Drug-induced Reactions Research Articles

Acute Phase Reactants: Relevance in Dermatology.

Acute phase reactants (APRs) are a heterogeneous group of plasma proteins whose concentration either increases or decreases by at least 25% during an inflammatory process. The conditions that commonly lead to acute phase response are infection, trauma, burns, tissue infarction, inflammatory conditions, and advanced malignancy. APRs are elevated in all infective conditions. In skin and soft tissue infection, the levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) help to predict the severity of infection. Procalcitonin can be used to differentiate between viral and bacterial infections. During active stages of systemic lupus erythematosus (SLE), ESR is elevated, but CRP either remains normal or shows only moderate elevation. In the case of superadded bacterial infection in SLE, CRP is elevated. In SLE, ferritin levels are elevated during the active stage of the disease. Serum amyloid antigen (SAA) and CRP levels are significantly higher in patients with early and late stages of diffuse systemic sclerosis. Elevated levels of serum ferritin are seen in rheumatoid arthritis and adult-onset Still's disease. CRP, SAA, and α2-macroglobulin (α 2M) are elevated in active psoriasis. In severe psoriasis, the ferritin-iron ratio is elevated. In drug-induced maculopapular rash, drug-induced hyperaemic vasculitis, and severe drug-induced cutaneous adverse reactions, CRP levels are elevated during the active stages. Neoplastic diseases in general are accompanied by increased serum ferritin. Further detailed studies are required to explore the clinical significance of APRs in dermatology and the scope of their possible application as a diagnostic tool.

The Role of NLRP3 Inflammasome in the Pathogenesis of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis.

Stevens Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) are mainly drug-induced severe cutaneous adverse reactions with increased mortality. It also involves the eyes causing ocular surface disease leading to visual impairment and blindness. The role of NLRP3 Inflammasome in causing ocular surface disease and keratinocyte apoptosis is not fully explored. This study is focused on determining the role of NLRP3 Inflammasome in the pathogenesis of Stevens Johnson Syndrome/Toxic Epidermal Necrolysis. The NLRP3 Inflammasome plays a crucial role in the pathogenesis of Stevens Johnson Syndrome/Toxic Epidermal Necrolysis and may correlate with the degree of severity of skin detachment and ocular surface disease. This study looked at the expression of the NLRP3 Inflammasome in the skin of patients with biopsy confirm Stevens Johnson Syndrome/Toxic Epidermal Necrolysis compared to the lichen planus and normal controls by immunohistochemistry as well as observing the mitochondrial function of platelets challenged with plasma from patients with Stevens Johnson Syndrome/Toxic Epidermal Necrolysis and Normal Human Plasma using Agilent Seahorse XF Analyzer. Under a current, Loyola IRB approved protocol, 12 collected and archived unstained slides of skin and blood plasma samples from patients with biopsy confirmed Stevens Johnson Syndrome/Toxic Epidermal Necrolysis was used for this study. Immunohistochemical analysis was performed using anti-NLRP3 antibodies followed by imaging on a Delta Vision microscope. The precise roles of cytokines and chemokine receptors in severity of skin detachment has not been completely studied. The identification of the roles of NLRP3 in Stevens Johnson Syndrome/Toxic Epidermal Necrolysis would bridge the gaps in the basic understanding regarding the pathogenesis of this disease spectrum. NLRP3 Inflammasome is a potential therapeutic target and its inhibition by phytochemicals may be appropriate effective treatment strategies in the management of this condition.

MATHEMATICAL ANALYSIS OF DRUG-INDUCED CHEMICAL REACTION ON UNSTEADY MHD BLOOD FLOW WITH RADIATION EFFECTS THROUGH A PERMEABLE STRETCHING CAPILLARY

In this paper, we investigate certain drug effects on heat transfer in the bloodstream due to the impact of magnetic fields and thermal radiation. Certain medications produce disruption in thermoregulatory processes, fever as a result of the drug's pharmacologic activity, and hypothermia as a result of lowering the temperature. All of this affects the vascular permeability and chemical reactions that happen in the blood flow. In the present investigation, the impact of heat radiation and magnetic fields on the velocity, temperature, and concentration of drug-containing blood in a permeable stretched capillary is investigated. The present problem takes into account the unsteady magnetohydrodynamic behavior of blood through the porous media of cells and tissues surrounding the capillary, as well as variable viscosity, thermal conductivity, and chemical diffusivity. The governing equations of the model are formulated, and the resulting partial differential equation is solved numerically by the fourth-order Runge-Kutta method. The numerical simulations are performed using MATLAB software, and the results are plotted in the form of graphs and tables. It has been observed that the permeability factor boosts blood's velocity, temperature, and concentration profiles while simultaneously lowering skin friction and increasing mass and heat transfer rates. Further, the magnetic field can regulate blood velocity and increase drug concentration at the boundary layer.

Dermatological adverse drug reactions with particular reference to Steven-Johnson syndrome and toxic epidermal necrolysis

Background: Drug therapy is an inevitable cause of cutaneous adverse reactions. Aims and Objectives: The primary aim was to identify the incidence and magnitude of various dermatological adverse reactions including Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Moreover, secondary aim was to quantify the risks associated with the use of specific medications. Materials and Methods: A prospective and hospital-based study was conducted in the department of dermatology SMHS hospital on hospitalized cases of cutaneous adverse drug reactions (CADRs). Informed consent was sought and reactions were reported on validated questionnaire based on adverse drug reaction (ADR) monitoring form provided by Central Drug Standard Control organization Ministry of Health and Family Welfare, Government of India. These dermatological reactions were assessed for the clinical pattern, causative agents, and prognosis. The WHO-Uppsala Monitoring centre system for standardized case was used for causality assessment of all cases identified. Results: A total of 101 hospitalized patients with varied dermatological ADRs were reported during the study period. Cases were found more in females (n=75, 74.25%) than in males (n=26, 25.75%). CADRs that were reported in our study were exanthematous rash, fixed drug eruptions, urticarial rashes, SJS, TEN, urticarial vasculitis, anticonvulsant hypersensitivity syndrome, erythema multiforme, contact dermatitis, exfoliative dermatitis, mucosal hyperpigmentation, and nail pigmentation, respectively. After a meticulous drug history, the drugs implicated in causing the cutaneous reactions were anticonvalscents such as phenytoin, carbamazepine, lamotrigine, and phenobarbitone. Other drugs identified were non-steroidal anti-inflammatory drugs such as oxicam, antibiotics such as sulfasalazine, cefixime, cefpodoxime, amoxicillin, fluoroquinolones such as levofloxacin and ciprofloxacin, chemotherapeutic agents such as cyclophosphamide, 5FU, and hydroxurea. Conclusion: The present study concluded that skin is most common target for ADRs. Drug-induced cutaneous reactions can be as simple as a mild rash to rare life-threatening SJS and TEN. Moreover, certain group of patients is at increased risk for developing CADR’s as women are more susceptible than men.

Association of Human Leukocyte Antigen Alleles with Carbamazepine- or Lamotrigine-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in an Iranian Population: A Case-control Study.

Genetic diversity in human leukocyte antigen (HLA) alleles across populations is a significant risk factor for drug-induced severe cutaneous adverse reactions (SCARs), e.g., carbamazepine (CBZ)- and lamotrigine (LTG)-induced Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The present study aimed to investigate the frequency of different HLA alleles in Iranian patients with CBZ- and LTG-induced SJS/TEN. A case-control study was conducted from 2011 to 2018 at various hospitals affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). A total of 31 patients receiving anticonvulsant drugs (CZB or LTG) were recruited and divided into two groups. The drug-induced group (n=14) included hospitalized patients due to CBZ- or LTG-induced SJS/TEN. The drug-tolerant group (n=17) included individuals receiving CBZ or LTG for at least three months with no adverse effects. In addition, 46 healthy individuals (control group) were recruited. The frequency of HLA-A, -B, and -DRB1 alleles in patients with CZB- or LTG-induced SJS/TEN was investigated. HLA typing was performed using the allele-specific polymerase chain reaction method. The Chi square test and Fisher's exact test were used to determine a potential association between SJS/TEN and HLA alleles. P<0.05 was considered statistically significant. CBZ- or LTG-induced SJS/TEN was not significantly associated with HLA alleles. However, HLA-DRB1*01 showed a significantly higher frequency in patients with CBZ-induced SJS/TEN than the CBZ-tolerant patients (30% vs. 9%, P=0.07). Overall, no significant association was found between CBZ- or LTG-induced SJS/TEN and HLA alleles. Further large-scale studies are required to substantiate our findings.

Clozapine once- versus multiple-daily dosing: a two-center cross-sectional study, systematic review and meta-analysis

Evidence regarding effectiveness and safety of clozapine once- vs. multiple-daily dosing is limited. We compared demographic and clinical parameters between patients with once- vs. multiple-daily dosing in the Department of Psychiatry and Psychotherapy, University of Regensburg, Germany (AGATE dataset), and the Department of Psychiatry, Lausanne University Hospital, Switzerland, using non-parametric tests. Effectiveness and safety outcomes were available in the AGATE dataset. We performed a systematic review in PubMed/Embase until February 2022, meta-analyzing studies comparing clozapine once- vs. multiple-daily-dosing. We estimated a pooled odds ratio for adverse drug-induced reactions (ADRs) and meta-analyzed differences regarding clinical symptom severity, age, percentage males, smokers, clozapine dose, and co-medications between patients receiving once- vs. multiple-daily dosing. Study quality was assessed using the Newcastle–Ottawa-Scale. Of 1494 and 174 patients included in AGATE and Lausanne datasets, clozapine was prescribed multiple-daily in 74.8% and 67.8%, respectively. In the AGATE cohort, no differences were reported for the clinical symptoms severity or ADR rate (p > 0.05). Meta-analyzing eight cohorts with a total of 2810 clozapine-treated individuals, we found more severe clinical symptoms (p = 0.036), increased ADR risk (p = 0.01), higher clozapine doses (p < 0.001), more frequent co-medication with other antipsychotics (p < 0.001), benzodiazepines (p < 0.001), anticholinergics (p = 0.039), and laxatives (p < 0.001) in patients on multiple- vs. once-daily dosing. Of six studies, five were rated as good, and one as poor quality. Patients responding less well to clozapine may be prescribed higher doses multiple-daily, also treated with polypharmacy, potentially underlying worse safety outcomes. Patient preferences and adherence should be considered during regimen selection.

The Large-scale Deletions and Copy Numbers of Mitochondrial DNA in Gout Patients Treated with Allopurinol

Allopurinol is now the first-line treatment for managing gout and its increasing usage has brought more gout patients at risk of developing allopurinol-induced hypersensitive reactions. Up to now, our attempts to identify the biomarkers for hypersensitivity to allopurinol are still finite. Besides, the association between drug-induced hypersensitive reactions and some mitochondrial DNA (mtDNA) alterations has been proved but remains unclear in gout patients. In this study, 41 blood samples of gout patients prescribed with allopurinol including 22 hypersensitive and 29 tolerant ones were used to analyze their mtDNA large-scale deletions through PCR and determine the mtDNA deletion level and the copy number by quantitative PCR. The results indicated that the mtDNA large-scale deletions and mtDNA copy number of the hypersensitive group were lower than that of the tolerant one (p &lt; 0.05). However, no association was found between the mtDNA deletion level and the appearance of hypersensitive reactions in gout patients. In addition, the study showed that the mtDNA deletion level and copy number were negatively correlated with the copy numbers of mitochondrial DNA in gout patients (R = -0.3495; p = 0.0119) and allopurinol hypersensitive group (R = -0.6744; p = 0.0005). Thus, a decrease in mtDNA copy number might serve as a potential biomarker for further investigation to assess the risk of hypersensitive reactions to allopurinol in gout patients.&#x0D;

Patient Preferences for Rescue Medications in the Treatment of Breakthrough Cancer Pain.

The discrete choice experiment (DCE) is conducted in this study to discuss Chinese cancer patients' risk-benefit preferences for rescue medications (RD) and their willingness to pay (WTP) in the treatment of breakthrough cancer pain (BTcP). Through literature reviews, specialist consultation, and patient surveys, this work finally included five attributes in the DCE questionnaire, i.e., the remission time of breakthrough pain, adverse reactions of the digestive system, adverse reactions of the neuropsychiatric system, administration routes, and drug costs (estimating patients' WTP). The alternative-specific conditional logit model is used to analyze patients' preferences and WTP for each attribute and its level and to assess the sociodemographic impact and clinical characteristics. A total of 134 effective questionnaires were collected from January, 1 to April, 5 in 2022. Results show that the five attributes all have a significant impact on cancer patients' choice of "rescue medications" (P<0.05). Among these attributes, the remission time after drug administration (10.0; 95%CI 8.5-11.5) is the most important concern for patients, followed by adverse reactions of the digestive system (8.5; 95%CI 7.0-10.0), adverse reactions of the neuropsychiatric system (2.9; 95%CI 1.4-4.3), and administration routes (0.9; 95%CI 0-1.8). The respondents are willing to spend 1182 yuan (95%CI 605-1720 yuan) per month for "rescue medications" to take effect within 15 minutes and spend 1002 yuan (95%CI 605-1760 yuan) per month on reducing the incidence of drug-induced adverse reactions in the digestive system to 5%. For Chinese cancer patients, especially those with moderate/severe cancer pain, the priority is to relieve the BTcP more rapidly and reduce adverse drug reactions more effectively. This study indicates these patients' expectations for the quick control of breakthrough pain and their emphasis on the reduction of adverse reactions. These findings are useful for doctors, who are encouraged to communicate with cancer patients about how to better alleviate the BTcP.

Revisiting the question of toxidermia classification

In connection with the upcoming transition to the International Classification of Diseases and Health-related Problems of the eleventh revision (ICD-11), the authors of the article propose to replace the term toxidermy with a new, widely used in the world term drug-induced skin reactions. The article presents a list of various variants of drug-induced rashes, which are included in the draft ICD-11. For standardization of definitions and diagnostic criteria, a unified working classification of this group of diseases is based on a mixed principle clinical manifestations (primary morphological elements of skin rash), etiological and pathogenetic aspects are taken into account. The applied unified classification of drug-induced skin reactions is proposed for discussion. Examples of the formulation of clinical diagnoses are given. Severe drug-induced skin reactions are described, which are potentially life-threatening for the patient, can lead to disability and require mandatory hospitalization.

054 Combination of thymus and activation-regulated chemokine and soluble OX40 as a diagnostic biomarker for DIHS/DRESS

Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe drug-induced adverse reaction with fever, cutaneous eruptions, hematological abnormalities, organ dysfunction, and reactivation of human herpesvirus 6 (HHV-6). Although rapid diagnosis is necessary for the management of DIHS/DRESS, it is difficult to distinguish the early phase of DIHS/DRESS from other drug eruptions. We have previously reported that thymus and activation-regulated chemokine (TARC), which plays an important role in Th2-mediated immune-inflammatory processes such as atopic dermatitis, and serum soluble OX40 (CD134), which has an important role in allergic inflammation and functions as a cellular receptor for HHV-6 entry, can be a useful diagnostic marker for DIHS/DRESS. The sensitivity and specificity of sOX40 (cut-off value 213 pg/ml) for the diagnosis of DIHS/DRESS were 67% and 80%, respectively. Those of TARC (cut-off value 4000 pg/ml) were 72% and 77%, respectively. In this study, in order to reveal the relationship between serum soluble OX40 and TARC levels in the acute phase of DIHS/DRESS as well as the sensitivity and specificity of serological test using both soluble OX40 and TARC for diagnosis of DIHS/DRESS, we analyzed the sera of DIHS/DRESS patients presenting to our department. We found that the two markers were significantly correlated, and the combination of sOX40 and TARC significantly increased sensitivity to 85% but decreased specificity to 73%. The combined determination using sOX40 and TARC levels may be useful to increase the detection rate of DIHS/DRESS.

Stevens-Johnson Syndrome – clinical symptoms, etiology, pathophysiology and medical treatment - a review of the literature

Stevens-Johnson syndrome (SJS) is a rare disease of the skin and mucous membrane. It develops as a result of a sudden skin reaction, which is most often triggered by the use of certain drugs. It is characterized by acute epidermal necrosis. The syndrome can lead to many complications and death. Currently, there are no guidelines and management schematics for this disease. Treatment has changed over the years due to the discovery of the possible pathomechanism of SJS. Nevertheless, because of the rarity of the disease, there is a lack of adequate prospective randomized studies that could provide valuable information on treatment. Objective: The purpose of this study was to present Stevens-Johnson syndrome, including clinical features, etiology, pathomechanism, complications and treatment. Methods: A literature search was performed in the PubMed medical publication database using the following keywords: Stevens-Johnson syndrome, acute drug-induced skin reaction, cutaneous adverse drug reactions. Results: Stevens-Johnson syndrome is an example of an acute cutaneous reaction to certain medicinal substances. The pathomechanism is not fully understood. There is an association of genetics with the risk of developing symptoms of the syndrome in selected populations. Treatment formerly was based on glucocorticosteroids, but now IVIG (intravenous immune globulin) is used. Dehydration, pneumonia or sepsis may develop as a complication of the syndrome. Conclusions: The discovery of a genetic predisposition to develop Stevens-Johnson syndrome offers the possibility of future effective disease prevention. It is necessary to create medical procedure schemes for the diagnosis and treatment of this disorder. The discovery of the possible pathomechanism has allowed the use of IVIG in the treatment of the syndrome. Effective and prompt diagnosis and treatment can prevent life-threatening complications and death from SJS.

Retrospective study of the incidence of sarcoidosis-like reaction in patients treated with immunotherapy

To assess the frequency of radiographically evident drug-induced sarcoidosis-like reaction (DISR) in patients treated with anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) therapy, anti-programmed cell death protein 1 (PD-1) therapy, or a combination of both in a single centre. The images and medical records of 457 patients with metastatic melanoma or head and neck cancer treated with either anti-CTLA-4 therapy, anti-PD-1 therapy, or a combination of both at University of California medical centre were reviewed retrospectively and the incidence of radiological manifestations of DISR was assessed among these treatment groups. Radiological manifestations of DISR were found in 19/457 patients (4.1%). The mean interval from the initiation of immunotherapy to development of DISR was 5.5 months (range 2.3-13.5 months). Mean interval from radiological detection of DISR to imaging evidence of resolution was 5.8 months (range 1.6-18.3 months). Three patients out of 81 (3.7%), 11/297 (3.7%), and 5/79 (6.3%) developed sarcoidosis-like reaction after treatment with anti-CTLA-4 antibody, anti-PD-1 antibody, and a combination of both, respectively. Most patients with DISR were asymptomatic and did not require systemic therapy. Most patients did not demonstrate concomitant increased maximum standardised uptake value (SUVmax) in other organs on their integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT). In the present retrospective study of patients treated with immune checkpoint inhibitors (ICIs), DISR occurred in approximately 3.7% of patients treated with either anti-CTLA-4 or anti-PD-1 antibody and 6.3% of patients treated with a combination of both.

PSAT239 Pregnant Patient With a History of Methimazole-Induced Agranulocytosis Presenting With Hyperthyroidism: A Case Report

Abstract Background Pregnancy has a profound impact on the thyroid gland and its function. Severe thyrotoxicosis can lead to many complications and endanger the mother or fetus. Antithyroid drug (ATD), at its lowest possible dose, should be given. However, one of the complications of treatment include agranulocytosis which is a rare but serious allergic event with a prevalence of 0.1 to 0.5 percent. Thus, alternative treatment should be prescribed because a cross-reaction between ATDs was observed in 15.2% of patients in a study. Insufficient data is available regarding the use of these medications in pregnant patients with history of drug-induced adverse reactions. There are other feasible alternative treatments but are contraindicated in pregnancy. Case We report a 29-year old patient gravida 5 para 4 at 10 weeks age of gestation at the time of consult presenting with palpitations. She is a known case of Graves’ disease for 7 years and maintained on Methimazole. She was admitted a year prior consult as a case of impending thyroid storm; Methimazole-induced agranulocytosis. Initially, maintained on Lithium but shifted back to Methimazole without a physician's advice and later on, discontinued the medication upon knowledge of pregnancy. She presented on her first trimester of pregnancy with palpitations and elevated free thyroxine (T4) at 71.29 pM (normal range: 11-24 pM). She was started on Propylthiouracil 50 mg/tablet 1 tablet three times a day. On her second trimester, no reported symptoms of hyperthyroidism and/or agranulocytosis such as fever or sore throat. Thyroidectomy was offered at this time explaining the risks and benefits but she strongly refused. Free T4 was then maintained at a value slightly above the upper normal limit. Propylthiouracil was also shifted to Methimazole 5 mg/tablet 1 tablet once daily and revised to 1 tablet every other day on the third trimester of pregnancy. Delivery was uneventful and the newborn was evaluated by a pediatrician with unremarkable findings. Four weeks postpartum, no noted symptoms of hyperthyroidism and/or agranulocytosis. Free T4 was noted within the normal range at 18.84 pM. Alternative treatment was offered due to the risk of ATD-induced agranulocytosis. Conclusion Hyperthyroidism in pregnancy is associated with a variety of complications for the mother and fetus. Three effective treatment options include ATD, thyroidectomy or RAI therapy. But, not all are relatively safe for pregnancy. In initiating ATD, cross-reaction between medications should be considered especially for patients with history of adverse reaction, such as agranulocytosis, which can be life-threatening. However, there are limited studies in the management of this specific case. Treating physician and patient should discuss each of the options, including the benefits, drawbacks and side effects. Keywords: Hyperthyroidism, Graves’ disease, Pregnancy, Agranulocytosis Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSUN62 A Rare Case of Atorvastatin Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome - A Case Report.

Abstract Clinical Case A 77 year-old female presented to emergency department with progressively worsening rash that started one week ago. On physical examination blanching erythema was noted in lower back, buttocks and extremities. There was no desquamation or involvement of oral mucosa. No lymphadenopathy or hepatosplenomegaly was noted. Laboratory investigations showed white blood cell count of 21.2×10^3/uL, with 33.1% eosinophils. Creatinine was elevated at 2.8mg/dL from baseline of 0.8mg/dL. Further lab work revealed alkaline phosphate 2314 IU/L, aspartate transaminase 587 IU/L, and alanine transaminase 620 U/L, total bilirubin 7.3mg/dL with direct bilirubin of 5.1mg/dL, Immunoglobulin E level of 2000 IU/ml and normal Tryptase levels. Serology for viral hepatitis, Epstein-Barr virus, Cytomegalovirus and Human immunodeficiency virus was negative. Autoimmune workup including antinuclear Antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), mitochondrial antibody, smooth muscle antibody, double stranded DNA, anti-histone antibody, rheumatoid factor, Sjogren's antibody and centromere antibody were negative. Urinalysis, urine protein electrophoresis and serum protein electrophoresis were also normal. Computed tomography (CT) scan of chest showed mild supraclavicular and mediastinal lymphadenopathy. Review of medical records revealed that patient was recently discharged from hospital with a prescription of Atorvastatin following admission for transient ischemic attack 6 weeks ago. Skin biopsy showed superficial perivascular dermatitis with extravasation of red blood cells with no diagnostic evidence of vasculitis, granuloma or malignancy. Based on biopsy findings, recent drug administration followed by appearance of rash, hematological abnormality, lymphadenopathy and multi-system involvement and after exclusion of other possible causes, diagnosis of DRESS syndrome was made. Atorvastatin was held and patient was given Methylprednisolone for three days followed by Prednisone 1mg/kg with taper. Rash as well as kidney and liver functions improved drastically within two days. Discussion Our patient presented with one week of rash associated with deteriorating kidney and liver functions. Atorvastatin was initiated five weeks prior to development of rash. All the possible infectious etiologies and malignancy was ruled out based on the laboratory work mentioned above. Work up for vasculitis was also negative. DRESS syndrome is a late onset drug induced hypersensitivity reaction which usually manifests 3 weeks to months after the offending drug is started. It is very rare with an incidence of 0.9-2 per 100,000 patients per year and accounts for 10-20% of all cutaneous adverse drug reactions. DRESS syndrome if untreated carries significant risk of mortality, between 10-20%. RegiSCAR (European Registry of Severe Cutaneous Adverse Reaction) scoring system can be used to help diagnose DRESS syndrome. It takes into account multiple factors including fever, lymphadenopathy, eosinophilia, rash, number of organs involved, disease duration, skin biopsy findings and negative results of investigations to rule out alternate causes of patient's symptoms. Patient responded well to systemic steroids followed by oral steroids with taper. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Case report: Recall dermatitis at patch-test sites after oral provocation with mesalazine

Recall dermatitis is a rare localized drug-induced acute inflammatory skin reaction mediated by skin-resident memory T (TRM) cells. We present a recall dermatitis following oral provocation with a 5-aminosalicylic acid (5-ASA) preparation occurring at previous 5-ASA skin patch sites.

Association of HLA Alleles with Antiepileptic Drug-Induced Mild Cutaneous Reactions: A Case-Control Study of a Northeast Han Chinese Population.

Human leukocyte antigen (HLA) is associated with drug-induced cutaneous adverse reactions, including antiepileptic drugs (AEDs). HLA gene polymorphism has a regional discrepancy, and it is therefore important to study it in different populations. To investigate the role of HLA in AED-induced mild cutaneous adverse drug reactions (cADRs) in a Northeast Han Chinese population. A case-control study was performed in the First Hospital of Jilin University between August 2016 and March 2017. In total, 26 patients with mild cADRs induced by AEDs and 23 AED-tolerant control patients were included. Sequence-based typing (SBT) was used to detect HLA-A and HLA-B genotypes. Differences in genotype frequencies between groups were assessed using Fisher's exact test. In the mild cADRs group, 22 patients (84.6%) presented with maculopapular exanthema (MPE) and four patients (15.4%) presented with an isolated itch. The median duration between the AED exposure and cADRs was 7.5 days (IQR, 3 - 14 days). We failed to find statistically significant differences in HLA alleles between the cADRs group and the control group when considering all the drugs included in our study together or when considering oxcarbazepine (OXC), carbamazepine (CBZ), and levetiracetam (LEV) alone (P > 0.05). Our findings indicated that there was no correlation between HLA alleles and AED-induced mild cADRs in the Northeast Han Chinese population.

The role of in vitro testing in pharmacovigilance for ß-lactam-induced serum sickness-like reaction: A pilot study.

Background: Current pharmacovigilance (PV) methods for detection of adverse drug reactions (ADRs) fail to capture rare immune-mediated drug hypersensitivity reactions (DHRs) due to their scarcity and the lack of clear diagnostic criteria. Drug-induced serum sickness-like reactions (SSLRs) are rare type of DHRs that occur in susceptible patients 1–3 weeks after exposure to the culprit drug with ß-lactam antibiotics being the most associated drugs. The diagnosis of drug induced SSLR is difficult due to the lack of safe and reliable diagnostic tests for identifying the culprit drug. The lymphocyte toxicity assay (LTA) is an in vitro test used as a diagnostic tool for drug hypersensitivity reactions (DHRs). Objective: To evaluate the role of the LTA test for diagnosing and capturing SSLR due to ß-lactam antibiotics in a cohort of patients. Methods: Patients were recruited from patients referred to the Drug Hypersensitivity Clinic at Clinic at London Health Science Centre with suspicion of drug allergy. Twenty patients (10 males and 10 females) were selected to be tested to confirm diagnosis. Demographic data was collected form the patents and blood samples were withdrawn from all patients and from 20 healthy controls. The LTA test was performed on all subjects and data is expressed as percentage increase in cell death compared to control (vehicle without the drug). Results: In the result of LTA tests performed on samples from the selected 20 patients. There was a significant (p < 0.05) concentration-dependent increase in cell death in cells isolated from patients as compared to cells from healthy controls when incubated with the drug in the presence of phenobarbitone-induced rat liver microsomes. Conclusion: Giving its safety and good predictive value the LTA test has very strong potential to be a useful diagnostic tool for ß-lactam-induced SSLR. The test procedure is relatively simple and not overly costly. Further studies including other drug classes are needed to evaluate the utility of the LTA test for SSLR due to other drugs.

DRUG-INDUCED SARCOIDOSIS-LIKE REACTION IN THE ORAL CAVITY: A CASE REPORT

Drug-induced sarcoidosis-like reaction (DISR) is almost indistinguishable from sarcoidosis, and it manifests as a systemic granulomatous tissue reaction occurring in a temporal association with initiation of an offending drug. This study presents a rare case of DISR with oral involvement. A 63-year-old woman with a history of rheumatoid arthritis who has been treated with adalimumab presented with multiple ulcerative nodules on the hard palate, with 15 days of duration. Imaging exams did not exhibit any alteration. Blood tests and serological investigations were negative. An incisional biopsy was performed. Microscopic examination demonstrated a granulomatous inflammatory process in the connective tissue, consisting of multiple granulomas, without evidence of caseating necrosis or microorganisms. Histochemical reactions were negative for acid-fast bacilli and fungi, and immunohistochemical assessment for CD3, CD20, and CD68 highlighted the presence of normal lymphocytes and histiocytes. Adalimumab was ceased and after 17 months complete resolution of the lesions was observed.

Phenytoin Induced Drug Reaction With Eosinophilia and Systemic Symptoms Syndrome: A Clinical Case Report

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially life-threatening hypersensitivity reaction with cutaneous presentation and internal organ involvement. We herein present a case of phenytoin induced DRESS syndrome in a 56- year-old male who presented with high-grade fever and chills, cough with expectoration and generalized maculopapular rash. Laboratory findings revealed eosinophilia, leukocytosis, thrombocytopenia, transaminitis and elevated inflammatory markers. Further clinical, radiological and histopathological assessments confirmed the diagnosis. Phenytoin was discontinued, and patient was started on intravenous dexamethasone, which was later switched to oral prednisone. Rapid resolution of fever, eosinophilia and progressive improvement in skin rash and liver dysfunction was observed. Our report highlights the importance of prompt recognition of DRESS syndrome and the need for a guideline directed therapy for the management of this adverse drug reaction.

Pustular diseases and keratinocyte-myeloid synergy.

Pustules are among the most common lesions produced in human skin. Infections by pathogens and drug-induced reactions are frequent causes of pustule formation. In recent years immune-mediated pustular diseases have drawn attention. It is proposed to classify pustular diseases according to the initiating events and sites: purely epidermal pustules, follicular pustules or pustules noted in autoinflammatory syndromes. The unifying pathology in all of the three categories is a microinvasion of activated neutrophils into epidermal or adnexal epithelia. Formation of pustules involves established IL-17 / IL-23, IL-36 / IL-36RN driven pathology, or IL-1 /caspase-activated autoinflammation. Pathophysiology demonstrates an intriguing synergy of keratinocytes with neutrophils. This is called keratinocyte-myeloid synergy (KMS). Non-infectious pustules are formed by IFNα controlling the production of chemoattractants (IL-8, LTB4) or induced by IL-1-regulated inflammasomes and caspase/ IFNβ-induced chemotaxins. The presence of physical barriers, for example, cornified cell layers (str. corneum), is instrumental in establishing chemotactic gradients and blocking migrating neutrophils. In follicular KMS-driven pustular disorders, in contrast to epidermal pustules, neutrophil-mediated toxicity propagates lasting and expanding ulcerating diseases with increased levels of circulating immunoglobulin A (IgA). Complexed IgA is suggested to propagate ongoing pustular diseases. These are prerequisites essential for developing pustules in burdensome human skin diseases.