Drug-induced Hypersensitivity Research Articles

P053 Interstitial Nephritis from IBD: Complicated Conclusions.

BACKGROUND: Kidney injury in IBD is challenging. Tubulointerstitial nephritis (TIN) is linked to aminosalicylates, but also described in drug-naïve patients, suggesting that TIN may be a direct manifestation of IBD. We describe three cases of TIN in IBD to illustrate the challenges in determining the etiology of the injury. Case #1: 58-year-old male with a horseshoe kidney deformity, uncontrolled hypertension, GERD and small bowel stricturing Crohn's disease (CD), previously on mercaptopurine and allopurinol, subsequently transitioned to adalimumab, maintaining clinical and radiologic remission. Two years later, he developed acute kidney injury in setting of high fevers and sweats, with negative infectious evaluation. Medications included adalimumab, PPI, valacyclovir and torsemide. Renal biopsy revealed TIN with dense, zonal and focal granulomatous features suggestive of drug-induced hypersensitivity, chronic infection, sarcoidosis or an extra-intestinal manifestation of CD. Case #2: 45-year-old female with SLE, nephrolithiasis, GERD, hypertension and ulcerative colitis (UC), initially on mesalamine, then vedolizumab, with clinical and endoscopic remission. Her SCr increased at the time of her UC diagnosis, and worsened over 6 months while on mesalamine, vedolizumab, PPI and losartan. Renal biopsy demonstrated acute and chronic TIN with eosinophils raising concern for an allergic/drug-induced injury. Nephrology concluded that her TIN was secondary to either UC or one of her medications. Case #3: 33-year-old male with UC transitioned to vedolizumab, having failed budesonide and mesalamine. He had latent TB and received 9 months of isoniazid. While on mesalamine, vedolizumab and PPI, he developed fever, chills and night sweats, with an acute rise in SCr, prompting discontinuation of meds. Three months later, still in remission and with improved SCr, he restarted vedolizumab. A year later he developed low-grade fever with elevated SCr, prompting discontinuation. Renal biopsy revealed acute and chronic TIN with severe interstitial fibrosis, tubular atrophy and focal global glomerulosclerosis. He started prednisone and remained off other IBD therapy for 6 months, but repeat colonoscopy revealed mild colitis. He restarted mesalamine, but again developed elevated SCr 2 months later. Repeat renal biopsy revealed TIN with less interstitial fibrosis and focal global glomerulosclerosis, and nephrology suggested his interstitial nephritis was likely secondary to UC over his medications. He started azathioprine with significant improvement in SCr and clinical remission of UC. In all three cases, neither nephrology consultation nor renal biopsy helped distinguish the etiology of renal injury, defaulting to either the IBD meds or an extra-intestinal manifestation of IBD, and not accounting for the acute inflammatory symptoms in two of the cases. While literature review reveals several cases that allege kidney injury as an extra-intestinal target of IBD serious doubts remain. TIN secondary to aminosalicylates is well-documented, but there are few reports of adalimumab-induced granulomatous TIN and only one report of vedolizumab-induced TIN. Each of our patients had well-controlled IBD and multiple confounding variables that could impact kidney function or cause TIN, including hypertension and multiple potential culprit medications, illustrating the dilemma of determining the etiology of renal injury in IBD patients.

Risk of Progression to Autoimmune Disease in Severe Drug Eruption: Risk Factors and the Factor-Guided Stratification

The identification of risk factors is key not only to uncover the pathogenesis of autoimmune disease but also to predict progression to autoimmune disease. Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms is likely the best prototypic example for analyzing the sequential events. We conducted a retrospective study of 55 patients with drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms followed up for the possibility of later development of autoimmune disease ∼18 years after resolution. Nine patients progressed to autoimmune sequelae regardless of treatment. The generation of autoantibodies was preceded by 8 years in eight of the nine patients. The combination of increases in lymphocyte counts, severe liver damage, a rebound increase in globulin, persistent reactivations of Epstein‒Barr virus and human herpesvirus-6, and low IL-2 and IL-4 at the acute/subacute phases were significant risk factors for the future development of autoimmune disease. On the basis of these factors, we established a scoring system that can identify high-risk patients. When stratified these patients into three risk categories (low/intermediate/high), occurrence of autoimmune disease was exclusively detected in the high group. Our data represent a scoring system to identify patients at high risk of developing autoimmune disease, although a larger study is required to validate the scoring system.

Ciprofloxacin and Metronidazole Allergy- A Case Report

Fluoroquinolones are well-tolerated antibiotics widely used for treating infections. According to the literature, ciprofloxacin is mostly involved in Drug-induced hypersensitivity reactions. The various reactions that are reported in various case reports due to ciprofloxacin include Steven Johnson syndrome, eczema, erythroderma, maculopapular rashes. Metronidazole is a 5-nitroimidazole compound introduced in 1959 to treat Trichomonas vaginalis infections. Ciprofloxacin and Metronidazole hypersensitivity is not very frequent it is usually well tolerated but allergic reactions to these drugs occur due to their increased use either alone or in combination. An 83-year-old female was admitted to the private ward of surgery at Shri Mahant Indiresh hospital with chief complaints of abdominal pain and chronic constipation as the patient was not passing stools for 10 days. The patient was diagnosed with Subacute intestinal obstruction (SAIO) based on various laboratory findings and the symptomatic treatment was given treatment. Hypersensitivity reactions can be of two types immediate that occurs within few hours of drug administration and delayed that occurs within 24-48 hours of drug administration. Here in this case the person developed vomiting immediately after few hours of Ciprofloxacin administration so it is an immediate IgE mediated anaphylactic reaction. Metronidazoleis causing Type 4 Delayed hypersensitivity reaction in this patient as rashes and itching developed the next day after administration of metronidazole drug. Healthcare professionals should maintain the record of a medication history of the patient to identify any drug allergy so that it can be avoided in the future and in case of any ADR it should be reported. The patient should be advised to go for a sensitivity test to check which drug he/ she is allergic to and should avoid taking that medication. The patient should tell his/ her history of drug allergy to the doctor so that doctor doesn’t prescribe that medication. Keywords: CBC-Complete Blood Count, RFT-Renal Function tests, LFT-Liver function tests, Hb-Hemoglobin, SGOT-Serum Glutamic oxaloacetic transaminases, ALP-Alkaline phosphatase, MCH-mean corpuscular Hemoglobin, MCHC-Mean corpuscular hemoglobin concentration, RBC-Red Blood Cells, SAIO-Subacute intestinal obstruction, USG- Ultrasound.

Drug-induced hypersensitivity syndrome caused by minodronic acid hydrate

BackgroundDrug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is an important adverse reaction caused by a few drugs. Reactivation of human herpesvirus 6 (HHV-6) is known to be associated with its pathogenesis. DIHS occasionally manifests as pulmonary lesions with a variety of imaging findings.Case presentationAn 83-year-old woman started taking minodronic acid hydrate 5 years before admission. She noticed a generalized skin rash 44 days before admission and started oral betamethasone-d-chlorpheniramine maleate combination tablets for allergic dermatitis. She developed a fever and cough in addition to the rash, and was referred to our hospital. Laboratory data showed a high level of eosinophils and liver and biliary enzymes. Computed tomography (CT) studies revealed bilateral diffuse ground-glass opacities with ill-defined centrilobular nodules from the central to peripheral regions of the lungs. Transbronchial lung cryobiopsy specimens showed that lymphocyte infiltration was observed in the alveolar walls and fibrinous exudates and floating macrophages in the alveolar lumina. Immunohistochemistry of biopsy specimens showed more CD4+ lymphocytes than CD8+ lymphocytes, while few Foxp3+ lymphocytes were recognized. The serum anti-HHV-6 immunoglobulin G titer increased at 3 weeks after the first test. Based on these findings, we diagnosed her with DIHS. We continued care without using corticosteroids since there was no worsening of breathing or skin condition. Eventually, her clinical symptoms chest CT had improved. Minodronic acid hydrate was identified as the culprit drug based on the positive results of the patch test and drug-induced lymphocyte stimulation test.ConclusionsWe described the first case of DIHS caused by minodronic acid hydrate. Lung lesions in DIHS can present with bilateral diffuse ground-glass opacities and ill-defined centrilobular nodules on a CT scan during the recovery phase. Clinicians should be aware of DIHS, even if patients are not involved with typical DIHS/DRESS-causing drugs.

M050 IMATINIB-INDUCED DRESS/DIHS

Drug rash with eosinophilia and systemic symptoms (DRESS), or drug-induced hypersensitivity syndrome (DiHS), is a rare, but severe adverse drug reaction. Rapid diagnosis and removal of the causative drug are critical to treatment. With the increasing use of targeted therapies, it is important to be aware of these drugs as potential causes of DRESS/DiHS. Imatinib is a tyrosine kinase inhibitor used in the treatment of various malignancies, hypereosinophilic syndrome (HES), and other eosinophilic disorders. We report a rare case of imatinib-induced DRESS/DiHS.

Serum Soluble OX40 as a Diagnostic and Prognostic Biomarker for Drug-Induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse drug reaction commonly associated with the reactivation of human herpesvirus 6 (HHV-6). There are currently no adequate biomarkers for the early diagnosis and detection of DIHS/DRESS. Notably, OX40 (CD134) has an important role in allergic inflammation and functions as a cellular receptor for HHV-6 entry. We previously reported that the membrane-bound form of OX40 in CD4+ T cells was upregulated in DIHS/DRESS. We sought to investigate the clinical significance of serum soluble OX40 (sOX40) in DIHS/DRESS. Serum sOX40 levels in patients with DIHS/DRESS (n= 39), maculopapular exanthema/erythema multiforme (n= 17), Stevens-Johnson syndrome/toxic epidermal necrolysis (n= 13), or autoimmune bullous diseases (n= 5), and levels in healthy volunteers (n= 5) were examined by enzyme-linked immunosorbent assay. Copy numbers of HHV-6, HHV-7, and cytomegalovirus in peripheral blood mononuclear cells were quantified using real-time PCR. Serum sOX40 levels in patients with DIHS/DRESS in the acute stage were elevated in parallel with high OX40 expression on CD4+ T cells. Serum sOX40 levels were significantly positively correlated with disease severity and serum levels of thymus and activation-regulated chemokine, IL-5, and IL-10. Human herpesvirus 6-positive patients had higher sOX40 levels than did HHV-6-negative patients, and serum sOX40 levels were correlated with HHV-6 DNA loads. Serum sOX40 levels can be a useful diagnostic marker for DIHS/DRESS that reflect disease severity. Elevated serum sOX40 levels also predict HHV-6 reactivation in patients with DIHS/DRESS.

ATT-Therapy Induced DRESS: A Case Report

A severe adverse reaction called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS syndrome), is usually described by eosinophilia, fever, swollen lymph nodes, severe skin rash and extensive systemic association. It is distinguished by a lengthy latency period, which is characteristic drug reaction with eosinophilia and systemic symptoms (DRESS). Formerly known as drug-induced delayed multi-organ hypersensitivity syndrome (DIDMOHS) or drug-induced hypersensitivity (DIHS). There are a variety of clinical symptoms associated with the syndrome yet it is still poorly understood. Drugs most commonly implicate in Anticonvulsants are the most common cause of DRESS syndrome, followed by sulfonamides and a variety of anti-inflammatory medications.Anti-tubercular therapy (ATT) is rarely associated with DRESS syndromeWe present the case of a 60-year-old female patient who had previously been treated with Anti-tubercular Therapy for Tubercular Meningitis (ATT).She was admitted to the hospital with presenting complaints of vomiting, burning micturition, fever associated with chills, generalized swelling and reddish skin all over the body including facial puffiness. The problem was successfully resolved by refraining from the offending medication and administering supportive care. Thus, the case illustrates the necessity of considering anti-tubercular drug reactions even when symptoms are delayed.
 Keywords: Anti-tubercular Therapy (ATT), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Adverse drug reaction (ADR), Drug-induced, Systemic symptoms syndrome,

DRESS SYNDROME

TOPIC: Allergy and Airway TYPE: Global Case Reports INTRODUCTION: Severe cutaneous adverse reactions (SCARs) are a group of disorders caused by a drug-induced hypersensitivity response. One important type of SCAR is Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) – a complex, multisystem, and possibly life-threatening drug response. Here we report a case of Lamictal associated DRESS which is rare and seldom reported. CASE PRESENTATION: A 44-year-old Caucasian female with past medical history significant for COPD on 3 liters home oxygen, bipolar disorder, recurrent mucocutaneous infections and seizures. She has been on Lamictal for treatment of seizures. Patient over last 2 years was admitted in hospital about 5 times with episodes of cough, wheezing and sob. she also had recurrent cutaneous abcesses. Her physician exam was consistent with middle aged female, with diffuse wheezing and skin lesions. Her historical chest x-ray has shown ongoing lll infiltrates, and so it was confirmed with cat scan showing diffuse GGO infiltrates more in left lower lobe. she was investigated with hypersensitivity pneumonitis panel, fungal serology, strep, legionella antigen which was negative. she had slightly lower IGG level. She kept on having these episodes inspire of optimal therapy . Only notable abnormal findings in her laboratory was elevated eosinophils count, with normal IGE level. Her initial count was 19% with sputum eosinophils. AS diagnosis of exclusion DRESS syndrome- associated with lamictal was diagnosed, which is quite rare and so therapy was discontinued and switched to alternative anti seizure therapy. Follow up in 2 months showing eosinophils count dropping to 3% with no recurrent symptoms. DISCUSSION: Several mechanisms are implicated as part of the pathogenesis underlying DRESS syndrome:. Most commonly DRESS is classified as a type IV delayed hypersensitivity reaction. Organ involvement in DRESS is due to eosinophil infiltration of the tissue causing damage. Liver is commonest organ affected followed by kidney and then lungs. Lung involvement can present with symptoms of dyspnea, cough, and/or pleuritic pain, pneumonia, interstitial pneumonitis, pulmonary nodules, or even acute respiratory distress syndrome (ARDS) in severe cases he European Registry for Severe Cutaneous Adverse Reactions (RegiSCAR) is an internationally recognized aid for which provides a clear definition and criteria for diagnosing DRESS syndrome. Though there is reasonable controversy exist about the diagnosis. The most important step in treatment of DRESS syndrome is prompt recognition and withdrawal of the offending drug. Systemic corticosteroids are generally considered the mainstay of therapy. immunosuppressive therapy should be used cautiously. CONCLUSIONS: DRESS is rare syndrome but should be included in the differential diagnosis for patients with peripheral eosinophilia and a medication history with a drug known to be a culprit for it. REFERENCE #1: Cho, Y.-T., C.-W. Yang, and C.-Y. Chu, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): An Interplay among Drugs, Viruses, and Immune System. International journal of molecular sciences, 2017. 18(6): p. 1243. REFERENCE #2: Bocquet, H., M. Bagot, and J.C. Roujeau, Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg, 1996. 15(4): p. 250-7. REFERENCE #3: Taweesedt, P.T., et al., Pulmonary Manifestations of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Systematic Review. Biomed Res Int, 2019. 2019: p. 7863815. DISCLOSURES: No relevant relationships by Abhijit Raval, source=Web Response no disclosure on file for Dhruv Raval

Clinical features of drug-induced hypersensitivity syndrome to BRAF inhibitors with and without previous immune checkpoint inhibition: a review.

Cutaneous reactions to BRAF inhibitors are common, but severe reactions resembling or consistent with drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) are relatively rare. Several reports suggest that cutaneous reactions including DRESS/DIHS to BRAF inhibitors are more frequent and severe in the setting of previous immune checkpoint inhibition (ICI). To characterize existing literature on these reports, we queried the PubMed/MEDLINE database for cases of DIHS/DRESS to BRAF inhibitors. We identified 23 cases of DIHS to BRAF inhibitors following checkpoint inhibition and 14 cases without prior checkpoint inhibitor therapy. In both cohorts, DIHS occurred relatively early, with median time to onset from drug exposure of 8-10days. Patients who received prior ICI were less likely to have peripheral eosinophilia (26% vs 71%), atypical lymphocytes (9% vs 50%), renal involvement (61% vs 79%), hepatic involvement (52% vs 86%), and lymphadenopathy (9% vs 43%) compared to patients who did not receive prior ICI. Thrombocytopenia was more common with prior ICI (17% vs 7%). Only patients who received prior ICI experienced hypotension (26%) during the course of their DIHS. All cases of BRAF-induced DIHS generally improved on systemic steroids/supportive care, and no cases of death were identified. Dermatologists should consider a diagnosis of DIHS following BRAF inhibitor initiation, particularly in the setting of past checkpoint inhibition, with atypical features including relatively rapid onset and steroid responsiveness, lack of peripheral eosinophilia, lymphocytosis, or lymphadenopathy, and increased risk of thrombocytopenia and hypotension.

Development of new approaches to predict drug-induced hypersensitivity with an increased understanding of reaction mechanisms

Development of new approaches to predict drug-induced hypersensitivity with an increased understanding of reaction mechanisms

Cephalosporin-Induced Atypical DRESS Syndrome; a Tale of Two Cases

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, idiosyncratic subset of drug-induced hypersensitivity syndrome manifesting as skin eruption, fever, lymphadenopathy, hematologic abnormalities, and multi-organ involvement. It presents usually after a latent period of 2 to 6 weeks as a diffuse erythematous rash with systemic symptoms and facial edema. It is now recognized as one of the severe cutaneous adverse reactions (SCAR) associated with high mortality, chiefly because of derangement of renal or liver functions. The cutaneous morphologies can be myriad, encompassing maculopapular, exfoliative dermatitis-like, pustular, erythema multiforme-like, Stevens-Johnson syndrome-like, and toxic epidermal necrolysis-like presentations. Case Presentation: We hereby report two young males who developed pruritic exfoliating erythematous rash after taking cephalosporin with paradoxical worsening despite drug withdrawal. They were diagnosed with ‘atypical DRESS syndrome’ according to the Japanese study group severe cutaneous adverse reactions (J-SCAR) criteria and treated successfully with systemic steroids and emollients. The J-SCAR scoring and the concept of atypical DRESS are useful in situations, where either all clinical and laboratory criteria are not present simultaneously, or typical clinical presentations wherein human herpes virus-6 (HHV-6) reactivation cannot be documented. Conclusions: These two cases were used to illustrate the hitherto obscure concept of atypical DRESS syndrome that presented with compatible clinical features but did not satisfy all the requisite criteria. We also highlight cephalosporins (one of the most commonly prescribed standard group of drugs) as a plausible but infrequently reported cause of this severe adverse cutaneous drug reaction.

Severe drug-induced hypersensitivity syndrome in patients with liver cirrhosis and epilepsy induced by lamotrigine: A case report

Severe drug-induced hypersensitivity syndrome in patients with liver cirrhosis and epilepsy induced by lamotrigine: A case report

Dapsone Induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome - A Case Report

A 50-year-old male Sudanese patient presented with a three-week history of jaundice, high-grade fever, and mucocutaneous eruption. For last months he was on compound therapy for leprosy, which had been confirmed recently. The patient’s face was prominent, along with the erythematous dusky morbilliform rash covering all the body. On examination, we detected hepatosplenomegaly and generalized lymphadenopathy. Laboratory investigations revealed hepatorenal impairment, and hematological analysis revealed leukocytosis mainly due to eosinophilia. The clinical and laboratory findings interpretation ranked DRESS or Drug-Induced Hypersensitivity Syndrome (DIHS) on top of possible causes before Dapsone Hypersensitivity Syndrome (DHS) and lepra reactions. We promptly discontinued MDT, admitted him to the dermatological ward. Two skin biopsies were sent to two different histopathologists, MF was suggested by one and Sezary syndrome by the other one. Besides the general conservative measures and vital functions monitoring, he received systemic and topical steroids. However, unfortunately, within the next three weeks, his condition deteriorated, and passed away from multi-systems failure.

26775 Vancomycin-associated drug-induced hypersensitivity syndrome after IV therapy with vancomycin and implantation of a vancomycin-eluting spacer and absorbable beads

Drug-induced hypersensitivity syndrome (DIHS) is a life-threatening severe cutaneous adverse reaction with multisystem involvement. DIHS usually occurs in the context of orally or intravenously administered medications, but can be reactivated with epicutaneous application of culprit medications. We present a case of a 31-year-old woman who developed vancomycin-induced DIHS after treatment of a prosthetic joint infection. Her total hip arthroplasty prosthesis infection was treated with removal of the prosthesis, IV vancomycin and implantation of a polymethyl methacrylate vancomycin-eluting spacer along with vancomycin-eluting absorbable calcium beads. 26 days after treatment, she developed a pruritic morbilliform exanthema along with malaise, nausea, dysphagia, neck-swelling, chills and was noted to have an AST of 389 and an ALT of 338. IV vancomycin was replaced with daptomycin and patient was started on 100mg of daily prednisolone. After initiation of prednisolone, she had rapid improvement of her neck-swelling and rash, but her AST and ALT remained elevated for 10 days despite treatment with corticosteroids. Given her persistently elevated AST and ALT, multidisciplinary discussions were held to consider removing the implanted vancomycin-eluting spacer. Surgery was deferred due to the patient’s high dose corticosteroids, increased risk of infection and incremental clinical improvement. She continued to improve and eventually tapered off her steroids after discharge. This is the first reported case of DIHS in a patient treated with drug-eluting absorbable beads, implant and IV antibiotics. In conclusion, we recommend careful consideration of the relative risks and benefits along with close clinical monitoring before surgical revision in complex cases of DIHS.

Recent Advancement of Drug-Induced Hypersensitivity Syndrome

Recent Advancement of Drug-Induced Hypersensitivity Syndrome

An unusual case of ATT induced DRESS syndrome

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug-induced hypersensitivity reaction characterized by skin rash, fever, blood abnormalities, and multiple organ involvement. The diagnosis of DRESS syndrome is often delayed because of its variable presentation. DRESS syndrome induced by antituberculosis drugs has rarely been reported. A 45-year-old female patient taking anti-tubercular drugs since 2 weeks presented to our hospital with extensive skin lesion with mucosal involvement. The case responded well to treatment with systemic corticosteroids and withdrawal of isoniazid with no recurrence of lesions and further follow-up.

Chemokines in Severe Cutaneous Adverse Reactions (SCARs).

Although the incidence of severe cutaneous adverse reactions (SCARs) to medications is very low, SCARs can result in disability or even death if they are not diagnosed and treated properly. As the rapid recognition of SCARs is essential, it is necessary to develop diagnostic markers for them that can also be used to assess severity and predict outcomes in the early phase. In addition, it is important to identify novel therapeutic targets for SCARs. Chemokines are chemotactic cytokines that control the migratory patterns and locations of immune cells and usually exhibit markedly specific associations with certain human diseases. In Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), the Th1-associated chemokines chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 predominate, while in drug-induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS), the levels of the Th2-associated chemokines chemokine (C-C motif) ligand 17 (CCL17) and CCL22 are markedly elevated. We suggest that the distinct chemokine profiles of SJS/TEN and DIHS/DRESS can be used to aid their differential diagnosis. CXCL10 has also been reported to be associated with the development of long-term sequelae in DIHS/DRESS. This review focuses on the chemokines involved in the pathogenesis and adjuvant diagnosis of SCARs, particularly SJS/TEN and DIHS/DRESS, but also provides a brief overview of SCARs and the chemokine superfamily. As it is being increasingly recognized that an association exists between human herpesvirus 6 (HHV-6) and DIHS/DRESS, the possible roles of the chemokine/chemokine receptor homologs encoded by HHV-6 in the pathogenesis of DIHS/DRESS are also discussed.

Unravelling cases of clozapine-related Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) in patients reported otherwise: A systematic review.

The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a drug-induced hypersensitivity reaction. Aim was to review reports of clozapine-related reactions fulfilling the registry of severe cutaneous adverse reaction (RegiSCAR) criteria for DRESS syndrome reported as such or otherwise, to provide a descriptive overview of demographic patterns, clinical manifestations, and DRESS course and investigate associations between demographic, DRESS parameters, and clinical outcomes. This review was conducted following preferred reporting items for systematic reviews and meta-analyses guidelines and registered with PROSPERO (registration number CRD42020156385). We searched PubMed/Embase/PsychInfo/Cochrane for reports of clozapine-related reactions meeting RegiSCAR criteria. Associations between RegiSCAR scores and time-to-recovery with demographic/clinical variables were assessed. Demographic/clinical characteristics of patients with versus without reported DRESS were compared using non-parametrical tests. We identified 26 reports of 27 patients meeting RegiSCAR criteria. Males (n = 19, 70.4%) and patients with schizophrenia (n = 18, 66.7%) were mainly affected. Twelve patients (44.4%) received clozapine-monotherapy. DRESS symptoms manifested within a month after clozapine initiation (n = 24, 88.9%). Lungs and liver were the most common organs involved (n = 12, 44.4%; n = 11, 40.7%), with a mean time to recovery of 33.75 days. Clozapine rechallenge led to DRESS recurrence in four patients. Death rate was 7.4%. No associations were detected between RegiSCAR criteria or days to recovery with any demographic/clinical variables. No differences between patients with versus without reported DRESS were detected. Clozapine-related DRESS may be rare, but also underreported. Clinicians need to be aware of it even in patients under clozapine-monotherapy or without skin rash.

Tacrolimus Immunosuppression Causes Drug-Induced Hypersensitivity Reactions in Liver-Transplant Patients: A 3-Case Report

Drug-induced hypersensitivity reactions attributed to the immunosuppressive agent tacrolimus after an organ transplant are rare in the literature. We present 3 cases of male adult patients grafted with a cadaveric liver who developed delayed hypersensitivity reactions to tacrolimus in the form of the prolonged-release capsules (Advagraf). Furthermore, the appropriate drug concentration solutions used for allergy testing are proposed. All patients received a liver transplant (LT) because of cirrhosis of various etiologies. They were immunosuppressed with tacrolimus once daily. Several months after they had been placed on an immunosuppressive regimen with tacrolimus in the form of prolonged-release capsules (Advagraf), the patients presented with delayed hypersensitivity reactions and torturous pruritic rash that affected the whole body and was unresponsive to treatment with oral ursodeoxycholic acid, cholestyramine, or levocetirizine. Allergy testing that was performed by skin prick testing was negative. Nevertheless, intradermal testing yielded positive results in all 3 patients. Management was by interruption of the culprit agent, which was followed by symptom resolution. The immunosuppressive treatment was continued with alternative drugs. Appropriate nonirritating drug concentration solutions of the drug used for intradermal testing were highly sensitive and confirmed the clinical diagnosis of tacrolimus allergy in all the affected patients. Immunosuppressive treatment with tacrolimus in the form of prolonged-release capsules may cause a drug hypersensitivity reaction. A suspicion of allergy warrants a referral for allergy testing. Pruritic rash refractory to treatment in liver transplanted patients should be evaluated by an allergist for possible drug allergy when bile stasis and graft disease have been excluded. Intradermal testing has proven a highly sensitive method for confirming a drug allergy diagnosis, whereas skin prick testing did not.

脊椎固定術術後感染に対しバンコマイシン含有セメント留置術後に薬剤性過敏症症候群（DIHS）を発症した1例

脊椎固定術術後感染に対しバンコマイシン含有セメント留置術後に薬剤性過敏症症候群（DIHS）を発症した1例