Clinical characteristics of snakebite patients attending a tertiary hospital in Hangzhou, southeast China.

BACKGROUND: Venomous snakebite is a neglected yet an important public health problem in China, and few studies have focused on them so far. The aim of this study is to investigate clinical characteristics of snakebites patients in a tertiary hospital in Hangzhou, southeast China. METHODS: A total of 416 snakebite cases were included in this retrospective study. The data were collected from the medical records including demographics, clinical manifestations, management and outcomes. RESULTS: Of the 416 patients with venomous snakebites, 248 were male, and the average age was 54.6 years. The majority of cases occurred in rural in May to September. Out of all the venomous bites, Gloydius brevicaudus accounted for the highest percentage (55.3%). Hands were the most vulnerable site to snakebites (47.4%). Patients had clinical manifestations of pain (100%), swelling (100%), wound necrosis (25.7%), hemorrhagic blister (18.3%), and blister (8.7%). Three hundred and ninety-two patients received antivenom administration, and most were treated within six hours after bites. Twenty-six patients received surgical treatments, and 90 patients developed venom-induced consumption coagulopathy. No deaths have occurred in this study. CONCLUSION: Hangzhou is one of the regions with high affecting of snakebites in China. The results of this study will increase the understanding of the clinical characteristics of venomous snakebites in Hangzhou area.

Thromboembolism and bleeding in patients with autoimmune blistering disease.

The prevention and early detection of venous thromboembolism (VTE), including pulmonary embolism (PE), is essential in daily medical practice. We previously reported the risk of VTE in patients with autoimmune blistering disease (AIBD). We have also experienced multiple cases of pemphigus or pemphigoid that developed severe complications related to abnormal blood coagulation other than VTE. This study summarizes and discusses those cases. Nine patients with AIBD developed thromboembolism and/or bleeding; these included (some patients overlapped) six patients with VTE, including five patients with PE; three patients with severe bleeding; one patient with sudden critical limb ischaemia resulting in thigh amputation; and one patient with cerebral infarction. Although five patients developed PE, only one had apparent respiratory symptoms with PE, and a second developed severe bleeding during the treatment for PE. Clinicians should be aware of the systemic complications related to abnormal blood coagulation when treating patients with AIBD.

An Unusual Laboratory Accident: Bromine Burn.

Bromine is a water-soluble, severely toxic element. It leads to tissue injury by causing the release of radical oxygen species from mucosal membranes. Redness or brownish discoloration of the skin, pain, measles-like rash, vesicles, blisters, pustules, furuncles, burns, and ulcers may be seen in the acute phase. A 32-year-old male presented to the emergency department after an accidental spill of bromine on his left forearm. Erythematous skin, including brownish discoloration and occasional small blisters, were seen on the forearm and wrist. The affected extremity was washed with plenty of water. The lesions were covered with antibiotic cream and wrapped with sterile gauzes; they healed without any complications. Mild burn scars with slightly pale discoloration of the affected skin remained after the lesions healed. Although bromine burn is rare, it causes severe damage to the skin, and injury starts insidiously without causing a visible skin reaction at the beginning. Irrigation with plenty of water in the early period is critically important in reducing the severity of the injury. Key Words: Bromine, Burn, Skin, Radical oxygen species.

Severe blistering eruptions induced by immune checkpoint inhibitors: a multicentre international study of 32 cases.

Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), bullous life-threatening reactions are rare. To better define the clinical and histological features, treatment, and prognosis of ICI-related severe blistering cutaneous eruptions. This retrospective case series was conducted between 2014/05/15 and 2021/04/15 by the dermatology departments of four international registries involved in drug reactions. Inclusion criteria were age ≥18 years old, skin eruption with blisters with detachment covering ≥1% body surface area and at least one mucous membrane involved, available pictures, and ICI as suspect drug. Autoimmune bullous disorders were excluded. Each participant medical team gave his own diagnosis conclusion: epidermal necrolysis (EN), severe lichenoid dermatosis (LD), or unclassified dermatosis (UD). After a standardized review of pictures, cases were reclassified by four experts in EN or LD/UD. Skin biopsies were blindly reviewed. Thirty-two patients were included. Median time to onset was 52 days (3-420 days). Cases were originally diagnosed as EN in 21 cases and LD/UD in 11 cases. After review by experts, 10/21 EN were reclassified as LD/UD. The following manifestations were more frequent or severe in EN: fever, purpuric macules, blisters, ocular involvement, and maximal detachment. Most patients were treated with topical with or without systemic corticosteroids. Eight patients (25%) died in the acute phase. The culprit ICI was not resumed in 92% of cases. In three patients, another ICI was given with a good tolerance. Histology did not reveal significant differences between groups. Severe blistering cutaneous drug reactions induced by ICI are often overdiagnosed as EN. Consensus for management is pending.

Drug triggered pruritus, rash, papules, and blisters - is AGEP a clash of an altered sphingolipid-metabolism and lysosomotropism of drugs accumulating in the skin?

Rash, photosensitivity, erythema multiforme, and the acute generalized exanthematous pustulosis (AGEP) are relatively uncommon adverse reactions of drugs. To date, the etiology is not well understood and individual susceptibility still remains unknown. Amiodarone, chlorpromazine, amitriptyline, and trimipramine are classified lysosomotropic as well as photosensitizing, however, they fail to trigger rash and pruritic papules in all individuals. Lysosomotropism is a common charcteristic of various drugs, but independent of individuals. There is evidence that the individual ability to respond to external oxidative stress is crosslinked with the elongation of long-chain fatty acids to very long-chain fatty acids by ELOVLs. ELOVL6 and ELOVL7 are sensitive to ROS induced depletion of cellular NADPH and insufficient regeneration via the pentose phosphate pathway and mitochondrial fatty acid oxidation. Deficiency of NADPH in presence of lysosomotropic drugs promotes the synthesis of C16-ceramide in lysosomes and may contribute to emerging pruritic papules of AGEP. However, independently from a lysosomomotropic drug, severe depletion of ATP and NAD(P)H, e.g., by UV radiation or a potent photosensitizer can trigger likewise the collapse of the lysosomal transmembrane proton gradient resulting in lysosomal C16-ceramide synthesis and pruritic papules. This kind of papules are equally present in polymorphous light eruption (PMLE/PLE) and acne aestivalis (Mallorca acne). The suggested model of a compartmentalized ceramide metabolism provides a more sophisticated explanation of cutaneous drug adverse effects and the individual sensitivity to UV radiation. Parameters such as pKa and ClogP of the triggering drug, cutaneous fatty acid profile, and ceramide profile enables new concepts in risk assessment and scoring of AGEP as well as prophylaxis outcome.

Toxic blister agents: Chemistry, mode of their action and effective treatment strategies.

Since their use during the First World War, Blister agents have posed a major threat to the individuals and have caused around two million casualties. Major incidents occurred not only due to their use as chemical warfare agents but also because of occupational hazards. Therefore, a clear understanding of these agents and their mode of action is essential to develop effective decontamination and therapeutic strategies. The blister agents have been categorised on the basis of their chemistry and the biological interactions that entail post contamination. These compounds have been known to majorly cause blisters/bullae along with alkylation of the contaminated DNA. However, due to the high toxicity and restricted use, very little research has been conducted and a lot remains to be clearly understood about these compounds. Various decontamination solutions and detection technologies have been developed, which have proven to be effective for their timely mitigation. But a major hurdle seems to be the lack of proper understanding of the toxicological mechanism of action of these compounds. Current review is about the detailed and updated information on physical, chemical and biological aspects of various blister agents. It also illustrates the mechanism of their action, toxicological effects, detection technologies and possible decontamination strategies.

Heparin-Induced Bullous Hemorrhagic Dermatosis: A Report of an Exceptionally Exuberant Case and Literature Review.

INTRODUCTION: Heparin-induced bullous hemorrhagic dermatosis (HBHD) is an unusual cutaneous adverse reaction to heparin characterized by acute onset of hemorrhagic bullae. METHODOLOGY: An exuberant case of HBHD is reported, and a revision of previously reported cases indexed on PubMed is provided. Cases were tabulated to the following parameters: sex, age, type of heparin and route of administration, associated medical procedure, number of days between heparin start and onset of lesions, site of the lesions, level of blister on histopathology, inflammatory infiltrate on histopathology, direct immunofluorescence findings, heparin-related intervention, number of days to resolution of skin lesions, associated hemorrhagic event, and outcome. CASE REPORT: A 21-year-old woman with end-stage renal disease was receiving intravenous unfractioned heparin (UFH) during hemodialysis section for the past 3 months. Four hours after using for the first time an arteriovenous fistula punctured on her right wrist, the patient noticed the onset of vesicles and blisters on the right forearm containing citrus or serohemorrhagic exudate, which became overt hemorrhagic in 24 hours. Histopathology depicted a nonacantholytic subcorneal blister containing erythrocytes and plasma without any significant dermal inflammatory infiltrate. RESULTS: Sixty cases of HBHD were included. HBHD affected predominantly men, with a male/female rate of 2.75. The age range was from 21 to 94 years, with an average of 70.8 and a median of 72 years. Nine patients used UFH, and 54 patients used low molecular weight heparins (3 patients used both). The lapse of time between the start of heparin and the onset of skin lesion varied from 6 hours to 240 days, with an average of 17.3 days and a median of 7 days. Limbs were affected in most of the cases. The level of the blister was subcorneal in 10 patients, intraepidermal in 30, subepidermal in 8, and both intraepidermal and subepidermal in 1. In 33 cases, there was no significant dermal inflammatory infiltrate. Pure lymphocytic inflammatory infiltrate was present in 10 cases. Eosinophils were found within the dermal inflammatory infiltrate in 2 cases, neutrophils in 2, and a mixture of eosinophils and neutrophils in other 2. Direct immunofluorescence was performed in 18 cases, all of them with negative results. DISCUSSION: We hypothesize that mechanical trauma, skin fragility, and the anticoagulation effect of heparin might contribute concomitantly to the development of the lesions and speculate that subepidermal blisters in HBHD could be formed by rupture of the floor of a former intraepidermal blister.

Cantharidin-Induced Skin Blister as an In Vivo Model of Inflammation.

The cantharidin-induced skin blister is a simple model for investigating cell migration and inflammatory mediator production at a site of inflammation. Application of cantharidin solution to the ear pinna results in formation of a blister with cell influx and induction of inflammatory mediators at the skin site, as well as local swelling of the ear pinna. The model can be used for investigating anti-inflammatory compounds, such as dexamethasone, and for preclinical drug discovery research, especially in areas where neutrophilic inflammation plays a role in disease pathophysiology. The cantharidin blister model is one of very few translational models described in humans, and the mechanism of inflammation induction is comparable in mice and man. In human studies, the cantharidin blister assay has been used to assess the effects of potential new therapies in early-stage clinical studies. © 2021 Novartis AG. Basic Protocol 1: Application of cantharidin to induce ear inflammation Basic Protocol 2: Assessment of ear edema Basic Protocol 3: Assessment of inflammatory mediators in ear tissue Basic Protocol 4: Histological assessment of ear tissue.

Bullous fixed drug eruption related to multivitamins.

Multivitamins are commonly consumed over-the-counter supplements. Drug reactions related to multivitamins are rare and very few cases have been reported. This is a case of a young woman who developed bullous fixed drug eruption to multivitamins.