A Rare Presentation of an Adverse Reaction to Minocycline.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, severe adverse drug reaction, usually associated with antibiotics and anticonvulsants. A 17-year-old girl with maculopapular rash, arthralgia, fever, and facial edema (plus eosinophilia and hepatitis) repeatedly goes to the emergency department, initially omitting having started minocycline three weeks before symptom onset. Diagnosis of serum-like sickness was first established, minocycline was suspended, and a short course of corticosteroid therapy was started. However, the fast taper of corticotherapy resulted in the reappearance of previous symptoms, as well as renal dysfunction and respiratory distress. Chest CT showed interstitial pneumonitis. With these findings, the final diagnosis of DRESS was made, and the re-adjustment of corticoid therapy resulted in symptom improvement. This case highlights the diagnostic and treatment challenges of DRESS and the importance of an all-around approach to the patient.

Case report: Drug reaction with eosinophilia and systemic symptoms (DRESS) induced by ceftazidime in a connective tissue disease (CTD) patient.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and severe cutaneous adverse drug reactions (SCARs) with high mortality. Antibiotics are the most frequent causative agents related to DRESS. However, it is rarely reported in cephalosporins, especially for ceftazidime. Here, we reported a case of ceftazidime-induced DRESS with HLA genotypic polymorphism as a risk factor. A 58-year-old woman with connective tissue disease was intravenously infused with ceftazidime for the treatment of pneumonia and intestinal infection, followed by the presence of fever, rash, and hematologic and hepatic laboratory abnormalities. DRESS was diagnosed and the positive polymorphism in HLA-B*15:02 was found. Our case illustrated the necessity to clarify the patho-mechanism and the use of pretreatment HLA analysis to prevent ceftazidime-related DRESS may be a valuable option soon.

Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Case Report From South India.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome usually presents two to six weeks after treatment with a drug implicated in this disorder. However, in some cases, it can present more than eight weeks after the initiation of an implicated medication. This is a type 4 drug hypersensitivity reaction in which any internal organ may be involved. While the liver is commonly involved, cardiac involvement is not unheard of. Comorbidities and multiorgan involvement may obscure the diagnosis, and Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) criteria are a useful diagnostic aid. It is best treated by withdrawing the offending agent and administering systemic steroids. Oxidative stress is high in DRESS syndrome. Hepatoprotection is a priority in all patients and yields a better prognosis.

Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome Preceding Toxic Epidermal Necrolysis Secondary to Sildenafil: A Case Report.

Drug reactions with eosinophilia and systemic symptoms (DRESS) syndrome and Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) are reactive entities of aberrant cytotoxic immunologic reactions to exogenous medications. While they are conventionally seen as distinct, separate conditions, we present a case of a rare evolution of DRESS syndrome into SJS-TEN in the setting of simultaneous amoxicillin-clavulanate initiation and long-term sildenafil use in a 66-year-old South Asian female with a known history of prior DRESS syndrome and pulmonary arterial hypertension. We discuss the conditions leading to her unique clinical presentation and provide considerations for future clinical encounters.

Fatal Myocarditis in Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Without Mortality-Related Risk Factors: A Case Report and Literature Review.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction characterized by skin rash, organ involvement, lymph node swelling, eosinophilia, and atypical lymphocytosis, with myocarditis being a rare but potentially fatal complication. It has been reported that in patients with cardiac involvement due to DRESS, older age and shorter periods between offending drug exposure and symptom onset are associated with mortality. We report a case of fatal DRESS-associated myocarditis in a young woman, occurring one month after drug exposure, despite intensive immunosuppressive therapy. This case report highlights the risk of mortality from DRESS-associated myocarditis even in patients lacking known risk factors.

Atypical Presentation of Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) in a Patient on Pembrolizumab: A Case Report.

Pembrolizumab is an immune checkpoint inhibitor that has been associated with numerous immune-mediated adverse effects. Several of these cutaneous side effects may include bullous pemphigoid, Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS). Other case reports have reported DRESS as a rare side effect of immune checkpoint inhibitors but due to its variable presentation and similarities with other cutaneous diseases, it has proven to be a diagnostic challenge. In addition, no effective methods have been developed to monitor for such adverse skin reactions in patients on immunotherapy. Here, we report a diagnostic challenging case of pembrolizumab-induced blistering lesions that were initially treated as suspected Herpes zoster and/or bullous pemphigoid but further pathology was consistent with DRESS.

Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome to Hemodialysis Polysulfone Membrane.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe and potentially life-threatening hypersensitivity reaction. Although commonly associated with specific drugs, there have been no reports of DRESS syndrome caused by medical devices. We report a unique case of DRESS syndrome linked to a particular hemodialysis membrane during treatment. An 83-year-old man on hemodialysis exhibited fever, rash, and elevated eosinophils. Despite medication changes and consultations with specialists, his condition persisted. A drug-induced lymphocyte stimulation test revealed a positive response to the dialysis membrane. His symptoms and lab results met DRESS syndrome diagnostic criteria. After substituting the membrane and administering glucocorticoids, the patient displayed early improvement. Diagnosing DRESS syndrome is complex due to its varied presentation and lack of specific benchmarks. This instance underscores the need to consider medical devices as potential DRESS syndrome triggers. Enhanced physician awareness can facilitate prompt detection and proper management, ultimately refining patient outcomes.

ALDRESS: A Retrospective Pilot Study to Develop a Pharmacological Causality Algorithm for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe form of drug hypersensitivity reaction characterized by significant morbidity, mortality, and long-term sequelae, coupled with limited therapeutic avenues. Accurate identification of the causative drug(s) is paramount for acute management, exploration of safe therapeutic alternatives, and prevention of future occurrences. However, the absence of a standardized diagnostic test and a specific causality algorithm tailored to DRESS poses a significant challenge in its clinical management. Methods: We conducted a retrospective case-control study involving 37 DRESS patients to validate a novel causality algorithm, the ALDRESS, designed explicitly for this syndrome, comparing it against the current standard algorithm, SEFV. Results: The ALDRESS algorithm showcased superior performance, exhibiting an 85.7% sensitivity and 93% specificity with comparable negative predictive values (80.6% vs. 97%). Notably, the ALDRESS algorithm yielded a substantially higher positive predictive value (75%) compared to SEFV (51.40%), achieving an overall accuracy rate of 92%. Conclusions: Our findings underscore the efficacy of the ALDRESS algorithm in accurately attributing causality to drugs implicated in DRESS syndrome. However, further validation studies involving larger, diverse cohorts are warranted to consolidate its clinical utility and broaden its applicability. This study lays the groundwork for a refined causality assessment tool, promising advancements in the diagnosis and management of DRESS syndrome.

Fatal Itching and Failing Liver: A Case Report and Literature Review of Rare, Atypical DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) Syndrome.

DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome is a rare, life-threatening, hypersensitivity reaction. The prolonged course and non-specific symptoms of the condition make diagnosis challenging. We present a case of DRESS syndrome that was misdiagnosed as urticaria. Investigations revealed deranged liver and kidney functions and abnormal blood count. The presented case emphasizes the need to have a high suspicion for DRESS syndrome in patients who present with jaundice, generalized rash, acute renal failure, and acute liver failure.

Clinical Presentation and Diagnosis of Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) in Children: A Scoping Review.

Effective treatment of drug reactions with eosinophilia and systemic symptoms (DReSS) requires early diagnosis and close monitoring. Diagnosing DReSS is especially challenging in children due to a low incidence rate, heterogeneous clinical presentation, and a lack of (pediatric) diagnostic criteria and clinical practice guidelines. We performed a scoping review, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to summarize the clinical presentation and diagnostic process of DReSS in children (aged 0-18 years). Data from 644 individuals showed that DReSS manifests differently in children compared to adults. Children have a higher number of organs involved, including higher rates of cardiac and respiratory involvement compared to adults. Children < 6 years of age appear more prone to develop neurologic symptoms. Conversely, eosinophilia, edema, and kidney involvement are less frequently observed in children. Anti-seizure medications are by far the most common causative drug class, but the range of implicated drugs increases as children get older. This study highlights that children with DReSS not only differ from adults but also that differences exist between children of different ages. As such, there is a need to establish pediatric-specific diagnostic criteria. These efforts will promote earlier diagnosis of DReSS and likely lead to improved clinical care offered to children and their families.

Case Report: Minocycline-induced drug reaction with eosinophilia and systemic symptoms syndrome: a case report and literature review.

Minocycline is a tetracycline commonly used for several dermatological diseases. Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but severe adverse event which can be caused by minocycline. An 18-year-old male patient developed fever, acute rash, pharyngeal pain, lymphadenopathy, hematologic abnormalities, increased creatinine level, elevated liver enzyme levels, and splenomegaly 4 weeks after the oral treatment of minocycline, 100 mg daily, for acne. Once diagnosed with DRESS syndrome, intravenous methylprednisolone was applied and his clinical manifestations and laboratory results remarkably improved. Then, a total of 13 DRESS syndrome cases induced by minocycline were reviewed and their clinical characteristics were summarized. In these cases, only two patient (15.4%) was present with pharynx involved. In conclusion, we reported a rare minocycline-induced DRESS syndrome who developed fever, eosinophilia, acute rash, pharyngitis, lymphadenopathy, acute kidney injury, hepatitis, and splenomegaly. Our report provides detailed clinical features of minocycline-induced DRESS syndrome, which helps us further understand this severe adverse event.

Amoxicillin-Induced Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Syndrome With Acute Onset of Diffuse Rash and Acute Kidney Injury (AKI).

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon and potentially fatal adverse drug reaction that can affect individuals with immunosuppression, viral reactivation, pharmacogenetic susceptibility, and recent exposures to new medications. Due to the ambiguous symptomology of DRESS syndrome along with a lack of diagnosis and treatment criteria, there can be delays in diagnosis and management. Here, we present a case of a 60-year-old female with an uncommon presentation of DRESS syndrome due to a less commonly implicated drug. We aim to bring awareness to the various presentations associated with DRESS syndrome and inform readers about current diagnostic and treatment modalities used today. In addition, this case serves to provide insights that further evidence is needed to have standardized guidelines in place to effectively diagnose and manage affected patients.

Fat Embolism: A Rare Complication of Bone Biopsy.

We report a woman who was admitted to the hospital with a sudden onset of extensive maculopapular erythematous rash involving the trunk and extremities, six weeks after initiating antihypertensive medication. She had atypical lymphocytosis with Gumprecht shadows, elevated liver enzymes, and acute kidney injury. The diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome secondary to antihypertensive drugs was suspected and the antihypertensive drugs were suspended. A hypothesis of lymphoproliferative disease was also considered, and consequently, a myelogram and bone biopsy of the iliac crest were performed. After the procedure, the patient developed acute hypoxemia. After the exclusion of pulmonary thromboembolism by CT angiography, we assumed a presumptive diagnosis of iatrogenic fat embolism syndrome (FES) associated with bone biopsy. The patient deteriorated with worsening hypoxemia and ultimately died. This case represented a diagnostic challenge and highlighted iatrogenesis's undesirable and potentially fatal effects. Careful consideration of the risk-benefit ratio of all medical procedures is paramount in daily medical practice and knowledge of the possible risks is necessary for their early recognition and therapeutic approach.

A Unique Case of Conservatively Treated Actinomyces Empyema Complicated Due to Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome.

This case contemplates the unusual presentation, challenging diagnostic workup and conservative therapeutic process of a patient with Actinomyces empyema complicated along the way due to drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. The patient was a 40-year-old male, who presented with pleurodynia and fever. Laboratory exams showed elevated inflammatory markers and imaging revealed two biconvex fluid pockets located in the right lower lobe, from which the fluid was positive for Actinomyces meyeri. The initial conservative process with intravenous antibiotics and successful drainage with intrapleural fibrinolysis improved our patient. However, after a few days, the patient's fevers relapsed, and as regress of the empyema was discussed as a complication, he developed a maculopapular symmetrical rash of the trunk and legs accompanied by enlarged lymph nodes, eosinophilia, thrombocytopenia, and atypical lymphocytes. The diagnosis of DRESS syndrome due to antibiotic therapy for actinomyces empyema was established and a balance between bactericidal and immunosuppression medication had to be found. Fortunately, the patient withstood prolonged antibiotic therapy and got fully treated without any relapses.

Drug Reaction With Eosinophilia and Systemic Symptoms-Associated Perimyocarditis After Initiation of Anti-tuberculosis Therapy: A Case Report.

A 34-year-old female who was recently placed on anti-tuberculosis medication with rifampin, isoniazid, pyrazinamide, and levofloxacin therapy for suspected tuberculosis reinfection presented with subjective fevers, rash, and generalized fatigue. Labs showed signs of end-organ damage with eosinophilia and leukocytosis. One day later, the patient became hypotensive with a worsening fever, and an electrocardiogram showed new diffuse ST segment elevations with an elevated troponin. An echocardiogram revealed a reduction in ejection fraction with diffuse hypokinesis, and cardiac magnetic resonance imaging (MRI) showed circumferential myocardial edema with subepicardial and pericardial inflammation. Prompt diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome using the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria and discontinuation of therapy was initiated. Due to the hemodynamic instability of the patient, the patient was started on systemic corticosteroids and cyclosporine, with the improvement of her symptoms and rash. A skin biopsy was performed, which revealed perivascular lymphocytic dermatitis, consistent with DRESS syndrome. As the patient's ejection fraction improved spontaneously with corticosteroids, the patient was discharged with oral corticosteroids, and a repeat echocardiogram showed full recovery of ejection fraction. Perimyocarditis is a rare complication of DRESS syndrome that is associated with degranulation and the release of cytotoxic agents into myocardial cells. Early discontinuation of offending agents and initiation of corticosteroids are essential to rapid recovery of ejection fraction and improved clinical outcomes. Multimodality imaging, including MRI, should be used to confirm perimyocardial involvement and guide the necessity for mechanical support or transplant. Further research should be on the mortality of DRESS syndrome with and without myocardial involvement, with an increased emphasis on cardiac evaluation in DRESS syndrome.

Novel targeted inhibition of the IL-5 axis for drug reaction with eosinophilia and systemic symptoms syndrome.

Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe hypersensitivity reaction. Up-to-date treatment is based on withdrawal of medication, supportive care, and immunosuppression using high-dose corticosteroid (CS) therapy. However, evidence-based data are lacking regarding second-line therapy for steroid-resistant or steroid-dependent patients. Objectives: We hypothesize that the interleukin (IL)-5 axis plays a critical role in the pathophysiology of DRESS; hence, inhibition of this signaling pathway could offer a potential therapy for steroid-dependent and/or steroid-resistant cases, and it may offer an alternative to CS therapy in certain patients more prone to CS toxicity. Methods: Herein, we collected worldwide data on DRESS cases treated with biological agents targeting the IL-5 axis. We reviewed all cases indexed in PubMed up to October 2022 and performed a total analysis including our center experience with two additional novel cases. Results: A review of the literature yielded 14 patients with DRESS who were treated with biological agents targeting the IL-5 axis as well as our two new cases. Reported patients are characterized by a female-to-male ratio of 1:1 and a mean age of 51.8 (17-87) years. The DRESS-inducing drugs, as expected from the prospective RegiSCAR study, were mostly antibiotics (7/16), as follows: vancomycin, trimethoprim-sulfamethoxazole, ciprofloxacin, piperacillin-tazobactam, and cefepime. DRESS patients were treated with anti-IL-5 agents (mepolizumab and reslizumab) or anti-IL-5 receptor (IL-5R) biologics (benralizumab). All patients have clinically improved under anti-IL-5/IL-5R biologics. Multiple doses of mepolizumab were needed to achieve clinical resolution, whereas a single dose of benralizumab was often sufficient. Relapse was noted in one patient receiving benralizumab treatment. One patient receiving benralizumab had a fatal outcome, although mortality was probably related to massive bleeding and cardiac arrest due to coronavirus disease 2019 (COVID-19) infection. Conclusion: Current treatment guidelines for DRESS are based on case reports and expert opinion. Understanding the central role of eosinophils in DRESS pathogenicity emphasizes the need for future implementation of IL-5 axis blockade as steroid-sparing agents, potential therapy to steroid-resistant cases, and perhaps an alternative to CS treatment in certain DRESS patients more prone to CS toxicity.

Guselkumab-Associated Pulmonary Disease and Diffuse Alveolar Hemorrhage with Drug Rash with Eosinophilia and Systemic Symptoms.

Psoriasis is a common skin condition worldwide. Moderate-to-severe disease is treated with biologic or non-biologic disease-modifying anti-rheumatic drugs. These include tumor necrosis factor (TNF)-a inhibitors, interleukin (IL)-17 inhibitors, and IL-23 inhibitors. Case reports of inhibitors of TNF-a and IL-12p40 subunits causing interstitial pneumonia (IP) have been published in the literature, but no case of anti-IL-23p19 subunit biologics causing IP and acute respiratory distress syndrome (ARDS) has been reported before. We report a case of a patient with restrictive lung disease secondary to a body mass index of 36.54 kg/m2, obstructive sleep apnea, and psoriasis, who developed IP and ARDS presumed to be secondary to guselkumab, an anti-IL-23p19 subunit monoclonal antibody. He was on ustekinumab, an anti-IL-12/23p40 for the treatment of psoriasis, but was switched to guselkumab eight months before the presentation, and since then he had been complaining of progressive shortness of breath. He initially presented to the hospital after having drug reaction with eosinophilia and systemic symptoms (DRESS) after being started on amoxicillin for a tooth infection. He was treated with high-dose intravenous steroids but developed progressive shortness of breath. Broad-spectrum antibiotics were added. An extensive infectious, autoimmune, and hypersensitivity work-up was undertaken, which returned negative. A bronchoscopy with bronchoalveolar lavage was performed, which revealed diffuse alveolar hemorrhage (DAH). His lung imaging and oxygenation progressively got worse; hence, no lung biopsy was taken. He was intubated and required inhaled nitric oxide, but due to the lack of improvement, the family elected for comfort measures, and the patient was extubated and passed away. To our knowledge, this is the first case of an association between guselkumab, IP, ARDS, and DAH. Rare instances of DAH with DRESS have been reported before. Whether it was DRESS or guselkumab that caused DAH was uncertain in our patient. Clinicians should monitor for DAH and shortness of breath in patients on guselkumab so that more data can be obtained and studied in the future.