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Infection and Immunity Jun 2024causes the genital ulcer disease chancroid and painful cutaneous ulcers in children who live in the tropics. To acquire heme from the host, expresses a TonB-dependent...
causes the genital ulcer disease chancroid and painful cutaneous ulcers in children who live in the tropics. To acquire heme from the host, expresses a TonB-dependent hemoglobin receptor, HgbA, which is necessary and sufficient for to progress to the pustular stage of disease in a controlled human infection model. HgbA transports hemoglobin across the outer membrane; how heme is transported across the cytoplasmic membrane is unclear. In previous studies, transcripts encoding the YfeABCD heme transporter were upregulated in experimental lesions caused by in human volunteers, suggesting the latter may have a role in virulence. Here we constructed a double deletion mutant, 35000HPΔΔ, which exhibited growth defects relative to its parent 35000HP in media containing human hemoglobin as an iron source. Five human volunteers were inoculated at three sites on the skin overlying the deltoid with each strain. The results of the trial showed that papules formed at 100% (95% CI, 71.5, 100) at both 35000HP and 35000HPΔΔ-inoculated sites ( = 1.0). Pustules formed at 60% (95% CI, 25.9, 94.1) at parent-inoculated sites and 53% (95% CI, 18.3, 88.4) at mutant-inoculated sites ( = 0.79). Thus, the ABC transporter encoded by and was dispensable for virulence in humans. In the absence of YfeABCD, likely utilizes other periplasmic binding proteins and ABC-transporters such as HbpA, SapABCDF, and DppBCDF to shuttle heme from the periplasm into the cytoplasm, underscoring the importance of redundancy of such systems in gram-negative pathogens.
Topics: Haemophilus ducreyi; Humans; Chancroid; Bacterial Proteins; Virulence; Iron; Male; Adult; Heme
PubMed: 38780215
DOI: 10.1128/iai.00058-24 -
Journal of the European Academy of... May 2024The interleukin (IL)-1 superfamily upregulates immune responses and maintains homeostasis between the innate and adaptive immune systems. Within the IL-1 superfamily,... (Review)
Review
The interleukin (IL)-1 superfamily upregulates immune responses and maintains homeostasis between the innate and adaptive immune systems. Within the IL-1 superfamily, IL-36 plays a pivotal role in both innate and adaptive immune responses. Of the four IL-36 isoforms, three have agonist activity (IL-36α, IL-36β, IL-36γ) and the fourth has antagonist activity (IL-36 receptor antagonist [IL-36Ra]). All IL-36 isoforms bind to the IL-36 receptor (IL-36R). Binding of IL-36α/β/γ to the IL-36R recruits the IL-1 receptor accessory protein (IL-1RAcP) and activates downstream signalling pathways mediated by nuclear transcription factor kappa B and mitogen-activated protein kinase signalling pathways. Antagonist binding of IL-36Ra to IL-36R inhibits recruitment of IL-1RAcP, blocking downstream signalling pathways. Changes in the balance within the IL-36 cytokine family can lead to uncontrolled inflammatory responses throughout the body. As such, IL-36 has been implicated in numerous inflammatory diseases, notably a type of pustular psoriasis called generalized pustular psoriasis (GPP), a chronic, rare, potentially life-threatening, multisystemic skin disease characterised by recurrent fever and extensive sterile pustules. In GPP, IL-36 is central to disease pathogenesis, and the prevention of IL-36-mediated signalling can improve clinical outcomes. In this review, we summarize the literature describing the biological functions of the IL-36 pathway. We also consider the evidence for uncontrolled activation of the IL-36 pathway in a wide range of skin (e.g., plaque psoriasis, pustular psoriasis, hidradenitis suppurativa, acne, Netherton syndrome, atopic dermatitis and pyoderma gangrenosum), lung (e.g., idiopathic pulmonary fibrosis), gut (e.g., intestinal fibrosis, inflammatory bowel disease and Hirschsprung's disease), kidney (e.g., renal tubulointerstitial lesions) and infectious diseases caused by a variety of pathogens (e.g., COVID-19; Mycobacterium tuberculosis, Pseudomonas aeruginosa, Streptococcus pneumoniae infections), as well as in cancer. We also consider how targeting the IL-36 signalling pathway could be used in treating inflammatory disease states.
PubMed: 38779986
DOI: 10.1111/jdv.19935 -
BMC Infectious Diseases May 2024Chromobacterium violaceum is a rare but severe and often fatal cause of disease in humans. We present 2 clinical cases of sepsis and skin abscesses / cellulitis caused...
Chromobacterium violaceum is a rare but severe and often fatal cause of disease in humans. We present 2 clinical cases of sepsis and skin abscesses / cellulitis caused by C. violaceum seen in a referral hospital for infectious diseases in Vietnam. Both patients survived, but appropriate antibiotic treatment was only installed after culture of the organism. We reviewed and summarised the characteristics of C. violaceum infection and treatment.
Topics: Female; Humans; Anti-Bacterial Agents; Cellulitis; Chromobacterium; Gram-Negative Bacterial Infections; Sepsis; Vietnam; Child; Adolescent
PubMed: 38773469
DOI: 10.1186/s12879-024-09390-1 -
Dermatology Online Journal Mar 2024Tumor necrosis factor (TNF) inhibitors may paradoxically induce pustular eruptions, most of which are classified as pustular psoriasis. Amicrobial pustulosis of the...
Tumor necrosis factor (TNF) inhibitors may paradoxically induce pustular eruptions, most of which are classified as pustular psoriasis. Amicrobial pustulosis of the folds (APF) is a much rarer entity that was recently recognized to occur in the setting of chronic anti-TNF therapy and inflammatory bowel disease, with 12 existing cases in the literature. Amicrobial pustulosis of the folds is a neutrophilic dermatosis characterized by aseptic pustules involving the major and minor skin folds, genital regions, and scalp. Herein, we report an additional case of paradoxical APF induced by chronic infliximab therapy in a patient with Crohn disease.
Topics: Humans; Infliximab; Crohn Disease; Adult; Skin Diseases, Vesiculobullous; Male; Female; Tumor Necrosis Factor-alpha
PubMed: 38762858
DOI: 10.5070/D330163286 -
The Journal of Dermatology May 2024Palmoplantar pustulosis (PPP) is a chronic relapsing inflammatory skin disease characterized by multiple vesicles, pustules, and erythematous plaques on the palms and...
Palmoplantar pustulosis (PPP) is a chronic relapsing inflammatory skin disease characterized by multiple vesicles, pustules, and erythematous plaques on the palms and soles. The exacerbation of PPP is strongly associated with focal infections, such as tonsillitis, dental infections, and sinusitis, in Japan. Recently, the neutrophil-to-lymphocyte ratio (NLR) has been widely used as a convenient and useful marker for clinical conditions and various diseases; however, an association between PPP and NLR has not yet been established. We retrospectively analyzed 79 patients with PPP from our hospital to evaluate the clinical significance of the NLR. The average NLR value in patients with PPP was significantly higher than that in healthy controls (2.30 ± 1.02 vs 1.69 ± 0.45, P < 0.001). A comparative analysis of patients with PPP with and without infectious complications showed that there was a statistical difference in the NLR between patients with PPP with and without focal infections, whereas no significant difference was found for metal allergy, smoking, and pustulotic arthro-osteitis. Multivariate analysis indicated that the NLR was significantly associated with focal infections (odds ratio = 18.38, 95% confidence interval 3.86-87.35, P < 0.001). The NLR was also significantly correlated with C-reactive protein levels (P = 0.013, r = 0.2857). Interestingly, after symptom improvement, the NLR significantly decreased from the baseline levels. Furthermore, statistical analysis using the Youden's index revealed that an NLR of 2.28 or higher was associated with the risk of any focal infections in patients with PPP. These results suggest that the NLR has potential applications as a biomarker of the presence of focal infections in patients with PPP.
PubMed: 38760982
DOI: 10.1111/1346-8138.17272 -
Medicine International 2024Skin and soft tissue infections (SSTIs), which are mainly caused by Gram-positive cocci existing on the skin surface, are more common than those caused by Gram-negative...
Skin and soft tissue infections (SSTIs), which are mainly caused by Gram-positive cocci existing on the skin surface, are more common than those caused by Gram-negative bacteria; however, the role of Gram-negative bacteria as emerging pathogens in SSTIs cannot to be ignored. is an opportunistic pathogenic bacterium that mainly inhabits the respiratory and intestinal tracts of humans and animals, as well as the environment, including aquaculture farms. This bacterium can cause multiple infections in humans and animals. The present study reports the case of a SSTI which was suspected to be caused by in a 74-year-old farmer with venous thrombosis. The patient had exposed his four bare limbs to the farmed shrimps and shrimp pond routinely. Pustule and skin ulcers were observed on both the legs of the patient. After receiving anti-infection therapy, the SSTI was almost completely resolved on day 9 and the patient was then discharged.
PubMed: 38756456
DOI: 10.3892/mi.2024.158 -
The Annals of Pharmacotherapy May 2024This article reviews clinical trial data that assesses the safety, efficacy, and clinical application of spesolimab, an interleukin-36 (IL-36) blocker, for the treatment... (Review)
Review
OBJECTIVE
This article reviews clinical trial data that assesses the safety, efficacy, and clinical application of spesolimab, an interleukin-36 (IL-36) blocker, for the treatment of generalized pustular psoriasis (GPP).
DATA SOURCES
A review of the literature was conducted using the search terms: "spesolimab," "BI 655130," and "spevigo" in MEDLINE (PubMed) and Clinicaltrials.gov from January 1, 1950 to October 31, 2023.
STUDY SELECTION AND DATA EXTRACTION
Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of spesolimab were included.
DATA SYNTHESIS
In one phase 2 clinical trial evaluating single dose IV spesolimab for GPP flares at day 8, 54% of patients receiving spesolimab had a GPP physician global assessment (GPPGA) pustulation subscore of 0, and 43% had a GPPGA total score of 0 compared with 6% and 11% for the placebo group, respectively. Another phase 2 clinical trial assessing subcutaneous spesolimab found 23% of patients in low-dose, 29% in medium-dose, and 10% of high-dose spesolimab had flares by week 48 compared with 52% of the placebo group. Hazard ratios for time to GPP flare compared with placebo were 0.16 ( = 0.0005), 0.35 ( = 0.0057), and 0.47 ( = 0.027) for the spesolimab groups, respectively. Infection rates were similar across treatment and placebo groups, and severe adverse events such as drug reactions with eosinophilia and systemic symptom (DRESS), cholelithiasis, and breast cancer occurred with spesolimab.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS
Spesolimab is a first-in-class IL-36 monoclonal antibody receptor antagonist approved for the treatment of acute GPP flares. It is a safe and effective therapeutic agent in preventing future GPP flares, with no current comparator trials with other GPP agents.
CONCLUSION
Spesolimab is a safe and effective treatment for acute GPP flares in adults. Future clinical trials can establish safety and efficacy compared with other agents.
PubMed: 38755971
DOI: 10.1177/10600280241252688 -
JAMA Dermatology May 2024
PubMed: 38748440
DOI: 10.1001/jamadermatol.2024.1082 -
Clinical and Experimental Dermatology May 2024Generalized pustular psoriasis (GPP) is a relapsing-remitting chronic disease characterized by painful pustules with systemic symptoms that negatively impacts quality of...
BACKGROUND
Generalized pustular psoriasis (GPP) is a relapsing-remitting chronic disease characterized by painful pustules with systemic symptoms that negatively impacts quality of life. The psychosocial and economic burden of this rare condition is not well characterized.
OBJECTIVES
To qualitatively characterize the cumulative burden of generalized pustular psoriasis on patients' quality of life and psychosocial wellbeing.
METHODS
A retrospective chart review of patients with generalized pustular psoriasis was performed to collect demographic information, followed by prospective semi-structured clinical interviews. Interview transcripts were analyzed using thematic analysis.
RESULTS
Three major themes were revealed: (1) Burden of having a chronic disease with an unpredictable course, (2) an inability to fulfill societal roles results in a loss of identity, and (3) a physician-patient relationship grounded in trust and transparency can be invaluable in helping patients endure chronic disease.
CONCLUSION
GPP has a negative impact on patients' quality of life and psychosocial wellbeing. Impairments in daily function and mental health primarily affects patients during flares and influences behavior during periods of quiescence. A strong patient-physician relationship may help mitigate the impact of GPP.
PubMed: 38739726
DOI: 10.1093/ced/llae194 -
Journal of Cutaneous and Aesthetic... 2024Acne keloidalis nuchae is a chronic inflammatory condition affecting the occipital area or nape of the neck characterized by fibrotic papules, firm pustules, and nodules...
Treatment of Acne Keloidalis Nuchae by Simply Combining Two Conventionally Available Modalities: Ablation with Carbon Dioxide Laser and Intralesional Triamcinolone Acetonide.
Acne keloidalis nuchae is a chronic inflammatory condition affecting the occipital area or nape of the neck characterized by fibrotic papules, firm pustules, and nodules that coalesce into keloid like mass or plaques. It was first described by Kaposi in 1969. It is also known as lichen keloidalis nuchae, dermatitis papillaris capillitia, and folliculitis nuchae scleroticans. If not treated in the early stages of the disease it tends to be refractory to conventional methods like topical, intralesional steroids with antibiotics or retinoids. Surgical interventions remain the only choice in such cases. Various surgical modalities including surgical excision with primary or secondary closure, split-thickness skin grafts, and laser-assisted treatments have been tried. Most surgical methods have longer downtime with a higher chance of relapse. We studied the results of a combined treatment option carbon dioxide laser ablation followed by intralesional triamcinolone injection in the same sitting. This outpatient procedure has shown good results with no relapse and less downtime.
PubMed: 38736851
DOI: 10.4103/JCAS.JCAS_112_23