Multiple Drug Intolerance Syndrome Research Articles

Multiple drug intolerance in antihypertensive patients: what is known and what is missing.

Drug allergy and intolerance are increasingly recognized as significant public health concerns, leading to adverse reactions in patients undergoing pharmacological treatments. Multiple drug intolerance syndrome (MDIS), characterized by adverse reactions to at least three different drug classes without a clear immunological mechanism, poses a substantial challenge, particularly in hypertensive patients. Despite its link to suboptimal adherence and uncontrolled blood pressure, MDIS in the context of hypertension remains insufficiently explored. This review synthesizes existing literature on MDIS, emphasizing clinical characteristics, pathogenesis, and psychiatric comorbidity. Furthermore, it delves into MDIS in the context of hypertension, highlighting the importance of a multidisciplinary approach in diagnosis and management, including innovative therapeutic strategies such as novel therapeutic algorithms or renal denervation. The review concludes by emphasizing the necessity for further research and clinical trials to enhance our understanding and address MDIS, especially in hypertensive patients.

Drug Allergy Mimics

When approaching a case of apparent drug allergy, the consulting clinician should consider a broad differential diagnosis. This article presents a series of cases that could be commonly referred to an Allergist for assessment as "drug allergy," however, where a real diagnosis exists that mandates a different diagnostic and treatment strategy. Including a case of Inducible Laryngeal Obstruction, Multiple Drug Intolerance Syndrome, viral rash, seizure due to metastatic malignancy, and Hemophagocytic lymphohistiocytosis (HLH) initially diagnosed as drug reaction and eosinophilia with systemic symptoms (DRESS). The initial misdiagnoses of these patients delayed or interfered with their medical care, emphasizing the importance of accurate diagnoses for the benefit of our patients.

Drug Allergy in Women

Across all settings, women self-report more drug allergies than do men. Although there is epidemiologic evidence of increased drug allergy labeling in postpubertal females, the evidence base for female sex as a risk factor for true immune-mediated drug hypersensitivity reactions (DHRs), particularly in fatal drug-induced anaphylaxis, is low. A focus on the known immunologic mechanisms described in immediate and delayed DHR, layered on known hormonal and genetic sex differences that drive other immune-mediated diseases, could be the key to understanding biological sex variations in DHR. Particular conditions that highlight the impact of drug allergy in women include (1) pregnancy, in which a drug allergy label is associated with increased maternal and fetal complications; (2) multiple drug intolerance syndrome, associated with anxiety and depression; and (3) female-predominant autoimmune medical conditions in the context of mislabeling of the drug allergy or increased underlying risk. In this review, we describe the importance of drug allergy in the female population, mainly focusing on the epidemiology and risk, the mechanisms, and the associated conditions and psychosocial factors. By performing a detailed analysis of the current literature, we provide focused conclusions and identify existing knowledge gaps that should be prioritized for future research.

Anesthetic Management of Transoral Odontoidectomy in a Child with Multiple Drugs Intolerance Syndrome

AbstractPatients with an adverse reaction to more than three groups of drugs have multiple drug intolerance syndrome (MDIS). Regional anesthesia can be an attractive alternative when patients presenting for surgery are diagnosed with MDIS for opioids and nonsteroidal anti-inflammatory drugs (NSAIDs). Moreover, supplementary regional anesthetic techniques reduce exposure to multiple anesthetic medications, reducing the incidence of allergic reactions. We report the case of a pediatric patient diagnosed with MDIS presenting for transoral odontoidectomy and tracheostomy, wherein regional anesthesia techniques aided us in providing perioperative analgesia and maintaining hemodynamic stability.

A masquerade of recurrent anaphylaxis.

Background: We present a case of a 37 year old man with a history of human immunodeficiency virus, latent syphilis, anxiety, posttraumatic stress disorder. attention deficit/hyperactivity disorder, multiple drug intolerance syndrome who presented with concerns of recurrent episodes of rash and respiratory symptoms with questionable "anaphylaxis" episodes without clear etiology or known trigger. Methods: To evaluate some of the potential causes of recurrent anaphylaxis in our patient. Further evaluation through laboratory analysis and ultimately direct visualization of the patient's vocal cords by laryngoscopy assisted in the final diagnosis. Results: Inappropriate adduction of the vocal cords was observed during an acute reaction. Conclusion: The patient's presentation was consistent with inducible laryngeal obstruction and highlights the importance of confirming a suspected diagnosis of anaphylaxis and keeping a broad differential when establishing an etiology.

Multiple drug intolerance in patients with arterial hypertension: prevalence and determining factors.

One of the reasons for poor medication compliance among patients is the occurrence of adverse drug reactions. The aim of this study was to determine the prevalence of multiple drug intolerance syndrome (MDIS), defined as adverse reactions to 3 or more classes of drugs, among patients with arterial hypertension, and to assess the predisposing factors. The study population included hospitalized patients diagnosed with arterial hypertension as well as patients undergoing chronic treatment in an outpatient hypertension clinic. The authors used a structured proprietary questionnaire, which focused on demographic and clinical data, including current or past history of adverse drug reactions. The study population comprised 1000 patients, including 560 women. The mean (SD) age was 62.8 (14.9) years. Eighty patients (8%) suffered from MDIS. There were more women in this group, as compared with the entire study population (71% vs 55%; P = 0.01). The patients with MDIS had a longer history of hypertension (median 15 vs 10 years; P = 0.01), and were more likely to suffer from respiratory (P = 0.01), gastrointestinal (P = 0.003), rheumatoid (P <0.001), and endocrine (P = 0.01) disorders. The risk of MDIS was the highest with the concomitant use of analgesics, followed by β‑blockers, antiplatelet drugs, and antibiotics. MDIS in patients with hypertension is common and more frequently affects women and patients with a longer known disease duration. Comorbidities increase the risk of MDIS. Its risk is strongly associated with the use of analgesics, β‑blockers, antiplatelet drugs, and antibiotics.

Characterization, epidemiology and risk factors of multiple drug allergy syndrome and multiple drug intolerance syndrome: A systematic review.

BackgroundMultiple drug allergy and multiple drug intolerance syndrome (MDAS/MDIS) labels are an impediment to clinical care and knowledge regarding these conditions is limited. This systematic review investigated the characterization, epidemiology, risk factors, clinical impact and pharmaco‐economics of MDAS and MDIS.MethodsSystematic literature search across 11 databases (01 January 2000–06 November 2020) for MDIS, MDAS and related terminology. Studies were reviewed for quality of evidence and risk of bias by employing Critical Appraisal Skills Programme cohort study checklist. A narrative synthesis approach facilitated by systematic textual descriptions, tabulation and thematic analysis was adopted.ResultsThere was heterogeneity in terminology and methodology. Few studies applied standard drug allergy diagnostic methods. There is some evidence to suggest that multiple drug hypersensitivity syndrome (MDHS; i.e., confirmed allergies in MDAS) is a distinct clinical entity. Prevalence of MDIS and MDAS labels in unselected & selected populations varied between 2.1%–6.4% & 4.9%–90% and 1.2% & 0%–36% respectively. Reported risk factors included female gender, increasing age, body mass index, anxiety, depression, co‐morbidities, concurrent allergies and increased healthcare utilization. Drugs commonly implicated were antibiotics and non‐steroidal anti‐inflammatory drugs. No studies relating to clinical impact and pharmaco‐economics were found.ConclusionThere is considerable burden of MDAS and MDIS labels. Data needs cautious interpretation as majority of studies described involved unverified labels. Despite this limitation and heterogeneity of studies, there is some evidence to suggest that MDHS is a distinct clinical entity. Well‐designed multi‐centre studies applying standardized terminology and diagnostic methodology are needed to gain further insight into these conditions.

MULTIPLE DRUG INTOLERANCE IN PATIENTS WITH ARTERIAL HYPERTENSION: PREVALENCE AND DETERMINING FACTORS

Objective: One of the reasons for patients’ poor medication compliance is the occurrence of drug-induced adverse events. The aim of this study was to determine the prevalence of Multiple Drug Intolerance Syndrome (MDIS), defined as adverse events after 3 or more drug classes, in a group of patients with arterial hypertension and to assess the predisposing factors. Design and method: The study population comprised hospitalized patients diagnosed with arterial hypertension as well as patients undergoing chronic treatment in an outpatient hypertension clinic. A structured proprietary questionnaire was used, which focused on demographic and clinical data, including current or past incidences of adverse drug reactions. Results: The study population comprised a total of 1000 patients, including 560 women. The mean age was 62.84 ± 14.96 years. Eighty patients (8%) suffered from MDIS. A significantly higher percentage of patients with MDIS were women (71% vs. 55%, p = 0.006) and patients with longer-lasting hypertension (median 15 vs. 10 years, p = 0.008). Moreover, among patients with MDIS, the following disorders were more frequent: respiratory (21% vs. 11%, p = 0.013), gastrointestinal (25% vs. 13%, p = 0.003), rheumatic (24% vs. 9%, p &lt; 0.001) and endocrine (29% vs. 16%, p = 0.007). The risk of MDIS was highest in the case of concomitant use of analgesics, OR = 65.59, p &lt; 0.001, followed by beta-blockers, OR = 48.42, p &lt; 0.001, antiplatelet drugs, OR = 47.26, p &lt; 0.001 and antibiotics OR = 30.04, p &lt; 0.001. Conclusions: MDIS in patients with hypertension is common and affects more frequently women and patients with a longer disease duration. Comorbidities increase risk of MDIS. The risk of MDIS is most strongly associated with the use of analgesics, beta-blockers, antiplatelet drugs and antibiotics.

Population-Based Incidence, Severity, and Risk Factors Associated with Treated Acute-Onset COVID-19 mRNA Vaccination–Associated Hypersensitivity Reactions

BackgroundCOVID-19 mRNA vaccination–associated acute-onset hypersensitivity reactions have caused anxiety and may be contributing to vaccine hesitancy.ObjectiveTo determine the incidence, severity, and risk factors for treated acute-onset COVID-19 mRNA vaccination–associated hypersensitivity reactions in a well-characterized population.MethodsAll Kaiser Permanente Southern California (KPSC) members who received COVID-19 mRNA vaccinations between December 15, 2020, and March 11, 2021, at a KPSC facility were identified and characterized, along with all treated acute-onset vaccination-associated hypersensitivity events.ResultsWe identified 391,123 unique vaccine recipients (59.18% female, age 64.19 ± 17.86 years); 215,156 received 2 doses (53.54% Moderna), 157,615 only a first dose (50.13% Moderna) (1961 [1.46%] >2 weeks late getting a second dose), and 18,352 (74.43% Moderna) only a second dose. Only 104 (0.028%) (85.58% female, age 53.18 ± 15.96 years) had treated first dose events, 68 (0.030%) Moderna. Only 32 (0.014%) (93.75% female, age 57.28 ± 17.09 years) had treated second dose events, 21 (0.016%) Moderna. Only 2 (0.00033%) vaccinations resulted in anaphylaxis. Only 27 (20.77%) of those with treated first dose reactions failed to get a second dose. Only 6 of 77 (7.8%) with first dose reactions also had second dose reactions. Individuals with treated events were more likely to be female (P < .0001), younger (P < .0001), and had more pre-existing drug “allergies” (2.11 ± 2.12 vs 1.02 ± 1.41 [P < .0001] for average recipients).ConclusionsTreated acute-onset hypersensitivity events were mostly benign, more common with first COVID-19 mRNA vaccine doses, more likely to occur in younger females with typical risk factors associated with multiple drug intolerance syndrome, and very unlikely to be primarily immunologically mediated.

Multiple Drug Intolerance Syndrome in Fibromyalgia

Multiple drug intolerance syndrome (MDIS) describes patients with non-immunologic reactions to ≥3 drug classes. This can severely limit treatment options for affected patients. Rates of MDIS in fibromyalgia have not been previously described 1,479 patients with a diagnosis of fibromyalgia seen within our university health system in the last year were evaluated by retrospective chart review. Based on prior studies, patients with 10 or more listed allergies were considered to have MDIS. Chi-square testing and binary logistic regression were used for analysis. 128 (8.65%) patients with fibromyalgia met the definition of MDIS. The average number allergies listed for fibromyalgia patients was 3.7, while the average for age and sex matched controls was 1.4. On regression analysis, patients with fibromyalgia were found to be 6 times more likely to have MDIS (OR 6.29, CI 4.74-8.36). An active diagnosis of anxiety (X2 = 13.00, p < 0.0001) or depression (X2 = 7.14, p =0.008) was associated with MDIS. A Charlson Comorbidity Index score of ≥4 was associated with MDIS in patients with fibromyalgia (X2 = 41.44, p < 0.0001) and estimates a 10 year survival of 53%. Additionally, having >10 outpatient visits within the last year was associated with MDIS (X2 = 30.79, p < 0.0001 The association of MDIS with multiple comorbidities and frequent health care utilization in patients with fibromyalgia raises concerns that MDIS may limit therapies in these already complex patients. Additional studies are needed to explore this further.

Tackling the Patient with Multiple Drug “Allergies”: Multiple Drug Intolerance Syndrome

As populations age, the prevalence of reported drug "allergy" increases, often leading to suboptimal care and increased morbidity because of unnecessary avoidance of safe and effective medications. Evaluation by a drug allergy specialist is often warranted when a patient has more than 2 unrelated drug "allergies" listed in the medical record. In this commentary, we clarify and propose standard terminology to use when evaluating patients with multiple drug allergy labels including and more specifically when diagnosing multiple drug intolerance syndrome and the much rarer multiple drug hypersensitivity syndrome. We review epidemiology and key features of multiple drug intolerance syndrome and multiple drug hypersensitivity syndrome. We summarize the methodologic and practical diagnostic workup and management of individuals with MDIS to assist with the accurate delabeling of drug "allergies" in the electronic health record.

High-cost, high-need patients: the impact of reported penicillin allergy.

More than 90% of patients who report a penicillin allergy have the allergy disproved when tested. Unnecessary use of alternative (non-beta-lactam) antibiotics can result in more treatment failures and adverse reactions. We described the prevalence and impact of a reported penicillin allergy in high-cost, high-need (HCHN) patients. Retrospective cohort. We identified HCHN patients in a care management program of an urban academic medical center (January 1, 2014, to December 31, 2016). We used multivariable logistic regression models to determine the association between a reported penicillin allergy and antibiotic use. We used multivariable Poisson regression models to determine the association between a reported penicillin allergy, with or without multiple drug intolerance syndrome (MDIS; ≥3 reported drug allergies), and healthcare resource utilization (HRU). Of 1870 HCHN patients, 383 (20%) reported penicillin allergy, 835 (45%) had MDIS, and 290 (16%) had both. HCHN patients reporting penicillin allergy had an increased odds of beta-lactam alternative antibiotic use (adjusted odds ratio, 3.84; 95% CI, 2.17-6.80). HRU was significantly higher for patients reporting a penicillin allergy alone (adjusted relative risk [aRR], 1.13; 95% CI, 1.03-1.25) and with concurrent MDIS (aRR, 1.20; 95% CI, 1.08-1.34). HCHN patients had a high burden of reported drug allergy. A reported penicillin allergy conferred a 4-fold increased odds of beta-lactam alternative antibiotic use. Reporting penicillin allergy, with and without MDIS, was associated with significantly more HRU. HCHN care management programs should consider systematic drug allergy evaluations to optimize antibiotic use in these fragile patients.

Multiple Drug Intolerance Syndrome: An Underreported Distinct Clinical Entity.

Aim:Multiple drug intolerance syndrome (MDIS) is a unique clinical entity distinct from other drug hypersensitivity syndromes. The aim of this review was to critically appraise the various aspects of MDIS.MethodsA review was conducted to search for the causes, mechanism, clinical features, and management of MDIS.ResultsThe most common cause of MDIS is antibiotics followed by non-steroidal anti-inflammatory drugs (NSAIDs). Although some non-specific immunological mechanisms are involved, the immunological tests for MDIS are negative. Rashes, gastrointestinal reflux, headache, cough, muscle ache, fever, dermatitis, hypertension, and psychiatric symptoms are the usual manifestations. Treatment is mostly symptomatic with the withdrawal of the offending drug. Drug re-challenges and desensitization may be required for the management of this syndrome.ConclusionMDIS occurs by a nonimmune mechanism which requires a prompt withdrawal of the offending drug(s), and in some cases may require drug re-challenge and desensitization.

Multiple drug intolerance syndrome and multiple drug allergy syndrome: Epidemiology and associations with anxiety and depression.

The epidemiology of multiple drug intolerance syndrome (MDIS) and multiple drug allergy syndrome (MDAS) is poorly characterized. We used electronic health record (EHR) data to describe prevalences of MDIS and MDAS and to examine associations with anxiety and depression. Patients with ≥3 outpatient encounters at Partners HealthCare System from 2008 to 2015 were included. Patients with MDIS had intolerances to ≥3 drug classes, and patients with MDAS had hypersensitivities to ≥2 drug classes. Psychiatric conditions and comorbidities were defined from the EHR and used in multivariable logistic regression models to assess the relation between anxiety/depression and MDIS/MDAS. Of 746888 patients, 47634 (6.4%) had MDIS and 8615 (1.2%) had MDAS; 3171 (0.4%) had both. Anxiety (adjusted odds ratio [aOR] 1.72 [1.65, 1.80]), depression (aOR 1.46 [1.41, 1.52]), and both anxiety and depression (aOR 1.97 [1.86, 2.08]) were associated with increased odds of MDIS. Depression was associated with increased odds of MDAS (aOR 1.41 [1.28, 1.56]), but there were no clear associations with anxiety (aOR 1.13 [0.99, 1.30]) nor both depression and anxiety (aOR 1.13 [0.92, 1.38]). While 6% of patients had MDIS, only 1% had MDAS. MDIS was associated with both anxiety and depression; patients with both anxiety and depression had an almost twofold increased odds of MDIS. MDAS was associated with a 40% increased odds of depression, but there was no significant association with anxiety. Psychological assessments may be useful in the evaluation and treatment of patients with MDIS and MDAS; physiologic causes for MDAS warrant further investigation.

P002 Multiple drug allergy syndrome: epidemiology and association with anxiety disorders

Multiple Drug Intolerance Syndrome (MDIS) is associated with increased patient anxiety. We used electronic health record (EHR) data to define the epidemiology of MDIS and Multiple Drug Allergy Syndrome (MDAS), and assess whether anxiety was independently associated with these conditions.

A multiple drug allergy syndrome, multiple drug intolerance syndrome and/or allergic drug reaction with multiple immune reactants

A multiple drug allergy syndrome, multiple drug intolerance syndrome and/or allergic drug reaction with multiple immune reactants

Multiple drug intolerance syndrome: risk factors examined

Multiple drug intolerance syndrome: risk factors examined

Multiple Drug Intolerance Syndrome: A Large-Scale Retrospective Study

BackgroundThe term multiple drug intolerance syndrome (MDIS) has been used to describe patients who express adverse drug reactions to three or more drugs without a known immunological mechanism.ObjectiveTo identify patient factors that could increase the risk of MDIS.MethodInpatient records over a 5-year period were captured from an electronic prescribing system to identify patients with at least one documented drug allergy. Univariable and multivariable analyses were used to compare the rates of MDIS across age, sex, weight, ethnicity, history of atopy or psychological disorders, and previous admissions.ResultsA total of 25,695 patients had a documented drug intolerance, 4.9 % of whom had MDIS. MDIS was significantly more likely in women (p < 0.001), patients with multiple comorbidities (p < 0.001), and patients with previous hospital admissions (p < 0.001). With the exception of penicillin (p = 0.749), MDIS was more frequent in those with allergies to other drugs (p < 0.001).ConclusionMDIS was associated with female gender, multiple comorbidities, and previous hospital admissions. A documented allergy to penicillin did not increase the likelihood of MDIS.

Safely Diagnosing Clinically Significant Penicillin Allergy Using Only Penicilloyl-Poly-Lysine, Penicillin, and Oral Amoxicillin

Penicillin skin testing is rarely used to undiagnose penicillin "allergy" in the United States, partially because of concern that commercially available materials are inadequate. We determined whether skin testing with only commercially available penicilloyl-poly-lysine and penicillin followed by an oral amoxicillin challenge, if skin test-negative, can safely identify clinically significant penicillin allergy. Five hundred sequential persons with positive history of penicillin "allergy" were evaluated by skin testing with penicilloyl-poly-lysine and penicillin between June 8, 2010, and March 29, 2012. All persons with negative skin tests were given an oral amoxicillin challenge and observed for 1 hour. Persons undergoing penicillin allergy testing were representative of all health plan members with penicillin allergy. Only 4 persons (0.8%; 95% CI, 0.32%-2.03%) had a positive skin test result. Only 4 persons (0.8%; 95% CI, 0.32%-2.03%) had an acute objective oral amoxicillin challenge reaction. Fifteen persons (3.0%; 95% CI, 1.83%-4.98%) had subjective oral challenge reactions, either acute transient itching or dizziness. All were women and 11 (73.3%) had multiple drug intolerance syndrome. None had severe reactions or objective signs. These were not considered to be positive challenge reactions. Sixty-eight subjects (13.6%) who were negative on testing were exposed to 88 courses of penicillins during 90 days of follow-up. New reactions were reported after 4 courses (4.5%), 3 (75%) occurring in subjects with multiple drug intolerance syndrome. Penicillin skin testing, using only penicilloyl-poly-lysine and penicillin, followed by oral amoxicillin challenge, if negative, can safely identify clinically significant IgE-mediated penicillin allergy in patients who use health care in the United States at this time.

Multiple Drug Intolerance Syndrome: Prevalence, Clinical Characteristics, And Management

Abstract Background Population-based data on the demographics and clinical characteristics of patients with multiple unrelated drug class intolerances noted in their medical records are lacking. Objectives To provide population-based drug incidence rates and prevalence, and to identify individuals with multiple drug intolerance syndrome (MDIS) defined by 3 or more unrelated drug class allergies, and to provide demographic and clinical information on MDIS cases. Methods Electronic medical record data from 2,375,424 Kaiser Permanente Southern California health plan members who had a health care visit and at least 11 months of health care coverage during 2009 were reviewed. Population-based drug incidence rates and prevalence were determined for 23 unrelated medication classes. Results On January 1, 2009, 478,283 (20.1%) health plan members had at least one reported allergy. Individuals with a history of at least 1 and females, in general, reported higher population-based new incidence rates. Multiple drug intolerance syndrome was present in 49,582 (2.1%). The MDIS cases were significantly older, 62.4 ± 16.1 years; heavier, body mass index 29.3 ± 7.1; and likely to be female, 84.9%, compared with average health plan members. They had high rates of health care utilization, medication usage, and new drug incidence. They sought medical attention for common nonmorbid conditions. Conclusions Multiple drug intolerance syndrome is in part iatrogenic. It is associated with overweight elderly women who have high rates of health care and medication usage. Urticarial syndromes only explain a small fraction of MDIS cases. Multiple drug intolerance syndrome is associated with anxiety, but not predominately with immunoglobulin E (IgE)-mediated allergy or life-threatening illness. Multiple drug intolerance syndrome can be managed by medication avoidance and judicious rechallenge.