Morbilliform Drug Eruption Research Articles

Dermatological conditions in the intensive care unit at a tertiary care hospital in Riyadh, Saudi Arabia.

To evaluate the various skin conditions diagnosed in intensive care unit (ICU) patients. This is a descriptive retrospective study of all adults, pediatric, and neonatal patients who were admitted to the ICU and had a dermatological manifestation during hospital stay or patients who had dermatological condition that requires ICU admission. All skin conditions were categorized and analyzed. A total of 344 ICU patients with 365 different dermatological conditions were included in the study. The age of patients ranged from less than 1-96 years, with a mean age of 43.6±30.1 years. Of the patients, 189 (54.9%) were males. The top 3 general disease categories observed were skin infections, inflammatory and autoimmune diseases, and drug reactions. The most commonly reported dermatological disorders included morbilliform drug eruption (6.8%), contact dermatitis (6.3%), vasculitis (5.5%), herpes zoster (4.6%), purpura due to thrombocytopenia (3.8%), dermatitis/eczema (3.8%), candidiasis (3.8%), infantile hemangioma (2.7%), unclassified drug reaction (2.5%), intertrigo (2.5%), and herpes simplex virus (2.5%). Dermatological disorders can occur at various levels of severity in the ICU. Skin infections, inflammatory and autoimmune diseases, and drug reactions were found to be the most prevalent conditions.

Systemic and skin-limited delayed-type drug hypersensitivity reactions associate with distinct resident and recruited T cell subsets.

Delayed-type drug hypersensitivity reactions are major causes of morbidity and mortality. The origin, phenotype, and function of pathogenic T cells across the spectrum of severity require investigation. We leveraged recent technical advancements to study skin-resident memory T cells (TRMs) versus recruited T cell subsets in the pathogenesis of severe systemic forms of disease, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS), and skin-limited disease, morbilliform drug eruption (MDE). Microscopy, bulk transcriptional profiling, and single-cell RNA-sequencing (scRNA-Seq) plus cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) plus T cell receptor sequencing (TCR-Seq) supported clonal expansion and recruitment of cytotoxic CD8+ T cells from circulation into skin along with expanded and nonexpanded cytotoxic CD8+ skin TRM in SJS/TEN. Comparatively, MDE displayed a cytotoxic T cell profile in skin without appreciable expansion and recruitment of cytotoxic CD8+ T cells from circulation, implicating TRMs as potential protagonists in skin-limited disease. Mechanistic interrogation in patients unable to recruit T cells from circulation into skin and in a parallel mouse model supported that skin TRMs were sufficient to mediate MDE. Concomitantly, SJS/TEN displayed a reduced Treg signature compared with MDE. DRESS demonstrated recruitment of cytotoxic CD8+ T cells into skin as in SJS/TEN, yet a pro-Treg signature as in MDE. These findings have important implications for fundamental skin immunology and clinical care.

Rare cutaneous adverse reactions associated with GLP-1 agonists: a review of the published literature.

Glucagon-like-peptide-1 (GLP-1) agonists are an emerging class of medications used to manage type 2 diabetes mellitus (T2DM) and weight loss, with demonstrated efficacy in reducing hemoglobin A1c levels, body mass index, and adverse cardiovascular events. While previous studies have reviewed notable cutaneous adverse effects with other antidiabetic medications, little is known about GLP-1 agonist-induced cutaneous reactions. Nevertheless, rare but significant cutaneous adverse reactions have been reported, including but not limited to dermal hypersensitivity reactions, eosinophilic panniculitis, bullous pemphigoid, and morbilliform drug eruptions. As GLP-1 induced cutaneous reactions are diverse, diagnosis requires clinical suspicion, thorough history-taking, and supportive histopathological findings when available. Management involves cessation of the offending agent with a tailored regimen to address inflammatory and/or immunogenic etiologies as well as irritative symptoms. This review aims to consolidate available information from case reports and case series regarding rare skin-related adverse outcomes due to GLP-1 use, aiming to provide a comprehensive overview of the presentation, pathogenesis, and management for dermatologists and other clinicians.

An asymmetric morbilliform eruption in an adult male

An asymmetric morbilliform eruption in an adult male

Association of Intraoperative Antibiotic Irrigation With Systemic Contact Dermatitis

This case series describes the development of morbilliform drug eruption after breast surgery.

Drug allergy: A 2022 practice parameter update

Drug allergy: A 2022 practice parameter update

Granulysin-Based Lymphocyte Activation Test for Evaluating Drug Causality in Antiepileptics-Induced Severe Cutaneous Adverse Reactions

Aromatic antiepileptic drugs (AEDs) are common causes of cutaneous adverse drug reactions, which range from morbilliform drug eruption to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens‒Johnson syndrome, and toxic epidermal necrolysis. Different invitro methods for identifying the culprit drugs have been developed; however, it is particularly challenging for Stevens‒Johnson syndrome-toxic epidermal necrolysis. In this study, we enrolled 63 patients (39 with Stevens‒Johnson syndrome-toxic epidermal necrolysis, 13 with drug reaction with eosinophilia and systemic symptoms, and 11 with morbilliform drug eruption) and 30 tolerant controls to examine the performance of lymphocyte activation tests by measuring the expression of granulysin, granzyme B, and IFN-γ. Granulysin-based lymphocyte activation tests displayed the best sensitivity and specificity to identify the causality: 73.9% sensitivity and 96.7% specificity for carbamazepine and 68.2% sensitivity and 96.7% specificity for phenytoin. Oxcarbazepine and lamotrigine show weak antigenicity. Granulysin-based lymphocyte activation tests expanded predominantly memory cytotoxic T lymphocytes with characteristics of drug-specific T-cell receptor, major histocompatibility complex I dependence, and cross reactivity to different aromatic AEDs. Among 29 follow-up patients, 28 alternatively used nonaromatic AEDs, and none developed cutaneous adverse drug reactions. Our data suggest that granulysin-based lymphocyte activation tests represent invitro cytotoxic T-lymphocyte memory response to offending drugs and are useful to confirm drug causality of AED-induced severe cutaneous adverse reactions. Implementing these tests will improve the AED-induced severe cutaneous adverse reactions prevention and clinical care.

An epidemiological and clinical analysis of cutaneous drug eruption: A cohort of 164 patients

Aim: Drug reactions are important and frequent complications of medical treatments. In this study we aimed to investigate the patients hospitalized with a diagnosis of cutaneous drug eruptions, implicated drugs, and related skin manifestations considering the literature. Methods: This retrospective cohort study was performed in Haydarpaşa Numune Training and Research Hospital, Dermatology and Venereology Department. The study comprised 164 patients that were diagnosed with cutaneous drug eruption between January 2010 and December 2016. Some parameters, such as demographic characteristics, type of the reaction, culprit drug groups, multiple drug usage, time between the onset of the drug intake and beginning of the eruption were recorded. Age, gender, symptoms, laboratory tests, diagnosis and treatment information were obtained through patient files. Causal relationship was assessed by Naranjo algorithm. Adverse drug reactions were categorized as definite, probable, possible, and absent. All values were expressed in percentages. The severity of the reaction caused by the drug was assessed with Hartwig's Severity Assessment Scale. Results: Among 164 patients, there were 104 females and 60 males with a mean age of 46.3 (18.8) years. The most commonly encountered type of drug reactions were urticaria and angioedema (42.1 %), followed by morbilliform drug eruption (31.7%). More cutaneous reactions were noted with NSAIDs (18.9%), antibiotics (15.2%) and the combination of NSAIDs and antimicrobial agents (9.8%). Time between the onset of eruption and the intake of the drug varied by hours to months. Some of these patients also described similar reactions related to drugs in the past. Conclusion: Knowledge of these drug eruptions, the causative drugs and the prognostic factors is important for clinicians. It is recommended to advise patients to carry a list in their wallets indicating their drug allergies and/or intolerances, especially if they had a severe reaction before. We conclude that a careful follow-up should be performed with NSAIDs, antibiotics and anti-epileptics. The combination of drugs, including NSAIDs and antibiotics should be avoided as much as possible.

17910 Using clonality of T-cell repertoire to distinguish between drug hypersensitivity reaction and acute graft-versus-host disease

Graft-versus-host disease (GVHD) is a serious complication of hematopoietic stem cell transplantation, which often leads to morbidity and mortality if not diagnosed and treated early. Acute GVHD is characterized by a clinical triad of cutaneous eruptions, gastrointestinal dysfunction, and liver abnormalities. Cutaneous manifestations of acute GVHD frequently appear before symptoms of other organ systems, but the clinical and histologic features are similar to those of acute morbilliform drug eruption, thus generating a major diagnostic pitfall. Previous studies attempted to define microscopic features of acute GVHD, but these features were later found to be non-specific. We hypothesize that GVHD is mediated by clonal amplification of T-cell repertoire, and therefore can be distinguished from drug hypersensitivity reaction (DHR) by the presence of dominant T-cell receptor clones. To test this hypothesis, we performed “immunosequencing” of T-cell receptors in ten patients with acute GVHD and seven patients with DHR. We calculated the clonality of T-cell repertoire by using normalized Shannon entropy, and found that GVHD patients had significantly higher clonality than DHR patients (P value = 0.05). When a numeric cutoff of clonality alone was used to distinguish GVHD from DHR, a receiver operating characteristic curve had an area under the curve of 0.77. Using a clonality cutoff of 0.042 resulted in sensitivity of 60% and specificity of 71%. Although further validation studies may be required, these results suggested that clonality of T-cell repertoire may be used to distinguish GVHD from DHR in combination of other clinical features.

The frequency of low-risk morbilliform drug eruptions observed in patients treated with different classes of antibiotics.

Antibiotics are among the most commonly prescribed medications worldwide but can lead to numerous cutaneous adverse events. Cutaneous adverse drug reactions can range from a common and low-risk morbilliform eruption to severe cutaneous adverse reactions (SCARs) such as toxic epidermal necrolysis. In the hospital setting, patients often start a myriad of new drugs and may be on multiple antibiotics when the dermatologist is consulted. With the current lack of commercially available testing for delayed-type hypersensitivity reactions, etiologic confirmation is challenging. While the Naranjo and other standardized assessment criteria are available, complete scoring is often impossible in hospitalized patients. Further, multiple drugs may have been initiated at the same time point. Therefore, the prevalence of antibiotic-associated drug eruptions often is required to facilitate causality assessments. This review summarizes the prevalence of morbilliform eruptions for the most frequently prescribed antibiotics based upon systematic reviews, retrospective, and prospective analyses, with case series and reports providing other salient details.

Distinguishing Stevens-Johnson syndrome/toxic epidermal necrolysis from clinical mimickers during inpatient dermatologic consultation—A retrospective chart review

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions that may present with similar findings to other severe dermatologic diseases. The primary objective of this exploratory study was to explore factors associated with SJS/TEN and develop a model that provides the predicted probability of SJS/TEN for patients for whom the diagnosis of SJS/TEN is considered. Retrospective review of consultations for patients with suspected SJS, TEN, or overlap at 4 academic dermatology consultation services. Overall, 208 patients were included; 59 (28.4%) had a final diagnosis of SJS/TEN, and 149 (71.6%) were given a different diagnosis. The most common mimickers were drug hypersensitivity syndrome (n=21, 10.1%), morbilliform drug eruption (n = 18, 8.7%), erythema multiforme (n = 15, 7.2%), and acute generalized exanthematous pustulosis (n = 13, 6.2%). Nikolsky sign, atypical targets, fever, and lymphopenia were included in a model for predicting the probability of SJS/TEN. All cases were obtained from academic centers, which may limit the generalization of findings to community-based settings. This was an exploratory study with a small number of cases, and external validation of the model performance is needed. Earlydermatologic evaluation of patients with suspected SJS/TEN is key to separating patients with this condition from those who ultimately receive diagnoses of other serious skin diseases.

Pattern of Dermatological Disease Encountered in a Hematology Ward: A Retrospective Analysis of Dermatology Consultation in a Hematology Ward in a Tertiary Care Center in Saudi Arabia.

Introduction. Skin manifestations are common in hematology ward patients and can result from infection, malignancy, or chemotherapy. The purpose of this study was to identify the most common dermatological problems encountered in the adult hematology ward at King Abdullah Specialist Children Hospital (KASCH). Methods. This was retrospective chart review of 78 dermatology consultations based on electronic health records for all inpatients in hematology wards at KASCH between January 2016 and December 2017. Data were presented as mean ± SD for continuous variables. Results. During the study period, a total of 1391 inpatients were referred to the dermatology department. A total of 403 (29.0%) referrals were from the internal medicine department and 78 (5.6%) were from the hematology department, six of which were rejected by the dermatology department. Almost all requests for referral were managed on the same or the next day with only two requests after 3 days. There were more female (n = 40; 51.3%) than male patients (n = 38; 48.7%) and the average age ± SD was 40.7 ± 19.8 years. Patients were diagnosed with a diverse range of hematological diseases. A total of 27 (35.1%) patients were diagnosed with acute myeloid leukemia. Overall, 98 differential diagnoses were made by dermatologists with only 26 being confirmed by skin biopsy. Eight (30.8%) patients were diagnosed with graft versus host disease confirmed by skin biopsy. The diagnoses were changed in 12 cases after skin biopsy. Several types of dermatitis were diagnosed in hematology ward patients including stasis dermatitis and contact dermatitis. The source of infection was not specified in most cases and the infection was treated empirically. Conclusion. Various dermatological disorders and cutaneous manifestations are observed in hematology inpatients with morbilliform drug eruption and graft versus host disease being the most common.

Amoxicillin Morbilliform Drug Eruption in Pediatric Male with Poor Feeding Treated with Cyproheptadine: A Case Report

Background: Cyproheptadine (CY) is an antihistaminic agent that is commonly used for symptom relief in skin conditions. The most common pattern of cutaneous drug eruption in children is the exanthematous type, with the penicillin family often cited. CY is also an antiserotoninergic agent with the side effect of appetite stimulation and has been used in children with poor feeding and poor weight gain.
 The Case: We report a case of a 31-month-old male patient seen in the outpatient setting with a diffuse morbilliform rash after use of amoxicillin for right otitis media. The patient was a post-operative congenital heart disease (CHD) patient, actively being treated with CY for feeding difficulties and low weight often seen in the CHD population. Amoxicillin was discontinued, while CY was continued. The patient did not encounter any pruritic symptoms during morbilliform rash, while weight gain of 3.1 kg occurred over a 9 months period, increasing patient from the 10th to 41st percentile.
 Conclusion: A review of studies on CY has shown antiallergic properties in histamine-mediated hypersensitivity reactions, most likely through H1 receptor antagonism. This mechanism may be used to address the pruritic symptoms during type IV T-cell mediated hypersensitivity cutaneous drug eruptions. CY also possesses 5-HT receptor antagonist properties with demonstrated ability to increase appetite in poor feeding pediatric patients. CY was successfully used for this purpose in our CHD patient.

The Potential Utility of Patch Testing in Identifying the Causative Agent of Morbilliform Drug Eruptions

The Potential Utility of Patch Testing in Identifying the Causative Agent of Morbilliform Drug Eruptions

Dermatology Consultation for Cutaneous Complications of Hematopoietic Stem Cell Transplantation

BackgroundThe acute onset of a skin eruption early in the post-transplant course of the hematopoietic stem cell transplant (HSCT) patient is challenging due to the clinical similarity of eruptions that are common in this population. These include of morbilliform drug eruptions, viral exanthema, eruption of lymphocyte recovery, erythema multiforme, toxic erythema of chemotherapy, and acute graft-versus-host disease (GVHD). We aimed to identify cutaneous eruptions in HSCT patients in the early post-transplant period, and the incidence of dermatologic consultation, along with the utility of skin biopsies and whether a change in management resulted from the consultation.MethodsA retrospective chart review was performed on patients at Northwestern Memorial Hospital who underwent their first allogenic or autologous HSCT in 2009. Information collected included incidence and presentation of cutaneous complications (including GVHD), as well as frequency and outcome of dermatologic consultation (including changes in patient management as a result of consultation).ResultsWe found 220 patients who received a HSCT in 2009. To date, 126 (80 autologous, 46 allogeneic) of these have been analyzed. Preliminary data shows that 50/126 (39.7%) patients had cutaneous complications in the early post-transplant period, and of these, 21/50 (42.0%) were diagnosed with acute GVHD. Dermatology was consulted for 29/50 (58.0%) patients with rash and a skin biopsy was perfomed on 16/29 (55%) patients seen by dermatology. Treatment plans were changed after dermatologic consultation in 15/29 (51.7%) patients.ConclusionDermatologic consultation for the recognition and diagnosis of the early cutaneous complications of HSCT is a valuable resource that often leads to changes in patient management. Further studies are necessary to analyze whether patient outcomes are affected by dermatologic consultation. BackgroundThe acute onset of a skin eruption early in the post-transplant course of the hematopoietic stem cell transplant (HSCT) patient is challenging due to the clinical similarity of eruptions that are common in this population. These include of morbilliform drug eruptions, viral exanthema, eruption of lymphocyte recovery, erythema multiforme, toxic erythema of chemotherapy, and acute graft-versus-host disease (GVHD). We aimed to identify cutaneous eruptions in HSCT patients in the early post-transplant period, and the incidence of dermatologic consultation, along with the utility of skin biopsies and whether a change in management resulted from the consultation. The acute onset of a skin eruption early in the post-transplant course of the hematopoietic stem cell transplant (HSCT) patient is challenging due to the clinical similarity of eruptions that are common in this population. These include of morbilliform drug eruptions, viral exanthema, eruption of lymphocyte recovery, erythema multiforme, toxic erythema of chemotherapy, and acute graft-versus-host disease (GVHD). We aimed to identify cutaneous eruptions in HSCT patients in the early post-transplant period, and the incidence of dermatologic consultation, along with the utility of skin biopsies and whether a change in management resulted from the consultation. MethodsA retrospective chart review was performed on patients at Northwestern Memorial Hospital who underwent their first allogenic or autologous HSCT in 2009. Information collected included incidence and presentation of cutaneous complications (including GVHD), as well as frequency and outcome of dermatologic consultation (including changes in patient management as a result of consultation). A retrospective chart review was performed on patients at Northwestern Memorial Hospital who underwent their first allogenic or autologous HSCT in 2009. Information collected included incidence and presentation of cutaneous complications (including GVHD), as well as frequency and outcome of dermatologic consultation (including changes in patient management as a result of consultation). ResultsWe found 220 patients who received a HSCT in 2009. To date, 126 (80 autologous, 46 allogeneic) of these have been analyzed. Preliminary data shows that 50/126 (39.7%) patients had cutaneous complications in the early post-transplant period, and of these, 21/50 (42.0%) were diagnosed with acute GVHD. Dermatology was consulted for 29/50 (58.0%) patients with rash and a skin biopsy was perfomed on 16/29 (55%) patients seen by dermatology. Treatment plans were changed after dermatologic consultation in 15/29 (51.7%) patients. We found 220 patients who received a HSCT in 2009. To date, 126 (80 autologous, 46 allogeneic) of these have been analyzed. Preliminary data shows that 50/126 (39.7%) patients had cutaneous complications in the early post-transplant period, and of these, 21/50 (42.0%) were diagnosed with acute GVHD. Dermatology was consulted for 29/50 (58.0%) patients with rash and a skin biopsy was perfomed on 16/29 (55%) patients seen by dermatology. Treatment plans were changed after dermatologic consultation in 15/29 (51.7%) patients. ConclusionDermatologic consultation for the recognition and diagnosis of the early cutaneous complications of HSCT is a valuable resource that often leads to changes in patient management. Further studies are necessary to analyze whether patient outcomes are affected by dermatologic consultation. Dermatologic consultation for the recognition and diagnosis of the early cutaneous complications of HSCT is a valuable resource that often leads to changes in patient management. Further studies are necessary to analyze whether patient outcomes are affected by dermatologic consultation.

Morbilliform drug eruption due to pegylated α‐interferon can show complete regression after switching to non‐pegylated interferon

Pegylated or non-pegylated α-interferon are frequently used medications for the treatment of both chronic hepatitis B and chronic hepatitis C. Skin disorders, which are mainly comprised of eczematous dermatitis, are frequently seen during treatment with this drug. However, drug eruption or morbilliform eruptions due to interferons have been rarely reported so far. We herein describe a patient who developed morbilliform drug eruption under treatment with pegylated interferon. She was able to continue treatment after switching from pegylated interferon to conventional interferon.

Cutaneous drug eruptions: A 5-year experience

The diversity of cutaneous drug eruptions encompasses many clinicopathologic entities. Cases with a pathologic diagnosis of drug eruption from 2000 to 2005 were retrieved from our institution. The histologic slides were reviewed, the patterns of inflammatory changes were recorded, and a chart review was performed. The majority of the cases (94%) were "morbilliform"-type rashes. Eighty-two percent of cases exhibited an inflammatory infiltrate confined to the superficial dermis. Eighty percent exhibited a perivascular and interstitial pattern of dermal infiltrate. The infiltrate was composed of lymphocytes and eosinophils in approximately 29% of cases, lymphocytes and neutrophils in approximately 10% of cases, and lymphocytes, eosinophils, and neutrophils in approximately 21% of cases. Eosinophils were present in only 50% of cases. Approximately half (53%) of the cases exhibited epidermal-dermal interface changes. The cases were limited to those with a pathologic diagnosis of cutaneous drug reaction, thereby excluding any cases with drug-induced disease not specifically diagnosed (histologically) as such. While the histologic features of most drug eruptions are not entirely specific, the finding of superficial infiltrates composed variably of lymphocytes, neutrophils, and eosinophils, either with or without interface changes, should suggest the possibility of a morbilliform drug eruption. Clinical correlation is very helpful to confirm the diagnosis. To our knowledge, this study is the most extensive documenting the histologic findings in morbilliform drug eruptions.

A Morbilliform Variant of Vancomycin-Induced Linear IgA Bullous Dermatosis

Linear IgA bullous dermatosis is an autoimmune blistering disease characterized clinically by the presence of small tense blisters and immunologically by the presence of IgA at the dermal-epidermal junction. Idiopathic, systemic disease-related, and drug-related versions of this disorder have been described, with the latter most commonly associated with vancomycin. We describe 2 patients with vancomycin-associated linear IgA bullous dermatosis who presented with a morbilliform eruption that lacked blistering. Lesional and perilesional tissue from each patient was examined by light microscopy and direct immunofluorescence. Histopathologic examination findings revealed vacuolar interface dermatitis with a mixed inflammatory infiltrate and occasional eosinophils, consistent with a drug eruption. Direct immunofluorescence revealed IgA deposited in a linear pattern at the dermoepidermal junction. In both patients, the results of indirect immunofluorescence using both IgG and IgA were negative. These cases highlight the existence of a new form of linear IgA bullous dermatosis presenting as a morbilliform drug eruption. Both patients were following extensive medication regimens, including use of multiple antibiotics. The diagnosis of linear IgA bullous dermatosis allowed us to target vancomycin as the likely allergen and begin treatment. In light of these findings, direct immunofluorescence may be a useful diagnostic adjunct in determining the cause of drug eruptions.

Approach to the Patient With a Suspected Drug Eruption

Diagnosis and management of adverse drug reactions constitutes a significant portion of U.S. health care costs. The clinical presentation of these reactions varies from self-limited, morbilliform drug eruptions to more severe, systemic reactions, such as drug hypersensitivity syndromes, Stevens-Johnson syndrome, and toxic epidermal necrolysis, which are associated with significant mortality. The role of the consulting dermatologist is to expeditiously and effectively recognize and classify these drug reactions on the basis of patient histories and awareness of the dermatologic literature as it pertains to the rates of and risk factors for adverse cutaneous events associated with use of numerous medications. This combined with a systematic approach to the workup of a patient with a suspected drug eruption allows for prompt recognition, classification and treatment of these unforeseen events.