Keratinocyte Necrosis Research Articles

Infectious complications of Stevens-Johnson syndrome and toxic epidermal necrolysis: A systematic review and meta-analysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe cutaneous adverse reactions to medications characterized by keratinocyte necrosis leading to loss of protective barrier function and increased susceptibility to infection. Infection is a major cause of morbidity, and septicemia is the leading cause of mortality in this population. This systematic review and meta-analysis aimed to determine infectious complications' prevalence and risk factors in adults with SJS and TEN. This review was registered with the International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) and conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Thirty-six articles describing results from 1446 cases were included. Skin infection was the most commonly diagnosed infection. The pooled prevalence of sepsis, respiratory tract infection, skin infection, and urinary tract infection was 27.3%, 21.5%, 37.5%, and 21.8%, respectively. Staphylococcus aureus was the most commonly identified organism. The overall quality of the studies was suboptimal, and the level of heterogeneity was high. The skin, bloodstream, respiratory, and urinary tracts are most commonly infected in the course of adult SJS and TEN. During hospitalization, clinicians should closely monitor and promptly investigate for these as well as several other infectious complications. More research is needed, with greater attention to the risk factors and causative organisms that cause these infections.

Analysis of clinical characteristics of terbinafine-induced subacute cutaneous lupus erythematosus

ABSTRACT Introduction Terbinafine may cause subacute cutaneous lupus erythematosus (SCLE), and we aimed to analyze its clinical characteristics. Methods We collected literature on terbinafine-induced SCLE from 1997 to 2023 for retrospective analysis. Thirty-seven patients (33 females and 4 males) were included. Results The patients have a median age of 49.5 years (range 18–79) and onset time of 5 weeks (range 1–12). SCLE is mainly manifested as annular erythematous (83.3%), scaly erythematous (44.4%), and maculopapular erythematous (13.9%). Mainly, histopathological manifestations are lymphocytic infiltrate (55.6%), hyperkeratosis (38.9%) and keratinocyte necrosis (38.9%). Positive immunological parameters mainly include antinuclear antibody (100.0%), anti-Ro/SSA antibody (94.1%), and anti-La/SSB antibody (72.2%). Past medical history usually includes photosensitivity (33.3%), inflammatory disease (33.33%), and lupus erythematosus (12.1%). Symptoms are completely resolved within a median time of 35 days (range 7–84) after discontinuation of terbinafine and treatment with topical corticosteroids, systemic corticosteroids, hydroxychloroquine, and immunosuppressant. No recurrence was observed within 12 months (range 1.5–48) of follow-up. Conclusion These results suggest that terbinafine-induced SCLE should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and past medical history. Terbinafine should be immediately discontinued when SCLE occurs, while systemic and topical corticosteroids combined with hydroxychloroquine may be an effective treatment.

In Silico and In Vitro Studies on an Asymmetrical Porphyrin Derivative with Therapeutic Potential in Skin Disorders.

For developing novel photosensitizers with therapeutic potential in non-malignant and malignant cutaneous disorders, the unsymmetrical porphyrin, 5-(2-hydroxy-3-methoxyphenyl)-10, 15, 20-tris-(4-carboxymethylphenyl) porphyrin, was evaluated in silico and in vitro. The cellular uptake of the investigated porphyrin and its ability to perform photodynamic therapy were investigated in terms of the viability, proliferation, and necrosis of human HaCaT keratinocytes and human Hs27 skin fibroblasts, in correlation with the predictions regarding diffusion through cell membranes, ADMET profile (absorption, distribution, metabolism, elimination, toxicity), and potential pharmacological mechanism. Molecular docking and 250 ns molecular dynamics simulations revealed that P5.2 has the potential to form a relatively stable complex with the carbonic anhydrase IX catalytic site, the lowest predicted free energy of binding (MM/PBSA) being -39.097 kcal/mol. The results of the in vitro study showed that P5.2 is incorporated within 24 h in the investigated cells, especially in HaCaT keratinocytes, indicating its photosensitizing ability. Nevertheless, P5.2 does not exert significant cytotoxicity in "dark" conditions. In turn, PDT induced a decrease in the number of metabolically active HaCaT keratinocytes within 24 h, accompanied by a 4-fold increase in lactate dehydrogenase release, indicating its ability to perform PDT in human skin cells. The experimental results suggest that the asymmetrical porphyrin is a promising candidate theranostics agent for skin disorders.

Clinical and molecular detection of fowl pox in domestic pigeons in Basrah Southern of Iraq

Bird species, particularly poultry and other bird types, including domestic pigeons, are susceptible to fowl pox, a contagious viral disease. The main goal of this study was to validate clinical avipoxvirus diagnoses using molecular analytical methods. The essential components of the investigation were the clinical signs, visible abnormalities, histological changes, and polymerase chain reaction analysis. Twenty out of 120 pigeons had clinical symptoms, which included yellowish crust or nodules near the feet, eyes, and beak. An erosive epidermal lesion and an epidermal acanthotic papular lesion with basal vacuolation were maculopapular evidence associated with significant epidermal hyperkeratosis, as confirmed by histological analysis. In addition, the results showed keratinocyte necrosis beneath the hyperkeratotic epidermal layer, together with superficial and deep dermal perivascular lymphocytic infiltration. In addition, the P4b core protein gene underwent phylogenetic analysis. The sequence analysis results indicated a high degree of similarity across the local strains, with just minor variations observed. Five sample sequences were selected and submitted to the NCBI database. These sequences were identified as OR187728, OR187729, OR187730, OR187731, and OR187732. All the various strains in this research may be classified under clade A of the chicken pox virus phylogenetic classification. This study presents the first description and characterization of pox virus infections in domestic pigeons inside the Basrah governorate.

Clinicopathological Spectrum of Interface Dermatitis

Introduction: Interface dermatitis, which is characterized by variable dermoepidermal interface inflammation and the presence of vacuolar damage to the basal layer, which causes keratinocyte death or necrosis, is a broad term that encompasses many distinct illnesses. . Aim: The present study was planned to correlate the significance of Interface dermatitis with their clinico-pathological aspects. Methodology: This was a retrospective study conducted on 170 cases diagnosed as interface dermatitis over a period of two years. Skin biopsy samples received from the outpatient department were analysed. Results: In the present study, a total of 170 cases were analysed which clinically presented as papulosquamous disorders. On histopathological diagnosis, LP and its variants were the most common type disorder. The most consistent histolopathological characteristic feature noted was basal cell vacuolar degeneration in the epidermis along with a band of lymphocytic inflammatory infiltrate. Clinicopathologic concordance was seen in 86.5% cases. Conclusion: Thus, combination of the histologic details, in correlation with the clinical data helps in arriving at a specific diagnosis of various ID.

Toxic epidermal necrolysis induced by COVID-19

Toxic epidermal necrolysis (TEN) is a life-threatening acute mucocutaneous syndrome. It is characterized by keratinocyte necrosis and apoptosis, which affect more than 30% of the body's surface. TEN is most commonly due to an altered immunological response to specific drugs, infections, and malignancies, or it can be idiopathic. The combination of TEN and COVID-19 can have a fatal outcome if not recognized and promptly treated. Therefore, fast reporting of such cases will draw doctors’ attention to quick and right intervention. In this article, we present a 66-year-old patient with a clinical presentation of toxic epidermal necrolysis along with a coexisting COVID-19 infection. To our knowledge, this is the first case of TEN in a patient diagnosed with SARS CoV‑2 infection in Saudi Arabia.

Stevens-Johnson Syndrome

Stevens-Johnson Syndrome (SJS) is an antibody-mediated disease characterized by prodromal symptoms followed by severe mucocutaneous manifestations. The more severe form of SJS is Toxic Epidermal Necrolysis (TEN), which causes an inflammatory response resulting in keratinocyte necrosis and perivascular lymphocyte infiltration. The incidence of SJS is said to be 1 - 6 per one million people per year, while the incidence of TEN is only 0.4 - 1.2 per one million people per year. So far, similar studies on SJS/TEN cases in Indonesia are minimal as this disease is one of the rare cases. SJS/TEN is an emergency with high mortality and disability. Moderate to severe cases have a mortality rate of 5-15%. In this case, the patient was a 62-year-old male. Based on history and physical examination, the patient was diagnosed with Stevens-Johnson Syndrome (SJS). In the dermatologic status of the manus region dextra and sinistra, sagging bulla was found, and in the anterior thorax region, erosive lesions due to ruptured bulla were found. In the medialis femoris region dextra, multiple erythematous, annular macular lesions were found. There were erosions and crusts on the labial and genital regions.

Assessment of Some Unsymmetrical Porphyrins as Promising Molecules for Photodynamic Therapy of Cutaneous Disorders.

In order to select for further development novel photosensitizers for photodynamic therapy in cutaneous disorders, three unsymmetrical porphyrins, namely 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2), 5-(2-hydroxy-5-methoxyphenyl)-10,15,20-tris-(4-carboxymethylphenyl) porphyrin (P3.2), and 5-(2,4-dihydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P4.2), along with their fully symmetrical counterparts 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1) and 5,10,15,20-tetrakis-(4-carboxymethylphenyl) porphyrin (P3.1) were comparatively evaluated. The absorption and fluorescence properties, as well as atomic force microscopy measurements were performed to evaluate the photophysical characteristics as well as morphological and textural properties of the mentioned porphyrins. The cellular uptake of compounds and the effect of photodynamic therapy on the viability, proliferation, and necrosis of human HaCaT keratinocytes, human Hs27 skin fibroblasts, human skin SCL II squamous cell carcinoma, and B16F10 melanoma cells were assessed in vitro, in correlation with the structural and photophysical properties of the investigated porphyrins, and with the predictions regarding diffusion through cell membranes and ADMET properties. All samples were found to be isotropic and self-similar, with slightly different degrees of aggregability, had a relatively low predicted toxicity (class V), and a predicted long half-life after systemic administration. The in vitro study performed on non-malignant and malignant skin-relevant cells highlighted that the asymmetric P2.2 porphyrin qualified among the five investigated porphyrins to be a promising photosensitizer candidate for PDT in skin disorders. P2.2 was shown to accumulate well within cells, and induced by PDT a massive decrease in the number of metabolically active skin cells, partly due to cell death by necrosis. P2.2 had in this respect a better behavior than the symmetric P.2.1 compound and the related asymmetric compound P4.2. The strong action of P2.2-mediated PDT on normal skin cells might be an important drawback for further development of this compound. Meanwhile, the P3.1 and P3.2 compounds were not able to accumulate well in skin cells, and did not elicit significant PDT in vitro. Taken together, our experiments suggest that P2.2 can be a promising candidate for the development of novel photosensitizers for PDT in skin disorders.

A retrospective analysis of mortality risk and immunosuppressive therapy for Stevens-Johnson Syndrome and toxic epidermal necrolysis syndrome using the TriNetX research network

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) exist on a spectrum of autoimmune conditions which cause epidermal detachment and keratinocyte necrosis. Due to the rare incidence of these conditions, a dramatic heterogeneity in treatment algorithms exists. To better appreciate pharmacologic immunosuppressive therapies' impact on survival, the authors queried a multi-institutional data network. Data for this study was extracted from TriNetX Research Network, a platform that contains ICD-9/ICD-10 coding data from a consortium of international healthcare organizations. Seventy-one institutions were queried to identify adult patients diagnosed with SJS, TEN or SJS-TEN Overlap. Cohorts were created based on the therapy received: systemic steroids (SS), diphenhydramine (DH), cyclosporine (CS), intravenous immunoglobulin (IVIG), tumor necrosis factor alpha inhibitors (TNFαi), or a combination of treatments. Cohorts were then propensity matched with patients who received supportive care. Patients who only received one of the above treatments showed no significant reduction in 90-day mortality. Patients who received CS or IVIG as part of their multitherapy showed a significantly increased risk of death when compared to supportive care (CS: RR = 1.583, 95% CI [1.119, 2.240]; IVIG: RR = 2.132, 95% CI [1.485, 3.059]). Despite their frequent utilization, this study’s analysis suggests that none of these therapies confer significant 90-day mortality survival over supportive care alone. These results highlight the heterogeneity of therapies and emphasize the need for critical prospective appraisal of their outcomes in SJS and TEN.

PEMPHIGUS VEGETANS OF NEUMANN: A CASE REPORT OF A RARE VARIANT OF PEMPHIGUS VULGARIS

Pemphigus vegetans is a rare variant of pemphigus vulgaris characterized by periorificial papillomatous vegetations. We present the case of a 77-year-old female patient with a history of type 2 diabetes and hypertension who presented with painful verrucous lesions on her tongue. The examination revealed a cerebriform tongue with small, hard, confluent verrucous swellings, which is a well-known sign seen in pemphigus vegetans. A biopsy revealed acantholysis and absence of keratinocyte necrosis, leading to the diagnosis of Neumann-type pemphigus vegetans. The patient was prescribed prednisone and trichloroacetic acid, which resulted in successful treatment. Management of pemphigus vegetans should be individualized based on the patients clinical presentation and response to treatment.

Neurologic and cutaneous infection by Clostridium piliforme in a kitten with systemic Tyzzer disease.

Tyzzer disease (TD) is a highly fatal condition of animals caused by Clostridium piliforme and characterized pathologically by enteritis, hepatitis, myocarditis, and occasionally encephalitis. Cutaneous lesions have been reported only rarely in animals with TD, and infection of the nervous system has not been described in cats, to our knowledge. We describe here neurologic and cutaneous infection by C. piliforme in a shelter kitten with systemic manifestations of TD and coinfection with feline panleukopenia virus. Systemic lesions included necrotizing typhlocolitis, hepatitis, myocarditis, and myeloencephalitis. The cutaneous lesions consisted of intraepidermal pustular dermatitis and folliculitis, with necrosis of keratinocytes and ulceration. Clostridial bacilli were identified within the cytoplasm of keratinocytes by fluorescence in situ hybridization, and a PCR assay was positive for C. piliforme. C. piliforme can infect keratinocytes leading to cutaneous lesions in cats with the location suggesting direct contact with contaminated feces as a route of infection.

Fixed drug eruption after Pfizer-BioNTech COVID-19 vaccine: A case report

Fixed drug eruption after Pfizer-BioNTech COVID-19 vaccine: A case report

Immunomodulatory Treatment of Lyell's Syndrome: A Simultaneous Plasmapheresis and Intravenous Immunoglobulins Therapy.

Lyell's syndrome, or toxic epidermal necrolysis (TEN) is a rare but life-threatening condition. It manifests with blistering of skin and mucous due to subepidermal bullae and keratinocyte necrosis. In most cases, it is an immune response to drugs or their metabolites. The mortality in TEN is high despite optimal infection and wound control. There are no unequivocal treatment guidelines in TEN. Immunosuppressive treatment may increase the wound infection risk and mortality. The aim of the study was to evaluate a 10-year experience with immunomodulatory therapy in TEN. We perform a combination of plasmapheresis and intravenous immunoglobulins to control the disease. There were 35 patients in the group and we performed a post hoc evaluation. Twenty-eight patients received the full protocol and there were seven patients who did not complete the treatment (single therapy group). The mortality in the test group was 14.29%, and the difference reached statistical significance in comparison with the single therapy group (P < .05). Our protocol reduced the mortality risk five times. Our study proved that simultaneous plasmaphereses with intravenous immunoglobulins administration were safe and improved patients' outcome in TEN.

Acrodermatitis enteropathica-like eruption

Acrodermatitis enteropathica-like eruption

795 Autologous skin cell suspension application for toxic epidermal necrolysis: a case report

IntroductionToxic epidermal necrolysis (TEN) is a drug-mediated disease which occurs at the same level of a partial thickness thermal injury. It has been treated with frequent dressing changes and supportive care as there are no definitive therapies. The pathophysiology involves necrosis of keratinocytes at the dermal-epidermal junction leading to sloughing of the epidermis and sub-epidermal bullae. Patients have massive fluid and electrolyte dysregulation due to chronic wounds that are susceptible to infection. This case report describes the application of autologous skin cell suspension (ASCS) to a patient with TEN. His hospital course included arrest of the disease process, timely closure of the wound, and minimal wound care. To our knowledge, this is the first case of TEN treated with ASCS.MethodsThe patient was mechanically debrided with a water scalpel hydrosurgery system to remove all devitalized tissue. A donor graft for ASCS was then obtained at standard depth from unaffected skin at the ankle and was processed in the standard fashion and applied to the wound. Clear plastic dressing with a non-adherent, antibiotic impregnated cloth dressing followed by dry non-shear dressing were then applied to the torso. Extremities were dressed in clear plastic dressing, antibiotic impregnated cloth dressing, zinc paste impregnated cloth, dry gauze roll, and elastic compression bandage. This was performed over the patient’s anterior surface and subsequently on the posterior one week later. Dressings were taken down on post-operative day (POD) 6 and replaced as appropriate.ResultsThe patient demonstrated 60% closure of wounds on his anterior torso at POD 6. By POD 8, the patient's anterior torso and face were completely closed. His second application of ASCS to his posterior closed in a similar timeline. The patient was discharged on POD 16 from his initial intervention with 2% total body surface area open. At POD 30, his wounds were healed with the return of a large portion of pigmentation.ConclusionsTEN is a rare, high-mortality disease without efficacious therapy. Given that the wounds are at a similar level to a partial thickness burn, ASCS could be a new intervention which could mitigate open wounds, frequent dressing changes, prolonged hospital stays, and mortality.

Histopathological and Clinical Analysis of Skin Rashes in Children With Multisystem Inflammatory Syndrome Associated With COVID-19.

A new entity, which occurs a few weeks after SARS-CoV-2 infection and resembling incomplete Kawasaki disease or toxic shock syndrome, has been defined and named multisystem inflammatory syndrome (MIS-C) associated with COVID-19 in children. The aim of our study was to describe histopathological characteristics of skin lesions of MIS-C patients to reveal whether there is a relationship between histopathological features and clinical manifestations. Seventeen who had skin involvement of 57 patients who were diagnosed with MIS-C between December 2020 and February 2021 were included in this prospective study. Demographic information, laboratory findings, and patients' managements were recorded. Skin biopsies were taken simultaneously of each patient. Formalin-fixed, paraffin-embedded skin samples were examined microscopically. The rate of skin rash was 30% in patients with MIS-C and was predominantly the maculopapular type. The anatomical distribution of the rash was evaluated as localized in 10 and generalized in 7 patients. In patients with myocarditis, C-reactive protein and fibrinogen were found to be significantly higher, and lymphocyte and albumin values were found to be low. Herpes-like inclusions were found in the microscopic examination of 2 patients with a history of zona zoster in themselves or in their mother. There was a significant difference between keratinocyte necrosis and some clinical parameters. Localized skin lesions appear to be associated with a more severe inflammatory.

Improvement of Mortality Prognostication in Patients With Epidermal Necrolysis

Epidermal necrolysis is a severe cutaneous adverse reaction in which severe systemic inflammation results in extensive epithelial keratinocyte necrosis. The most commonly used prognostic score in epidermal necrolysis, the Severity-of-Illness Score for Toxic Epidermal Necrolysis (SCORTEN), was recently found to overestimate mortality in contemporary cohorts. Identification of independent prognostic markers may help to stratify risk more accurately. This study evaluates the association between novel inflammatory markers and in-hospital mortality in patients with epidermal necrolysis to study the incremental prognostic value of these markers in combination with SCORTEN. A retrospective cohort study was conducted over a 17-year period from 2003 to 2019. Patients were enrolled from Singapore General Hospital, the national referral center for epidermal necrolysis. A total of 196 patients with epidermal necrolysis were recruited, 4 (2%) of whom were excluded owing to incomplete data. The main outcome assessed was the in-hospital mortality rate. Discrimination and calibration of risk scores were assessed using the area under the receiver operating characteristic curve (AUC) and calibration plot, respectively. Evaluation of the incremental prognostic value of these markers was done by comparing the AUC between the old and new risk score, and the use of net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Among 192 total patients (median [IQR] age 56 [42-70] years; 114 [59.4%] women), there were 43 (22.4%) who did not survive to discharge. Of the novel inflammatory markers, only red cell distribution width to hemoglobin ratio was significant in predicting in-hospital mortality (odds ratio [OR] 3.55; 95% CI, 1.76-7.16; P < .001) after adjusting for SCORTEN. The RDW/Hb as applied in 4 risk groups showed similar discrimination to SCORTEN (AUC [95% CI]: RDW/Hb in 4 groups, 0.76 [0.69-0.84], vs SCORTEN, 0.78 [0.70-0.85], P = .89). When RDW/Hb was added to SCORTEN, the composite score Re-SCORTEN showed significantly better discrimination than SCORTEN alone (AUC [95% CI]: Re-SCORTEN, 0.83 [0.77-0.89], vs SCORTEN, 0.78 [0.70-0.85], P = .02). The overall NRI was 0.94 (95% CI, 0.68-1.20), P < .001. The IDI was 0.06 (95% CI 0.03-0.08), P < .001. Re-SCORTEN showed good calibration based on the calibration plot. In this cohort of patients, RDW/Hb, an inexpensive and readily available marker, showed similar predictive accuracy with SCORTEN. Furthermore, when used in combination with SCORTEN, it also helped augment prognostic ability.

Radiation recall reactions: An oncologic enigma.

Radiation recall reactions (RRR) are uncommon but are a well-known phenomenon to oncologists. Tissue damage in a prior irradiation portal is 'recalled' after the administration of a drug, historically cytotoxics, or more recently, targeted or immunotherapeutic agents. Even COVID-19 vaccines are a reported cause. RRR are enigmatic in that their cause is unknown, but they generally have the histopathological and clinical features of acute or chronic inflammation. They can occur in a variety of tissues, the commonest being skin, which accounts for two-thirds of reported cases. They are generally relatively mild and self-limiting once the trigger drug is stopped, although severe cases with tissue necrosis have occurred. Rechallenge with drug does not necessarily cause reactivation of the reaction. Symptomatic treatment with steroids and antihistamines are usually effective, but their impact on the clinical course is unclear. Various hypotheses have been proposed as to the mechanism of RRR; a non-immune fixed drug reaction-like condition, dysregulated release of reactive oxygen species, abnormalities of tissue vasculature and impaired DNA repair. All could lead to a characteristic inflammatory microenvironment, resulting in dysfunction of tissue stem cells, keratinocyte necrosis and dermal abnormalities. Alternatively or in addition, low levels of inflammatory tissue cytokines induced by previous irradiation might be further upregulated by drug exposure. Most information in this review refers to data derived from cutaneous RRR, since they are the most common form reported.

Dermatologic Manifestations of Systemic Diseases in Childhood

Dermatologic Manifestations of Systemic Diseases in Childhood

Anti-damage effect of theaflavin-3'-gallate from black tea on UVB-irradiated HaCaT cells by photoprotection and maintaining cell homeostasis.

Keratinocytes are rich in lipids and are the main sensitive cells to ultraviolet (UV) rays. Theaflavins are the core functional components of black tea and are known as the "soft gold" in tea. In this study, ultraviolet-B (UVB) irradiation caused apoptosis and necrosis of human epidermal keratinocytes (HaCaT). EGCG and the four theaflavins had anti-UVB damage activity, among which theaflavin-3'-gallate (TF3'G) had the best activity. The results of biophysical and molecular biology experiments showed that TF3'G has anti-damage effects on UVB-irradiated HaCaT cells through the dual effects of photoprotection and maintenance of cell homeostasis. That is, TF3'G preincubation could absorb UV rays, reduce the accumulation of aging-related heterochromatin (SAHF) formation, increase mitochondrial membrane potential, downregulate NF-κB inflammation pathways, inhibit the formation of cytotoxic aggregates, and protect biological macromolecules Structure, etc. The accumulation of conjugated π bonds and the balance benzoquinone are the core functional structure of TF3'G with high efficiency and low toxicity. The study indicates that TF3'G has the potential to inhibit the photoaging and intrinsic aging of skin cells.