Severe Cutaneous Signs of Hipersensitivity to Drugs in a Pediatric Hospital.

Allopurinol, the most used urate-lowering drug for the treatment of gout, is associated with rare but life-threatening severe cutaneous adverse reactions (SCARs) such as Stevens–Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, but not Acute Generalised Exanthematous Pustulosis (AGEP). They are characterised by severe skin and systemic involvement and are associated with substantial morbidity and a high risk of mortality. This narrative review summarises evidence on the clinical presentation, epidemiology, risk factors, and preventive strategies for allopurinol-induced SCARs. Key risk factors include the presence of the HLA-B*58:01 allele, renal impairment, older age, female sex, heart disease, higher starting doses of allopurinol, and certain ethnicities, e.g., South Asian, Han Chinese, and African populations likely due to the higher prevalence of the HLA-B*58:01 allele. Risk mitigation strategies include genetic testing for HLA-B*58:01 in high-risk ethnic groups and avoiding allopurinol in those that are positive for the HLA-B*58:01 allele, starting allopurinol at a low-dose (e.g., 50–100 mg/day) and up-titrating it gradually at 4-week intervals, and avoiding high-dose allopurinol in those with risk factors (e.g., chronic kidney disease stage ≥3). In addition, risk stratification using prediction tools may enable a safer use of allopurinol.

Drug-induced hypersensitivity reactions (DIHR) represent abroad spectrum of immune-mediated disorders that occur after exposure to medications and can affect various organ systems. The most important entities include drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN, Lyell's syndrome), serum sickness, drug-induced eosinophilic pneumonias, and hypersensitivity pneumonitis. Pulmonary manifestations are common and can have adecisive impact on the clinical course. This review article explains the immunological foundations, pathogenesis, and etiology of drug-induced hyperreactivity disorders, describes their clinical relevance, and presents the typical thoracic manifestations and imaging patterns in chest computed tomography (CT). The focus is on the importance of radiological diagnostics for the early detection and differentiation of these potentially life-threatening conditions.

Aims: To describe a severe case of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) associated with sequential cephalosporin and vancomycin exposure, and to highlight the diagnostic challenges and hematologic and thromboembolic complications encountered during the clinical course. Place and Duration of Study: Central Maine Medical Center, Lewiston, Maine, USA; September 2025 to November 2025. Methodology: Clinical data were obtained through detailed review of the patient’s medical records, including medication timeline, laboratory trends, imaging studies, histopathology reports, and clinical response to therapeutic interventions. Serial eosinophil percentages and absolute neutrophil counts were analyzed in relation to antibiotic exposure and treatment milestones. Diagnostic probability was assessed using the RegiSCAR scoring system, and drug causality was evaluated using the World Health Organization–Uppsala Monitoring Centre (WHO–UMC) causality assessment method. Results: A 45-year-old woman with transfusion-dependent chronic anemia, cognitive delay, and chronic kidney disease developed a progressive morbilliform rash, facial edema, marked eosinophilia, and profound neutropenia following prolonged exposure to intravenous ceftriaxone and oral cefdinir for a complicated urinary tract infection secondary to an obstructive renal stone. Brief exposure to vancomycin was followed by rapid clinical worsening, raising concern for immunologic amplification of an evolving hypersensitivity reaction. Her course was further complicated by acute deep vein thrombosis and pulmonary embolism. Skin biopsy demonstrated findings consistent with a drug-induced hypersensitivity reaction. Initiation of systemic corticosteroids resulted in rapid improvement in both cutaneous and hematologic abnormalities. Discussion: This case underscores the importance of early recognition of DRESS in patients receiving sequential antibiotic therapy. The clinical timeline supports cephalosporins as the likely primary sensitizing agents, with vancomycin acting as a potential immunologic accelerator. Concurrent exposure to two cell wall synthesis inhibitors may also have contributed to immune activation in this case. Both cephalosporins and vancomycin target bacterial cell wall formation but are independently associated with severe delayed hypersensitivity reactions. Sequential exposure may increase antigenic stimulation and immune dysregulation in susceptible individuals, potentially contributing to clinical severity. Prompt initiation of systemic corticosteroids may be critical in reversing severe hematologic and systemic complications.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced hypersensitivity reaction often requiring prolonged corticosteroid (CS) therapy, yet tapering is difficult due to relapse. This retrospective single-center case series evaluated the efficacy and safety of selective JAK inhibitors in facilitating CS tapering in moderate-to-severe, refractory DRESS, and in ameliorating pruritis. Six patients (median age 35 years; five females) received baricitinib or abrocitinib with CS between July 2023 and June 2024. All achieved rapid clinical improvement, with generalized lesion resolution and pruritus reduction by more than three WI-NRS points. Successful initial CS tapering occurred within 7∼12 days, and four patients discontinued CS completely within 28∼62 days, two stayed with low-dose CS due to primary autoimmune disease. Serum cytokines, particularly interleukin-5, decreased markedly after JAK inhibition. No severe adverse events occurred, including in patients with pancytopenia or hepatic dysfunction. JAK inhibitors appear effective and well-tolerated in promoting CS tapering in refractory DRESS, suggesting larger controlled studies are needed.

Cyclosporine (CsA), an oral calcineurin inhibitor, is frequently used off-label in paediatric dermatology to manage severe inflammatory skin conditions rapidly. The current literature on this topic encompasses various sources, including systematic reviews, meta-analyses, case series, narrative reviews and clinical trials, with a focus on atopic dermatitis, chronic urticaria, drug reaction with eosinophilia and systemic symptoms (DReSS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), reactive infectious mucocutaneous eruption (RIME) and psoriasis. While some studies include adult data, they support the use of CsA as a viable treatment option in well-selected paediatric patients when accompanied by diligent monitoring. This review highlights common dosing strategies, typically weight-based and reports consistent rapid clinical improvement and steroid-sparing effects. Although adverse events may occur, they are generally reversible; however, careful monitoring is recommended.

Regarding "Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Induced by Meropenem in a Patient Receiving Avelumab and Subsequent Flare-up".

Response to the Letter Regarding "Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Induced by Meropenem in a Patient Under Therapy With Avelumab and Subsequent Flare-up".

An itchy situation: a pediatric case of DRESS syndrome in patient with atopic dermatitis

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe systemic hypersensitivity drug reaction with diverse skin morphologies, including erythema multiforme (EM)-like lesions. Limited literature exists on the prognostic significance of EM-like lesions in patients with DRESS. This was a prospective case-control study, comparing organ involvement and prognosis of DRESS with EM-like lesions with that of a matched control population of DRESS without EM-like lesions at a tertiary care centre in Northern India. Clinical records of patients enrolled in a prospective cohort of DRESS from January 2018 to August 2024 were reviewed. The diagnosis of DRESS was confirmed using European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria. Based on the RegiSCAR score, 72 patients with probable and definite DRESS were recruited and divided into two groups: those with EM-like lesions (cases, n = 25) and those without (controls, n = 47), matched by age, gender, and race. Patients with EM-like lesions had a significantly longer latency between drug intake and symptom onset (p=0.007), a higher incidence of purpuric lesions (p<0.001), a less common erythrodermic presentation (p=0.034), greater palm and sole involvement (p=0.003), facial edema (p<0.001), and mucosal involvement (p=0.016). Those with EM-like lesions had a significantly elevated total leukocyte count (p=0.028), higher CRP levels (p=0.023), abnormal liver enzymes (ALT, AST) and lower eosinophil counts (p=0.005) with a greater likelihood of hepatic involvement (OR=6.9). DRESS patients with EM-like lesions experience a more severe disease course with greater hepatic involvement. These could be clinical markers for more aggressive disease necessitating multidisciplinary care.

Graves' disease (GD) is the leading cause of childhood hyperthyroidism, resulting from excessive thyroid hormone production. In some cases, it can cause alterations in mineral homeostasis, including calcium, phosphorus, and magnesium, which are often overlooked. Hyperthyroidism increases osteoclastic bone resorption, and mild to moderate hypercalcemia occurs in approximately 20-50% of affected patients, typically resolving with appropriate therapy. Although uncommon, symptomatic hypercalcemia in the setting of GD requires immediate evaluation and management. An 8-year-11-month-old girl was brought to the clinic, presenting with recurrent nausea, vomiting, and fatigue. She had multiple hospital admissions over the previous seven months due to drug reaction with eosinophilia and systemic symptoms (DRESS) and acute inflammatory demyelinating polyneuropathy (AIDP). Blood tests showed hyperthyroidism, marked hypercalcemia and hypomagnesemia. She showed tachycardia and weight loss. Based on the Burch-Wartofsky Point Scale, she was diagnosed with impending thyroid storm. Treatment was initiated with intravenous hydration, furosemide, dexamethasone, along with oral methimazole and propranolol. Within a few days, her general condition improved, her heart rate decreased, and gastrointestinal symptoms resolved and serum calcium levels normalized. Follow-up tests showed stable thyroid function and normal calcium levels. This case highlights that symptomatic hypercalcemia associated with GD and suggests that hyperthyroidism should be considered in the differential diagnosis of unexplained persistent nausea and vomiting.

Abstract Background Beta-lactam antibiotics are among the most commonly prescribed antimicrobials worldwide, but they are also a frequent cause of drug-induced hypersensitivity reactions, ranging from mild rashes to life-threatening anaphylaxis. While clinical trial data provide initial safety signals, rare and delayed adverse events often emerge post-marketing. This study aimed to analyze post-marketing reports of hypersensitivity reactions associated with beta-lactam antibiotics using the U.S. FDA Adverse Event Reporting System (FAERS) database.Forest Plot: Hypersensitivity Signals of Beta-Lactam Antibiotics (FAERS, 2010–2023) This forest plot displays the reporting odds ratios (RORs) with 95% confidence intervals for hypersensitivity-related adverse events associated with beta-lactam antibiotics. Notable signals include: Cefazolin–associated anaphylaxis (ROR 3.89) Angioedema with amoxicillin-clavulanate (ROR 2.97) Urticaria with ceftriaxone (ROR 2.12) All events exceeding an ROR of 1 with lower CI &amp;gt;1 are considered statistically significant safety signals, reinforcing the need for careful antibiotic selection, particularly in sensitized patients. Methods A retrospective pharmacovigilance analysis was conducted using FAERS data from January 2010 to December 2023. Reports involving penicillins, cephalosporins, carbapenems, and monobactams were extracted using generic and brand names. Hypersensitivity-related Preferred Terms (PTs) were identified via the MedDRA hierarchy, including anaphylactic reaction, angioedema, urticaria, erythema multiforme, and DRESS syndrome. Disproportionality was assessed using Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR), with statistical significance defined as ROR 95% CI &amp;gt;1 and ≥3 cases. Results A total of 14,728 hypersensitivity-related adverse event reports were associated with beta-lactam antibiotics. Among them, amoxicillin accounted for the highest number of reports (n = 4,615), followed by ceftriaxone (n = 2,763) and piperacillin-tazobactam (n = 1,980). Disproportionality analysis showed the strongest signal for anaphylaxis with cefazolin (ROR: 3.89, 95% CI: 3.22–4.68) and angioedema with amoxicillin-clavulanate (ROR: 2.97, 95% CI: 2.45–3.61). Cephalosporins were more frequently associated with skin-related hypersensitivity (e.g., urticaria, erythema), whereas carbapenems were linked to a lower but consistent signal for severe reactions. Conclusion This large-scale post-marketing analysis using FAERS data highlights distinct hypersensitivity risk profiles among beta-lactam subclasses. The findings reinforce the need for careful history-taking and individualized antibiotic selection, especially in patients with prior allergy history. Real-world data from spontaneous reporting systems like FAERS remain crucial in identifying emerging safety signals. Disclosures All Authors: No reported disclosures

Drug reaction with Eosinophilia and Systemic Symptoms is a rare significant cutaneous adverse reaction with associated mortality. Extensive pseudolymphomatous multiorgan manifestations with prolonged latency from nonsteroidal anti-inflammatory exposure highlight the clinical spectrum and severity. Early recognition, timely intervention, prolonged treatment, and follow-up are essential.

Reactive Infectious Mucocutaneous Eruption (RIME) is a parainfectious condition characterized by lesions on mucous membranes (oral, genital, and ocular) and, less frequently, skin involvement. It differs from other similar diseases, such as Stevens-Johnson syndrome and DRESS syndrome, in that the trigger is an infection, the course is more benign, and skin involvement is less common. We present two clinical cases with skin lesions compatible with RIME syndrome in 12-year-old males with a history of infectious symptoms. We believe it is important to recognize this entity to appropriately conduct the differential diagnosis between these conditions.

Background: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) represents a rare yet potentially fatal hypersensitivity reaction. Although various medications have been associated with this condition, rifampicin is an infrequent culprit. Case Presentation: A 72-year-old male with hypertension and a history of spinal surgeries presented with fever, widespread pruritic rash, and edema following three weeks of empirical treatment with Rifampicin. Assessment using RegiSCAR criteria resulted in a score of 6, confirming a definitive diagnosis of DRESS syndrome. Laboratory tests indicated eosinophilia (30%), elevated liver enzymes, and increased serum IgE levels (409 IU/ml). The patient was treated with intravenous corticosteroids, followed by a tapering oral regimen, which resulted in significant clinical and biochemical improvement.Conclusion: Timely identification and immediate cessation of adverse effect of drug are crucial for achieving favorable outcomes in DRESS syndrome. This case underscores the importance of clinical awareness, even with frequently prescribed medications such as Rifampicin.

Lung disease (LD) in systemic juvenile idiopathic arthritis and adult-onset Still disease (Still-LD) is a severe manifestation strongly associated with HLA-DRB1*15 alleles and drug-associated immune reactions (DAIR), including eosinophilia, non-Still disease rashes, and elevated liver function tests. Despite the high morbidity and mortality of these phenomena, pathogenesis remains poorly understood. This study investigates whether Still-LD and DAIR are associated with pathogenic antigens through hypersensitivity reactions to Aspergillus fumigatus, for which HLA-DRB1*15 is a known risk allele, or drug reaction with eosinophilia and systemic symptoms (DRESS), which is frequently associated with human herpesvirus (HHV) reactivation. Pediatric and adult subjects were drawn from the National Institutes of Health Still disease cohort. Subjects with Still-LD and/or DAIR were identified by chart review. Serum samples were analyzed for anti-A. fumigatus IgE using ImmunoCap assay, and Epstein-Barr virus (EBV), cytomegalovirus (CMV), and HHV 6 (HHV-6) antibodies were analyzed by luciferase immunoprecipitation systems. Subjects were screened for EBV, CMV, and HHV-6 by nucleic acid amplification tests and/or Viral Transcript Usage Sensor (VIRTUS) analysis of whole-blood RNA sequencing data. Fifty-four subjects were included in the study, 11 had LD and DAIR, and 8 had DAIR alone. Thirty-three subjects were tested for anti-A. fumigatus antibodies and all were negative. Forty-nine subjects were tested for CMV, EBV, and HHV-6; 2 were positive for EBV, both of whom did not have Still-LD or DAIR. The absence of anti-A. fumigatus IgE antibodies and detectable herpesvirus nucleic acids in subjects with Still-LD and DAIR does not support a mechanistic association with hypersensitivity to A. fumigatus or with HHV reactivation.

BackgroundNutritionally variant streptococci (NVS), including Granulicatella and Abiotrophia genera, are fastidious Gram-positive cocci requiring pyridoxal or thiol for growth. They are implicated in 1%–2% of infective endocarditis (IE) cases and associated with large vegetations and poorer outcomes.¹ Multiple reports describe treatment of Granulicatella adiacens IE with guideline-supported regimens such as penicillin, ceftriaxone, and vancomycin.2–4 We present a case of G. adiacens IE in a patient with aortic homograft, with ceftriaxone resistance and allergies to penicillin and vancomycin, and review literature on treatment of NVS IE with alternative agents outside of recognized guidelines.Case reportA 45-year-old female with Turner’s syndrome, prior bioprosthetic aortic valve replacement and aortic homograft presented with one month of malaise, dyspnoea and fever. Echocardiography revealed severe aortic regurgitation with a 9×4 mm aortic valve vegetation. Four sets of blood culture cultured G. adiacens on standard blood agar without pyridoxal supplementation. Empirical ceftriaxone, vancomycin and gentamicin were commenced, pending susceptibility testing. She underwent aortic valve replacement. Valve culture was negative, but 16S PCR detected G. adiacens. Reference laboratory susceptibility testing demonstrated ceftriaxone resistance and penicillin/vancomycin susceptibility. Amoxicillin and vancomycin were then initiated, while amoxicillin susceptibility result was awaited. The patient developed a severe cutaneous reaction with eosinophilia of 0.93×10⁹/L, meeting criteria for DRESS syndrome (drug rash with eosinophilia and systemic symptoms), with β-lactams suspected as culprits. Amoxicillin was stopped; however the rash worsened, prompting vancomycin discontinuation also. Due to fastidious growth of G. adiacens and delayed susceptibility results, meropenem and linezolid were trialled empirically. Thrombocytopenia subsequently developed on linezolid (nadir platelet count 114×10⁹/L), which was ceased. Ultimately, she completed 6 weeks of therapy post-surgery with ertapenem and levofloxacin, with good clinical response. MICs were 0.064 for ertapenem and 0.5 for levofloxacin—while no EUCAST breakpoints exist for G. adiacens, the reference laboratory suggested both may be considered for therapy . Surveillance blood cultures one month after completing therapy were negative and repeat echocardiography showed a well-seated prosthetic valve with no vegetation.DiscussionInfective endocarditis guidelines from AHA, ESC and BSAC recommend penicillin, ampicillin, or ceftriaxone with gentamicin for six weeks in penicillin-susceptible Granulicatella IE, or vancomycin with gentamicin in β-lactam allergy.2,3,4 Data on daptomycin, linezolid and fluoroquinolone use for NVS IE are limited. One study found 87% of G. adiacens isolates meropenem-susceptible.⁵ Fastidious growth, prolonged turnaround for susceptibilities and lack of formal EUCAST breakpoints complicated antimicrobial selection in this case. Recurrence of NVS IE is common (17%–27%),⁶ and the retained aortic homograft raised relapse risk. Long-term oral suppressive therapy was avoided due to limited options and fluoroquinolone toxicity concerns. Instead, close outpatient monitoring was instituted.ConclusionsThe management of NVS endocarditis is already challenging due to its fastidious growth, more severe prognosis, high relapse rates and antibiotic resistances. This case was further complicated by severe antibiotic hypersensitivity reactions to guideline-supported antibiotic regimens. Guided by case series and MDT input, a non-guideline-supported regimen achieved successful outcomes. Publication of such cases is essential to inform future management strategies for rare and difficult infections.

Abstract Severe Cutaneous Adverse Reactions (SCARs), including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), are life-threatening and often linked to commonly used antibiotics. Older adults are particularly vulnerable due to polypharmacy and age-related pharmacokinetic changes. In this case, a 72-year-old male with basal cell carcinoma and global aphasia from a left parietal stroke developed delayed-onset exfoliative erythroderma. He was hospitalized 5 weeks prior for left leg osteomyelitis, undergoing multiple surgical debridements. Discharged to a skilled nursing facility (SNF) on IV vancomycin and piperacillin-tazobactam, he was switched to daptomycin after a week due to an IV antibiotic shortage. Three weeks later, the SNF noted a worsening full-body, erythematous, non-blanching rash. Despite discontinuing daptomycin for doxycycline, his condition progressed. On admission, he had diffuse petechial and maculopapular lesions with scaling involving his entire body, including the face, palms, and soles, but sparing mucosal membranes. Labs showed mild leukocytosis, elevated neutrophils, no eosinophilia, and elevated CRP/ESR. His rash resolved with antibiotic discontinuation, topical corticosteroids, and IV methylprednisolone. This case underscores the diagnostic challenge of SCARs in polypharmacy-prone older adults, particularly in patients who also face communication barriers secondary to their past medical histories. The delayed onset suggested vancomycin hypersensitivity despite lacking classical DRESS features. SJS/TEN were ruled out due to the timeline. Ultimately, Vancomycin was the most likely culprit for this unusual rash. Clinicians must recognize atypical drug reactions in geriatric patients, where polypharmacy and relevant past medical history complicates diagnosis and management.

Cutaneous Adverse Drug Reactions (CADRs) represent a significant clinical concern among individuals living with Human Immunodeficiency Virus (HIV), who exhibit heightened susceptibility due to profound immune dysregulation, declining CD4+ cell counts, and frequent exposure to multiple pharmacologic agents. This literature review synthesizes current evidence regarding the spectrum, risk factors, and drug triggers of CADRs in HIV-infected populations. CADRs in this group encompass a wide range of manifestations, from mild exanthematous eruptions to life-threatening reactions such as Stevens–Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Acute Generalized Exanthematous Pustulosis (AGEP). Multiple risk determinants, including polypharmacy, co-infection with tuberculosis (TB), impaired immunological status marked by low CD4+ cell counts, and host-related factors such as age, sex, and genetic predisposition, contribute to the increased incidence and severity of CADRs in this population. Antituberculosis agents, antiretroviral therapy (particularly nevirapine-based regimens), and cotrimoxazole frequently emerge as primary drug triggers, with several studies reporting high rates of hypersensitivity reactions linked to these medications. Overall, the evidence underscores the importance of vigilant monitoring, early recognition of cutaneous reactions, and appropriate therapeutic adjustments to prevent adverse outcomes in HIV-infected patients receiving complex multidrug regimens.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a highly severe drug-induced hypersensitivity reaction with significant morbidity. Its diagnosis can be particularly challenging in patients with autoimmune diseases receiving multiple medications. We present the case of a woman in her late 30s with recently diagnosed rheumatoid arthritis and hyperthyroidism who developed high-grade fever, diffuse rash and facial oedema following treatment with allopurinol, leflunomide and carbimazole. Her symptoms were attributed to DRESS syndrome, supported by findings of eosinophilia, hepatic involvement and positive autoantibodies, and confirmed by skin biopsy. Discontinuation of the suspected offending drugs and initiation of anti-inflammatory therapy led to complete clinical resolution. This case highlights the complexity of diagnosing DRESS syndrome in patients with autoimmune conditions, the need to differentiate drug hypersensitivity from autoimmune disease flares and the importance of prompt intervention for optimal outcomes.