Search Results (284)

Reactive infectious mucocutaneous eruption (RIME) is a rare pediatric condition characterized by severe mucositis, minimal cutaneous involvement, and an infectious rather than drug-induced etiology. Mycoplasma pneumoniae (M. Pneumoniae) represents the most frequently identified trigger, although an increasing number of alternative pathogens have been reported. Its clinical overlap with Stevens–Johnson syndrome (SJS) makes early recognition difficult. We reviewed literature data on the topic and described our center’s experience with three pediatric cases of M. pneumoniae-associated RIME. Medical records, laboratory results, and imaging were systematically analyzed. All patients were male, aged 2 to 12 years and originated from rural communities. Etiologic confirmation was achieved via M. pneumoniae IgM serology and/or polymerase chain reaction. Clinical exam modifications included multi-site mucositis (oral, ocular, genital) with variable skin involvement: absent in one case, a solitary palm ulcer in another, and widespread rash in the third. One patient required two hospitalizations within a six-month interval, confirming the possible relapsing phenotype of RIME. Another patient developed pneumonia, sepsis, and systemic inflammation. All received macrolide therapy, antifungals, mucosal supportive care, and systemic management as indicated. Recovery occurred within 10–21 days, with one patient exhibiting skin hyperpigmentation. These cases illustrate the heterogeneity of RIME, emphasize the importance of prompt recognition, etiology confirmation, and multidisciplinary management. RIME is a rare clinical condition in pediatric population, an uncommon but significant mucocutaneous clinical entity, important to be acknowledged by clinicians as a complication and/or extra-pulmonary manifestation of M. pneumoniae infection. Full article

Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) are pediatric inflammatory conditions with overlapping mucocutaneous features that may complicate early diagnosis. We performed a narrative review of the literature to characterize and compare cutaneous manifestations reported in children with KD and MIS-C and to assess their diagnostic relevance. Published studies describing dermatologic findings in patients aged 0–18 years were reviewed. The analysis revealed a broad heterogeneity of skin manifestations in both conditions, ranging from classic polymorphous rash and acral erythema to atypical presentations, including annular, psoriasiform, vesiculobullous, urticarial, and erythema nodosum-like lesions. Reactivation at Bacillus Calmette–Guérin vaccination sites and associated mucocutaneous findings, such as conjunctivitis and oral changes, emerged as supportive diagnostic clues, particularly for incomplete KD. Considerable overlap in cutaneous phenotypes between KD and MIS-C was observed, especially in patients with persistent fever and systemic inflammation, highlighting the risk of diagnostic delay. These findings underscore the importance of recognizing atypical dermatologic patterns as part of an integrated diagnostic approach, as delayed identification may increase the risk of cardiovascular complications. Early recognition of cutaneous clues can support timely initiation of immunomodulatory therapy and improve clinical outcomes. Full article

Bruton’s tyrosine kinase (BTK) inhibitors have revolutionized the treatment landscape for patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The most common adverse events include cardiac arrhythmia, bleeding, infection, diarrhea, arthralgias, hypertension, and skin changes. Second-generation BTK inhibitors, e.g., acalabrutinib and zanubrutinib and the non-covalent BTK inhibitor pirtobrutinib, are less toxic than the first-generation BTK inhibitor ibrutinib. The most common toxic skin symptoms related to BTKi treatment include hemorrhage, bleeding events, bruising, skin ecchymoses, and contusion; they are particularly common in patients treated with ibrutinib. Other dermatologic symptoms include rash, cellulitis, skin infections, subcutaneous abscesses and peripheral edema. This article discusses the development of skin symptoms in patients with ibrutinib and newer BTK inhibitors, and summarizes their clinical and pathological characteristics. A literature search was performed using PubMed, Web of Science, and Google Scholar for articles published in English. Additional relevant publications were obtained by reviewing the references from the chosen articles. Full article

Cutaneous viral infections result from the complex interaction between viruses and skin structures, influenced by viral tropism and the host immune response. They can generate lesions ranging from transient rashes to chronic or potentially tumorous formations. Cutaneous manifestations are often the first sign of infection and allow for early recognition. The aim of this review is to analyze the role of viruses in skin pathology, the mechanisms of infection, and the clinical impact. A narrative review of the recent literature was performed, including original articles, systematic reviews, and clinical guidelines on cutaneous viral infections. Data on pathogenic mechanisms, types of lesions, evolution, and therapeutic options were evaluated, covering the main viruses involved in dermatology: herpesviruses, papillomaviruses, poxviruses, and viruses associated with acute rashes. Cutaneous viral infections can be self-limited, recurrent, or chronic, and some can promote malignant transformation of skin cells. The variability of clinical manifestations reflects the virus–host interaction and influences diagnosis and management. Recent advances highlight the development of vaccines and targeted antiviral therapies, which improve prognosis and infection control. Viruses play a major role in the etiology of skin diseases, and their early recognition is essential for preventing complications. Understanding the mechanisms of infection and the cutaneous response contributes to the optimization of therapeutic and preventive strategies, strengthening the modern management of viral cutaneous pathology. Full article

Metastatic uveal melanoma (MUM) remains largely refractory to immune-checkpoint inhibition, so recent research has turned to bispecific T-cell engagers (BTCEs), adoptive-cell therapies (ACTs), and oncolytic viruses (OVs). To summarize the available clinical evidence, we performed a structured literature search across PubMed, Scopus, and Europe PMC for primary studies published between 1 January 2010 and 31 May 2025 that enrolled at least three adults with MUM, treated with one of these modalities, and that reported efficacy or grade-3+ safety outcomes; two reviewers independently performed screening, data extraction, and risk-of-bias assessment, and because of notable heterogeneity, we synthesized the findings narratively. Twenty-two studies met the criteria—thirteen phase I–III trials, eight observational cohorts, and one case series—covering fifteen BTCE cohorts, four ACT cohorts, and three OV cohorts. Tebentafusp, the dominant BTCE evaluated in roughly 1150 HLA-A*02:01-positive patients, extended median overall survival from 16.0 to 21.7 months (hazard ratio 0.51, with three-year follow-up HR 0.68) in its pivotal phase-III trial despite objective response rates of only 5–12%, with early skin rash and week-12 circulating-tumor-DNA clearance emerging as consistent markers of benefit. Tumor-infiltrating lymphocyte therapy, administered to about thirty patients, produced objective responses in 11–35% and occasional durable complete remissions, although median progression-free survival remained 2–6 months and severe cytopenias were universal. Three early-phase OV studies, totaling twenty-nine patients, yielded no radiographic responses but showed tumor-specific T-cell expansion and transient disease stabilization. Safety profiles reflected the mechanism of action: tebentafusp most often caused rash, pyrexia, and usually manageable cytokine-release syndrome with grade-3+ events in 40–70% yet discontinuation in roughly 2%; TIL therapy toxicity was driven by lymphodepleting chemotherapy and high-dose interleukin-2 with one treatment-related death; and OVs were generally well tolerated with no more than 20% grade-3 events. Full article

Background: Iron-deficient anemia (IDA) in pregnant women is a significant health issue globally. Oral iron supplementation is the primary treatment for IDA during pregnancy. For women who do not respond to or cannot tolerate oral iron treatment, intravenous (IV) iron preparations may offer a viable therapeutic option in the third trimester of pregnancy. Ferric carboxymaltose (FCM; Ferinject^®) is an IV iron preparation that allows rapid administration of high single doses of iron with a favorable safety profile. This study evaluated the potential impact of FCM therapy on fetal well-being by recording cardiotocography (CTG) before, during, and after iron infusions. Materials and Methods: We examined 105 women with IDA in the third trimester of pregnancy. During the initial evaluation, each patient was assessed for complete blood count, iron metabolism, B12, folates, hemoglobinopathies, CRP, kidney and liver function, and glucose levels. Each subject received intravenous ferric carboxymaltose (FCM), 500 mg. The study focused on the maternal and fetal safety of FCM infusion. The primary endpoint for maternal safety was the observation of adverse effects of iron infusion. For fetal safety, the primary endpoint was the assessment of CTG. Results: We considered 105 women, comprising 101 singleton and 4 twin pregnancies. The median hemoglobin (Hb) at initial observation was 95 g/L and 117 g/L post-therapy. Regarding maternal safety, side effects were observed during or after FCM infusion in four subjects; three cases involved local symptoms, while one case included nausea and skin rash. Concerning fetal safety, 100% of the cardiotocography records were deemed “normal” using the Dawes–Redman criteria. Conclusions: In conclusion, FCM proved effective in treating anemia in this clinically complex population of pregnant women in the third trimester and appeared safe in this cohort, though larger prospective studies are warranted. Full article

Lyme disease, caused by the Borrelia burgdorferi bacterium and transmitted through black-legged (deer) tick bites, is becoming increasingly prevalent globally. According to data from the Lyme Disease Association, the number of cases has surged by more than 357% over the past 15 years. According to the Infectious Disease Society of America, traditional diagnostic methods are often slow, potentially allowing bacterial proliferation and complicating early management. This study proposes a novel hybrid deep learning framework to classify Lyme disease rashes, addressing the global prevalence of the disease caused by the Borrelia burgdorferi bacterium, which is transmitted through black-legged (deer) tick bites. This study presents a novel hybrid deep learning framework for classifying Lyme disease rashes, utilizing pre-trained models (ResNet50 V2, VGG19, DenseNet201) for initial classification. By combining VGG19 and DenseNet201 architectures, we developed a hybrid model, SkinVisualNet, which achieved an impressive accuracy of 98.83%, precision of 98.45%, recall of 99.09%, and an F1 score of 98.76%. To ensure the robustness and generalizability of the model, 5-fold cross-validation (CV) was performed, generating an average validation accuracy between 98.20% and 98.92%. Incorporating image preprocessing techniques such as gamma correction, contrast stretching and data augmentation led to a 10–13% improvement in model accuracy, significantly enhancing its ability to generalize across various conditions and improving overall performance. To improve model interpretability, we applied Explainable AI methods like LIME, Grad-CAM, CAM++, Score CAM and Smooth Grad to visualize the rash image regions most influential in classification. These techniques enhance both diagnostic transparency and model reliability, helping clinicians better understand the diagnostic decisions. The proposed framework demonstrates a significant advancement in automated Lyme disease detection, providing a robust and explainable AI-based diagnostic tool that can aid clinicians in improving patient outcomes. Full article

Background/Objectives: Cow’s milk allergy (CMA) manifests with various clinical syndromes and has a wide range of symptoms in infants. This study aims to investigate the prevalence, clinical presentation, and outcome of clinical types and subtypes of CMA diagnosed in children within the first 12 months of life. Methods: Children with a CMA diagnosis were included in this mixed retrospective and prospective cohort study and were followed up for four years. Data recorded included clinical manifestations, feeding modes, and outcomes. Follow-up included oral cow’s milk (CM) challenge and/or elimination—reintroduction of CM, provided there was parental consent. Also, skin prick test and serum CM-specific IgE were assessed when needed. Results: A total of 93 infants (age: 3 days to 24 months) diagnosed with CMA were included. Prevalence was 28% for IgE-mediated CMA and 72%, 49.5%, 18.3%, and 3.7% for non-IgE-mediated CMA and its subtypes, Allergic Proctocolitis (AP), Food Protein induced Enteropathy (FPE), and Food Protein Induced Enterocolitis Syndrome (FPIES), respectively. Main manifestations were gastrointestinal (74%), skin rash (31%), failure to thrive (11.8%), feeding aversion (15.1%), respiratory symptoms (5.4%), and irritability/restlessness (9.7%). Follow-up revealed a high rate of AP and FPE tolerance within the first year, while FPIES and IgE-mediated CMA achieved tolerance at an older age. Conclusions: Our study demonstrated the predominance of AP and increased incidence of gastrointestinal involvement. Outcome was good for AP and FPE but less favorable for FPIES and IgE-mediated CMA. Our results, combined with published data, could increase our understanding of CMA-associated syndromes in infants and contribute to the guidance of effective management. Full article

Dermatitis in the diapered area (DDA) is the most common skin condition in infants and can cause significant pain and discomfort, leading to disturbed sleep, changes in temperament, and heightened concern and anxiety for caregivers. This study investigates the relationship between skin pH, microbiome composition, and DDA severity in 158 infants from China, the US, and Germany, focusing on the buttocks, perianal, and thigh regions. Significant variations in DNA biomass and microbiota profiles were noted. Escherichia coli and Veillonella atypica were linked to higher rash scores and elevated skin pH, while Bifidobacterium longum showed a negative correlation with buttocks pH and rash severity but not with perianal rash. Correlation patterns emerged for other species, like Enterococcus faecalis, between perianal and buttocks rashes. Functional analysis identified key categories, including lipid and fatty acid metabolism, cofactor, amino acid, and carbohydrate metabolism, homeostasis and osmolarity stress, and microbial virulence and oxidative stress response, which are vital for skin health, DDA, and pH regulation in infants. These findings underscore the importance of maintaining a mildly acidic skin pH and minimizing fecal and urine residues for optimal infant skin health, suggesting that microbiota significantly influence DDA development, and provide insights for future preventive strategies and therapeutic interventions. Full article

Background/Objectives: Secondary syphilis typically presents with a non-pruritic maculopapular rash. However, vesicular and bullous manifestations are exceedingly rare in adults and may mimic autoimmune blistering diseases. The objective of this report is to describe atypical presentation of secondary syphilis with predominant vesiculobullous lesions and to emphasize the importance of including syphilis in the differential diagnosis of blistering skin diseases. Methods: We describe the case of a 46-year-old bisexual man with syphilis of unknown duration who presented with recurrent polymorphic skin eruptions, predominantly bullous and vesicular in nature. Clinical examination, serologic testing, and histopathologic evaluation were performed to establish the diagnosis. Results: Serologic tests confirmed active syphilis infection. A brief review of similar reported cases was conducted to highlight the clinical variability of vesiculobullous syphilis. Conclusions: Atypical vesiculobullous presentations of secondary syphilis pose significant diagnostic challenges and may be mistaken for autoimmune blistering disorders. Clinicians should maintain a high index of suspicion for syphilis in patients with polymorphic or blistering eruptions, particularly in those with risk factors for sexually transmitted infections. Awareness of these uncommon manifestations can facilitate timely diagnosis and appropriate treatment. Full article

Background/objective: Carboplatin, pemetrexed, and pembrolizumab are established as a key first-line regimen for metastatic non-small cell lung cancer, although selecting the optimal therapy for each patient remains challenging in real-world clinical practice. This retrospective multicenter study compared the efficacy and safety of two atezolizumab-based combination regimens, ACnP (carboplatin, nab-paclitaxel, atezolizumab) and ABCP (carboplatin, paclitaxel, bevacizumab, atezolizumab), in patients with non-small cell lung cancer in real-world clinical practice. Methods: A total of 91 patients treated between May 2018 and December 2023 at six Japanese hospitals were analyzed: 40 received ACnP and 51 received ABCP. Patient characteristics, treatment outcomes, and adverse events were compared, with subgroup analyses adjusted by inverse probability of treatment weighting using propensity scores. Results: The objective response rates were 55.0% with ACnP and 45.1% with ABCP. Median progression-free survival was 5.5 months for ACnP and 6.9 months for ABCP, while median overall survival was 16.2 and 18.3 months, respectively. Subgroup analyses showed significantly improved progression-free survival with ABCP in patients with brain metastases, liver metastases, EGFR-positive tumors, PD-L1-positive tumors, and impaired renal function (CCr < 45 mL/min). ABCP also conferred overall survival benefits in patients with brain and liver metastases. However, ACnP was associated with a lower incidence of neutropenia, peripheral neuropathy, and skin rash. Conclusions: These findings suggest that ABCP may offer superior efficacy in specific non-small cell lung cancer subgroups, while ACnP remains a valuable option for patients requiring a more tolerable safety profile. Full article

Elexacaftor/tezacaftor/ivacaftor (ETI) is a cystic fibrosis (CF) transmembrane conductance regulator modulator, which has shown efficacy in people with CF (pwCF) carrying the F508del (F) variant, both in homozygosity and heterozygosity with a minimal function (MF) variant. Limited data exist on the effects of ETI in pwCF with advanced lung disease. Our aim was to investigate ETI safety and effectiveness in this patient group in a real-life setting over 2 years. A multicenter observational cohort study was designed to gather real-world information on the effect of ETI treatment on CF patients (aged >12 years, genotype: F/MF mutation) with advanced lung disease as defined by a FEV1 < 40% predicted. Retrospective demographic and clinical data were recorded for the two years preceding and the two years following ETI initiation. The following outcomes were investigated: treatment-associated adverse events (AEs), drug interruptions (temporary or permanent), variations in percent predicted FEV1 (ppFEV1), sweat chloride concentration (SwCl), antibiotic use, body mass index (BMI), and quality of life. A total of 124 (51.6% males) pwCF were treated with ETI over 2 years. The median (IQR) age and ppFEV₁ were 34 (26, 43) years and 34 (29, 41) percentage points, respectively. ETI was discontinued in two pwCF due to lung transplantation, and temporarily interrupted in two because of skin rash, and in three following elevated levels of aminotransferase. Most AEs were mild and short-lasting. In 12.1% pwCF, we registered an increase greater than twice the upper limit of the normal range in alanine aminotransferase, and in 16% we registered an increase in conjugated bilirubin with no increase in aminotransferase. Both increases were recurrent in about half of the subjects. The mean differences (95% CI) for ppFEV₁ and SwCl, assessed as mean values in the pre-ETI and ETI treatment periods, were +11.8 (11.1 to 12.6) and −43.7 (−47.6 to −39.9) mmol/L. A modest increase in ppFEV₁ persisted during the second year of treatment. Number of oral and IV antibiotic cycles/year, as well as hospitalizations/year, decreased significantly from 3.6 to 1.2, from 2.4 to 0.6, and from 2.1 to 0.5 during ETI treatment. A total of 8 of 16 (50%) pwCF were taken off the waiting list for lung transplantation, and significant reductions in the percentages of pwCF using long-term oxygen therapy and non-invasive ventilation were observed. A poor concordance between ppFEV1 and SwCl was found. In only 3/82 (3.7%), subjects with chronic airway infection by Pseudomonas aeruginosa cultures were always negative during ETI treatment. In CF patients with advanced lung disease on ETI treatment, we observed an improvement in a number of clinically significant outcomes over a 2-year study period. However, several additional observations, such as liver dysfunction, variable degrees of lung function improvement, and limited impact on chronic airway infection, underscore the fact that the benefit–risk profile of ETI treatment in cystic fibrosis patients with advanced lung disease has not been fully elucidated and warrants prolonged-term monitoring. Full article

Background: The primary objectives of platelet-rich plasma (PRP) therapy are to enhance the wound-healing process, reduce pain, and minimize the loss of productivity due to recovery time. Localized application of PRP, which is enriched with growth factors such as PDGF, TGF-β1, IGF-1, VEGF, and FGF-2, as well as interleukins (IL-1, IL-4, IL-6, IL-10, and IL-13), has been documented to accelerate the healing process by approximately 30–40%. This study aimed to assess the safety and efficacy of platelet-rich plasma (PRP) in enhancing outcomes following circumcision in male children. Methods: The patients were divided into two groups: one undergoing standard circumcision and the other receiving PRP application during circumcision. Pain scores, edema level, bleeding, local infection, and safety of PRP were evaluated. Results: This study evaluated 80 male children undergoing circumcision, divided into two groups: Group CS (n = 44) underwent classical circumcision, and Group PRP (n = 36) received PRP application. Median ages were comparable (p = 0.101). Penile edema occurred less frequently in the PRP group (5.6%) compared to the CS group (18.2%) (p = 0.089), with no severe edema observed in the PRP group. Postoperative bleeding was present in 6.8% of the CS group but absent in the PRP group (p = 0.110). Other complications, such as nausea (CS: 6.8%, PRP: 5.6%, p = 0.816), vomiting (CS: 4.5%, PRP: 2.8%, p = 0.679), local infection (CS: 2.3%, PRP: 0%, p = 0.363), wound dehiscence (CS: 2.3%, PRP: 0%, p = 0.363), and skin tunnel formation (CS: 6.8%, PRP: 2.8%, p = 0.409), showed no significant differences. No cases of necrosis, chordee, rotational anomaly, or secondary phimosis were observed. Safety analysis of PRP revealed minor complications during blood draw: hypotension in one patient (2.8%) and local ecchymosis in two patients (5.6%), resolving without intervention. During PRP application, one allergic reaction (2.8%) occurred, presenting as a transient rash that resolved spontaneously. Group PRP consistently reported lower pain scores than Group CS at all time points. Conclusions: PRP application during circumcision is safe. The findings provide preliminary but important evidence regarding the potential benefits of PRP in pediatric circumcision. Full article

Background/Objectives: Henoch–Schönlein purpura (HSP), or IgA vasculitis, is the most common small-vessel vasculitis in children, yet Indian cohort data remain limited. We aimed to describe the clinical profile, renal involvement, treatment patterns, relapse, and outcomes of pediatric HSP at a tertiary centre in South India. Methods: We conducted a retrospective review of children <18 years diagnosed with HSP (January 2013–October 2018) using EULAR/PRINTO/PRES criteria. Demographics, clinical features, laboratory parameters, treatments, and outcomes were abstracted from records and analyzed in SPSS (descriptive statistics; Chi-square/Fisher’s exact and t/non-parametric tests as appropriate). Subgroup comparisons included renal vs. non-renal disease and age <6 vs. ≥6 years. An exploratory analysis examined predictors of nephritis. Results: Of 43 children identified, 2 were excluded (misclassified as systemic lupus erythematosus); 41 were analyzed. Mean age was 8.5 years (range 3–17), male: female 1.4:1. A preceding febrile illness or upper respiratory tract infection was noted in 41.4% and 17%, respectively. Palpable purpura was universal; joint involvement 73.1%, abdominal pain 61.0%, vomiting 41.5%. Renal involvement 17% occurred only in children ≥6 years; exploratory testing supported a strong age-linked signal for nephritis. Laboratory abnormalities included anemia (48.7%), thrombocytosis (19.5%), and elevated ESR (51.2%). Skin biopsy (n = 29) showed IgA and complement deposition; renal biopsy (n = 2) showed ISKDC grades II–III. Treatments included NSAIDs 71.6%, corticosteroids 31.7%, and dapsone 24.4% (used for severe systemic/persistent cutaneous disease). Rash relapse 7.3% clustered with joint plus abdominal symptoms and was not observed among children with nephritis. At a mean 18.9-month follow-up, one child required long-term antihypertensives; no child progressed to end-stage renal disease. Conclusions: Pediatric HSP in this South-Indian cohort followed a largely self-limited course with favourable renal outcomes. Age ≥6 years flagged higher renal risk, supporting age-targeted urine and blood-pressure surveillance, while relapse appeared to follow a non-renal trajectory (joint/abdominal clustering). Steroid and dapsone use reflected clinical severity rather than relapse risk. Findings align with Indian series and suggest lower renal morbidity than some East-Asian reports, adding region-specific evidence to guide monitoring and counselling. Full article

Erythema ab igne (EAI), also known as “hot water bottle rash” or “toasted skin syndrome”, is a benign cutaneous condition caused by chronic exposure to low-level infrared heat. It typically begins as transient erythema and evolves into a reticulated brown pigmentation with telangiectasias. A skin biopsy, ideally taken from the central area of the hyperpigmented lesion, is recommended to exclude differential diagnoses. Although usually benign, EAI has been associated with rare malignant transformations, supported only by low-level evidence. Elimination of the heat source is essential, and topical treatments such as hydroquinone or retinoids may be considered, while agents like 5-fluorouracil or imiquimod are reserved for dysplastic lesions. Women with endometriosis frequently use heating devices to alleviate dysmenorrhea and chronic pelvic pain. However, prolonged or inappropriate heat application can lead to chronic thermal injury, including EAI, and may delay medical consultation. While controlled trials confirm short-term analgesic efficacy of heat therapy, extrapolating these findings to unrestricted home use without standardized safety recommendations can be misleading. EAI illustrates the broader impact of chronic pain in endometriosis, linking cutaneous manifestations with neuroplastic alterations and psychiatric comorbidities. A nuanced approach combining patient education on safe use of heat, close dermatologic monitoring, and multidisciplinary pain management is warranted. Full article