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Reumatologia Clinica Jun 2024VEXAS syndrome is a rare entity secondary to UBA1 gene mutations, located on the X chromosome. This mutation generates, as a consequence, a characteristic vacuolation on...
VEXAS syndrome is a rare entity secondary to UBA1 gene mutations, located on the X chromosome. This mutation generates, as a consequence, a characteristic vacuolation on haematopoietic stem-cells. It is characterized by multiple autoinflammatory and haematologic manifestations, which respond and end up being dependent on corticosteroid treatment. In this publication we present a 2-case series diagnosed at our hospital and make a brief literature review of the published evidence so far.
PubMed: 38918162
DOI: 10.1016/j.reumae.2024.05.006 -
International Journal of Molecular... May 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Known as COVID-19, it has affected billions of people worldwide, claiming...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Known as COVID-19, it has affected billions of people worldwide, claiming millions of lives and posing a continuing threat to humanity. This is considered one of the most extensive pandemics ever recorded in human history, causing significant losses to both life and economies globally. However, the available evidence is currently insufficient to establish the effectiveness and safety of antiviral drugs or vaccines. The entry of the virus into host cells involves binding to angiotensin-converting enzyme 2 (ACE2), a cell surface receptor, via its spike protein. Meanwhile, transmembrane protease serine 2 (TMPRSS2), a host surface protease, cleaves and activates the virus's S protein, thus promoting viral infection. Plant protease inhibitors play a crucial role in protecting plants against insects and/or microorganisms. The major storage proteins in sweet potato roots include sweet potato trypsin inhibitor (SWTI), which accounts for approximately 60% of the total water-soluble protein and has been found to possess a variety of health-promoting properties, including antioxidant, anti-inflammatory, ACE-inhibitory, and anticancer functions. Our study found that SWTI caused a significant reduction in the expression of the ACE2 and TMPRSS2 proteins, without any adverse effects on cells. Therefore, our findings suggest that the ACE2 and TMPRSS2 axis can be targeted via SWTI to potentially inhibit SARS-CoV-2 infection.
Topics: Angiotensin-Converting Enzyme 2; Humans; SARS-CoV-2; Animals; Serine Endopeptidases; Ipomoea batatas; Antiviral Agents; COVID-19 Drug Treatment; COVID-19; Trypsin Inhibitors; Virus Internalization; Chlorocebus aethiops; Vero Cells; Down-Regulation; Mice
PubMed: 38892254
DOI: 10.3390/ijms25116067 -
Pediatric Dermatology Jun 2024An otherwise healthy 4-week-old term female of Japanese heritage presented with a 1-week history of asymptomatic progressive, generalized skin lesions. The lesion...
An otherwise healthy 4-week-old term female of Japanese heritage presented with a 1-week history of asymptomatic progressive, generalized skin lesions. The lesion morphology, distribution, and dermatopathology result was consistent with Sweet syndrome. The patient was found to have a congenital type H rectovestibular fistula. This case highlights the rare association of rectovestibular fistula in neonatal Sweet syndrome which has only been described in neonates of Japanese heritage.
PubMed: 38886158
DOI: 10.1111/pde.15670 -
International Journal of Gynaecology... Jun 2024The aim of this review is to increase obstetrician awareness of pregnancy-associated Sweet syndrome. Patients present with fever, leukocytosis, and skin eruption, which... (Review)
Review
The aim of this review is to increase obstetrician awareness of pregnancy-associated Sweet syndrome. Patients present with fever, leukocytosis, and skin eruption, which can mimic other infectious or inflammatory conditions, but do not respond to antibiotics. A search using PubMed, EMBASE, and Web of Science Core Collection was conducted to review all reported cases of pregnancy-associated Sweet syndrome, an acute febrile neutrophilic dermatosis occurring during pregnancy or postpartum. A total of 33 episodes among 30 patients were identified, with the majority (54.5% [18]) of cases occurring within the second trimester. Among the 30 patients, skin lesions most commonly affected the head and neck (73.3% [22]), with rare oral or ocular involvement. Leukocytosis was the most common laboratory finding, reported in 96.7% [29] of patients, with neutrophil predominance noted in 70.0% [21]. The diagnosis was confirmed for all patients with pathognomonic results of skin biopsies. Of the 27 cases detailing treatment, systemic corticosteroids were most frequently used (19 cases), followed by conservative management (seven cases), and dapsone (one case). The dapsone-treated patient and 15 of the 19 steroid-treated patients experienced resolution, but additional management strategies were required in the remaining four individuals. Spontaneous resolution occurred during pregnancy in six of the seven conservatively managed individuals, with one patient experiencing spontaneous abortion shortly after skin eruption at 10 weeks of gestation. No associated maternal deaths were reported. Obstetric complications of pregnancy-associated Sweet syndrome included endomyometritis, sterile placental abscesses, and abdominal wall necrosis. Delivery of healthy infants occurred in 24 of the 25 cases that presented fetal outcome, which included two infants who underwent medically indicated preterm deliveries.
PubMed: 38881204
DOI: 10.1002/ijgo.15713 -
JAMA Dermatology Jun 2024VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined genetic disease with an estimated prevalence of 1 in 4269 men older than 50...
IMPORTANCE
VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined genetic disease with an estimated prevalence of 1 in 4269 men older than 50 years and is marked by systemic inflammation, progressive bone marrow failure, and inflammatory cutaneous manifestations.
OBJECTIVE
To define the spectrum of cutaneous manifestations in VEXAS syndrome and the association of these findings with clinical, genetic, and histological features.
DESIGN, SETTING, AND PARTICIPANTS
This observational cohort study included data from 112 patients who were diagnosed with VEXAS-defining genetic variants in UBA1 between 2019 and 2023. Data were collected from medical record review or from patients with VEXAS directly evaluated at the National Institutes of Health in Bethesda, Maryland.
MAIN OUTCOMES AND MEASURES
To define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histological, and other clinical findings. A secondary outcome was cutaneous response to treatment in VEXAS.
RESULTS
Among the 112 patients (median [range] age, 69 [39-79] years; 111 [99%] male), skin involvement was common (93 [83%]), and the most frequent presenting feature of disease (68 [61%]). Of 64 histopathologic reports available from 60 patients, predominant skin histopathologic findings were leukocytoclastic vasculitis (23 [36%]), neutrophilic dermatosis (22 [34%]), and perivascular dermatitis (19 [30%]). Distinct pathogenic genetic variants were associated with specific cutaneous manifestations. The p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates (14 of 17 patients [82%]), often resembling histiocytoid Sweet syndrome. In contrast, the p.Met41Val variant was associated with vasculitic lesions (11 of 20 patients [55%]) with a mixed leukocytic infiltrate (17 of 20 patients [85%]). Oral prednisone improved skin manifestations in 67 of 73 patients (92%). Patients with VEXAS treated with anakinra frequently developed severe injection-site reactions (12 of 16 [75%]), including ulceration (2 of 12 [17%]) and abscess formation (1 of 12 [8%]).
CONCLUSIONS AND RELEVANCE
Results of this cohort study show that skin manifestations are a common and early manifestation of VEXAS syndrome. Genetic evaluation for VEXAS should be considered in older male patients with cutaneous vasculitis, neutrophilic dermatoses, or chondritis. Awareness of VEXAS among dermatologists is critical to facilitate early diagnosis.
PubMed: 38865133
DOI: 10.1001/jamadermatol.2024.1657 -
Minerva Medica Jun 2024
PubMed: 38863393
DOI: 10.23736/S0026-4806.24.09405-9 -
Cureus Jun 2024Sweet syndrome is an uncommon inflammatory disorder characterized by the abrupt appearance of painful, erythematous papules, plaques, or nodules on the skin. Fever and...
Sweet syndrome is an uncommon inflammatory disorder characterized by the abrupt appearance of painful, erythematous papules, plaques, or nodules on the skin. Fever and leukocytosis frequently accompany the cutaneous lesions. In addition, involvement of the eyes, musculoskeletal system, and internal organs may occur. Sweet syndrome has been associated with a broad range of disorders. There are three subtypes: classical Sweet syndrome, malignancy-associated Sweet syndrome, and drug-induced Sweet syndrome. Classical Sweet syndrome is not associated with malignancy or drugs. It is essentially associated with an upper respiratory infection, gastrointestinal infection, inflammatory bowel disease, and pregnancy. Malignancy-associated Sweet syndrome is associated with hematologic malignancy more than solid malignancy, most commonly with acute myeloid leukemia. Drug-induced Sweet syndrome usually develops approximately two weeks after drug exposure, in patients who lack a prior history of exposure to the inciting drug. Here we are discussing our patient, a 68-year-old male who presented eight weeks after starting chemotherapy with pemetrexed, carboplatin, and pembrolizumab for left lung adenocarcinoma with macular rash. On further investigation with biopsy was found to have neutrophilic dermatitis, hence being diagnosed with drug-induced Sweet syndrome. Histopathology revealed a dermis with infiltration of neutrophils with lekocytoclasia.
PubMed: 38859947
DOI: 10.7759/cureus.62027 -
Anais Brasileiros de Dermatologia Jun 2024
PubMed: 38851895
DOI: 10.1016/j.abd.2024.03.001 -
EBioMedicine Jun 2024Human milk oligosaccharides (HMOs), their determinants, infant gut microbiota and health are under extensive research; however, seldom jointly addressed. Leveraging data...
Human milk oligosaccharide composition is affected by season and parity and associates with infant gut microbiota in a birth mode dependent manner in a Finnish birth cohort.
BACKGROUND
Human milk oligosaccharides (HMOs), their determinants, infant gut microbiota and health are under extensive research; however, seldom jointly addressed. Leveraging data from the HELMi birth cohort, we investigated them collectively, considering maternal and infant secretor status.
METHODS
HMO composition in breastmilk collected 3 months postpartum (n = 350 mothers) was profiled using high-performance liquid chromatography. Infant gut microbiota taxonomic and functional development was studied at 3, 6, and 12 months (n = 823 stool samples) via shotgun metagenomic sequencing, focusing on HMO metabolism via glycoside hydrolase (GH) analysis. Maternal and infant secretor statuses were identified through phenotyping and genotyping, respectively. Child health, emphasizing allergies and antibiotics as proxies for infectious diseases, was recorded until 2 years.
FINDINGS
Mother's parity, irritable bowel syndrome, gestational diabetes, and season of milk collection associated with HMO composition. Neither maternal nor infant secretor status associated with infant gut microbiota, except for a few taxa linked to individual HMOs. Analysis stratified for birth mode revealed distinct patterns between the infant gut microbiota and HMOs. Child health parameters were not associated to infant or maternal secretor status.
INTERPRETATION
This comprehensive exploration unveils intricate links between secretor genotype, maternal factors, HMO composition, infant microbiota, and child health. Understanding these nuanced relationships is paramount for refining strategies to optimize early life nutrition and its enduring impact on long-term health.
FUNDING
Sweet Crosstalk EU H2020 MSCA ITN, Academy of Finland, Mary and Georg C. Ehrnrooth Foundation, Päivikki and Sakari Sohlberg Foundation, and Tekes.
Topics: Humans; Milk, Human; Gastrointestinal Microbiome; Oligosaccharides; Female; Finland; Infant; Parity; Seasons; Birth Cohort; Metagenomics; Pregnancy; Infant, Newborn; Adult; Metagenome; Male; Feces
PubMed: 38838470
DOI: 10.1016/j.ebiom.2024.105182 -
Journal of Investigative Medicine High... 2024Skin lesions in chronic lymphocytic leukemia (CLL) have been reported in between 4% and 20% of patients with CLL and are a rare entity compared with T-cell leukemia....
Skin lesions in chronic lymphocytic leukemia (CLL) have been reported in between 4% and 20% of patients with CLL and are a rare entity compared with T-cell leukemia. They can present mainly as leukemic cutis or, frequently, as secondary lesions such like urticaria, itching, pyoderma gangrenosum, cutaneous vasculitis, Sweet's syndrome, and erythroderma. We report on an adult patient who developed a skin lesion of forearms and hands, leading to the discovery of isolated cutaneous CLL after two biopsies. Isolated CLL cutaneous location is very rare and may be diagnosed late, as in the case of our patient. A better knowledge of the course of the illness and rapid diagnosis of this CLL cutis leukemia will enhance the therapeutic efficacy of the disease.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Skin Neoplasms; Male; Biopsy; Skin; Aged; Middle Aged
PubMed: 38813875
DOI: 10.1177/23247096231204736