Systemic Drug Reactions Research Articles

One-month daily and three-month weekly rifapentine plus isoniazid are comparable in completion rate and safety for latent tuberculosis infection in non-HIV Population: a randomized controlled trial

ObjectivesThe weekly rifapentine plus isoniazid for 3 months (3HP) improves completion rate of latent tuberculosis infection treatment, but flu-like symptoms are common. The novel 1HP regimen, involving daily rifapentine plus isoniazid for 28 days, has demonstrated low toxicity in HIV-infected populations. We aimed to investigate whether 1HP has a lower incidence rate of systemic drug reaction (SDR) compared with 3HP during treatment in non-HIV populations. MethodsThis randomized, multicentre trial compared the completion rate and risks of SDRs of 1HP and 3HP in aged ≥13 years non-HIV subjects with latent tuberculosis infection between September 2019 and September 2023 (ClinicalTrials.gov: NCT04094012). We also investigated associations between SDRs and plasma levels of drugs and their metabolites. ResultsA total of 251 and 239 individuals were randomly assigned to 1HP and 3HP groups, respectively, with completion rates of 82.9% (208/251) and 84.5% (202/239), respectively. Among them, 12.7% (32/251) and 10.9% (26/239) of 1HP and 3HP groups experienced SDRs, respectively (p 0.522), predominantly urticaria in 1HP group (59.4% [19/32]) and flu-like syndrome in 3HP group (80.8% [21/26]). Among participants experiencing SDRs, 43.8% (14/32) and 34.6% (9/26) in 1HP and 3HP groups, respectively, completed treatment (p 0.470). Cutaneous reactions were more common in 1HP than 3HP group (32.7% [82/251] vs. 13.0% [31/239], p < 0.001). In 1HP group, urticaria was associated with a higher plasma desacetyl-rifapentine level (ug/mL) at both 2 (median [interquartile range]: 36.06 [17.46–50.79] vs. 22.94 [14.67–31.65], p 0.018) and 6 hours (26.13 [15.80–53.06] vs. 29.83 [18.13–34.01], p 0.047) after dosing. DiscussionIn non-HIV population, the incidence rate of SDR under 1HP is not lower than 3HP. Notably, urticaria, rather than flu-like syndrome, was the predominant SDR associated 1HP. The findings of this study underscore the feasibility of 1HP regimen in non-HIV populations with a high-completion rate exceeding 80%.

Ciprofloxacin Ophthalmic DRESS Syndrome: Case Report

Introduction: Drug rash with eosinophilia and systemic symptoms (DRESS syndrome), also known as drug-induced hypersensitivity syndrome, is a rare severe systemic hypersensitivity drug reaction. Diagnosing DRESS syndrome is challenging due to non-specific manifestations that can make it difficult to recognize. Therefore, addressing and discussing this issue is extremely important, considering the potential lethality of a treatable syndrome. Clinical case: We describe the clinical characteristics of a 39-year-old female who presented with DRESS syndrome associated with the use of ciprofloxacin ophthalmic. The patient manifested a mild maculopapular rash located in the pelvic limbs with subsequent ascending distribution and generalized erythematoviolaceous affecting four extremities, trunk, facial region and scalp, together with fever and lymphadenopathy. Paraclinical tests revealed leukocytosis and eosinophilia. According to RegiScar's ranking, it scored 6 points, classifying it as the definitive case for DRESS. He concluded a schedule with prednisone 1 mg/kg/day with a slow reduction dose, obtaining a good response to treatment. Conclusions: DRESS syndrome should be suspected in a patient receiving medical treatment who presents with the following signs and symptoms: rash, fever (38°C), facial edema, and lymphadenopathy. Fortunately, this reaction is usually reversible, with a low incidence of residual damage or mortality, in the case of timely discontinuation of antibiotics and use of topical or systemic corticosteroids.

A new alternative approach to management of acute phase Peyronie's disease: low intensity extracorporeal shockwave therapy and platelet-rich plasma.

The aim of this study was to investigate the efficacy, safety, and outcomes of the combination of low ıntensity external shock wave therapy (Li-ESWT) and platelet-rich plasma (PRP) therapy in acute phase Peyronie's disease (PD). The datas of patients admitted with acute phase Peyronie's between January 2014 and January 2022 were reviewed retrospectively. In total, we included total 159 patients who used combination of vitamin E 600 mg/day plus colchicine 1.5 mg/day plus oral daily 5 mg tadalafil (N.=77) in group 1 and received Li-ESWT+PRP combination therapy plus oral daily 5 mg tadalafil (N.=82) in group 2. We noted characteristics of fibrous plaques, pain status, penile curvature degree, and erectile function parameters. All patients were visited at the 3rd and 12th months after the treatment. Preoperative demographic characteristics were similar in the two groups. There was a statistically significant improvement in the mean plaque size, penile curvature degree, IIEF-5 and VAS scores in the intervention group after the treatment. Ecchymosis and hematoma were not observed at the injection site and Li-ESWT application areas in the intervention group. No local or systemic drug reactions were noted in either group. Combination of Li-ESWT and PRP are highly effective and safety to early treatment in the acute phase PD.

When Common Medications Trigger a Rare Reaction: A Review of Clinical Features, Diagnosis, and Treatment Options of DRESS Syndrome

Introduction and purpose: Drug-induced reaction with eosinophilia and systemic symptoms (DRESS) is a severe, life-threatening systemic drug reaction. The challenges in identifying DRESS syndrome result from its symptoms being variable, diverse, and unspecific. Due to the potentially lethal consequence, any clinician should be aware of the symptomatology and be prepared to initiate the appropriate steps. This review summarizes the clinical manifestations and provides essential information on the management of the illness. State of knowledge: DRESS appears to be a rare reaction that frequently remains undetected due to its atypical clinical presentation. Fever, skin rash, lymphadenopathy, eosinophilia, and organ involvement as well as other manifestations, may occur. The onset may be delayed by weeks after exposure to the offending drug. DRESS syndrome is classified as a type IV hypersensitivity. It is thought to be triggered by antiepileptic drugs and antibiotics although many other medications can cause the condition. Certain genetic factors may also predispose some individuals to develop DRESS. Combining clinical and laboratory findings can help confirm the diagnosis. Discontinuation of the offending drug is the fundamental component of treatment such as supportive care including the use of antihistamines and corticosteroids, but recent research has discovered additional promising therapy options. Conclusions: Detecting DRESS syndrome early is crucial to ensure prompt treatment, prevent serious complications, and improve patient outcomes. Healthcare providers should be aware of the signs and symptoms of DRESS syndrome, especially in patients taking particular medications, and be prepared to investigate further if it is suspected.

Rifapentine plus isoniazid: AEs and systemic drug reactions

Rifapentine plus isoniazid: AEs and systemic drug reactions

Symptoms and Systemic Drug Reactions in Persons Receiving Weekly Rifapentine Plus Isoniazid (3HP) Treatment for Latent Tuberculosis Infection.

Three months of weekly rifapentine plus isoniazid (3HP) therapy for latent tuberculosis infection (LTBI) is recommended worldwide. The development of symptoms and systemic drug reactions (SDRs) on 3HP have not been fully characterized. We aimed to determine the patterns of symptom development and identify SDRs and associated factors in patients taking 3HP. We analyzed symptoms data in participants receiving 3HP in the Tuberculosis Trials Consortium's iAdhere study (Study 33). We examined the patterns of symptom reporting across participants from baseline and 4 monthly visits. Bivariate analyses and multivariable regression models were used to identify factors associated with SDRs. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated. Among 1002 participants receiving 3HP, 768 (77%) reported at least 1 symptom; 97% of these symptoms were grade 1 (79%) or grade 2 (18%). Most symptoms developed in the first month and resolved. A total of 111 (11%) participants had symptoms that met criteria for SDRs; however, 53 (48%) of these participants completed therapy. Factors associated with SDRs and discontinuation included female sex (RR: 2.05; 95% CI: 1.19-3.54), age ≥45 years (RR: 1.99; 95% CI: 1.19-3.31), and use of concomitant medications (RR: 2.26; 95% CI: 1.15-4.42). Although most patients receiving 3HP reported symptoms, most were mild, occurred early, and resolved without stopping treatment. Among patients experiencing SDRs, nearly half were able to complete therapy. Patient and provider education should focus on differentiating severe reactions where 3HP should be stopped from minor symptoms that will resolve. Clinical Trials Registration. NCT01582711.

Rho-kinase Inhibitor: A Potential Alternative to Current Glaucoma Therapy

Glaucoma is a group of progressive and irreversible optic neuropathies linked to intraocular pressure-related damage of the optic head. It is the second leading cause of blindness with estimation of 76 million people affected. Among many types of glaucoma, Primary Open-Angle Glaucoma (POAG) is the most common. Management of POAG primarily focus on lowering IOP with a variety of topical, oral, intravenous therapy, and surgery. Prostaglandin Analogue and Beta-blocker have long been the first line therapy for POAG with proven efficacy and safety profile. Rho-kinase Inhibitor is a novel class of drug with IOP lowering property through its ability to increase aqueous humor drainage via trabecular meshwork. Rho-kinase Inhibitor is proven to have mild local adverse effects and rare systemic drug reaction. This might be beneficial for patients with contraindication to Prostaglandin Analogue and/ or Beta-blocker use. Keywords: glaucoma, rho-kinase inhibitor

Cytokine/Chemokine assessment as a complementary diagnostic tool for inflammatory skin diseases.

Inflammatory skin conditions are the 4th leading cause of non-fatal health burden in the general population worldwide. The diagnosis of skin lesions due to systemic drug reactions, viral or bacterial exanthems, or in patients with psoriasis, atopic dermatitis or contact dermatitis is often difficult and relies heavily upon conventional histopathologic examination. Conversely, it is widely accepted that the cutaneous profile of inflammatory markers, or 'inflammatory signature', is differentially expressed in various skin conditions. In this pilot study, we investigated the possibility of inflammatory skin disease diagnosis from an immunological perspective in small punch biopsies. We collected lesional and perilesional punch biopsies from 139 patients suffering from a variety of inflammatory skin conditions and attending the Dermatology Department at the Princess Alexandra Hospital in Brisbane, Australia. Using bead-based immunoassays we were able to measure 13 out of 17 inflammatory markers from a pre-selected multi-analyte panel and to detect significant differences between lesional and perilesional biopsies from each individual patient. Hierarchical and unbiased clustering methods based on inflammatory signatures grouped psoriasis and atopic dermatitis lesions into individual clusters in contrast to other skin conditions, highlighting the potential of inflammatory signatures to be used as diagnostic differentiators and to inform alternative targets in anti-inflammatory treatment strategies.

Comparing chair time required for systemic agent drug reaction (DR) management to allocated chair time for systemic protocol.

40 Background: Chemotherapy scheduling and determining associated nursing resources are complex multiobjective decision problems. Management of DRs are thought to take additional chair and nurse time and should be accounted for in appointment scheduling in order to having an efficiently running clinic. BC Cancer – Victoria is a tertiary care regional site of BC Cancer in Victoria, British Columbia, Canada and currently schedules patients using a regimen-based resource intensity model (Greene et al, 2012). Methods: DRs were tracked in real time over 3 months, where BC Cancer ID, reaction, protocol, agent, cycle number and time of reaction were recorded. Our electronic medical record was interrogated to determine start and end of chair time. We then compared the actual chair time required to manage patients with a DR to scheduled chair time. Results: Thirty reactions occurred, including DRs to paclitaxel (43%), rituximab (13%), docetaxel (10%), nivolumab (7%), oxaliplatin (7%), pertuzumab (7%), bendmustine (3%), and daratumumab (3%). The reactions most commonly occurred with cycles 1 or 2. The averages for total chair time during DR, time from arrival to reaction, and time from reaction to discharge were 281 min (+79.5), 106 min (+ 55), and 171 min (+ 94), respectively. An average of 449 min/month extra were required for DR management above scheduled chair time. Conclusions: The agents precipitating DRs were common and predictable. An average of 7 hours and 29 minutes per month above scheduled chair time was required to manage DRs. This information could be used to more efficiently schedule chair and nursing time. This also highlights the need to minimize the number of DRs as management is resource intensive.[Table: see text]

Drug-induced hypersensitivity syndrome induced by propylthiouracil: case report and literature review

BackgroundDrug-induced hypersensitivity syndrome (DIHS) is a rare, potentially life-threatening systemic drug reaction. Antithyroid drugs (ATDs) causing DIHS have seldom been reported before.Case presentationWe present a case of propylthiouracil (PTU)-induced DIHS, which included fever, skin rash, lymphadenopathy, hepatosplenomegaly, serious liver and kidney dysfunction, peripheral blood eosinophilia, and atypical lymphocytosis. Following supportive therapy, intravenous immunoglobulin (IVIG), and systemic corticosteroid, the patient experienced a resolution of fever and rash combined with progressive normalization of hematological index and organ function. These clinical features, and the skin lesion biopsy confirmed DIHS diagnosis.ConclusionsTo our knowledge, this is the second reported case of PTU-induced DIHS worldwide and the first human leukocyte antigen (HLA) typing of PTU-induced DIHS. Clinicians should cautiously distinguish hyperthyroidism etiology and identify the indication of ATDs. Timely recognition and formal DIHS treatment are required in patients with ATDs.

Sofpironium bromide: an investigational agent for the treatment of axillary hyperhidrosis

ABSTRACT Introduction In recent years, increased knowledge about pathophysiology of primary hyperhidrosis has led to novel therapeutic advances. Topical and systemic anticholinergic agents have been proven beneficial in reducing sweat production in primary axillary hyperhidrosis (PAH), although their use is limited by the increased likelihood of systemic anticholinergic drug reactions, particularly regarding systemic agents. Areas covered This paper provides an overview of pharmaceutical characteristics, efficacy and safety data from phase II and III clinical trials on sofpironium bromide (SB), a topical anticholinergic agent that has been employed for the treatment of PAH and has already received its first approval in Japan for the treatment of PAH in the form of 5% gel formulation. Expert opinion The retrometabolic drug design of topical SB presents distinct advantages, by limiting systemic absorption and therefore development of anticholinergic adverse events. This along with the popularity of the non-greasy gel formulation is expected to increase compliance. However, this therapy still offers a temporary control of PAH, compared to sympathectomy or device-based treatments, such as microwave thermolysis. Hence, physicians should balance the effectiveness against adverse events of each therapeutic modality and use a personalized approach based on patient’s needs.

Trial of Spesolimab for Generalized Pustular Psoriasis

BackgroundGeneralized pustular psoriasis (GPP) is a rare, life-threatening, inflammatory skin disease characterized by widespread eruption of sterile pustules. Interleukin-36 signaling is involved in the pathogenesis of this disorder. Spesolimab, a humanized anti–interleukin-36 receptor monoclonal antibody, is being studied for the treatment of GPP flares.MethodsIn a phase 2 trial, we randomly assigned patients with a GPP flare in a 2:1 ratio to receive a single 900-mg intravenous dose of spesolimab or placebo. Patients in both groups could receive an open-label dose of spesolimab on day 8, an open-label dose of spesolimab as a rescue medication after day 8, or both and were followed to week 12. The primary end point was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (range, 0 [no visible pustules] to 4 [severe pustulation]) at the end of week 1. The key secondary end point was a GPPGA total score of 0 or 1 (clear or almost clear skin) at the end of week 1; scores range from 0 to 4, with higher scores indicating greater disease severity.ResultsA total of 53 patients were enrolled: 35 were assigned to receive spesolimab and 18 to receive placebo. At baseline, 46% of the patients in the spesolimab group and 39% of those in the placebo group had a GPPGA pustulation subscore of 3, and 37% and 33%, respectively, had a pustulation subscore of 4. At the end of week 1, a total of 19 of 35 patients (54%) in the spesolimab group had a pustulation subscore of 0, as compared with 1 of 18 patients (6%) in the placebo group (difference, 49 percentage points; 95% confidence interval [CI], 21 to 67; P<0.001). A total of 15 of 35 patients (43%) had a GPPGA total score of 0 or 1, as compared with 2 of 18 patients (11%) in the placebo group (difference, 32 percentage points; 95% CI, 2 to 53; P=0.02). Drug reactions were reported in 2 patients who received spesolimab, in 1 of them concurrently with a drug-induced hepatic injury. Among patients assigned to the spesolimab group, infections occurred in 6 of 35 (17%) through the first week; among patients who received spesolimab at any time in the trial, infections had occurred in 24 of 51 (47%) at week 12. Antidrug antibodies were detected in 23 of 50 patients (46%) who received at least one dose of spesolimab.ConclusionsIn a phase 2 randomized trial involving patients with GPP, the interleukin-36 receptor inhibitor spesolimab resulted in a higher incidence of lesion clearance at 1 week than placebo but was associated with infections and systemic drug reactions. Longer and larger trials are warranted to determine the effect and risks of spesolimab in patients with pustular psoriasis. (Funded by Boehringer Ingelheim; Effisayil 1 ClinicalTrials.gov number, NCT03782792.)

O9‐1: Urticaria—A Major systemic drug reaction under 1HP tuberculosis prevention in non‐HIV population

O9‐1: Urticaria—A Major systemic drug reaction under 1HP tuberculosis prevention in non‐HIV population

Completion Rate and Safety of Programmatic Screening and Treatment for Latent Tuberculosis Infection in Elderly Patients With Poorly Controlled Diabetic Mellitus: A Prospective Multicenter Study.

BackgroundPoor control of diabetes mellitus (DM) increases active tuberculosis (TB) risk. Understanding risk factors for latent TB infection (LTBI) in this population and intervention completion rates is crucial for policy making.MethodsUnder a collaborative multidisciplinary team consisting of public health professionals, endocrinologists, and pulmonologists, patients aged >45 years with poorly controlled DM (pDM), defined as having a glycated hemoglobin level of ≥9% within the preceding year, were enrolled by endocrinologists from 2 hospitals; these patients underwent LTBI screening by using QuantiFERON (QFT). Once-weekly isoniazid and rifapentine for 12 weeks (3HP) or daily isoniazid for 9 months (9H) was administered by pulmonologists. QFT-positivity predictors were evaluated using logistic regression. Completion rates and safety were also investigated.ResultsAmong 980 patients with pDM (age: 64.2 ± 9.7 years), 261 (26.6%) were QFT-positive. Age, DM duration, chronic kidney disease stage ≥3, and dipeptidyl peptidase-4 inhibitor use, not using metformin, were associated with QFT-positivity. Preventive therapy (3HP: 138; 9H: 62) was administered in 200 (76.6%) QFT-positive patients. The completion rates of 3HP and 9H were 84.1% and 79.0%, respectively (P = .494). Nine (6.5%) and zero patients in the 3HP and 9H groups, respectively, developed systemic drug reactions (P = .059); 78.3% and 45.2% had ≥1 adverse drug reactions (P < .001); and post-treatment QFT conversion rates were 32% and 20%, respectively (P = .228).ConclusionsLTBI prevalence exceeds 25% in elderly patients with pDM. Under care from a collaborative multidisciplinary team, the completion rate of preventive therapy, regardless of regimen could approach, or even exceed 80% in this population.

Onychomadesis, a post infectious sequelae of Hand-Foot-and-Mouth disease: A case report

Onychomadesis is an idiopathic shedding of a proximal part of the nail as a result of the temporary suspension of a nail matrix function. It is seen in fingernails, toenails, or both. Various underlying causes like systemic illness, drug reactions, Viral diseases, and bullous diseases have been associated with Onychomadesis. However, the mechanism of any such association remains unclear. Here we present a case of On-ychomadesis and Beau lines in the fingernails of a 13-month-old girl following Hand, foot, and mouth disease.

Impact of Age on Outcome of Rifapentine-Based Weekly Therapy for Latent Tuberculosis Infection.

BackgroundWeekly rifapentine and isoniazid (3HP) is gaining popularity for latent tuberculosis infection treatment because of its short course and high completion rate. Prior to widespread use, comprehensive 3HP treatment assessment covering an all-age population is essential.MethodsParticipants receiving ≥1 3HP dose from September 2014 to December 2019 were stratified into elderly (≥65 years), middle-aged (>35 & <65 years), and younger (≤35 years) age groups. This study investigated the impact of age on treatment outcome, particularly systemic drug reactions (SDRs) and 3HP discontinuation.ResultsOverall, 134 of 579 (23.1%) participants were elderly. The completion rate was 83.1% overall and was highest and lowest in the younger group (94.5%) and elderly (73.9%) group, respectively. However, the 3HP discontinuation rate was not significantly different among the 3 groups in multivariate logistic regression analysis. In total, 362 (62.5%) participants experienced 1 or more adverse drug reactions (ADRs), of which 38 (10.5%) and 98 (27.1%) required temporary and permanent treatment interruption, respectively. The SDR risk was 11.2% in overall and 17.1% in the middle-aged group, 3.04-fold higher than that in the elderly group (P = .025). This finding was consistently observed in different clinical settings. Hypertensive events accompanied with flu-like symptoms occurred in 11.2% of elderly participants, and accounted for 50% of grade ≥3 ADRs.ConclusionsWith proper medical support and programmatic follow-up, the 3HP completion rate is >70% even in elderly participants. In middle-aged and elderly individuals, 3HP should be employed with caution because of risk of SDRs and hypertensive events, respectively.Summary: Under programmatic medical support, widespread use of weekly rifapentine and isoniazid (3HP) for latent tuberculosis treatment is possible for its high completion rate. 3HP should be employed with caution for risk of systemic drug reactions and hypertensive events in middle-aged and elderly individuals, respectively.

Efficacy and safety of weekly rifapentine and isoniazid for tuberculosis prevention in Chinese silicosis patients: a randomized controlled trial

ObjectiveThe aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients. MethodsMale silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated. ResultsA total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity. DiscussionWeekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects. Clinical trial registrationClinicalTrials.gov number: NCT02430259

Isoniazid Concentration and NAT2 Genotype Predict Risk of Systemic Drug Reactions during 3HP for LTBI

Weekly rifapentine and isoniazid therapy (known as 3HP) for latent tuberculosis infection (LTBI) is increasingly used, but systemic drug reactions (SDR) remain a major concern. Methods: We prospectively recruited two LTBI cohorts who received the 3HP regimen. In the single-nucleotide polymorphism (SNP) cohort, we collected clinical information of SDRs and examined the NAT2, CYP2E1, and AADAC SNPs. In the pharmacokinetic (PK) cohort, we measured plasma drug and metabolite levels at 6 and 24 h after 3HP administration. The generalised estimating equation model was used to identify the factors associated with SDRs. Candidate SNPs predicting SDRs were validated in the PK cohort. A total of 177 participants were recruited into the SNP cohort and 129 into the PK cohort, with 14 (8%) and 13 (10%) in these two cohorts developing SDRs, respectively. In the SNP cohort, NAT2 rs1041983 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 7.00 [2.03–24.1]) and CYP2E1 rs2070673 (AA vs. TT+TA, OR [95% CI]: 3.50 [1.02–12.0]) were associated with SDR development. In the PK cohort, isoniazid level 24 h after 3HP administration (OR [95% CI]: 1.61 [1.15–2.25]) was associated with SDRs. Additionally, the association between the NAT2 SNP and SDRs was validated in the PK cohort (rs1041983 TT vs. CC+CT, OR [95% CI]: 4.43 [1.30–15.1]). Conclusions: Isoniazid played a role in the development of 3HP-related SDRs. This could provide insight for further design of a more optimal regimen for latent TB infection.

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to lamotrigine differs from that due to other drugs.

Drug-induced hypersensitivity syndrome (DIHS), also referred to as drug reaction with eosinophilia and systemic symptoms (DRESS), is a multi-organ systemic drug reaction characterized by hematological abnormalities and reactivation of human herpesvirus-6 (HHV-6). DIHS/DRESS is typically associated with a limited number of drugs, such as the anticonvulsants. Our group has treated 12 patients for DIHS/DRESS due to lamotrigine (LTG), but their presentation differed from that of patients with DIHS/DRESS caused by other drugs. The aim of the present study was to identify significant differences between DIHS/DRESS caused by LTG versus other drugs. We retrospectively reviewed data of 12 patients with DIHS/DRESS caused by LTG and 32 patients with DIHS/DRESS due to other drugs. The increase in alanine aminotransferase level was significantly milder in the LTG group than the DIHS/DRESS group due to other drugs. The percentage of atypical lymphocytes in the blood during DIHS/DRESS was lower in the LTG group. Serum levels of lactate dehydrogenase and thymus and activation-regulated chemokine were also lower in the LTG group. There were fewer DIHS/DRESS patients with HHV-6 reactivation in the LTG group than in the group treated with other drugs. Lymphocyte transformation after DIHS/DRESS onset was faster in the LTG group. The two groups did not differ with respect to the interval from first drug intake to rash, white blood cell count, blood eosinophilia or DRESS score. There were no significant histopathological differences between the two groups. The features of LTG-associated DIHS/DRESS and DIHS/DRESS due to other drugs differ.

Plasma Concentration of Isoniazid and Single-Nucleotide Polymorphisms of N-Acetyltransferase 2 Predict Risk of Systemic Drug Reactions During Weekly Rifapentine and Isoniazid Therapy for Latent Tuberculosis Infection: A Prospective Observational Cohort Study

Background: Weekly rifapentine and isoniazid therapy (known as 3HP) for latent tuberculosis infection (LTBI) is increasingly used, but systemic drug reactions (SDR) remain a major concern. Little, however, is known regarding the predictors of 3HP-related SDRs. Methods: We prospectively recruited 2 LTBI cohorts who received the 3HP regimen. In the single-nucleotide polymorphism (SNP) cohort, we collected clinical information of SDRs and examined the NAT2, CYP2E1, and AADAC SNPs. In the pharmacokinetic (PK) cohort, we measured plasma drug and metabolite levels at 6 and 24 hours after 3HP administration. The generalised estimating equation model was used to identify the factors associated with SDRs. Candidate SNPs predicting SDRs were validated in the PK cohort. Findings: A total of 177 participants were recruited into the SNP cohort and 129 into the PK cohort, with 14 (8%) and 13 (10%) in these two cohorts developing SDRs, respectively. In the SNP cohort, NAT2 rs1041983 (TT vs CC CT, odds ratio [OR] [95% CI]: 7.38 [2.17-25.1]) and CYP2E1 rs2070673 (AA vs TT TA, OR [95% CI]: 3.49 [1.02-12.0]) were associated with SDR development. In the PK cohort, isoniazid level 24 hours after 3HP administration (OR [95% CI]: 1.61 [1.15-2.25]) was associated with SDRs. Additionally, the association between the NAT2 SNP and SDRs was validated in the PK cohort (rs1041983 TT vs CC CT, OR [95% CI]: 4.14 [1.24-13.8]). Interpretations: Isoniazid played a role in the development of 3HP-related SDRs. This could provide insight for further design of a more optimal regimen for latent TB infection. Funding: The study was supported by grants from the Ministry of Health and Welfare (MOHW106-CDC-C-11400104 and MOHW107-CDC-C-114-000105) and the Ministry of Science and Technology (MOST106-2314-B-002-055, MOST107-2314-B-002-191 and MOST107-2314-B-037-106-MY3). Declaration of Interest: The authors have no conflicts of interest to declare. Ethical Approval: The study was approved by the institutional ethics committees of both medical centres (NTUH REC 201609044RINB and KMUHIRB-G[II]-20170033).