face. Clinical and immunopathological features were consistent with the diagnosis of infant BP. In the course of the disease, he developed a pigmented heterogeneous macule with irregular contour and satellite-dotted lesions, located on the right flank. Dermoscopy revealed a regular pigmented network distributed in an agminated manner interspersed with areas of healthy skin. Due to its similarity to EBN, an expectant approach was carried out. The lesion regressed during the 24-month follow-up. To our knowledge, there is only one literature case report of a child who presented with EBN-like in a previous BP lesion. Our case reinforces the presence of atypical melanocytic nevi in bullous diseases. Knowing this type of lesion clinically and dermatoscopically in patients with bullous dermatoses may prevent unnecessary surgical procedures in children.

Vildagliptin-Associated Bullous Pemphigoid: A Case Report

Objective: Bullous pemphigoid is a rare autoimmune skin disorder characterized by blistering, urticarial lesions, which are sometimes associated with adverse drug reactions. Vildagliptin is an oral anti-diabetic agent that selectively inhibits the dipeptidyl peptidase-4 (DPP-4) enzyme Materials and Methods: A 75-year-old female with a known case of type 2 Diabetes Mellitus, hypertension, and hypothyroidism for the last 10 years presented with pruriginous tense bullous skin lesions over her both palms and soles. There was no mucosal involvement. Further interrogation revealed that she started taking Vildagliptin 5 days ago which was prescribed due to high levels of post-prandial blood sugar level despite already intake of Glimepiride-4 mg and Metformin-3 gm. Results: Vildagliptin was immediately advised to be stopped. She was treated with antihistamines, steroids, and conservative management which led to remission of the blisters Conclusion: Vildagliptin is the probable causative drug for developing bullous pemphigoid skin lesion which shows temporal association in this case as other concomitant drugs has no direct correlation. Therefore physicians must be aware of this rare life-threatening side effect of this medicine and advice patients to visit the hospital even the slightest cutaneous manifestation. Bullous pemphigoid can result in fatal life-threatening conditions if not treated early.

Cautery excision of oral mucocele in pediatric children: A case report

Introduction: Oral mucocele is a common, oral lesions that mostly present as painless, clear, or bluish cysts on the lower lip of children and young adults. These are harmless, mucus-filled growths usually resulting from a little salivary gland or duct injury. Mucus can leak into surrounding subepithelial tissue when the salivary glands are injured by lip biting, sucking, or trauma. This is known as a mucus extravasation cyst, and it is the most frequent variety of mucoceles. This report presents two cases of mucocele. Case History: Two case studies of oral mucoceles reported that almost all included lip mucoceles were clinically bullous lesions, it was soft, fluctuant, and palpable, which corroborates the hypothesis that lip mucoceles are commonly incited by traumatic injury such as tooth impingement and lip-biting habit. All cases were treated with a simple excision using an electrocautery. Two lesion diagnosis was confirmed by Histopathology anatomy (HPA). Discussion: Mucoceles are common oral lesions often seen in children and adolescents, typically caused by lip biting due to psychological stress. Diagnosis is based on clinical features such as rapid appearance, size variations, and bluish color. Treatments include scalpel excision and electrocautery, with electrocautery providing minimal bleeding and painless wounds. Conclusion: One of the typical salivary gland lesions in the oral cavity is mucocele. The use of electrocautery is known to be beneficial for wound healing. Awareness education for children and parents is necessary to eliminate a lip-biting habit.

Dystrophic Epidermolysis Bullosa (DEB): How Can Pregnancy Alter the Course of This Rare Disease? An Updated Literature Review on Obstetrical Management with an Additional Italian Experience.

Epidermolysis Bullosa (EB) is an extremely rare and disabling inherited genetic skin disease with a predisposition to develop bullous lesions on the skin and inner mucous membranes, occurring after mild friction or trauma, or even spontaneously. Within the spectrum of EB forms, dystrophic EB (DEB) represents the most intriguing and challenging in terms of clinical management, especially with regard to pregnancy, due to the highly disabling and life-threatening phenotype. Disappointingly, in the literature little focus has been directed towards pregnancy and childbirth in DEB patients, resulting in a lack of sound evidence and guidance for patients themselves and clinicians. The current study aims to contribute to the DEB literature with an updated summary of the existing evidence regarding the obstetrical and anesthesiological management of this rare disease. Furthermore, this literature review sought to answer the question of whether, and if so, in which way, the pregnancy condition may alter the course of the underlying dermatologic skin disease. Having all this information is indispensable when counseling a patient with DEB who desires a child or is expecting one. Finally, we reported own experience with a pregnant woman with a recessive DEB whom we recently managed, with a favorable outcome.

Granular C3 dermatosis-A report of two cases and a mini-review of literature.

Granular C3 dermatosis (GCD) is characterized by bullous, erythematous, and eczematous skin lesions similar to dermatitis herpetiformis, and granular deposition of complement C3 and C5b-9 along the epidermal basement membrane zone (BMZ) by direct immunofluorescence (IF). Here, we present two cases of GCD with different clinical features. Case 1, a 49-year-old man, showed pruritic blisters and erythema of the extremities. Case 2, a 53-year-old woman, showed severely pruritic papules, erythema, and erosions on the entire body with scattered blisters, mainly on the lower extremities. Both patients showed mild eosinophilia on blood tests, subepidermal blisters and prominent eosinophilic infiltration in the upper dermis on histopathological examination, and granular BMZ deposition of C3, but not of immunoglobulins or other complement components, on direct IF. No circulating autoantibodies were detected on enzyme-linked immunosorbent assays, chemiluminescent enzyme immunoassays, indirect IF using 1 mol/L NaCl-split normal human skin, or immunoblotting. Diagnosis of GCD was made in both cases. Case 1 was successfully treated with topical steroids, oral minocycline, and nicotinamide without any recurrence of symptoms. Case 2 was treated with oral steroids and showed remarkable improvement, although mild pruritic papules remained. We reviewed 30 reported GCD cases, including the two cases presented here, since Hashimoto etal. first described GCD in 2016. GCD should be more widely recognized, and further accumulation and validation of cases are required.

Isolated Breast Sarcoidosis

Background: Sarcoidosis is a rare non-caseating granulomatous disease of unknown origin that affects multiple systems in the body occurring more frequently in young women age 17-24 years. Cases with manifestations that doesn’t affect the common organs can be difficult to identify and delay the patient’s diagnosis, meaning that the finding of an isolated breast mass should include sarcoidosis as one of its differentials, to ensure early detection and a better prognosis. Case presentation: We present the case report of a 21-year-old female patient, who had noticed a palpable breast nodule associated with local pain and fever for 2 months. Physical examination detected palpable bilateral axillary lymph nodes, a nodule occupying the lateral quadrants of the left breast and bullous lesions, along with phlogistic signs in the same topography. The imaging exams of the chest, showed a solid-cystic complex in the lateral quadrants of the left breast, in addition to bilateral axillary lymph node enlargement. Laboratory tests was unremarkable. The histopathological tests detected fibroadipose tissue with noncaseating granulomas, neutrophilic microabscesses and Langerhans-type giant cells, causing chronic granulomatous mastitis, which may represent sarcoidosis. The lesions regresed after the use of corticosteroids. Conclusion: Despite its rarity, the clinical and imaging findings such as those of this patient, should warrant the consideration of breast sarcoidosis as a possible diagnosis given the importance of excluding similar conditions, such as neoplasms, early on.

Recurrent spontaneous pneumothorax in four surgically treated Japanese Spitz dogs

AbstractFour Japanese Spitz dogs between 5 and 11 months old were presented for acute dyspnoea. Thoracic radiographs and CT identified bilateral pneumothorax and pulmonary cavitary lesions. The median lesion size was 30 mm (range 7‒50 mm). After initial stabilisation, one dog underwent median sternotomy, while three dogs underwent intercostal thoracotomy. Surgical exploration found grossly haemorrhagic pulmonary bullous lesions in all cases. Histopathology revealed blood‐filled cavities with interstitial fibrosis and pneumocyte hyperplasia. Dyspnoea recurred in all dogs postoperatively, with recurrence of lesions confirmed either radiographically or via CT in three of four cases. The median time from surgery to recurrence of pneumothorax was 9 days (range 5‒15 days). The mortality rate was 100%, and the median postoperative survival time was 22 days (range 5‒558 days). This report aims to raise awareness of this group of dogs presenting with spontaneous pneumothorax at a young age and with high recurrence rates despite surgery, contrary to the literature.

Bullous pemphigoid as a paraneoplastic manifestation of metastatic adenocarcinoma of the lung

A 73-year-old male smoker presented with complaints of fever and multiple clear fluid-filled lesions for 3 months. He was initially being treated for primary bullous pemphigoid but lesions recurred. On a chest X-ray, he was found to have a right hilar mass, and contrast-enhanced computed tomography of the chest revealed a right lung mass lesion with cervical, hilar, and mediastinal lymphadenopathy. A bronchoscopy was done, and bronchoalveolar lavage cytology was suggestive of lung adenocarcinoma. An excision biopsy of the left supraclavicular lymph node showed features consistent with adenocarcinoma lung. Hence, he was diagnosed with metastatic adenocarcinoma of the lung with bullous pemphigoid as a paraneoplastic manifestation. He was subsequently treated with chemotherapy, and his skin lesions resolved.

Unveiling rarity: Ocular manifestations of recessive dystrophic epidermolysis bullosa (RDEB) syndrome with localized corneal edema

This case report illustrates the ocular manifestations of recessive dystrophic epidermolysis bullosa (RDEB) syndrome in a 7-year-old boy from Bangladesh. During his overall examination, the boy exhibited active and chronic bullous lesions associated with black eschar throughout his body. In addition, he presented dental abnormalities, tooth decay, nail dystrophy, and the absence of nails on his fingers and toes. His ocular presentation included localized corneal edema extending from the subepithelium to Descemet’s membrane and blistering of the eyelids, which spared the corneal epithelium and the conjunctiva. We treated the lesion successfully using topical loteprednol and artificial tear (carboxymethyl cellulose) eye drops, resulting in an excellent outcome.