Drug-induced hypersensitivity syndrome, also known as DRESS syndrome, is a serious and potentially fatal reaction that occurs in response to prolonged use (generally between 14 and 60 days) of certain drugs, and which has no predilection for gender or age group. It is believed that DRESS syndrome has a genetic basis and results from the interaction between metabolites of certain pharmacological groups, reactivation of latent viruses (especially from the Herpesviridae family), and a cellular immune response. The classic manifestation of DRESS syndrome includes a generalized rash accompanied by fever, eosinophilia, lymphadenopathy, and systemic involvement such as hepatitis, nephritis, or pneumonitis. With the continuous increase in the availability of drugs and the aging of the population, there is a favorable scenario for the development of adverse drug reactions. Physicians should be prepared for the early diagnosis of DRESS syndrome, the identification and immediate suspension of the drug involved, and also manage systemic involvement, which may require prolonged immunosuppressive therapy. This article provides an update on the clinical, physiopathological and therapeutic aspects of DRESS syndrome.

Diagnosing drug reaction with eosinophilia and systemic symptoms (DRESS) can be challenging.

We sought to identify clinical and laboratory features outside of the Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria that distinguish patients with probable DRESS (RegiSCAR ≥ 4) from those with drug rash and eosinophilia (DRE).

Using international coding classifications of drug-induced fever, generalized skin eruption due to medications, and eosinophilia, a retrospective audit from 2008 to 2023 of hospitalized patients was performed.

Forty-four cases of DRESS were compared to 80 cases of DRE. In addition to the RegiSCAR distinguishing factors for DRESS were longer drug latency before symptom onset (median 21 vs 5 days, P < .001) and higher alanine transaminase levels (increase by a factor of 2.49 [95% confidence interval, 1.56, 4.00; P = .009]). Follow-up (mean 5.67 years) revealed a low rate of statewide drug alert reporting (29.6%) and drug allergy testing in DRESS (20.5%). Inadvertent reexposure to a culprit or structurally related drug resulted in recurrent DRESS in 3 patients (7.5%), and tolerance of structurally related drugs occurred in 8 patients (17.5%).

In this large study evaluating DRE patients whose disease does not meet the RegiSCAR criteria for DRESS, we found that additional factors outside the RegiSCAR criteria may help clinicians differentiate DRESS, which is critical for optimal and timely patient management. Our study also highlights the need for development of local protocols to ensure appropriate allergy labeling and testing are performed to prevent recurrent DRESS.

Adverse drug reactions are defined as unexpected reactions, either derived from the pharmacokinetics of the treatment (Type A) or as a host immune response (Type B), resulting in harmful or undesirable manifestations in the patient following the administration of pharmacological therapy. Type B reactions are less defined and are considered a result of hypersensitivity to pharmacological treatment, categorized as immediate (within 1 to 6 hours after exposure) and delayed or non-immediate (occurring 6 hours after exposure).

A review to describe the immunological mechanisms of delayed hypersensitivity reactions to drugs.

A search of major medical databases on delayed hypersensitivity reactions to drugs was conducted. The review was limited to articles published in the period between 2013 and 2023, taking into consideration articles written in English and Spanish.

The terms defining delayed hypersensitivity reactions to drugs, their classification, clinical manifestations, diagnosis, treatment algorithms, and prognosis.

Adverse drug reactions represent a challenge for the specialist physician, with a complex pathophysiology. A prompt diagnosis and treatment focused on the drug phenotype and its immunological expression are required to provide a multidisciplinary approach.

Drug hypersensitivity syndrome (DIHS) is a rare but potentially fatal adverse drug reaction characterized by fever, rash, and visceral organ damage, particularly affecting the liver. Early recognition and appropriate management are crucial to prevent serious complications. However, there is limited information on the clinical presentation and management of DIHS, especially in the context of antiepileptic drugs. This case report aims to highlight the importance of recognizing subtle clinical signs and symptoms of DIHS, which can be easily overlooked, particularly in the context of antiepileptic drug use.

We report a case of a 15-year-old male patient who developed DIHS after being prescribed phenytoin sodium for epilepsy. The patient presented with symptoms of fever, sore throat, rash, jaundice, and liver dysfunction. Initially, the patient did not receive glucocorticoids and experienced additional reactions to cefoxitin and phosphatidylcholine, likely due to cross-reactivity.

The diagnosis of DIHS was made based on the patient's clinical presentation, including fever, extensive rash, organ involvement, and hematological abnormalities. The temporal association with the use of phenytoin sodium, along with the exclusion of other causes of fever and rash, supported the diagnosis.

Upon initiation of glucocorticoid therapy with dexamethasone, the patient's symptoms significantly improved. The rash and pruritus decreased, and laboratory values showed improvement, with a decrease in liver enzymes and normalization of white blood cell counts.

The patient's fever resolved within 48 hours of starting corticosteroids, and there was no evidence of ongoing inflammation as indicated by a decrease in C-reactive protein levels. Furthermore, the patient's 30-month follow-up revealed no recurrence of rash, liver dysfunction, or organic damage, indicating the long-term effectiveness of the treatment administered.

This case highlights the importance of recognizing the subtle clinical signs and symptoms of DIHS, especially in the context of antiepileptic drug use. It underscores the potential benefits of early initiation of glucocorticoid therapy in managing DIHS. The case also serves as a reminder of the potential for drug cross-reactivity in DIHS and the need for cautious drug selection during the acute phase of the syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, adverse drug reaction that is notoriously complex in both its presentation and treatment. Although early diagnosis and cessation of the causative agent are universally accepted as the initial interventions for DRESS, the subsequent management lacks a standardized approach. Historically, systemic steroids have been used as first-line treatment, but there is debate about the optimal dosing and route of administration, and evidence persists on the long-term complications associated with steroid use. Novel treatment approaches with targeted therapy, cyclosporine, intravenous immunoglobulin, and plasmapheresis have been gaining interest as alternative mono- and adjuvant therapies, but their use has yet to be supported by clinical trials. This narrative review provides a summary of the current knowledge of DRESS, with a focus on clinical management. The various mono- and adjuvant therapy options are discussed, with literature-supported suggestions for their optimal use in clinical practice. The risks for relapses, viral reactivation, and long-term complications are also considered. The PubMed and Medline databases were searched for articles on DRESS, published between January 1, 2008, and May 1, 2023. 334 articles met the inclusion criteria. Based on the literature, a DRESS management tool with step-by-step guidance is provided. Further suggestions for management are woven throughout this review, giving clinicians a toolbelt of resources with which to approach diagnosis, treatment, and follow-up.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and severe adverse drug reaction involving multiple organs. Data on DRESS syndrome among children are currently limited. The purpose of this study was to determine the clinical features, causative drugs, systemic organ involvement, laboratory findings, disease severity score, and treatment outcomes in pediatric DRESS patients. The medical records of all pediatric DRESS patients, based on the RegiSCAR diagnostic criteria and admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand from January 2010 to December 2021, were reviewed. Twenty-two cases were identified (males 54.5%) with a median age of 9.5 years. Anticonvulsants (54.5%) and antibiotics (27.3%) were the leading culprit drugs. Skin rash was reported in all cases, followed closely by liver involvement (95.5%). Eosinophilia and atypical lymphocytosis were identified in 54.5% and 31.8% of cases, respectively. The median latency period was 17.5 days. Liver enzyme elevation was detected at an average onset of 20.0 days and hepatocellular type was the most common pattern of liver injury. Nineteen patients (86.4%) were treated with systemic corticosteroids with prednisolone being the most prescribed medication. One case developed Graves' disease after DRESS and multiple relapses of DRESS. One case (4.5%) died due to refractory status epilepticus that was unrelated to DRESS. Anticonvulsants were the major cause of DRESS in pediatric patients. High suspicion for DRESS is crucial in patients receiving these drugs and presenting with fever, rash, and internal organ involvement.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe adverse event (mortality of 10%). Its pathophysiology involves herpesviruses, particularly HHV-6, but the exact mechanisms are still poorly understood.

To describe severe cases of DRESS and especially their association with herpesvirus reactivation.

This study was a multicentre case series conducted between 2007 and 2021 at five University Hospital Centres in France. The study included patients who had severe DRESS, which was defined as death, transfer to the intensive care unit (ICU), or severe damage to internal organs. We excluded patients without blood PCR sample, without a drug formally attributed or with RegiSCAR score < 6. We collected data on severity, causative drug, associated visceral damage and results of viral blood PCRs. HHV-6 reactivation was studied in skin biopsies by detection of small non-coding transcripts (HHV-6 miR-aU14) and a late viral protein (GP82/105).

Fifty-two patients were included (29 female, median age 62, interquartile range (IQR) [37;72]). Eight patients (15%) died, 13 (27%) were admitted to ICU. Most patients (n = 34; 65%) had multisystem involvement: most frequent was liver (n = 46; 88%), then renal failure (n = 24; 46%). Forty patients (77%) had at least one blood viral reactivation among HHV-6, EBV or CMV, of which 21 (53%) had at least two. Median time of blood HHV-6 reactivation was 24 days (IQR [20;35]). HHV-6 reactivation was demonstrated in 15 out of 20 skin biopsies, with a median time of 11 days [9;17].

We confirmed the high rate of HHV-6 reactivation in severe DRESS and demonstrated cutaneous HHV-6 reactivation using small non-coding transcripts (HHV-6 miR-aU14), which preceded viral PCR positivity in blood. These results suggest that HHV-6 reactivation during DRESS may start in skin. Furthermore, search for miR-aU14 in skin biopsy could become a useful diagnostic tool for early detection of HHV-6 reactivation.

Unlike other adverse drug reactions, visceral organ involvement is a prominent feature of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and correlates with mortality. The aim of this study was to systematically review cases published in PubMed-indexed, peer-reviewed journals in which patients had renal injury during the episode of DRESS syndrome (DS). We found 71 cases, of which 67 were adults and 56% were males. Female sex was associated with higher mortality. Chronic kidney disease (CKD) was present in 14% of patients who developed acute kidney injury (AKI) during DS. In 21% of cases, the kidneys were the only visceral organ involved, while 54% of patients had both liver and kidney involvement. Eosinophilia was absent in 24% of patients. The most common classes of medication associated with renal injury in DS were antibiotics in 34%, xanthine oxidase inhibitors in 15%, and anticonvulsants in 11%. Among antibiotics, vancomycin was the most common culprit in 68% of patients. AKI was the most common renal manifestation reported in 96% of cases, while isolated proteinuria or hematuria was present in only 4% of cases. In cases with AKI, 88% had isolated increase in creatinine and decrease in glomerular filtration (GFR), 27% had AKI concomitantly with proteinuria, 18% had oliguria, and 13% had concomitant AKI with hematuria. Anuria was the rarest manifestation, occurring in only 4% of patients with DS. Temporary renal replacement therapy was needed in 30% of cases, and all but one patient fully recovered renal function. Mortality of DS in this cohort was 13%, which is higher than previously reported. Medication class, latency period, or pre-existing CKD were not found to be associated with higher mortality. More research, particularly prospective studies, is needed to better recognize the risks associated with renal injury in patients with DS. The development of disease-specific biomarkers would also be useful so DS with renal involvement can be easier distinguished from other eosinophilic diseases that might affect the kidney.

Delayed drug hypersensitivity reactions (DDHRs) represent a major health problem. They are unpredictable and can cause life-long disability or even death. The pathophysiology of DDHRs is complicated, multifactorial, and not well understood mainly due to the lack of validated animal models or in vitro systems. The role of the immune system is well demonstrated but its exact pathophysiology still a matter of debate.

This review summarizes the current understanding of DDHRs pathophysiology and abridges the available new evidence supporting each hypothesis. A comprehensive literature search for relevant publications was performed using PubMed, Google Scholar, and Medline databases with no date restrictions and focusing on the most recent 10 years.

Although multiple milestones have been achieved in our understanding of DDHRs pathophysiology as a result of the development of useful experimental models, many questions are yet to be fully answered. A deeper understanding of the mechanistic basis of DDHRs would not only facilitate the development of robust and reliable diagnostic assays for diagnosis, but would also inform therapy by providing specific target(s) for immunomodulation and potentially permit pre-therapeutic risk assessment to pursue the common goal of safe and effective drug therapy.

To describe the phenotype of DRESS syndrome induced by antituberculosis drugs.

Descriptive study, withdrawn from the review of the records of patients with DRESS syndrome, identified in the interconsultation of the Department of Research in Immunogenetics and Allergy, of the Insti-tuto Nacional de Enfermedades Respiratorias (INER) Ismael Cosío Villegas, among 2014 and 2020. Frequency analysis was performed. The associations between biomarkers and latency are calculated with the χ2 test and log-rank, and the evaluation of the change in the biomarkers with the Wilcoxon test. The value of p < 0.05 is considered statistically significant. For data analysis, the SPSS v.21 program was obtained.

15 patients were identified; represented by 0.02% of total cases treated in the Department for so-meimmuno-allergic condition (15/7052); the main symptomatology were: rash (100%), eosinophilia (93%), fe-ver (80%), adenomegaly (60%), kidney damage (40%), liver damage (33%), and latency of 21 days. Liver damage was associated with prolonged latency (p = 0.02). After treatment, the total levels of eosinophils (p < 0.001) and liver and kidney biomarkers (p < 0.04) decreased. DRESS syndrome induced by antituberculosis drugs is not associated with the number of drugs prescribed or with the pattern of resistance of Mycobacterium tuberculosis.

DRESS syndrome induced by antituberculosis drugs is an atypical clinical reaction, similar to other types of DRESS syndrome that respond favorably to systemic corticosteroids.

Juvenile idiopathic Arthritis (JIA) is a common rheumatic disorder in children that can cause multiple systems to be affected simultaneously, leading to severe clinical symptoms and a high mortality rate in those with pulmonary involvement. Pleurisy is the most common manifestation of pulmonary involvement. At the same time, other conditions, such as pneumonia, interstitial lung disease, occlusive bronchiectasis, and alveolar protein deposition, have been increasingly reported in recent years. This review aims to provide an overview of the clinical manifestations of JIA lung damage and the current treatment options to assist in identifying and treating JIA lung involvement.

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.

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.

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.

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.

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.

One of the most severe forms of cutaneous adverse drug reactions is 'drug reaction with eosinophilia and systemic symptoms' (DRESS), hence subsequent avoidance of the causal drug is imperative. However, attribution of drug culpability in DRESS is challenging and standard skin allergy tests are not recommended due to patient safety reasons. Whilst incidence of DRESS is relatively low, between 1:1000 to 1:10,000 drug exposures, antibiotics are a commoner cause of DRESS and absence of confirmatory diagnostic test can result in unnecessary avoidance of efficacious treatment. We therefore sought to identify potential biomarkers for development of a diagnostic test in antibiotic-associated DRESS. Peripheral blood mononuclear cells (PBMCs) from a 'discovery' cohort (n = 5) challenged to causative antibiotic or control were analysed for transcriptomic profile. A panel of genes was then tested in a validation cohort (n = 6) and compared to tolerant controls and other inflammatory conditions which can clinically mimic DRESS. A scoring system to identify presence of drug hypersensitivity was developed based on gene expression alterations of this panel. The DRESS transcriptomic panel identified antibiotic-DRESS cases in a validation cohort but was not altered in other inflammatory conditions. Machine learning or differential expression selection of a biomarker panel consisting of six genes (STAC, GPR183, CD40, CISH, CD4, and CCL8) showed high sensitivity and specificity (100% and 85.7-100% respectively) for identification of the culprit drug in these cohorts of antibiotic-associated DRESS. Further work is required to determine whether the same panel can be repeated for larger cohorts, different medications, and other T cell mediated drug hypersensitivity reactions.

Drug reaction with eosinophilia and systemic symptoms (DReSS), also known as drug-induced hypersensitivity syndrome (DiHS), is a severe, systemic, T cell mediated drug reaction with combinations of cutaneous, hematologic, and internal organ involvement. Pathogenesis of DReSS is multi-factorial, involving drug-exposure, genetic predisposition through specific human leukocyte antigen (HLA) alleles and metabolism defects, viral reactivation, and immune dysregulation. Clinical features of this condition are delayed, stepwise, and heterogenous, making this syndrome challenging to recognize and diagnose. Two sets of validated diagnostic criteria exist that can be employed to diagnose DReSS/DiHS. Methods to improve early recognition of DReSS and predict disease severity has been a recent area of research focus. In vitro and in vivo tests can be employed to confirm the diagnosis and help identify culprit drugs. The mainstay treatment of DReSS is prompt withdrawal of the culprit drug, supportive treatment, and immunosuppression depending on the severity of disease. We present a comprehensive review on the most recent research and literature on DReSS, with emphasis on pathogenesis, clinical features, diagnosis, confirmatory testing modalities, and treatment. Additionally, this summary aims to highlight the differing viewpoints on this severe disease and broaden our perspective on the condition known as DReSS.

The literature on positive patch test results in drug reaction with eosinophilia and systemic symptoms (DRESS) is reviewed. 105 drugs were identified that have together caused 536 positive patch tests in 437 patients suffering from DRESS. By far most reactions (n=145) were caused by carbamazepine, followed by amoxicillin, isoniazid, phenytoin, ethambutol, fluindione, phenobarbital, rifampicin, and ceftriaxone; 43 drugs each caused a single case only. The drug classes causing the highest number of reactions are anticonvulsants (39%), beta-lactam antibiotics (20%), antituberculosis agents (11%), non-beta-lactam antibiotics (6%) and iodinated contrast media (5%). The sensitivity of patch testing (percentage of positive reactions) is high for anticonvulsants (notably carbamazepine), beta-lactam antibiotics (notably amoxicillin) and possibly iodinated contrast media. Allopurinol and sulfasalazine frequently cause DRESS, but never give positive patch tests. Patch testing in DRESS appears to be safe, although mild recurrence of DRESS symptoms, mostly skin reactions, may not be rare. Multiple drug hypersensitivity was found to occur in 16% of all patients, but it is argued that the true frequency is (far) higher. Clinical aspects of DRESS, including diagnosing the disease and identifying culprit drugs (patch tests, intradermal tests, in vitro tests, challenge tests) are also provided, emphasizing the role of patch testing. This article is protected by copyright. All rights reserved.

Coronavirus disease-2019 (COVID-19) has been associated with cutaneous findings, some being the result of drug hypersensitivity reactions such as maculopapular drug rashes (MDR). The aim of this study was to investigate whether COVID-19 may impact the development of the MDR.

Blood and skin samples from COVID-19 patients (based on a positive nasopharyngeal PCR) suffering from MDR (COVID-MDR), healthy controls, non-COVID-19-related patients with drug rash with eosinophilia and systemic symptoms (DRESS), and MDR were analyzed. We utilized imaging mass cytometry (IMC) to characterize the cellular infiltrate in skin biopsies. Furthermore, RNA sequencing transcriptome of skin biopsy samples and high-throughput multiplexed proteomic profiling of serum were performed.

IMC revealed by clustering analyses a more prominent, phenotypically shifted cytotoxic CD8+ T cell population and highly activated monocyte/macrophage (Mo/Mac) clusters in COVID-MDR. The RNA sequencing transcriptome demonstrated a more robust cytotoxic response in COVID-MDR skin. However, severe acute respiratory syndrome coronavirus 2 was not detected in skin biopsies at the time point of MDR diagnosis. Serum proteomic profiling of COVID-MDR patients revealed upregulation of various inflammatory mediators (IL-4, IL-5, IL-6, TNF, and IFN-γ), eosinophil and Mo/Mac -attracting chemokines (MCP-2, MCP-3, MCP-4 and CCL11). Proteomics analyses demonstrated a massive systemic cytokine storm in COVID-MDR compared with the relatively milder cytokine storm observed in DRESS, while MDR did not exhibit such features.

A systemic cytokine storm may promote activation of Mo/Mac and cytotoxic CD8+ T cells in severe COVID-19 patients, which in turn may impact the development of MDR.

Drug-induced liver injury (DILI) encompasses the unexpected damage that drugs can cause to the liver. DILI may develop in the context of an immunoallergic syndrome with cutaneous manifestations, which are sometimes severe (SCARs). Nevirapine, allopurinol, anti-epileptics, sulfonamides, and antibiotics are the most frequent culprit drugs for DILI associated with SCARs. Interestingly, alleles HLA-B*58:01 and HLA-A*31:01 are associated with both adverse reactions. However, there is no consensus about the criteria used for the characterization of liver injury in this context, and the different thresholds for DILI definition make it difficult to gain insight into this complex disorder. Moreover, current limitations when evaluating causality in patients with DILI associated with SCARs are related to the plethora of causality assessment methods and the lack of consensual complementary tools. Finally, the management of this condition encompasses the treatment of liver and skin injury. Although the use of immunomodulant agents is accepted for SCARs, their role in treating liver injury remains controversial. Further randomized clinical trials are needed to test their efficacy and safety to address this complex entity. Therefore, this review aims to identify the current gaps in the definition, diagnosis, prognosis, and management of DILI associated with SCARs, proposing different strategies to fill in these gaps.

Growing evidence indicates that amoxicillin induces herpesvirus replication in vitro. As these play a central pathophysiological role in Drug Reaction with Eosinophilia and Systemic Symptoms syndrome (DRESS), amoxicillin could present with specific DRESS features.

To characterize the onset patterns of amoxicillin-associated DRESS.

All cases of DRESS (Kardaun score ≥4) involving amoxicillin and reported in the French Pharmacovigilance Database between January 1, 2004 and November 30, 2019 were included. Onset circumstances for these cases were categorized considering the onset delay from amoxicillin initiation, and the presence of concomitant medications with a compatible time to onset.

A total of 146 probable cases or definite cases of DRESS were included. Three onset circumstances were identified: (i) 'amoxicillin clear culprit' where amoxicillin was the sole suspect drug or when concomitant drugs of compatible time to onset were not reported to cause DRESS (n = 62); (ii) 'amoxicillin possible culprit' in the presence of other potentially culprit drugs in addition to amoxicillin (n = 44) and (iii) 'flare' where amoxicillin, used after DRESS onset, induced flare-up reactions (n = 40). The median time to onset was 5 days (IQR 2-11) in 'clear culprit', and 18 days (IQR 7-26) in 'possible culprit' cases. In 'flare' cases, the median latency between amoxicillin initiation and flare-up reactions was 3 days (IQR 2-5).

Amoxicillin can induce DRESS with a specific early onset and exacerbate DRESS from another drug.

Severe Acute Respiratory Virus Corona Virus 2 (SARS-CoV-2) has got its name Corona from Latin meaning "crown." It has crown-like spikes present on the surface, which encloses the RNA, genetic material of this deadly virus. The virus attacks pneumocytes after binding with the angiotensin-converting enzyme 2 (ACE2) of the cell surface, which ultimately leads to chemotaxis followed by leukocyte infiltration, increased permeability of blood vessels and alveolar walls, and decreased surfactant in the lung leading to various symptoms. Skin provides a window to the internal changes of the body and also to mechanisms that are not readily visible. Commonly observed skin manifestations include vesicular lesions, maculopapular exanthema, urticarial eruptions, livedo or necrosis, and other forms of vasculitis, chilblain-like lesions. The skin lesions are attributed to either the virus directly affecting the skin or interferon dysregulation due to viral RNA or vascular involvement associated with alteration in coagulation or drug-induced skin manifestations. Observation of skin involvement and the vasculature due to SARS-CoV-2 illustrates the need for a precise stratification and differential diagnostic valuation so that the mechanisms of this novel virus are clearer for better management of the condition in the future. Vascular skin lesions are not seen in all the patients of COVID, but certain lesions should definitely alarm us to evaluate for coagulation abnormalities, complement levels, and skin biopsy, especially in critically ill patients. This review attempts to outline the pathogen briefly and the pathomechanism behind the development of various cutaneous manifestations.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a cutaneous and systemic drug allergy disorder. Patients exist on a severity spectrum, with some experiencing a mild form of the disorder that fails to meet the Registry of Severe Cutaneous Adverse Reactions (SCAR) to Drugs diagnostic criteria for DRESS.

We sought to determine whether there were any cutaneous or dermatopathologic features that discriminate between the mild form of DRESS (DRESS minor) and the severe phenotype (DRESS major).

Hospitalized patients from a single center with a diagnosis of DRESS were prospectively recruited over a 7-year period. Clinical and dermatopathologic features were analyzed to discriminate between DRESS minor and DRESS major.

Forty-five patients were included, of whom 19 had a Registry of Severe Cutaneous Adverse Reactions (SCAR) to Drugs score of ≤3 (DRESS minor) and 26 had a score of ≥4 (DRESS major). The mean latency period (P = .001), fever >38.5 °C (P = .001), and a reaction lasting >15 days (P = .010) discriminated DRESS major from DRESS minor. Facial edema was the sole discerning cutaneous feature (P = .025). Discriminating histopathologic features included basal squamatization (P = .005), dermal red blood cell extravasation (P = .009), and interface inflammation (P = .005).

We propose a new classification system-DRESS minor-to distinguish the milder illness from the severe form, DRESS major. Facial edema and certain histopathologic features can help discriminate between major and minor versions.

Severe cutaneous adverse reactions (SCARs) are potentially life-threatening, with considerable morbidity and mortality. They are nonimmediate hypersensitivity reactions that occur in specifically predisposed patients with delayed T-cell-mediated hypersensitivity reaction. Antiseizure medications (ASMs) are among the drugs that can induce SCAR. Increased awareness of SCAR among clinicians treating patients with ASMs is critically important for early recognition of symptoms, prompt identification and removal of the causal drug, and early intervention to reduce SCAR-related acute and long-term morbidity and mortality. The diagnosis, management, and prevention of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) are reviewed, along with the current understanding of the pathomechanisms and role of genetics in SCAR development. Supportive care and immunomodulating treatments for SCAR are discussed.

The pandemic condition coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can take asymptomatic, mild, moderate, and severe courses. COVID-19 affects primarily the respiratory airways leading to dry cough, fever, myalgia, headache, fatigue, and diarrhea and can end up in interstitial pneumonia and severe respiratory failure. Reports about the manifestation of various skin lesions and lesions of the vascular system in some subgroups of SARS-CoV-2-positive patients as such features outside the respiratory sphere, are rapidly emerging. Vesicular, urticarial, and maculopapular eruptions and livedo, necrosis, and other vasculitis forms have been reported most frequently in association with SARS-CoV-2 infection. In order to update information gained, we provide a systematic overview of the skin lesions described in COVID-19 patients, discuss potential causative factors, and describe differential diagnostic evaluations. Moreover, we summarize current knowledge about immunologic, clinical, and histologic features of virus- and drug-induced lesions of the skin and changes to the vascular system in order to transfer this knowledge to potential mechanisms induced by SARS-CoV-2.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse drug reaction with systemic symptoms. This study aims to investigate clinical features, causative drugs, and available treatments for pediatric DRESS, particularly for relapsing cases.

A systematic search of the English and French literature on pediatric DRESS was conducted using the Medline, Embase, and Cochrane collaboration databases. Confirmed cases of pediatric DRESS fulfilling the RegiSCAR diagnostic criteria with a probable or a definite diagnosis were included.

After full-text article review, 144 articles were included, representing a total of 354 pediatric patients with a mean age of 8.8 years. The mean time from the drug intake until the onset of the first symptom was 18.9 days. Antiepileptic drugs were the main trigger, followed by anti-infectious agents. Relapsing DRESS was reported in 17 children. In comparison to non-relapsing cases, relapsing patients had more comorbidities. The initial clinical presentation was more commonly erythroderma. Facial edema, fever, and enlarged lymph nodes in more than two sites were more commonly found in relapsing cases. Systemic steroids were more frequently administered.

Pediatric DRESS is a potentially severe adverse drug reaction. Antiepileptic agents are the most common causative agents. Fever, facial edema, lymph node enlargement, and pharyngeal and visceral involvement predicted DRESS reactivation in children. Corticosteroids were the mainstay of treatment.

Eosinophilic dermatoses encompass a broad spectrum of diseases of different etiologies hallmarked by eosinophilic infiltration of the skin and/or mucous membranes, with or without associated blood eosinophilia. The wide range of dermatological manifestations of this spectrum, including nodules and plaques, pustules, blisters, ulcers, and urticarial lesions, is reflected in a non-univocal classification system. We identified six groups of eosinophilic dermatoses based on the predominant anatomic level of involvement: (1) epidermal; (2) of the dermal-epidermal junction; (3) dermal; (4) of the hypodermis and muscle fascia; (5) of the pilosebaceous unit; and (6) vascular/perivascular. We review clinicopathologic features and management of diseases belonging to each group, particularly: (1) pemphigus herpetiformis and atopic dermatitis as prototypes of the epidermal group; (2) bullous pemphigoid as prototypic eosinophilic dermatosis of the dermal-epidermal junction; (3) eosinophilic cellulitis (Wells syndrome), hypereosinophilic syndromes, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, eosinophilic dermatosis of hematologic malignancy and chronic spontaneous urticaria as paradigmatic dermal eosinophilic dermatoses; (4) eosinophilic fasciitis as an eosinophilic dermatosis with predominant involvement of the hypodermis and muscle fascia; (5) eosinophilic pustular folliculitis as a model of the pilosebaceous unit involvement; and (6) granuloma faciale, angiolymphoid hyperplasia with eosinophilia, and eosinophilic granulomatosis with polyangiitis, belonging to the vascular/perivascular group.

In rheumatological practice situations repeatedly occur where critical problems which need to be quickly addressed in order to prevent permanent damage to the patient. The focus of this article is on rapidly progressive inflammatory diseases, severe side effects of many medications and complications of infections during immunosuppressive treatment.

To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).

In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.

LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.

A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.