Bullous Eruption Research Articles

Bullous Drug Eruption.

A 63-year-old woman presented at our emergency department with a disseminated dermatosis that developed after undergoing a cardiac catheterization procedure. Her past medical history included an end-stage renal disease undergoing hemodialysis. Clinical examination revealed erosions and hemorrhagic crusts located on her lips and along the arteriovenous fistula. Additionally, we observed five hyperpigmented macules on her left hand's dorsum and palm and multiple hypopigmented macules in the genital area. Upon medical record review, we discovered the occurrence of prior bullous eruptions following contrast administration. A fixed drug eruption (FDE) due to radiocontrast was diagnosed based on clinical history, clinical examination, eruption timeframe, and positive drug provocation test. Intravenous contrast media reactions can be immediate or delayed, with delayed hypersensitivity reactions (DHR) occurring one hour to seven days post-administration. DHRs often present as maculopapular rashes. FDEs are rare. Skin tests are used to identify culprit agents. Ideally, intradermal tests, with delayed readings, and patch tests are combined for optimal sensitivity. Despite lacking standardized protocols, premedication with corticosteroids may mitigate reaction severity.

INDIVIDUAL ARTICLE: NECOM 4: Algorithm Integrating Skincare for the Management of Immunotherapy-Related Cutaneous Adverse Events for Cancer Patients and Survivors.

In the Nordic European Countries, cancer is the leading cause of death. The last decade has brought revolutionizing cancer treatments including immune checkpoint inhibitors (ICIs). Patients on ICIs have a high risk of developing cutaneous immune-related adverse events. Treating these side effects is of high importance to improve patient's quality of life (QoL) and continue the anti-cancer treatment. The Nordic European Cutaneous Oncodermatology Management (NECOM) project develops tools to prevent and treat cancer therapy-related cutaneous adverse events (cAEs). The first 2 NECOM papers presented various cAEs and skincare regimens involving hygiene, moisturization, sun protection, and camouflage products for preventing and managing cAEs. The NECOM 3 practical algorithm was on the prevention and treatment of acute radiation dermatitis. This NECOM 4 practical algorithm is intended to prevent and manage cutaneous immunotherapy-related adverse events (cirAEs), improving cancer patients' QoL and outcomes. The NECOM advisors discussed the results of a systematic literature review and obtained consensus on the evidence and expert opinion-based practical algorithm for cirAEs to support all healthcare providers treating cancer patients in the Nordic European Countries. The algorithm starts with a simple skincare regimen of cleansing, moisturizing, and protection, followed by the exclusion of severe cutaneous adverse reactions, and then specific interventions to treat the most common cirAEs (pruritus, maculopapular eruption, eczematous eruption, psoriasis, lichenoid eruption, and bullous eruption). CirAEs are the most common side effects induced by ICIs and may lead to cancer treatment interruption or even discontinuation. Patient education on the prevention of cirAEs using a skincare regimen and treatment recommendations given in the NECOM 4 algorithm may help prevent and manage cirAEs and improve the QoL and outcome of patients receiving ICIs. J Drugs Dermatol. 2024;23:8(Suppl 2):s4-10.

Drug induced bullous fixed drug eruption: a case report

Bullous fixed drug eruption, which is a cutaneous adverse drug reaction, is commonly seen with antimicrobials and analgesics. Bullous drug eruptions are infrequent, but because they pose a challenge both to affected patients and to treating physicians, they are considered to be the most severe cutaneous adverse reactions (SCAR). It is important to recognize these conditions and to differentiate them from other clinical entities involving blister formation. There may be early signs and symptoms that indicate a severe bullous drug eruption even before blisters and erosions of the skin and mucous membranes become obvious. Once the diagnosis is suspected, appropriate diagnostic procedures and adequate management must be initiated. The latter includes identification of the potentially inducing drug, although it should be taken into account that not all cases of bullous eruptions are drug-induced. In cases with drug causality the potentially culprit agent must be withdrawn, while in cases with other aetiology the underlying condition, e.g. an infection, must be treated appropriately. In addition to best supportive care, immunomodulating therapy may be considered. Here we report 64-year-old male with bullous fixed drug eruptions due to doxycycline administration.

A severe case of swimmer's itch in Victoria, Australia with bullous eruption.

We describe a severe case of swimmer's itch in Victoria with widespread bullous eruption, which is a rare manifestation of this condition and presented a diagnostic challenge. This is the first case reported in Victoria, having been previously reported in more northern parts of Australia; with climate change trends, swimmer's itch is likely to become increasingly common in southern parts of the region.

Sudden Bullous Eruption in a Healthy Infant-A Diagnostic Dilemma.

Sudden Bullous Eruption in a Healthy Infant-A Diagnostic Dilemma.

Lichen planus pemphigoides erupting after COVID‐19 vaccination and infection, successfully treated with methotrexate

AbstractWe report a case of lichen planus pemphigoides (LPP) in a 36‐year‐old woman who presented bullous skin eruptions following both COVID‐19 infection and vaccination. The patient had a history of biopsy‐confirmed lichen planus since 2013 and had been previously investigated for suspected dermatitis herpetiformis since 2014, with inconclusive biopsy results. On two separate occasions, following her COVID‐19 vaccination and infection, she suffered the eruption of similar bullous lesions. A final diagnosis of LPP was established, believed to have been triggered by both the vaccination and the COVID‐19 infection. Treatment with prednisolone offered temporary relief, but sustained remission was achieved with methotrexate. This is, to our knowledge, the first documented case of LPP post‐COVID‐19 vaccination or infection.

P18 Bullous leukocytoclastic vasculitis in a patient with known undifferentiated autoimmune rheumatic disease

P18 Bullous leukocytoclastic vasculitis in a patient with known undifferentiated autoimmune rheumatic disease

Why drug exposure is frequently associated with T-cell mediated cutaneous hypersensitivity reactions.

Cutaneous hypersensitivity reactions represent the most common manifestation of drug allergy seen in the clinic, with 25% of all adverse drug reactions appearing in the skin. The severity of cutaneous eruptions can vastly differ depending on the cellular mechanisms involved from a minor, self-resolving maculopapular rash to major, life-threatening pathologies such as the T-cell mediated bullous eruptions, i.e., Stevens Johnson syndrome/toxic epidermal necrolysis. It remains a significant question as to why these reactions are so frequently associated with the skin and what factors polarise these reactions towards more serious disease states. The barrier function which the skin performs means it is constantly subject to a barrage of danger signals, creating an environment that favors elicitation. Therefore, a critical question is what drives the expansion of cutaneous lymphocyte antigen positive, skin homing, T-cell sub-populations in draining lymph nodes. One answer could be the heterologous immunity hypothesis whereby tissue resident memory T-cells that express T-cell receptors (TCRs) for pathogen derived antigens cross-react with drug antigen. A significant amount of research has been conducted on skin immunity in the context of contact allergy and the role of tissue specific antigen presenting cells in presenting drug antigen to T-cells, but it is unclear how this relates to epitopes derived from circulation. Studies have shown that the skin is a metabolically active organ, capable of generating reactive drug metabolites. However, we know that drug antigens are displayed systemically so what factors permit tolerance in one part of the body, but reactivity in the skin. Most adverse drug reactions are mild, and skin eruptions tend to be visible to the patient, whereas minor organ injury such as transient transaminase elevation is often not apparent. Systemic hypersensitivity reactions tend to have early cutaneous manifestations, the progression of which is halted by early diagnosis and treatment. It is apparent that the preference for cutaneous involvement of drug hypersensitivity reactions is multi-faceted, therefore this review aims to abridge the findings from literature on the current state of the field and provide insight into the cellular and metabolic mechanisms which may contribute to severe cutaneous adverse reactions.

Store-and-forward inpatient teledermatology improves care for hospitalized patients with bullous eruptions after a primary inpatient team consultation: A retrospective study

Store-and-forward inpatient teledermatology improves care for hospitalized patients with bullous eruptions after a primary inpatient team consultation: A retrospective study

Taxane-induced scleroderma-like skin changes – review of the literature and case report

Abstract: Taxanes (paclitaxel, docetaxel) are antineoplastic agents used in advanced ovarian, breast, lung, head and neck cancer. Diverse cutaneous adverse reactions associated with taxane administration have been reported such as bullous eruption, onycholysis, acral erythema, erythema multiforme, pustular eruption, scleroderma-like skin changes of both upper and lower extremities. Here, we report a case of 48-year-old female patient, who presented for consultation with rheumatologist with complaints of hand and finger oedema and stiffness. Oedema and mild skin thickening of the fingers and hands were evident at physical examination. Inflammatory joint pain, synovitis, Raynaud’s phenomenon and trophic changes were not present. Standard laboratory tests i.e., complete blood count and biochemistry tests were within normal values. The patient was euthyroid. Immunological tests were negative (antinuclear antibodies; antibodies against extractable nuclear antigens – dsDNA, Sm, RNP, Scl-70; antiphospholipid antibodies – anticardiolipin, anti-beta-2-glycoprotein; anti-CCP antibody and rheumatoid factor). Capillaroscopic examination did not reveal signs of microangiopathy. Skin biopsy was perfomed in the area of a proximal phalanx and the histological examination revealed dermal oedema and superficial scant perivascular infiltrate containing lymphocytes and histiocytes. The patient had undergone an operation for breast cancer 13 years ago and subsequent second operation because of cancer recurrence 7 years ago. After the second operation chemotherapy was performed that included 1 cycle with paclitaxel and 4 cycles with docetaxel. The analysis of the case led to the conclusion that the scleroderma-like skin changes of the fingers and hands are induced by taxane administration in the past. The patient received corticosteroid treatment for 7 months with gradual resolution of symptoms.

Stevens-johnson Syndrome and Toxic Epidermal Necrolysis: An Overview of Diagnosis, Therapy Options and Prognosis of Patients.

Both Stevens-johnson syndrome (SJS) and Toxic-epidermal necrolysis (TEN) are generally medication-induced pathological conditions that mostly affect the epidermis and mucus membranes. Nearly 1 to 2 patients per 1,000,000 population are affected annually with SJS and TEN, and sometimes these maladies can cause serious life-threatening events. The reported death rates for SJS range from 1 to 5%, and 25 to 35% for TEN. The mortality risk may even be higher among elderly patients, especially in those who are affected by a significant amount of epidermal detachment. More than 50% of TEN patients who survive the illness may experience long-term lower quality of life and lesser life expectancy. The clinical and histopathological conditions of SJS and TEN are characterized by mucocutaneous discomfort, haemorrhagic erosions, erythema, and occasionally severe epidermal separation that can turn into ulcerative patches and dermal necrosis. The relative difference between SJS and TEN is the degree of ulcerative skin detachment, making them two extremes of a spectrum of severe cutaneous adverse drug-induced reactions (cADRs). In the majority of cases, serious drug-related hypercreativities are considered the main cause of SJS & TEN; however, herpes simplex virus and Mycoplasma pneumoniae infections may also produce similar type clinical conditions. The aetiology of a lesser number of cases and their underlying causative factors remain unknown. Among the drugs with a 'greater likelihood' of causing TEN & SJS are carbamazepine (CBZ), trimethoprim-sulfamethoxazole, phenytoin, aminopenicillins, allopurinol, cephalosporins, sulphonamides, antibiotics, quinolones, phenobarbital, and NSAIDs of the oxicam variety. There is also a strong genetic link between the occurrence of SJS and IEN in the Han Chinese population. Such genetic association is based on the human leukocyte antigen (HLA-B*1502) and the co-administration of carbamazepine. The diagnosis of SJS is made mostly on the gross observations of clinical symptoms, and confirmed by the histopathological examination of dermal biopsies of the patients. The differential diagnoses consist of the exclusion of Pemphigus vulgaris, bullous pemphigoid, linear IgA dermatosis, paraneoplastic pemphigus, disseminated fixed bullous drug eruption, acute generalized exanthematous pustulosis (AGEP), and staphylococcal scalded skin syndrome (SSSS). The management of SJS & TEN is rather difficult and complicated, and there is sometimes a high risk of mortality in seriously inflicted patients. Urgent medical attention is needed for early diagnosis, estimation of the SCORTEN prognosis, identification and discontinuation of the causative agent as well as highdose injectable Ig therapeutic interventions along with specialized supportive care. Historical aspects, aetiology, mechanisms, and incidences of SJS and TEN are discussed. An update on the genetic occurrence of these medication-related hypersensitive ailments as well as different therapy options and management of patients is also provided.

Pemphigus Vulgaris - A pragmatic approach through Panchakarma

Blistering disorders are a group of diseases presenting with vesicles and bullae over skin and mucous membrane.[1] Pemphigus describes a group of chronic bullous eruptions of the skin, where Pemphigus vulgaris is the commonest one.[2] Which is a life threatening autoimmune mucocutaneous blistering disease with a mortality rate of 5-15%. In Ayurveda all the skin disorders are collectively named under the heading of Kushta. Ayurveda Acharyas have described all the Kushta are having the involvement of all the three Dosha’s. But the signs, symptoms and the treatment depend on the predominance of the Dosha involved. Visphotaka and Agnivisarpa can be compared to Pemphigus vulgaris due to its resemblance in signs and symptoms. This disease needs early and proper treatment to prevent further morbidity or mortality. To control these diseases, generally physicians use corticosteroids and immunosuppressive drugs as adjuvants. Here, an attempt is made to study in detail about the disease Pemphigus vulgaris and its understanding through Ayurveda. Management of such diseases through Ayurveda is rarely reported. A case report of 32yr old male patient presenting with the similar complaints treated with Vamana followed by Virechana Karma along with Shaman drugs is presented in this paper.

Case report on localized bullous pemphigoid in two young females

Bullous pemphigoid (BP) is a chronic autoimmune bullous eruption that is characterized by pruritic, tense sub-epidermal bullae. It commonly affects those aged 60 years and above. It has no gender predilection. It can be generalized or localized. This is a case report of 2 female patients with localized BP presenting as recurrent skin rash of more than 1 year duration which were later referred to the dermatology clinic. The patients were both females less than 40 years of age who have been having recurrent skin rash that have been associated with intense itching localized to a unilateral lower limb. The first patient had obvious bullae and ulcers while the second didn’t have any obvious bullae. Initial clinical diagnoses did not consider BP. Punch skin biopsy was done in both cases that revealed histologic features confirming BP. Clinicians should have high index of suspicion of BP even in cases of localized chronic wound or recurrent ulcers irrespective of the age of patient.

Autoimmune bullous dermatoses in cancer patients treated by immunotherapy: a literature review and Italian multicentric experience.

Cutaneous immune-related adverse events are frequently associated with immune checkpoint inhibitors (ICIs) administration in cancer patients. In fact, these monoclonal antibodies bind the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/ligand 1 leading to a non-specific activation of the immune system against both tumoral cells and self-antigens. The skin is the most frequently affected organ system appearing involved especially by inflammatory manifestations such as maculopapular, lichenoid, psoriatic, and eczematous eruptions. Although less common, ICI-induced autoimmune blistering diseases have also been reported, with an estimated overall incidence of less than 5%. Bullous pemphigoid-like eruption is the predominant phenotype, while lichen planus pemphigoides, pemphigus vulgaris, and mucous membrane pemphigoid have been described anecdotally. Overall, they have a wide range of clinical presentations and often overlap with each other leading to a delayed diagnosis. Achieving adequate control of skin toxicity in these cases often requires immunosuppressive systemic therapies and/or interruption of ICI treatment, presenting a therapeutic challenge in the context of cancer management. In this study, we present a case series from Italy based on a multicenter, retrospective, observational study, which included 45 patients treated with ICIs who developed ICI-induced bullous pemphigoid. In addition, we performed a comprehensive review to identify the cases reported in the literature on ICI-induced autoimmune bullous diseases. Several theories seeking their underlying pathogenesis have been reported and this work aims to better understand what is known so far on this issue.

Bullous Eruption after Off-label Use of Topical Tirbanibulin on the Chest

Tirbanibulin 1% ointment (Klisyri), an FDA-approved topical treatment for actinic keratosis, is advertised to serve as a first-in-class topical with high efficacy and low adverse effects compared to other field therapies. We report a case of severe bullous eruption associated with application of tirbanibulin in an adult female. Though application of tirbanibulin did resolve the actinic keratoses on the patient’s chest, the severe local skin reaction precludes future use of tirbanibulin in her case.

Bed Bugs (Hemiptera, Cimicidae): A Global Challenge for Public Health and Control Management.

Bed bugs, Cimex lectularius, and C. hemipterus are among the most common ectoparasites in human life worldwide. They feed on humans of all ages and sexes across all socioeconomic levels. Bed bugs' blood feeding is responsible for a wide range of clinical manifestations varying from minor reactions to bullous eruptions or severe allergies. In addition, they are responsible for considerable psychological distress. Therefore, diagnosis of bed bug bites and their consequence manifestations is beneficial in adapting remedies and treatment protocols advised by clinicians. So far, there is regrettably no definitive way to control these ectoparasites despite extensive efforts of public health authorities to manage them. An overview of the literature and medical documents gathered from bed bug-infested patients referred to the Parasitology and Dermatology departments of Avicenne Hospital (Bobigny, France) allowed us to document and illustrate a range of clinical disorders and psychological concerns caused by bed bugs' bites and their clinical diagnosis. We also review the available tools currently used to control the bed bugs and present potential candidate methods for their successful eradication.

Two cases of generalized bullous fixed-drug eruption triggered by etodolac

Two cases of generalized bullous fixed-drug eruption triggered by etodolac

PA12 A case of pustular psoriasis in epidermolytic ichthyosis: coincidence or common pathway?

Abstract An 8-year-old boy with epidermolytic ichthyosis (EI) due to a heterozygous KRT1 mutation presented with a striking bullous skin eruption. Microbiological swabs were sent, and oral antibiotics were prescribed for suspected bullous impetigo. He deteriorated clinically, developing a fever and more extensive pustular rash reminiscent of generalized pustular psoriasis (GPP). Skin biopsies from two distinct cutaneous sites revealed histology strongly supportive of pustular psoriasis. Oral ciclosporin was commenced in addition to intensive topical emollient therapy. Following widespread desquamation, the pustular eruption fully resolved. Recurrence upon weaning of ciclosporin necessitated the introduction of ustekinumab. The rash remains controlled on this therapy. The EI is caused by heterozygous mutations in KRT1 or KRT10, and presents at birth with erythroderma and widespread skin denudation. The erythema and skin fragility abate in early childhood, giving way to prominent hyperkeratosis. Severe palmoplantar keratoderma is seen in those with KRT1 mutations. The GPP is a rare but life-threatening condition characterized by sterile pustules with or without systemic involvement. Interleukin (IL)-36-mediated inflammatory signalling plays a pathogenic role, as evidenced by loss of function mutations in IL36RN, which encodes an IL-36 receptor antagonist (Marrakchi S, Guigue P, Renshaw BR et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 2011; 365:620–8), and the efficacy of IL-36 receptor inhibitor spesolimab in a recent phase II trial. Both EI and GPP are rare, and the confluence of these entities in this case is striking. Four other cases in the literature describe a GPP-like eruption in patients with congenital ichthyoses. The coexistence of these conditions might be explained by their immunological profiles. Studies of the skin of patients with congenital ichthyoses have shown immune dysregulation with T helper 17/IL-23 skewing, and upregulation of associated inflammatory cytokines, including IL-36γ. The latter encodes for an IL-36 receptor agonist (Paller AS, Renert-Yuval Y, Suprun M et al. An IL-17-dominant immune profile is shared across the major orphan forms of ichthyosis. J Allergy Clin Immunol 2017; 139:152–65). Thus, increased IL-36 receptor agonist activity in congenital ichthyosis could theoretically lead to GPP in genetically predisposed individuals with already upregulated IL-36 receptor-mediated signalling.

Antibiotics hypersensitivity reactions during COVID-19 pandemic

During the COVID-19 pandemic, there have emerged publications about various skin manifestations mainly caused by the related coronavirus, also including some case reports on dermal drug-related adverse reactions. In Armenia, the doctors in COVID-19 hospitals periodically consulted with allergists-immunologists regarding allergic conditions that many patients already suffered on admission or manifested after it. We present the series of three most interesting drug-induced cases with various skin manifestations in patients with COVID-19 pneumonia who requited antibiotic therapy. The causative significance of antibiotics was assessed according to Naranjos algorithm. In the first case (a 58-year-old female patient), a diagnosis of maculopapular exanthem was made based on the clinical picture. Although the coronavirus per se can result in similar manifestations, previous history of allergic reaction to ampicillin led to the conclusion that ceftriaxone (both are beta-lactam antibiotics) was the most probable cause. The second case (a 53-year-old male patient), clinically manifested as vasculitis, caused some difficulties because this is quite often skin manifestations related to SARS-CoV-2, and is rarely induced by medications. Taking into account the history of reaction to beta-lactam antibiotic, as well as the fact that the patient took amoxicillin without a prescription before hospitalization and with overt skin lesions at that time, amoxicillin was assessed as a possible cause. In the third case (a 64-years-old female patient), diagnosed with a bullous drug-induced skin eruption, despite isolated cases of such lesions can be manifestations of SARS-CoV-2 infection, moxitec (fluoroquinolone antibiotic) was assessed as the most probable cause, especially taking into account herpes in history. According to current recommendations, an issue of drug tests was discussed with all three patients to confirm the causative significance of indicated drugs and/or to select an alternative drug, if necessary. In this regard, the subjects were included in the database of patients with severe drug hypersensitivity reactions by their informed consent.

Systemic Treatment of Cutaneous Adverse Events After Immune Checkpoint Inhibitor Therapy: A Review.

As treatment with immune checkpoint inhibitors (CPIs) for cancer increases, so has the incidence of immune-related cutaneous adverse events (irCAEs). These toxicities can significantly impact quality of life and may be dose-limiting. Current guidelines for irCAEs offer only corticosteroids or CPI discontinuation. Evidence supports biologic immunomodulatory therapies when corticosteroids fail or need avoidance. A review of literature from 2010 to 2020 yielded 45 articles, resulting in 185 irCAEs, including bullous pemphigoid-like eruption (n = 55), psoriasis/psoriasiform dermatitis (n = 41), and maculopapular rash (n = 31). Treatments included immunomodulators, intravenous immunoglobulin, aprepitant, acitretin, tetracyclines, and biologic agents. Overall, 92.3% of patients saw improvement or resolution of their rash. Bullous pemphigoid-like eruptions were treated with a tetracycline +/- niacinamide (94.7% success [18/19]), omalizumab (100% success [7/7]), and rituximab (100% success [10/10]). Although prospective research is required, this review provides a comprehensive list of successful, non-corticosteroid treatment options for irCAEs to improve compliance with lifesaving cancer therapy.