Edward M Klepper1*, Danielle M Auth1, Liesl M Buskirk1, Maria L Andrzejewski1, Kishore E Clark1, Samira Vuchula1, Eber Guzman-Cruz1, Vicki Huang1, Eric J Chattin1, Jon R Christoferson Jr1, Rista Upadhyay1, Emma A Kvandahl1, Howard N Robinson1
1Robinson and Max Dermatology PA, Lutherville-Timonium, Maryland, USA
*Correspondence author: Edward M Klepper, Robinson and Max Dermatology PA, Lutherville-Timonium, Maryland, USA; Email: [email protected]
Published Date: 14-03-2024
Copyright© 2024 by Klepper EM, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Cutaneous drug reactions come in many different morphologies, distributions and severities ranging from pruritus and erythema to diffuse epidermal denudation requiring hospitalization. The wide variety of presentations and medications responsible make identification and elimination of the offending agent difficult. Here these authors present a review of the common morphologic drug eruptions and their offending drugs.
Keywords: DRESS; Erythema Multiforme; Erythema Nodosum; Lichenoid; Morbilliform; Urticaria, Morphology; Bullous; Erosive; Fixed; Follicular; Pigmentation; Photo; Stevens-Johnsons; Drug Eruption; Sulfonamides; NSAIDs; Anticonvulsants; Monoclonal Antibody
Introduction
There has been an exponential rise in reportable drug eruptions over the last decade [1]. This is partly due to multiple new drug releases, as well as over prescribing of oral antibiotics [2]. Previous reviews have been extremely helpful in providing the necessary information to healthcare professionals. Our goal is to help the practicing clinicians in outpatient and inpatient medicine to determine rapidly by patterns and clinical morphology the associated list of drugs that are implicated in causation.
We have delineated the following morphologic patterns: Acral, bullous, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), erosive, Erythema Multiforme (EM), Erythema Nodosum (EN), Fixed (FD), follicular, hypopigmentation/hyperpigmentation, lichenoid, morbilliform/maculopapular, Photo Drug (PD), pustular, Stevens-Johnson Syndrome (SJS), Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Overlap (SJS/TEN), Toxic Epidermal Necrolysis (TEN) and urticarial. The clinical descriptions for each morphological drug induced pattern is delineated below in Table 1 [3-25].
What follows is a rapid way to pair a clinical morphology with an associated drug eruption. The chart below will list the drugs most frequently reported in the literature and the chart that follows it represents the compilation of reviews over the last five years of the delineated morphologies and their most commonly associated drugs.
Morphology | Clinical Characteristics |
Acral | Distally distributed eruptions of the hands, feet, nails and ears. |
Bullous | Fluid filled blister larger than 1 centimeter. |
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) | Drug reaction with eosinophilia and systemic symptoms mainly appear with an extensive morbilliform rash but can also appear eczematous, pustular, or exfoliative |
Erosive | Erythematous sloughing denuded eruption |
Erythema Multiforme (EM) | Targetoid annular erythematous macules of varying sizes less than or equal to 1 cm |
Erythema Nodosum (EN) | Solitary or multiple erythematous nodules usually localized to extremities |
Fixed Drug (FD) | Localized erythematous, usually annular, patch or plaque which can also appear as a solitary bullous eruption |
Follicular | Commonly presents as multiple erythematous papules surrounding hair follicles in a truncal pattern, but is not limited to that distribution |
Hyperpigmentation | Hyperpigmentation presents as increased pigment such as brown, darker brown, violaceous, salmon-colored, blue-gray, tan, or intense pigmentation such as black coloration |
Hypopigmentation | Hypopigmentation presents as diminished pigment presenting either as white or lighter pigmentation |
Lichenoid | Usually symmetric, erythematous or violaceous, pruritic papules/plaques on the trunk and extremities |
Morbilliform/Maculopapular | Wide-spread truncal erythematous macules and papules |
Photo Drug (PD) | Usually striking erythematous macules, patches, papules, plaques distributed in sun exposed areas with sharp cut-offs where clothing abuts via neck, dorsum of hands and forearms |
Pustular | Pus-filled papules surrounding hair follicles, but can be non-follicular, in crops |
Stevens Johnson Syndrome (SJS) | SJS is sometimes called erythema multiforme major. SJS has multiple erythematous and dusky macules and patches on the trunk, palms and soles with conjunctival erythema or erosions, along with oral, genital, or other mucosal erosions. Often involving 5-10% or more of body surface area |
SJS/TEN | Overlap of each morphology above and below |
Toxic Epidermal Necrolysis (TEN) | Erythematous or dusky violaceous and erythematous sheets of denuding epidermis often involving greater than 10% body surface area |
Urticarial | May appear as erythematous papules or plaques with a wheal-like or erythematous border |
Table 1: Morphologies and clinical characteristics [3-11].
Material and Method
We performed a literature review using PubMed. Thirteen researchers reviewed English, full text, open-access, peer-reviewed meta-analyses, reviews and systematic review articles that were published within the last five years using our specific search terms and inclusion/exclusion criteria. The search was conducted utilizing the morphologic search term and the term “drug eruption” to find and identify the included articles. The title and abstracts were screened for relevance. Articles written prior to five years ago and not in English were excluded. Case reports were excluded due to the lack of quantifiable research. Purpuric drug eruptions were excluded due to the high association with underlying illnesses such as vasculitis. Vaccines were excluded. There was a total of 98 articles included and 8 excluded due to containing vaccines as a causative agent. Each article that was identified, was reviewed and data was extracted. This review was conducted from 2 January 2024 through 25 January 2024 [26,27].
Results
The results include Table 2, Fig.1,2 which are displayed below. Table 2 shows the included drug eruption morphologies with their implicated drug classes and drugs. For better understanding, hand drawn sketches were included in Table 2 to allow the reader to associate the morphology with its appearance. A bar chart (Fig. 1) and pie chart (Fig. 2) are illustrated to represent the patterns found in our research regarding the most offending agents for each morphology and the morphologies that had the most drug classes associated with them [27-104].
Morphology | Implicated Drug Classes | Commonly Implicated Drugs | Appearance |
Acral | – Antineoplastics (Antimicrotubule taxanes, tyrosine kinase inhibitors) | – Docetaxel – Imatinib – Nilotinib |
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Bullous | – Analgesics – Angiotensin Converting Enzyme Inhibitors (ACEI) -Angiotensin Receptor Blockers (ARBs) – Antiarrhythmics – Antibiotics (Beta lactams, cephalosporins, nitroimidazoles, quinolones, rifamycins, sulfonamides) – Anticonvulsants – Anti-manics – Antimetabolites – Antivirals – Calcium Channel Blockers (CCBs) – Corticosteroids – Cytokines – Disease-Modifying Antirheumatic Drugs (DMARDs) – Granulocyte-Colony Stimulating Factor (G-CSF) inhibitors – Immunosuppressants – Loop Diuretics – Monoclonal Antibodies – Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) – Statins – Sulfonylureas – Tumor Necrosis Factor Inhibitors (TNF) – Xanthine Oxidase Inhibitors | – Acetaminophen – Buprenorphine – Captopril – Candesartan – Amiodarone – Amoxicillin-clavulanate – Amoxicillin – Ampicillin-sulbactam – Ceftriaxone – Cefuroxime axetil – Cotrimoxazole – Metronidazole – Moxifloxacin – Penicillin – Piperacillin-tazobactam – Rifampicin – Trimethoprim-Sulfamethoxazole (TMP-SMX) – Vancomycin – Carbamazepine – Phenytoin – Vigabatrin – Lithium – Gemcitabine – Entecavir – Interferon-α 2a – Amlodipine – Verapamil – Prednisone – Interferon γ / Interleukin 2 – Sulfasalazine – Filgrastim – Cyclosporine – Furosemide – Atezolizumab – Avelumab – Cemiplimab – Durvalumab – Ipilimumab – Nivolumab – Pembrolizumab – Diclofenac – Ketoprofen – Metamizole – Naproxen – Piroxicam – Atorvastatin – Somatostatin – Glibenclamide – Infliximab – Allopurinol |
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Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) | – Antiarrhythmics – Antibiotics (nitroimidazoles, penicillins, sulfonamides) – Anticoagulants – Anticonvulsants – Antidiabetics – Antifungals – Antimalarials – Antituberculars – Antivirals – DMARDs – Erythropoiesis-Stimulating Agents (ESAs) – Histamine antagonist – Monoclonal antibodies – Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) – NSAIDs – Proton Pump Inhibitors (PPIs) – Statins – Tricyclic antidepressants – Tyrosine Kinase Inhibitors – Xanthine Oxidase Inhibitors | – Mexiletine – Amoxicillin – Amoxicillin-clavulanic acid – Ampicillin – Ampicillin/sulbactam – Azithromycin – Benznidazole – Cefadroxil – Cefepime – Cefixime – Cefotaxime – Ceftazidime – Clindamycin – Dapsone – Imipenem – Levofloxacin – Linezolid – Meropenem – Metronidazole – Minocycline – Piperacillin/tazobactam – Streptomycin – Teicoplanin – TMP-SMX – Vancomycin – Rivaroxaban – Carbamazepine – Ethosuximide – Gabapentin – Lamotrigine – Oxcarbazepine – Phenobarbital – Phenytoin – Valproate – Zonisamide – Sitagliptin – Voriconazole – Hydroxychloroquine – Quinine – Ethambutol – Isoniazid – Pyrazinamide – Rifampin – Boceprevir – Telaprevir – Sulfasalazine – Epoetin alfa – Ranitidine – Daclizumab – Abacavir – Nevirapine – Aspirin – Celecoxib – Diclofenac – Ibuprofen – Piroxicam – Esomeprazole – Omeprazole – Atorvastatin – Amitriptyline – Imatinib – Sorafenib – Vemurafenib – Allopurinol | |
Erosive | – Antibiotics (ß lactams, cephalosporins, macrolides, quinolones, sulfonamides, tetracyclines) – Anticonvulsants – DMARDs – NNRTIs – NSAIDs – Xanthine Oxidase Inhibitors | – Cotrimoxazole – Carbamazepine – Lamotrigine – Phenobarbital – Phenytoin – Sulfasalazine – Nevirapine – Diclofenac – Meloxicam – Allopurinol | |
Erythema Multiforme (EM) | – Angiotensin converting enzyme inhibitors – Antibiotics (ß lactams, sulfonamides) – Anticonvulsants – Antifungals – Antimalarials – Antimetabolites – Antineoplastics – Interleukin-6 (IL-6) receptor inhibitor – Monoclonal Antibodies – Mucolytics – NSAIDs – Statins | – Lisinopril – Doxycycline – Carbamazepine – Phenobarbital – Phenytoin – Valproate – Itraconazole – Terbinafine – Hydroxychloroquine – Fluorouracil – Actinomycin D – Paclitaxel – Tocilizumab – Sintilimab – Ambroxol – Bromhexine – Ketoprofen – Naproxen – Phenylbutazone – Pravastatin – Simvastatin | |
Erythema Nodosum (EN) | – Angiotensin converting enzyme inhibitors – Antibiotics (aminoglycosides, cephalosporins, sulfonamides) – Anticonvulsants – Antidepressants – Angiotensin receptor blockers – Aromatase Inhibitors – Bromides – Gold Salts – Leukotriene Inhibitors – Oral Contraceptives – PPIs | – Amoxicillin – Ampicillin – Ciprofloxacin – Cotrimoxazole – Minocycline – Nitrofurantoin – Penicillin – Streptomycin – Carbamazepine – Hydantoin – Fluoxetine – Montelukast – Norethindrone – Norgestimate – Levonorgestrel – Omeprazole | |
Fixed Drug (FD) | – Antibiotics (Penicillins, Nitroimidazoles, Sulfonamides, Tetracyclines) – Antimalarials – Barbiturates – NSAIDs – Oral Contraceptives | – Amoxicillin – Doxycycline – Metronidazole – Penicillin – TMP-SMX – Quinine – Phenobarbital – Ibuprofen – Celecoxib – Naproxen – Ethinyl estradiol – Medroxyprogesterone acetate – Norethindrone acetate | |
Follicular | – Antibiotics (Macrolides, Penicillins) – Anticonvulsants – Antidepressants – Antifungals – Antimalarials – Antimanic – Antipsychotics – Antituberculars – Corticosteroids – Epidermal Growth Factor Receptor Inhibitors – NSAIDs – TNF Inhibitors | – Nystatin – Carbamazepine – Phenytoin – Fluoxetine – Paroxetine – Sertraline – Itraconazole – Hydroxychloroquine – Lithium – Olanzapine – Isoniazid – Corticotropin – Dacomitinib – Gefitinib – Naproxen – Infliximab | |
Hyperpigmentation | – Antiarrhythmics – Antibiotics (Tetracyclines) – Anticoagulants – Anticonvulsants – Antimalarials – Antimetabolites – Antimicrobials – Antineoplastics
– Antipsychotics – Cytotoxics – Heavy Metals – NRTIs – NSAIDs – Statins – Xanthine Oxidase Inhibitors | – Amiodarone – Minocycline – Carbamazepine – Chlorpromazine – Lamotrigine – Phenytoin – Chloroquine – Hydroxychloroquine – 5-fluorouracil – Clofazimine – Cyclophosphamide – Docetaxel – Doxorubicin – Ifosfamide – Melphalan – Paclitaxel – Thiotepa – Chlorpromazine – Desipramine – Imipramine – Bleomycin – Busulfan – Cyclophosphamide – Gold – Silver – Zidovudine – Aspirin – Ibuprofen – Meloxicam – Paracetamol – Simvastatin – Allopurinol | |
Hypopigmentation | – Immune Response Modifiers – Monoclonal Antibodies | – Imiquimod – Atezolizumab – Avelumab – Durvalumab – Ipilimumab – Nivolumab – Pembrolizumab | |
Lichenoid | – Angiotensin converting enzyme inhibitors – Antibiotics – Anticonvulsants – Antihypertensives – Antineoplastics – Antivirals – Calcium Channel Blockers – Diuretics – Monoclonal Antibodies – NSAIDs | – Captopril – Enalapril – Sulfamethoxazole – Carbamazepine – Phenytoin – Methyldopa – Ponatinib – Acyclovir – Nifedipine – Furosemide – Hydrochlorothiazide – Dupilumab – Mogamulizumab – Nivolumab – Rituximab – Ibuprofen – Naproxen | |
Morbilliform/ Maculopapular | – Androgen Receptor Signaling Inhibitors – Antibiotics (Beta lactams, cephalosporins, sulfonamides) – Anticonvulsants – Antimalarials – Antivirals – Monoclonal Antibodies – NSAIDs – Tyrosine Kinase Inhibitors | – Apalutamide – Amoxicillin – Penicillin – TMP-SMX – Carbamazepine – Lamotrigine – Phenobarbital – Phenytoin – Hydroxychloroquine – Dasabuvir – Ombitasvir – Paritaprevir – Simeprevir – Cemiplimab – Daclizumab – Ibalizumab‐uk – Ipilimumab – Nivolumab – Pembrolizumab – Siltuximab – Oxicam types (i.e meloxicam) – Fostamatinib | |
Photo Drug (PD) | – Angiotensin converting enzyme inhibitors – Antiarrhythmics – Antibiotics (fluoroquinolones, sulfonamides, tetracyclines) – Antifungals – Antimalarials – Antimetabolites – Antineoplastics – Antipsychotics – Antituberculars – Antivirals – CCBs – NNRTIs – NSAIDs – Thiazide diuretics | – Enalapril – Quinapril – Ramipril – Amiodarone – Cefotaxime – Ceftazidime – Dapsone – Doxycycline – Lymecycline – Minocycline – Nalidixic acid – TMP-SMX – Griseofulvin – Itraconazole – Ketoconazole – Terbinafine – Voriconazole – Hydroxychloroquine – Fluorouracil – Paclitaxel – Chlorpromazine – Isoniazid – Pyrazinamide – Sofosbuvir-Velpatasvir – Diltiazem – Efavirenz – Benoxaprofen – Ibuprofen – Ketoprofen – Naproxen – Tiaprofenic acid – Hydrochlorothiazide | |
Pustular | – Antibiotics (ß-lactams, macrolides, quinolones, sulfonamides) – Antifungals – Antimalarials – CCBs – Tyrosine Kinase Inhibitors | – Amoxicillin – Ampicillin – Pristinamycin – TMP-SMX – Terbinafine – Hydroxychloroquine – Diltiazem – Gefitinib | |
Stevens Johnson Syndrome (SJS) | – Antibiotics (ß lactams, cephalosporins, fluoroquinolones, sulfonamides) – Anticonvulsants – Antituberculars – DMARDs – Monoclonal antibodies – NRTIs – NSAIDs – Xanthine Oxidase Inhibitors | – Amoxicillin – Azithromycin – Cefotaxime – Doxycycline – Erythromycin – TMP-SMX – Vancomycin – Carbamazepine – Lamotrigine – Levetiracetam – Phenobarbital – Phenytoin – Valproic acid – Isoniazid – Rifampicin – Sulfasalazine – Nivolumab – Pembrolizumab – Abacavir – Nevirapine – Meloxicam – Allopurinol | |
SJS/TEN | – Antibiotics (ß lactams, cephalosporins, fluoroquinolones, macrolides, sulfonamides, tetracyclines) – Anticonvulsants – Antituberculars – DMARDs – Monoclonal antibodies – NRTIs – NSAIDs – Xanthine Oxidase Inhibitors | – Amoxicillin – Azithromycin – Cefotaxime – Doxycycline – Erythromycin – TMP-SMX – Vancomycin – Carbamazepine – Lamotrigine – Levetiracetam – Phenobarbital – Phenytoin – Valproic acid – Isoniazid – Rifampicin – Sulfasalazine – Nivolumab – Pembrolizumab – Abacavir – Nevirapine – Meloxicam – Allopurinol | See above and below |
Toxic Epidermal Necrolysis (TEN) | – Antibiotics (fluoroquinolones, sulfonamides, tetracyclines) – Antivirals – Anticonvulsants – DMARDs – NNRTIs – NSAIDs – Xanthine Oxidase Inhibitors | – Cotrimoxazole – Acyclovir – Carbamazepine – Lamotrigine – Phenobarbital – Phenytoin – Sulfasalazine – Nevirapine – Meloxicam – Allopurinol | |
Urticarial | – Angiotensin converting enzyme inhibitors – Antibiotics (aminoglycosides, ß lactams, cephalosporins, macrolides, penicillins, sulfonamides) – Anticonvulsants – Antifungals – Antimalarials – NSAIDs – Opioids – Oral contraceptives | – Captopril – Lisinopril – Ramipril – Azithromycin – Clarithromycin – Erythromycin – Gentamicin (IV) – Neomycin (topical) – Penicillin – Tobramycin (IV & Inhaled) – Phenytoin – Terbinafine – Hydroxychloroquine – Aspirin – Celecoxib – Diclofenac – Codeine – Morphine – Levonorgestrel – Levonorgestrel/ethinyl estradiol |
Table 2: Categorization of drug eruptions with implicated drug classes and generic drug names with associated morphologic pattern [8-105].
Figure 1: Graphical representation of which drug classes were the most associated with each morphological drug eruption [7-105].
Figure 2: Graphical representation of how many drug classes were associated with each morphological drug eruption [7-105].
Discussion
The morphologies and distributions of these drug eruptions vary significantly (Table 1) but understanding how they present and their cause is crucial for the practicing clinician. Some patients require more medications than others and determining the offending agent amongst a long medication list can be difficult. Discontinuing all medications and reinstituting one medication at a time, to find the offending medication, is not always a reasonable option for patients either. Here is a discussion of each morphology and the most common responsible drugs reviewed in the literature to aid the clinician in identifying the offending agents.
Our research showed that out of the 46 total drug classes, 10 of them were highly associated with most of the morphologies (Fig. 1). These drug classes included antibiotics, anticonvulsants, antifungals, antineoplastics, antituberculars, antivirals, monoclonal antibodies, NSAIDs, oral contraceptives and xanthine oxidase inhibitors. Once data was compiled, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), sulfonamide antibiotics and anticonvulsants were the most commonly associated offenders for most morphologies (Table 2). Of all the offending drug classes, antibiotics appeared to be at the top of the list, but strikingly enough, NSAIDs were very close behind.
Interestingly, for the acral drug eruption morphology, there was extreme localization to antineoplastics, specifically antimicrotubule taxanes and tyrosine kinase inhibitors. Bullous drug eruptions have the highest number of implicated drug classes, 22, followed by Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) with 20, hyperpigmentation with 15, photo drug with 14 and erythema multiforme and follicular with 12 (Fig. 2). Specific drugs that were shown to have a high causative association with bullous eruptions included acetaminophen, cotrimoxazole, carbamazepine, metamizole and allopurinol. Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has the second highest number of implicated drug classes with sulfonamides, anticonvulsants, antituberculars, antivirals and xanthine oxidase inhibitors being the biggest culprits. Erosive drug eruptions had extreme localization to anticonvulsants such as carbamazepine, lamotrigine, phenobarbital and phenytoin. Erythema Multiforme (EM) was closely associated with sulfonamides, anticonvulsants and NSAIDs. Erythema Nodosum (EN) had high associations with antibiotics in the cephalosporin and penicillin classes, as well as oral contraceptives.
Fixed Drug (FD) eruptions were seen to also have close ties with oral contraceptives as causative agents, as well as NSAIDs and sulfonamides like Trimethoprim/Sulfamethoxazole (TMP-SMX). Follicular drug eruptions had 12 associated drug classes with some of the most common contributors being antibiotics, anticonvulsants, antifungals, epidermal growth factor receptor inhibitors and NSAIDs. Hyperpigmentation eruptions were implicated by 14 drug classes and amongst those, amiodarone, minocycline, chlorpromazine, phenytoin, cyclophosphamide, chlorpromazine and allopurinol were the drugs that had the highest association with this eruption. Hypopigmentation eruptions were not found to have many associated drug classes but did have a strong localization to monoclonal antibodies.
Interestingly, lichenoid drug eruptions had many cardiovascular drugs associated with it such as captopril, enalapril, methyldopa, nifedipine, furosemide and hydrochlorothiazide. As well, monoclonal antibodies such as nivolumab and rituximab were strong causative agents. Morbilliform rashes were strongly associated with antibiotics, anticonvulsants, antivirals and monoclonal antibodies, with over 3 implicated drugs in each of those classes. Photo Drug Eruptions (PDE) had solid correlations to tetracyclines, specifically doxycycline, but the most implicated drugs included TMP-SMX, voriconazole, isoniazid, pyrazinamide, efavirenz and naproxen. Pustular drug eruptions were seen to be implicated by 5 drug classes including antibiotics, antifungals, antimalarials, calcium channel blockers and tyrosine kinase inhibitors.
Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) shared many of the same drug classes and drugs as causative agents, amongst the most popular were antibiotics, specifically TMP-SMX, anticonvulsants such as carbamazepine and lamotrigine, NSAIDS like meloxicam and Xanthine Oxidase Inhibitors such as allopurinol. Urticarial eruptions were strongly associated with antibiotics such as penicillins and sulfonamides. This drug eruption was also seen to be tied to anticonvulsants, antifungals, antimalarials, NSAIDs, opioids and oral contraceptives. There were overlaps in the review between erythema multiforme, SJS and TEN. The reader will realize that there were four groupings associated with these morphologies because in multiple reviews they were separated and in others they were paired. Although this may be a redundancy, this avoids missing important trends in particular manifestations of drug eruptions [104,105]. Over the last five years, many new drugs and drug classes have been introduced which makes it necessary to update correlation between these drugs and drug eruptions by morphology. The reason we associate the morphology with the drug eruption was to help all healthcare providers rapidly correlate clinical situations and determine a shorter list of probable offending agents.
Conclusion
The drugs that appear within this review represent what has been historically documented along with the newer antineoplastic and biologics. We predict that more eruptions will be linked to these classes of drugs as they are increasingly utilized. We believe that these reviews are necessary and should be completed approximately every five years to include new clinical experiences. The trends that we have seen, however, still implicate NSAIDs, antibiotics, specifically sulfonamides and anticonvulsants as the most offending agents.
Conflicts of Interests
The authors declare that there is no conflict of interest for this paper.
References
- Broyles AD, Banerji A, Castells M. Practical guidance for the evaluation and management of drug hypersensitivity: general concepts. The J Allergy and Clinical Immunol: In Practice. 2020;8(9):S3-15.
- Llor C, Bjerrum L. Antimicrobial resistance: risk associated with antibiotic overuse and initiatives to reduce the problem. Ther Adv Drug Saf. 2014;5(6):229-41.
- Maul JT, Guillet C, Oschmann A, Maul LV, Meier-Schiesser B, Stadler PC, et al. Cutaneous lichenoid drug eruptions: A narrative review evaluating demographics, clinical features and culprit medications. J Eur Acad Dermatol Venereol. 2023;37(5):965-75.
- Wu WH, Chu CY. Annular drug eruptions. Clin Dermatol. 2022;40(5):450-65.
- Hoetzenecker W, Nägeli M, Mehra ET, Jensen AN, Saulite I, Schmid-Grendelmeier P, et al. Adverse cutaneous drug eruptions: current understanding. Semin Immunopathol. 2016;38(1):75-86.
- Flowers H, Brodell R, Brents M, Wyatt JP. Fixed drug eruptions: presentation, diagnosis and management. South Med J. 2014;107(11):724-7.
- Geisler AN, Phillips GS, Barrios DM, Wu J, Leung DYM, Moy AP, et al. Immune checkpoint inhibitor-related dermatologic adverse events. J Am Acad Dermatol. 2020;83(5):1255-68.
- Khaddour K, Singh V, Shayuk M. Acral vascular necrosis associated with immune-check point inhibitors: case report with literature review. BMC Cancer. 2019;19(1):449.
- Pérez-Garza DM, Chavez-Alvarez S, Ocampo-Candiani J, Gomez-Flores M. Erythema nodosum: a practical approach and diagnostic algorithm. Am J Clin Dermatol. 2021;22(3):367-78.
- Giménez García RM, Carrasco Molina S. Drug-induced hyperpigmentation: review and case series. J Am Board Fam Med. 2019;32(4):628-38.
- Lozzi F, Di Raimondo C, Lanna C, Diluvio L, Mazzilli S, Garofalo V, et al. Latest evidence regarding the effects of photosensitive drugs on the skin: pathogenetic mechanisms and clinical manifestations. Pharmaceutics. 2020;12(11):1104.
- Zaiem A, Hammamia SB, Aouinti I, Charfi O, Ladhari W, Kastalli S, et al. Hand-foot syndrome induced by chemotherapy drug: Case series study and literature review. Indian J Pharmacol. 2022;54(3):208-15.
- Teixido C, Castillo P, Martinez-Vila C, Arance A, Alos L. Molecular markers and targets in melanoma. cells. 2021;10(9):2320
- Carvalho LAD, Aguiar FC, Smalley KSM, Possik PA. Acral melanoma: new insights into the immune and genomic landscape. Neoplasia. 2023;46:100947.
- Jung S, Johnson DB. Management of acral and mucosal melanoma: medical oncology perspective. Oncologist. 2022;27(8):703-10.
- Kichina JV, Maslov A, Kandel ES. PAK1 and therapy resistance in melanoma. Cells. 2023;12(19):2373.
- Ito T, Hashimoto H, Kaku-Ito Y, Tanaka Y, Nakahara T. Nail apparatus melanoma: current management and future perspectives. J Clin Med. 2023;12(6):2203.
- Pham DDM, Guhan S, Tsao H. KIT and melanoma: biological insights and clinical implications. Yonsei Med J. 2020;61(7):562-71.
- Mockenhaupt M. Bullous drug reactions. Acta Derm Venereol. 2020;100(5):adv00057.
- Temiz SA, Özer İ, Ataseven A, Fındık S. A case of entecavir-associated bullous fixed drug eruption and a review of literature. Turk J Gastroenterol. 2019;30(3):299-302.
- Aoyama Y, Sugiyama S, Yamamoto T. Anti-cytomegalovirus therapy: whether and when to initiate, those are the questions. Pharmaceuticals (Basel). 2022;15(7):797.
- Lammer J, Hein R, Roenneberg S, Biedermann T, Volz T. Drug-induced linear IgA bullous dermatosis: a case report and review of the literature. Acta Derm Venereol. 2019;99(6):508-15.
- Kuo AM, Markova A. High grade dermatologic adverse events associated with immune checkpoint blockade for cancer. Front Med (Lausanne). 2022;9:898790.
- Bellinato F, Maurelli M, Gisondi P, Girolomoni G. Cutaneous adverse reactions associated with SARS-CoV-2 vaccines. J Clin Med. 2021;10(22):5344.
- Sarcina D, Giovannini M, Oranges T, Barni S, Pedaci FA, Liccioli G, et al. Case report and review of the literature: bullous skin eruption after the booster-dose of influenza vaccine in a pediatric patient with polymorphic maculopapular cutaneous mastocytosis. Front Immunol. 2021;12:688364.
- Calle AM, Aguirre N, Ardila JC, Cardona Villa R. DRESS syndrome: A literature review and treatment algorithm. World Allergy Organ J. 2023;16(3):100673.
- Ramirez GA, Ripa M, Burastero S, Benanti G, Bagnasco D, Nannipieri S, et al. Drug reaction with eosinophilia and systemic symptoms (dress): focus on the pathophysiological and diagnostic role of viruses. Microorganisms. 2023;11(2):346.
- Schunkert EM, Divito SJ. Updates and insights in the diagnosis and management of DRESS Syndrome. Curr Dermatol Rep. 2021;10(4):192-204.
- Sharifzadeh S, Mohammadpour AH, Tavanaee A, Elyasi S. Antibacterial antibiotic-induced Drug Reaction with Eosinophilia And Systemic symptoms (DRESS) syndrome: a literature review. Eur J Clin Pharmacol. 2021;77(3):275-89.
- Stirton H, Shear NH, Dodiuk-Gad RP. Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS)/Drug-Induced Hypersensitivity Syndrome (DiHS)-Readdressing the DReSS. Biomedicines. 2022;10(5):999.
- Shiohara T, Mizukawa Y. Drug-induced Hypersensitivity Syndrome (DiHS)/drug reaction with eosinophilia and systemic symptoms (DRESS): An update in 2019. Allergol Int. 2019;68(3):301-8.
- Fakih A, Goens J, Grozdev I, Dangoisse C, Richert B. Acne fulminans induced by a low dose isotretinoin: case report and review of the literature. Dermatol Online J. 2020;26(12):130.
- Soares A, Sokumbi O. Recent updates in the treatment of erythema multiforme. Medicina (Kaunas). 2021;57(9):921.
- Zhang M, Wu R, Jia M, Sun S, Zhang L, Tang T. Sintilimab-induced erythema multiforme drug eruption in the treatment of sigmoid colon cancer: A case report and literature review. Medicine (Baltimore). 2023 102(41):e35659.
- Wang S, Li T, Wang Y, Wang M, Liu Y, Zhang X, et al. 5-Fluorouracil and actinomycin D lead to erythema multiforme drug eruption in chemotherapy of invasive mole: Case report and literature review. Medicine (Baltimore). 2022;101(47):e31678
- Di Bartolomeo L, Irrera N, Campo GM, Borgia F, Motolese A, Vaccaro F, et al. Drug-induced photosensitivity: clinical types of phototoxicity and photoallergy and pathogenetic mechanisms. Front Allergy. 2022;3:876695.
- Blaess M, Kaiser L, Sommerfeld O, Csuk R, Deigner HP. Drug triggered pruritus, rash, papules and blisters – is AGEP a clash of an altered sphingolipid-metabolism and lysosomotropism of drugs accumulating in the skin? Lipids Health Dis. 2021;20(1):156.
- Mashayekhi F, Seirafianpour F, Pour Mohammad A, Goodarzi A. Severe and life-threatening COVID-19-related mucocutaneous eruptions: A systematic review. Int J Clin Pract. 2021;75(12):e14720.
- Jansen FM, Vavricka SR, den Broeder AA, de Jong EM, Hoentjen F, van Dop WA. Clinical management of the most common extra-intestinal manifestations in patients with inflammatory bowel disease focused on the joints, skin and eyes. United European Gastroenterol J. 2020;8(9):1031-44.
- Wermuth HR, Badri T, Takov V. Montelukast. Treasure Island (FL): StatPearls Publishing; 2024 .
- Winfrey OK, Farahzad MM, Quint EH. 104. Erythema nodosum following hormonal contraceptive use. J Pediatric and Adolescent Gynecol. 2023;36(2):218.
- Elsawah HK, Elsokary MA, Elrazzaz MG, Elshafie AH. Hydroxychloroquine for treatment of nonsevere COVID-19 patients: Systematic review and meta-analysis of controlled clinical trials. J Med Virol. 2021;93(3):1265-75.
- Del Pozzo-Magaña BR, Liy-Wong C. Drugs and the skin: A concise review of cutaneous adverse drug reactions. Br J Clin Pharmacol. 2022.
- Ferreira C, Corrales T, Guilherme A. Fixed drug eruption on the tongue due to naproxen. J Investig Allergol Clin Immunol. 2020;30(5):358-9.
- Peter J, Choshi P, Lehloenya RJ. Drug hypersensitivity in HIV infection. Curr Opin Allergy Clin Immunol. 2019;19(4):272-82.
- Dilley M, Geng B. Immediate and delayed hypersensitivity reactions to antibiotics: aminoglycosides, clindamycin, linezolid and metronidazole. Clin Rev Allergy Immunol. 2022;62(3):463-75.
- Panda PK, Panda P, Dawman L, Sihag RK, Sharawat IK. Efficacy and safety of thalidomide in patients with complicated central nervous system tuberculosis: a systematic review and meta-analysis. Am J Trop Med Hyg. 2021;105(4):1024-30.
- Huang S, Li D, Zhuang L, Sun L, Wu J. A meta-analysis of the efficacy and safety of adjuvant sorafenib for hepatocellular carcinoma after resection. World J Surg Oncol. 2021;19(1):168.
- Xian F, Wu J, Yuan YL, Bie J, Xu GH. Efficacy and safety of PD1/PDL1 inhibitors combined with radiotherapy and antiangiogenic drugs for hepatocellular carcinoma: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2023;27(4):1494-502.
- Anderson HJ, Lee JB. A Review of fixed drug eruption with a special focus on generalized bullous fixed drug eruption. Medicina (Kaunas). 2021;57(9):925.
- Long CY, Wong N, Burns A. Fixed drug eruption to trimethoprim-sulfamethoxazole and doxycycline. Cureus. 2021;13(4):e14502.
- Chamorro-Pareja N, Carrillo-Martin I, Haehn DA, Gonzalez-Estrada A. Documented exogenous progesterone hypersensitivity related to the use of combined oral contraceptive. BMJ Case Rep. 2019;12(9):e230416.
- Patel K, Cervantes JA, Keeling B, Adamson AS. A fixed drug eruption to medroxyprogesterone acetate injectable suspension. Cutis. 2022;109(3):E12-4.
- Parisi R, Shah H, Navarini AA, Muehleisen B, Ziv M, Shear NH, et al. Acute generalized exanthematous pustulosis: clinical features, differential diagnosis and management. Am J Clin Dermatol. 2023;24(4):557-575.
- Godi SM, Singh LK. Escitalopram-induced skin rash: dermatitis medicamentosa. Indian J Dermatol. 2022;67(1):93.
- Goldberger T, Benshushan S, Davidovics Z, Wilschanski M, Molho-Pessach V. Tumor necrosis factor-α inhibitor-induced follicular psoriasiform eruption. Pediatr Dermatol. 2022;39(4):598-600.
- Iwasaku M, Uchino J, Chibana K, Tanzawa S, Yamada T, Tobino K, et al. Prophylactic treatment of dacomitinib-induced skin toxicities in epidermal growth factor receptor-mutated non-small-cell lung cancer: A multicenter, Phase II trial. Cancer Med. 2023;12(14):15117-27.
- Nair PA, Saleh HM, Salazar FJ. Acneiform eruptions. Treasure Island (FL): StatPearls Publishing. 2024.
- Ran D, Wang N, Bao F, Liu Y, Zhou G, Zhou S, et al. Carbamazepine-induced follicular mucinosis-like drug eruption. Indian J Dermatol Venereol Leprol. 2022;88(6):826-8.
- Ellis SR, Vierra AT, Millsop JW, Lacouture ME, Kiuru M. Dermatologic toxicities to immune checkpoint inhibitor therapy: A review of histopathologic features. J Am Acad Dermatol. 2020;83(4):1130-43.
- Yu H, Cen J, Lin X, Cheng H, Seifert O. Imiquimod induced vitiligo-like lesions-A consequence of modified melanocyte function. Immun Inflamm Dis. 2022;10(1):70-7.
- Hassan S, Zhou XA. Drug-Induced Pigmentation. Treasure Island (FL): StatPearls Publishing; 2024.
- Cohen PR, Erickson CP, Calame A. Terbinafine-induced lichenoid drug eruption: case report and review of terbinafine-associated cutaneous adverse events. Dermatol Online J. 2020;26(7):13030.
- Marques LC, de Medeiros Nunes da Silva LA, Santos PPM, de Almeida Lima Borba Lopes A, Cunha KS, Milagres A, et al. Oral lichenoid lesion in association with chemotherapy treatment for non-Hodgkin lymphoma or lichen planus? Review of the literature and report of two challenging cases. Head Face Med. 2022;18(1):32.
- Shah RR, Bhate C, Hernandez A, Ho CH. Lichen planus pemphigoides: A unique form of bullous and lichenoid eruptions secondary to nivolumab. Dermatol Ther. 2022;35(5):e15432.
- Trager MH, de Clippelé D, Ram-Wolff C, de Masson A, Vignon-Pennamen MD, Battistella M, et al. Mogamulizumab-induced Mucocutaneous Lichenoid Reaction: A Case Report and Short Review. Acta Derm Venereol. 2020;100(10):adv00158.
- Ranugha PSS, Betkerur JB. Antihypertensives in dermatology Part II – Cutaneous adverse reactions to antihypertensives. Indian J Dermatol Venereol Leprol. 2018;84(2):137-47.
- Teigen IA, Sæle AKM, Reikvam H. A patient with maculopapular rash and lichenoid skin damage caused by ponatinib. J Int Med Res. 2020;48(4):300060520903660.
- Chen CH, Yu HS, Yu S. Cutaneous adverse events associated with immune checkpoint inhibitors: a review article. Curr Oncol. 2022;29(4):2871-86.
- Copaescu AM, Ben-Shoshan M, Trubiano JA. Tools to improve the diagnosis and management of T-cell mediated adverse drug reactions. Front Med (Lausanne). 2022;9:923991.
- Fouda GE, Bavbek S. Rituximab hypersensitivity: from clinical presentation to management. Front Pharmacol. 2020;11:572863.
- Geisler AN, Phillips GS, Barrios DM, Wu J, Leung DYM, Moy AP, et al. Immune checkpoint inhibitor-related dermatologic adverse events. J Am Acad Dermatol. 2020;83(5):1255-68.
- Giles A, Foushee J, Lantz E, Gumina G. Sulfonamide allergies. Pharmacy (Basel). 2019;7(3):132.
- Gisondi P, Piaserico S, Bordin C, Bellinato F, Tozzi F, Alaibac M, et al. The safety profile of hydroxychloroquine: major cutaneous and extracutaneous adverse events. Clin Exp Rheumatol. 2021;39(5):1099-107.
- Katayama H, Saeki H, Osada SI. Maculopapular drug eruption caused by apalutamide: case report and review of the literature. J Nippon Med Sch. 2022;89(5):550-4.
- Khan DA, Banerji A, Bernstein JA, Bilgicer B, Blumenthal K, Castells M, et al. Cephalosporin allergy: current understanding and future challenges. J Allergy Clin Immunol Pract. 2019;7(7):2105-14.
- Macklis PC, Dulmage B, Evans B, Rosenbach M, Gudjonsson JE, Kaffenberger BH. Cutaneous adverse events in newly approved FDA non-cancer drugs: a systematic review. Drugs RD. 2020;20(3):171-87.
- Si X, He C, Zhang L, Liu X, Li Y, Wang H, et al. Management of immune checkpoint inhibitor-related dermatologic adverse events. Thorac Cancer. 2020;11(2):488-92.
- Watanabe T, Yamaguchi Y. Cutaneous manifestations associated with immune checkpoint inhibitors. Front Immunol. 2023;14:1071983.
- Takenaka D, Nishizawa T. Morbilliform drug eruptions caused by trimethoprim-sulfamethoxazole. BMJ Case Rep. 2020;13(9):e238255.
- Isaacs T, Lehloenya R. HIV-associated photodermatitis in African populations. Front Allergy. 2023;4:1159387.
- Glombicki SE, Cohen PR. Sofosbuvir-velpatasvir (epclusa)-associated photosensitivity in a hepatitis C patient: case report and review of photosensitivity to hepatitis c antiviral agents. Cureus. 2021;13(7):e16496.
- Nazzaro G, Giacalone S, Bortoluzzi P, Veraldi S, Marzano AV. Erosive pustular dermatosis of the scalp induced by gefitinib: case and review of the literature. Dermatol Online J. 2021;27(2):13030.
- Ryder CY, Matthews NH, Lowe L, Wang F. A striking presentation of pustular Sweet syndrome induced by trimethoprim-sulfamethoxazole. Australas J Dermatol. 2022;63(4):e356-9.
- Schwartz RA, Janniger CK. Generalized pustular figurate erythema: A newly delineated severe cutaneous drug reaction linked with hydroxychloroquine. Dermatol Ther. 2020;33(3):e13380.
- Stadler PC, Oschmann A, Kerl-French K, Maul JT, Oppel EM, Meier-Schiesser B, et al. Acute generalized exanthematous pustulosis: clinical characteristics, pathogenesis and management. Dermatol. 2023;239(3):328-33.
- Sussman M, Napodano A, Huang S, Are A, Hsu S, Motaparthi K. Pustular psoriasis and acute generalized exanthematous pustulosis. Medicina (Kaunas). 2021;57(10):1004.
- Edinoff AN, Nguyen LH, Fitz-Gerald MJ, Crane E, Lewis K, Pierre SS, K, et al. Lamotrigine and stevens-johnson syndrome prevention. Psychopharmacol Bull. 2021;51(2):96-114.
- Fowler T, Bansal AS, Lozsádi D. Risks and management of antiepileptic drug induced skin reactions in the adult out-patient setting. Seizure. 2019;72:61-70.
- Liotti L, Caimmi S, Bottau P, Bernardini R, Cardinale F, Saretta F, et al. Clinical features, outcomes and treatment in children with drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis. Acta Biomed. 2019;90(3-S):52-60.
- Ramien M, Goldman JL. Pediatric SJS-TEN: Where are we now? F1000Res. 2020;9:F1000.
- Charlton OA, Harris V, Phan K, Mewton E, Jackson C, Cooper A. Toxic epidermal necrolysis and steven-johnson syndrome: a comprehensive review. Adv Wound Care (New Rochelle). 2020;9(7):426-39.
- Hasegawa A, Abe R. Recent advances in managing and understanding Stevens-Johnson syndrome and toxic epidermal necrolysis. F1000Res. 2020;9:F1000 Faculty Rev-612.
- Jacobsen A, Olabi B, Langley A, Beecker J, Mutter E, Shelley A, et al. Systemic interventions for treatment of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS/TEN overlap syndrome. Cochrane Database Syst Rev. 2022;3(3):CD013130.
- Lee EY, Knox C, Phillips EJ. Worldwide prevalence of antibiotic-associated Stevens-Johnson Syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA Dermatol. 2023;159(4):384-92.
- Frantz R, Huang S, Are A, Motaparthi K. Stevens-Johnson Syndrome and Toxic epidermal necrolysis: a review of diagnosis and management. Medicina (Kaunas). 2021;57(9):895.
- Jaroenpuntaruk V, Gray A. Deadly drug rashes: Early recognition and multidisciplinary care. Cleve Clin J Med. 2023;90(6):373-81.
- Kozubek P, Wołoszczak J, Gomułka K. Immune reactions in major types of oncological treatment. Int J Mol Sci. 2023;24(14):11257.
- Lo C, Nguyen S, Yang C, Witt L, Wen A, Liao TV, et al. Pharmacogenomics in Asian subpopulations and impacts on commonly prescribed medications. Clin Transl Sci. 2020;13(5):861-70.
- Singh N, Phillips M. Toxic epidermal necrolysis: a review of past and present therapeutic approaches. Skin Therapy Lett. 2022;27(5):7-13.
- Sen SS, Sil A, Chakraborty U, Chandra A. Stevens-Johnson syndrome-toxic epidermal necrolysis: a fatal cutaneous adverse reaction to oral acyclovir. BMJ Case Rep. 2020;13(8):e238555.
- Ganguli MP, Dimov V. Chronic urticaria suspected to be caused by a 13.5 mg levonorgestrel intrauterine device (Skyla®). Cureus. 2023;15(7):e42287.
- Anci E, Braun C, Marinosci A, Rodieux F, Midun E, Torres MJ, et al. Viral infections and cutaneous drug-related eruptions. Front Pharmacol. 2021;11:586407.
- Zhu LJ, Liu AY, Wong PH, Arroyo AC. Road less traveled: drug hypersensitivity to fluoroquinolones, vancomycin, tetracyclines and macrolides. Clin Rev Allergy Immunol. 2022;62(3):505-18.
- Kayiran MA, Akdeniz N. Diagnosis and treatment of urticaria in primary care. North Clin Istanb. 2019;6(1):93-9.
Article Type
Review Article
Publication History
Received Date: 16-02-2024
Accepted Date: 06-03-2024
Published Date: 14-03-2024
Copyright© 2024 by Klepper EM, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation: Klepper EM, et al. Most Common Drug Eruptions by Pattern and Drug Class: A Review. J Dermatol Res. 2024;5(1):1-18.
Figure 1: Graphical representation of which drug classes were the most associated with each morphological drug eruption [7-105].
Figure 2: Graphical representation of how many drug classes were associated with each morphological drug eruption [7-105].
Morphology | Clinical Characteristics |
Acral | Distally distributed eruptions of the hands, feet, nails and ears. |
Bullous | Fluid filled blister larger than 1 centimeter. |
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) | Drug reaction with eosinophilia and systemic symptoms mainly appear with an extensive morbilliform rash but can also appear eczematous, pustular, or exfoliative |
Erosive | Erythematous sloughing denuded eruption |
Erythema Multiforme (EM) | Targetoid annular erythematous macules of varying sizes less than or equal to 1 cm |
Erythema Nodosum (EN) | Solitary or multiple erythematous nodules usually localized to extremities |
Fixed Drug (FD) | Localized erythematous, usually annular, patch or plaque which can also appear as a solitary bullous eruption |
Follicular | Commonly presents as multiple erythematous papules surrounding hair follicles in a truncal pattern, but is not limited to that distribution |
Hyperpigmentation | Hyperpigmentation presents as increased pigment such as brown, darker brown, violaceous, salmon-colored, blue-gray, tan, or intense pigmentation such as black coloration |
Hypopigmentation | Hypopigmentation presents as diminished pigment presenting either as white or lighter pigmentation |
Lichenoid | Usually symmetric, erythematous or violaceous, pruritic papules/plaques on the trunk and extremities |
Morbilliform/Maculopapular | Wide-spread truncal erythematous macules and papules |
Photo Drug (PD) | Usually striking erythematous macules, patches, papules, plaques distributed in sun exposed areas with sharp cut-offs where clothing abuts via neck, dorsum of hands and forearms |
Pustular | Pus-filled papules surrounding hair follicles, but can be non-follicular, in crops |
Stevens Johnson Syndrome (SJS) | SJS is sometimes called erythema multiforme major. SJS has multiple erythematous and dusky macules and patches on the trunk, palms and soles with conjunctival erythema or erosions, along with oral, genital, or other mucosal erosions. Often involving 5-10% or more of body surface area |
SJS/TEN | Overlap of each morphology above and below |
Toxic Epidermal Necrolysis (TEN) | Erythematous or dusky violaceous and erythematous sheets of denuding epidermis often involving greater than 10% body surface area |
Urticarial | May appear as erythematous papules or plaques with a wheal-like or erythematous border |
Table 1: Morphologies and clinical characteristics [3-11].
Morphology | Implicated Drug Classes | Commonly Implicated Drugs | Appearance |
Acral | – Antineoplastics (Antimicrotubule taxanes, tyrosine kinase inhibitors) | – Docetaxel – Imatinib – Nilotinib |
|
Bullous | – Analgesics – Angiotensin Converting Enzyme Inhibitors (ACEI) -Angiotensin Receptor Blockers (ARBs) – Antiarrhythmics – Antibiotics (Beta lactams, cephalosporins, nitroimidazoles, quinolones, rifamycins, sulfonamides) – Anticonvulsants – Anti-manics – Antimetabolites – Antivirals – Calcium Channel Blockers (CCBs) – Corticosteroids – Cytokines – Disease-Modifying Antirheumatic Drugs (DMARDs) – Granulocyte-Colony Stimulating Factor (G-CSF) inhibitors – Immunosuppressants – Loop Diuretics – Monoclonal Antibodies – Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) – Statins – Sulfonylureas – Tumor Necrosis Factor Inhibitors (TNF) – Xanthine Oxidase Inhibitors | – Acetaminophen – Buprenorphine – Captopril – Candesartan – Amiodarone – Amoxicillin-clavulanate – Amoxicillin – Ampicillin-sulbactam – Ceftriaxone – Cefuroxime axetil – Cotrimoxazole – Metronidazole – Moxifloxacin – Penicillin – Piperacillin-tazobactam – Rifampicin – Trimethoprim-Sulfamethoxazole (TMP-SMX) – Vancomycin – Carbamazepine – Phenytoin – Vigabatrin – Lithium – Gemcitabine – Entecavir – Interferon-α 2a – Amlodipine – Verapamil – Prednisone – Interferon γ / Interleukin 2 – Sulfasalazine – Filgrastim – Cyclosporine – Furosemide – Atezolizumab – Avelumab – Cemiplimab – Durvalumab – Ipilimumab – Nivolumab – Pembrolizumab – Diclofenac – Ketoprofen – Metamizole – Naproxen – Piroxicam – Atorvastatin – Somatostatin – Glibenclamide – Infliximab – Allopurinol |
|
| |||
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) | – Antiarrhythmics – Antibiotics (nitroimidazoles, penicillins, sulfonamides) – Anticoagulants – Anticonvulsants – Antidiabetics – Antifungals – Antimalarials – Antituberculars – Antivirals – DMARDs – Erythropoiesis-Stimulating Agents (ESAs) – Histamine antagonist – Monoclonal antibodies – Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) – NSAIDs – Proton Pump Inhibitors (PPIs) – Statins – Tricyclic antidepressants – Tyrosine Kinase Inhibitors – Xanthine Oxidase Inhibitors | – Mexiletine – Amoxicillin – Amoxicillin-clavulanic acid – Ampicillin – Ampicillin/sulbactam – Azithromycin – Benznidazole – Cefadroxil – Cefepime – Cefixime – Cefotaxime – Ceftazidime – Clindamycin – Dapsone – Imipenem – Levofloxacin – Linezolid – Meropenem – Metronidazole – Minocycline – Piperacillin/tazobactam – Streptomycin – Teicoplanin – TMP-SMX – Vancomycin – Rivaroxaban – Carbamazepine – Ethosuximide – Gabapentin – Lamotrigine – Oxcarbazepine – Phenobarbital – Phenytoin – Valproate – Zonisamide – Sitagliptin – Voriconazole – Hydroxychloroquine – Quinine – Ethambutol – Isoniazid – Pyrazinamide – Rifampin – Boceprevir – Telaprevir – Sulfasalazine – Epoetin alfa – Ranitidine – Daclizumab – Abacavir – Nevirapine – Aspirin – Celecoxib – Diclofenac – Ibuprofen – Piroxicam – Esomeprazole – Omeprazole – Atorvastatin – Amitriptyline – Imatinib – Sorafenib – Vemurafenib – Allopurinol | |
Erosive | – Antibiotics (ß lactams, cephalosporins, macrolides, quinolones, sulfonamides, tetracyclines) – Anticonvulsants – DMARDs – NNRTIs – NSAIDs – Xanthine Oxidase Inhibitors | – Cotrimoxazole – Carbamazepine – Lamotrigine – Phenobarbital – Phenytoin – Sulfasalazine – Nevirapine – Diclofenac – Meloxicam – Allopurinol | |
Erythema Multiforme (EM) | – Angiotensin converting enzyme inhibitors – Antibiotics (ß lactams, sulfonamides) – Anticonvulsants – Antifungals – Antimalarials – Antimetabolites – Antineoplastics – Interleukin-6 (IL-6) receptor inhibitor – Monoclonal Antibodies – Mucolytics – NSAIDs – Statins | – Lisinopril – Doxycycline – Carbamazepine – Phenobarbital – Phenytoin – Valproate – Itraconazole – Terbinafine – Hydroxychloroquine – Fluorouracil – Actinomycin D – Paclitaxel – Tocilizumab – Sintilimab – Ambroxol – Bromhexine – Ketoprofen – Naproxen – Phenylbutazone – Pravastatin – Simvastatin | |
Erythema Nodosum (EN) | – Angiotensin converting enzyme inhibitors – Antibiotics (aminoglycosides, cephalosporins, sulfonamides) – Anticonvulsants – Antidepressants – Angiotensin receptor blockers – Aromatase Inhibitors – Bromides – Gold Salts – Leukotriene Inhibitors – Oral Contraceptives – PPIs | – Amoxicillin – Ampicillin – Ciprofloxacin – Cotrimoxazole – Minocycline – Nitrofurantoin – Penicillin – Streptomycin – Carbamazepine – Hydantoin – Fluoxetine – Montelukast – Norethindrone – Norgestimate – Levonorgestrel – Omeprazole | |
Fixed Drug (FD) | – Antibiotics (Penicillins, Nitroimidazoles, Sulfonamides, Tetracyclines) – Antimalarials – Barbiturates – NSAIDs – Oral Contraceptives | – Amoxicillin – Doxycycline – Metronidazole – Penicillin – TMP-SMX – Quinine – Phenobarbital – Ibuprofen – Celecoxib – Naproxen – Ethinyl estradiol – Medroxyprogesterone acetate – Norethindrone acetate | |
Follicular | – Antibiotics (Macrolides, Penicillins) – Anticonvulsants – Antidepressants – Antifungals – Antimalarials – Antimanic – Antipsychotics – Antituberculars – Corticosteroids – Epidermal Growth Factor Receptor Inhibitors – NSAIDs – TNF Inhibitors | – Nystatin – Carbamazepine – Phenytoin – Fluoxetine – Paroxetine – Sertraline – Itraconazole – Hydroxychloroquine – Lithium – Olanzapine – Isoniazid – Corticotropin – Dacomitinib – Gefitinib – Naproxen – Infliximab | |
Hyperpigmentation | – Antiarrhythmics – Antibiotics (Tetracyclines) – Anticoagulants – Anticonvulsants – Antimalarials – Antimetabolites – Antimicrobials – Antineoplastics
– Antipsychotics – Cytotoxics – Heavy Metals – NRTIs – NSAIDs – Statins – Xanthine Oxidase Inhibitors | – Amiodarone – Minocycline – Carbamazepine – Chlorpromazine – Lamotrigine – Phenytoin – Chloroquine – Hydroxychloroquine – 5-fluorouracil – Clofazimine – Cyclophosphamide – Docetaxel – Doxorubicin – Ifosfamide – Melphalan – Paclitaxel – Thiotepa – Chlorpromazine – Desipramine – Imipramine – Bleomycin – Busulfan – Cyclophosphamide – Gold – Silver – Zidovudine – Aspirin – Ibuprofen – Meloxicam – Paracetamol – Simvastatin – Allopurinol | |
Hypopigmentation | – Immune Response Modifiers – Monoclonal Antibodies | – Imiquimod – Atezolizumab – Avelumab – Durvalumab – Ipilimumab – Nivolumab – Pembrolizumab | |
Lichenoid | – Angiotensin converting enzyme inhibitors – Antibiotics – Anticonvulsants – Antihypertensives – Antineoplastics – Antivirals – Calcium Channel Blockers – Diuretics – Monoclonal Antibodies – NSAIDs | – Captopril – Enalapril – Sulfamethoxazole – Carbamazepine – Phenytoin – Methyldopa – Ponatinib – Acyclovir – Nifedipine – Furosemide – Hydrochlorothiazide – Dupilumab – Mogamulizumab – Nivolumab – Rituximab – Ibuprofen – Naproxen | |
Morbilliform/ Maculopapular | – Androgen Receptor Signaling Inhibitors – Antibiotics (Beta lactams, cephalosporins, sulfonamides) – Anticonvulsants – Antimalarials – Antivirals – Monoclonal Antibodies – NSAIDs – Tyrosine Kinase Inhibitors | – Apalutamide – Amoxicillin – Penicillin – TMP-SMX – Carbamazepine – Lamotrigine – Phenobarbital – Phenytoin – Hydroxychloroquine – Dasabuvir – Ombitasvir – Paritaprevir – Simeprevir – Cemiplimab – Daclizumab – Ibalizumab‐uk – Ipilimumab – Nivolumab – Pembrolizumab – Siltuximab – Oxicam types (i.e meloxicam) – Fostamatinib | |
Photo Drug (PD) | – Angiotensin converting enzyme inhibitors – Antiarrhythmics – Antibiotics (fluoroquinolones, sulfonamides, tetracyclines) – Antifungals – Antimalarials – Antimetabolites – Antineoplastics – Antipsychotics – Antituberculars – Antivirals – CCBs – NNRTIs – NSAIDs – Thiazide diuretics | – Enalapril – Quinapril – Ramipril – Amiodarone – Cefotaxime – Ceftazidime – Dapsone – Doxycycline – Lymecycline – Minocycline – Nalidixic acid – TMP-SMX – Griseofulvin – Itraconazole – Ketoconazole – Terbinafine – Voriconazole – Hydroxychloroquine – Fluorouracil – Paclitaxel – Chlorpromazine – Isoniazid – Pyrazinamide – Sofosbuvir-Velpatasvir – Diltiazem – Efavirenz – Benoxaprofen – Ibuprofen – Ketoprofen – Naproxen – Tiaprofenic acid – Hydrochlorothiazide | |
Pustular | – Antibiotics (ß-lactams, macrolides, quinolones, sulfonamides) – Antifungals – Antimalarials – CCBs – Tyrosine Kinase Inhibitors | – Amoxicillin – Ampicillin – Pristinamycin – TMP-SMX – Terbinafine – Hydroxychloroquine – Diltiazem – Gefitinib | |
Stevens Johnson Syndrome (SJS) | – Antibiotics (ß lactams, cephalosporins, fluoroquinolones, sulfonamides) – Anticonvulsants – Antituberculars – DMARDs – Monoclonal antibodies – NRTIs – NSAIDs – Xanthine Oxidase Inhibitors | – Amoxicillin – Azithromycin – Cefotaxime – Doxycycline – Erythromycin – TMP-SMX – Vancomycin – Carbamazepine – Lamotrigine – Levetiracetam – Phenobarbital – Phenytoin – Valproic acid – Isoniazid – Rifampicin – Sulfasalazine – Nivolumab – Pembrolizumab – Abacavir – Nevirapine – Meloxicam – Allopurinol | |
SJS/TEN | – Antibiotics (ß lactams, cephalosporins, fluoroquinolones, macrolides, sulfonamides, tetracyclines) – Anticonvulsants – Antituberculars – DMARDs – Monoclonal antibodies – NRTIs – NSAIDs – Xanthine Oxidase Inhibitors | – Amoxicillin – Azithromycin – Cefotaxime – Doxycycline – Erythromycin – TMP-SMX – Vancomycin – Carbamazepine – Lamotrigine – Levetiracetam – Phenobarbital – Phenytoin – Valproic acid – Isoniazid – Rifampicin – Sulfasalazine – Nivolumab – Pembrolizumab – Abacavir – Nevirapine – Meloxicam – Allopurinol | See above and below |
Toxic Epidermal Necrolysis (TEN) | – Antibiotics (fluoroquinolones, sulfonamides, tetracyclines) – Antivirals – Anticonvulsants – DMARDs – NNRTIs – NSAIDs – Xanthine Oxidase Inhibitors | – Cotrimoxazole – Acyclovir – Carbamazepine – Lamotrigine – Phenobarbital – Phenytoin – Sulfasalazine – Nevirapine – Meloxicam – Allopurinol | |
Urticarial | – Angiotensin converting enzyme inhibitors – Antibiotics (aminoglycosides, ß lactams, cephalosporins, macrolides, penicillins, sulfonamides) – Anticonvulsants – Antifungals – Antimalarials – NSAIDs – Opioids – Oral contraceptives | – Captopril – Lisinopril – Ramipril – Azithromycin – Clarithromycin – Erythromycin – Gentamicin (IV) – Neomycin (topical) – Penicillin – Tobramycin (IV & Inhaled) – Phenytoin – Terbinafine – Hydroxychloroquine – Aspirin – Celecoxib – Diclofenac – Codeine – Morphine – Levonorgestrel – Levonorgestrel/ethinyl estradiol |
Table 2: Categorization of drug eruptions with implicated drug classes and generic drug names with associated morphologic pattern [8-105].
