Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DiHS), is a severe type of cutaneous adverse reaction. The gold standard therapy for DRESS involves the discontinuation of the culprit drug, supportive therapies, and administration of corticosteroids. However, in cases of primary treatment failure or suboptimal response, there arises an urgent need for alternative interventions. This review focuses on exploring alternative systemic therapies for patients with steroid-resistant DRESS, steroid-dependent DRESS, or refractory DRESS, encompassing immunosuppressive agents, intravenous immunoglobulin, plasmapheresis, biologics, and small molecule drugs, with an emphasis on their clinical efficacy and the underlying mechanisms in the treatment of DRESS. Furthermore, this review provides a summary of potential management strategies and laboratory workup during the treatment of DRESS.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is characterized by a widespread maculopapular rash, lymphadenopathy, fever, and multisystem involvement. Conversely, hemophagocytic lymphohistiocytosis (HLH) is an infrequent yet critical condition presenting with fever, hepatosplenomegaly, cytopenias, coagulation abnormalities, and elevated inflammatory markers. The overlapping clinical and laboratory features between DRESS and HLH poses a significant diagnostic challenge. Secondary HLH (sHLH) typically occurs in adults triggered by viral infections, malignancies, rheumatologic diseases, or immune deficiencies. Recently, COVID-19 has also been identified as one of the triggers for sHLH. Herein, we present a case of Sulfasalazine-induced DRESS coinfected with COVID-19 that subsequently progressed into HLH. Our patient exhibited common hepatorenal and splenic involvement along with rare cholecystitis and appendicitis. However, a significant improvement was observed upon the addition of etoposide and azathioprine. We hypothesize that excessive activation of the immune system and cytokine storm due to DRESS combined with COVID-19 infection led to more extensive systemic damage resulting in HLH development. This highlights the potential for severe consequences when DRESS coincides with HLH during a COVID-19 infection.

Allergic reactions to drugs caused by piperacillin-tazobactam are common in clinical practice. However, we also found a few cases of drug-induced hypersensitivity syndrome (DiHS)/Drug reaction with eosinophilia and systemic symptoms (DRESS) caused by piperacillin-tazobactam in our clinical work. We report a case of a 60-year-old female patient who was treated with piperacillin-tazobactam anti-infective therapy after the diagnosis of hematogenous lung abscess, developed fever, rash, and blood abnormalities after 26 days of application, and was later diagnosed as DIHS, which was improved after the administration of glucocorticoid and anti-allergic drugs. In addition, we also retrospectively analyzed 17 cases of DiHS caused by piperacillin-tazobactam from the PubMed databases between March 1980 and September 2023. The majority of the patients had an incubation period of more than 14 days, and the common clinical features included elevated eosinophil count/percentage, fever, rash, liver damage, and lymph node enlargement. After treatment with topical or systemic glucocorticoids, 16 of the 17 patients improved and one died because of the underlying condition. The clinical features of DiHS were diverse and included a long incubation period, skin rash, elevated eosinophils, and impaired organ function. Since some patients have atypical clinical features, clinicians should raise awareness of the disease, recognize these features early, and treat them promptly.

Drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome (DRESS/DIHS) is one type of severe cutaneous adverse reaction (SCAR). It is featured by fever, widespread skin lesions, protracted clinical course, internal organ involvement, and possibly long-term autoimmune sequelae. The presence of high-risk human leukocyte antigen (HLA) alleles, hypersensitivity reaction after culprit drug ingestion, and human herpesvirus reactivation may all contribute to its complex clinical manifestations. Some recent studies focusing on the roles of involved cytokines/chemokines and T cells co-signaling pathways in DRESS/DIHS were conducted. In addition, some predictors of disease severity and prognosis were also reported. In this review, we provided an update on the current understanding of the pathogenesis, potential biomarkers, and the relevant therapeutic rationales of DRESS/DIHS.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon yet serious adverse drug hypersensitivity reaction with the presentations including rash, fever, lymphadenopathy, and internal organ involvement. Sarcoidosis is a systematic granulomatous disease with unknown etiology. We herein report a case of pulmonary sarcoidosis secondary to allopurinol-induced DRESS.
METHODS: A 37-year-old man with a history of hyperuricemia was treated with allopurinol for three weeks at a total dose of 7000 milligrams before developing symptoms including anorexia, fever, erythematous rash, and elevated transaminase. The patient was diagnosed with DRESS and was treated with prednisone for 6 mo until all the symptoms completely resolved. Three months later, the patient presented again because of a progressively worsening dry cough. His chest computed tomography images showed bilateral lung parenchyma involvement with lymph node enlargement, which was confirmed to be nonnecrotizing granuloma by pathological examination. Based on radiologic and pathological findings, he was diagnosed with sarcoidosis and was restarted on treatment with prednisone, which was continued for another 6 mo. Reexamination of chest imaging revealed complete resolution of parenchymal lung lesions and a significant reduction in the size of the mediastinal and hilar lymph nodes. Following a 6-month follow-up of completion of treatment, the patient\'s clinical condition remained stable with no clinical evidence of relapse.
CONCLUSIONS: This is the first case in which pulmonary sarcoidosis developed as a late complication of allopurinol-induced DRESS. The case indicated that the autoimmune reaction of DRESS may play an important role in the pathogenesis of sarcoidosis.

BACKGROUND: Severe cutaneous adverse drug reactions (SCAR) are life-threatening and contain drug reactions with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP).
METHODS: We aimed to evaluate clinical features and prognostic factors for SCAR patients. From January 2010 to April 2022, 209 patients with SCAR (DRESS, n = 46, SJS/TEN, n = 128, AGEP, n = 35) were included in this study. Clinical symptoms, laboratory tests, causative drugs, disease courses, treatments, and outcomes were investigated.
RESULTS: Antibiotics ranked first (35.9 %) followed by traditional Chinese medicine (15.8 %) and antiepileptic drugs (14.8 %) among causative drugs of SCAR. One patient (2.2 %) with DRESS and seven patients (5.5 %) with SJS/TEN died in the hospital, while there was no AGEP-related mortality. The multivariate logistic regression analysis showed that high Registry of Severe Cutaneous Adverse Reactions score (OR = 2.340, 95 % CI = 1.192-4.591) and hemoglobin < 100 g/L (OR = 0.126, 95 % CI = 0.016-0.983) were independent risk factors of DRESS. Anemia (OR = 0.191, 95 % CI = 0.037-0.984) and body surface area detached involved at day 1 (OR = 2.749, 95 % CI = 1.115-6.778) were independent risk factors of SJS/TEN for severe acute complications and hospital death (P < 0.05). Lymphocytopenia (OR = 0.004, 95 % CI = 0.000-0.553) was a risk factor of AGEP for acute complications (P = 0.028).
CONCLUSIONS: This study reveals the clinical features and independent prognostic factors for SCAR, which may be helpful in the clinical management for SCAR patients.

OBJECTIVE: Allopurinol-induced drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but serious and potentially life-threatening drug hypersensitivity syndrome. In this study, we aimed to investigate the clinical features, treatment outcomes, and prognostic factors of allopurinol-induced DRESS.
METHODS: Case reports of allopurinol-induced DRESS published by China from January 2000 to August 2021 were retrieved from CNKI, Wan Fang, VIP, and PubMed databases for analysis.
CONCLUSIONS: This study included 52 patients, consisting of 41 (78.8%) males and 11 (21.2%) females (M:F = 3.7:1). The mean of age was 56.1 ± 17.1 years (range: 18-86 years). The mean of latency periods was 24.6 ± 15.0 days (range:1-63 days). Most patients presented with fever, cutaneous eruption, eosinophilia, lymphadenopathy, and facial edema. 36/52 (69.2%) patients showed two or more internal organs involved. Liver and kidney injuries were the most common visceral manifestation. Pulmonary involvement (34.6%), cardiac involvement (25.0%) and gastrointestinal involvement (21.2%) were relatively less known but severe complications. 2/52 (3.8%) patients showed nervous system involved, presenting as leukoencephalopathy or peripheral neuropathy. 2/52 (3.8%) patients presented with secondary hemophagocytic lymphohistiocytosis.1/52 (1.9%) patient developed pure red cell aplasia and 1/52 (1.9%) patient developed painless thyroiditis. HLA*B 58:01 allele was tested in 18/52 (34.6%) patients. 16/18 (88.9%) cases were positive. 48/52 (92.3%) patients were treated with systemic corticosteroids. 16/52 (30.8%) patients were cured, 23/52 (44.2%) patients received partial recovery, and 13/52 (25.0%) patients were died. Septic shock, gastrointestinal bleeding and multiple organ failure were the leading causes of death. Advanced age, underlying cardiovascular disease, chronic kidney disease and high dose of allopurinol, infection and internal organ involvement (including kidney, heart, lung and gastrointestinal tract) were risk factors for death.
CONCLUSIONS: We explored clinical features, treatment outcomes and prognostic factors of 52 allopurinol-induced DRESS cases in China. Ethnicity, especially Han Chinese, and positive HLA-B*58:01 allele are the clearest risk factors so far. Advanced age, underlying cardiovascular disease, chronic kidney disease and high dose of allopurinol, infection and internal organ involvement (including kidney, heart, lung and gastrointestinal tract) were associated with poorer outcomes. Early identification and discontinuation of the causative drug are crucial to the management of DRESS. For patients with severe disease, corticosteroids are recommended as the first-line therapy. However, further studies are needed to address diagnostic criteria of DRESS for early diagnosis, as well as to develop standardized corticosteroid treatment regimens.

Adverse drug reactions involving the skin are commonly known as drug eruptions. Severe drug eruption may cause severe cutaneous adverse drug reactions (SCARs), which are considered to be fatal and life-threatening, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). Although cases are relatively rare, approximately 2% of hospitalized patients are affected by SCARs. There is an incidence of 2 to 7 cases/million per year of SJS/TEN and 1/1000 to 1/10,000 exposures to offending agents result in DRESS. However, the mortality rate of severe drug eruptions can reach up to 50%. SCARs represent a real medical emergency, and early identification and proper management are critical to survival. The common pathogenesis of severe drug eruptions includes genetic linkage with HLA- and non-HLA-genes, drug-specific T cell-mediated cytotoxicity, T cell receptor restriction, and cytotoxicity mechanisms. A multidisciplinary approach is required for acute management. Immediate withdrawal of potentially causative drugs and specific supportive treatment is of great importance. Immunoglobulins, systemic corticosteroids, and cyclosporine A are the most frequently used treatments for SCARs; additionally, new biologics and plasma exchange are reasonable strategies to reduce mortality. Although there are many treatment methods for severe drug eruption, controversies remain regarding the timing and dosage of drug eruption. Types, dosages, and indications of new biological agents, such as tumor necrosis factor antagonists, mepolizumab, and omalizumab, are still under exploration. This review summarizes the clinical characteristics, risk factors, pathogenesis, and treatment strategies of severe drug eruption to guide clinical management.

Severe cutaneous adverse drug reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) are high-mortality adverse drug reactions. The risk factors and prognosis of drug-induced liver injury (DILI) concomitant with SCAR warrant clarification. We aimed to evaluate the characteristics and outcomes of DILI with SCAR.
We analysed the database of a 10-year multi-centre prospective study in Taiwan from 2011 to 2020.
A total of 1415 patients with DILI were enrolled, including 81 cases combined with SJS/TEN, 74 with DRESS, 3 with AGEP and 1257 with pure DILI. Approximated 11.2% of patients had SCAR, of which allopurinol was the leading incriminated drug, followed by sulphonamides and carbamazepine. The SJS/TEN group had the highest mortality (34.6%). Jaundice, acute kidney injury and SJS/TEN were independent risk factors of mortality (odds ratio: 29.54, 4.43 and 4.86, respectively, P < .003). Chronic kidney disease with high-dose allopurinol also contributed to high mortality (78.9%) in cases of allopurinol-induced DILI with SCAR. The HLA-B*5801 was associated with a high risk and mortality of allopurinol-induced DILI with SCAR. Likewise, the HLA-B*1502 was closely related to carbamazepine-induced DILI with SCAR.
DILI patients combined with SCAR are common and have a high mortality in Taiwan. Allopurinol is the leading incriminated drug. Jaundice, acute kidney injury and SJS/TEN are risk factors of mortality. HLA-B*5801, chronic kidney disease and high drug dosage also contribute to high mortality in allopurinol-induced DILI with SCAR.

UNASSIGNED: Severe cutaneous adverse reactions (SCAR) to drugs are a crucial public health issue and the use of systemic corticosteroids in SCAR has been controversial.
UNASSIGNED: To analyze clinical features, causative drugs, treatment, outcomes, and prognostic factors of SCAR in the case-series of 173 patients, and add more information to the debate of using systemic corticosteroids in SCAR management.
UNASSIGNED: A retrospective study of 173 SCAR patients diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) at a tertiary care institution in China between January 2014 and December 2017 was conducted.
UNASSIGNED: Of 173 patients, allopurinol, carbamazepine, and antibiotics are the most frequently implicated drugs for DRESS (40.4%), SJS/TEN (26.0%), and AGEP (40.0%) respectively. Moreover, there is a strongly negative correlation between early corticosteroids use and the progression (p=0.000) and severity (p=0.01) of skin lesions. However, there is no association between early corticosteroids use and the mortality of SCAR (odds ratio: 1.01, 95% confidence interval: 0.95~1.08). In addition, lymphadenopathy, eosinophilia, and interval from onset to corticosteroids treatment were correlated with SCAR prognosis.
UNASSIGNED: Prompt short-course systemic corticosteroids use is associated with early-stage skin lesions remission without influencing the disease mortality. Lymphadenopathy and eosinophilia were the independent poor prognostic factors of SCAR.