Cutaneous reactions to drugs

Adverse reactions to medications are common and important cause of iatrogenic illness. Severe cutaneous adverse drug reactions include toxic epidermal necrolysis, Stevens–Johnson syndrome, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis, which together constitute 2% of all adverse drug reactions and may be life-threatening. Less severe drug-induced skin reactions such as exanthems, urticaria, lichenoid drug rashes, and fixed drug eruptions are more common, sometimes termed benign cutaneous adverse reactions, and generally resolve without sequelae. Drugs may also cause adverse events due to alteration of the normal function of the skin or its appendages. This may take the form of photosensitivity, abnormal pigmentation, or disrupted growth of hair or nails.

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Dermoscopic Aspects of Cutaneous Adverse Drug Reactions

Dermatology Practical & Conceptual ◽

10.5826/dpc.1101a136 ◽

2021 ◽

pp. e2021136

Author(s):

Gabriela Rossi ◽

André Da Silva Cartell ◽

Renato Marchiori Bakos

Keyword(s):

Adverse Drug Reactions ◽

Adverse Reactions ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Acute Generalized Exanthematous Pustulosis ◽

Johnson Syndrome ◽

Vascular Structures ◽

Systemic Symptoms ◽

Exanthematous Pustulosis ◽

Cutaneous Adverse Reactions

Background: Little is known about the dermoscopic evaluation of cutaneous adverse drug reactions (CADRs). Objectives: To evaluate the dermoscopic patterns of CADRs and identify those associated with severe cutaneous adverse reactions to drugs (SCARDs). Patients and Methods: Patients included in this study from May 2015 to April 2016 had presented with CADRs. CADR presentation and classification were based on standard criteria. SCARDs included Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), overlap SJS/TEN, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). The dermoscopic features of CADRs were described and compared according to the severity of the reactions. Results: Sixty-nine patients were included. Sixteen patients (23.2%) presented SCARDs. The main dermoscopic findings in SJS, overlap SJS/TEN and TEN were black dots or necrotic areas (100%). Erosion [respectively, 4/6 (66.7%), 3/3 (100%) and 1/1 (100%)], necrotic borders [respectively, 4/6 (66.7%), 3/3 (100%) and 1/1, (100%)] and epidermal detachment [respectively, 5/6 (83.3%); 2/3 (66.7%) and 1/1 (100%)] were also common among these reactions. Erythema and purpuric dots were the main dermoscopic findings [respectively, 5/6 (83.3%) and 4/6 (66.7%)] in DRESS. In non-severe reactions, the most prevalent structures were erythema and purpura in exanthema [respectively, 31/33 (93.9%) and 24/33 (72.7%)] and erythema and vascular structures in urticarial reactions [respectively, 6/6 (100%) and 3/6 (50%)]. Black dots or necrotic areas, epidermal detachment, necrotic borders and erosion were highly associated with SCARDs (P < 0.001). Conclusions: Dermoscopy improves clinical recognition of SCARDs.

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Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions

Journal of Immunology Research ◽

10.1155/2017/6928363 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Mari Orime

Keyword(s):

Adverse Drug Reactions ◽

Clinical Manifestations ◽

Hypersensitivity Syndrome ◽

Conclusive Evidence ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Drug Induced ◽

Cutaneous Manifestations ◽

Johnson Syndrome ◽

Systemic Symptoms

Diagnosis of severe cutaneous adverse drug reactions should involve immunohistopathological examination, which gives insight into the pathomechanisms of these disorders. The characteristic histological findings of erythema multiforme (EM), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) provide conclusive evidence demonstrating that SJS/TEN can be distinguished from EM. Established SJS/TEN shows full-thickness, extensive keratinocyte necrosis that develops into subepidermal bullae. Drug-induced hypersensitivity syndrome (DIHS) and exanthema in drug reaction with eosinophilia and systemic symptoms (DRESS) each display a variety of histopathological findings, which may partly correlate with the clinical manifestations. Although the histopathology of DRESS is nonspecific, the association of two or more of the four patterns—eczematous changes, interface dermatitis, acute generalized exanthematous pustulosis- (AGEP-) like patterns, and EM-like patterns—might appear in a single biopsy specimen, suggesting the diagnosis and severe cutaneous manifestations of DRESS. Cutaneous dendritic cells may be involved in the clinical course. AGEP typically shows spongiform superficial epidermal pustules accompanied with edema of the papillary dermis and abundant mixed perivascular infiltrates. Mutations in IL36RN may have a definite effect on pathological similarities between AGEP and generalized pustular psoriasis.

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A Comprehensive Review of HLA and Severe Cutaneous Adverse Drug Reactions: Implication for Clinical Pharmacogenomics and Precision Medicine

Pharmaceuticals ◽

10.3390/ph14111077 ◽

2021 ◽

Vol 14 (11) ◽

pp. 1077

Author(s):

Chiraphat Kloypan ◽

Napatrupron Koomdee ◽

Patompong Satapornpong ◽

Therdpong Tempark ◽

Mohitosh Biswas ◽

...

Keyword(s):

Clinical Practice ◽

Precision Medicine ◽

Adverse Drug Reactions ◽

Drug Hypersensitivity ◽

Human Leukocyte ◽

Population Level ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Drug Induced ◽

Systemic Symptoms

Human leukocyte antigen (HLA) encoded by the HLA gene is an important modulator for immune responses and drug hypersensitivity reactions as well. Genetic polymorphisms of HLA vary widely at population level and are responsible for developing severe cutaneous adverse drug reactions (SCARs) such as Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), maculopapular exanthema (MPE). The associations of different HLA alleles with the risk of drug induced SJS/TEN, DRESS and MPE are strongly supportive for clinical considerations. Prescribing guidelines generated by different national and international working groups for translation of HLA pharmacogenetics into clinical practice are underway and functional in many countries, including Thailand. Cutting edge genomic technologies may accelerate wider adoption of HLA screening in routine clinical settings. There are great opportunities and several challenges as well for effective implementation of HLA genotyping globally in routine clinical practice for the prevention of drug induced SCARs substantially, enforcing precision medicine initiatives.

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Clinical Phenotypes of Severe Cutaneous Drug Hypersensitivity Reactions

Current Pharmaceutical Design ◽

10.2174/1381612825666191107162921 ◽

2019 ◽

Vol 25 (36) ◽

pp. 3840-3854 ◽

Cited By ~ 2

Author(s):

Hakan Guvenir ◽

Tugba Arikoglu ◽

Emine Vezir ◽

Emine Dibek Misirlioglu

Keyword(s):

Adverse Drug Reactions ◽

Drug Hypersensitivity ◽

Stevens Johnson Syndrome ◽

Facial Oedema ◽

Hypersensitivity Reactions ◽

Drug Reactions ◽

Cutaneous Manifestations ◽

Clinical Phenotypes ◽

Drug Eruptions ◽

Drug Hypersensitivity Reactions

Drug hypersensitivity reactions are clinically heterogenous ranging from mild to severe. Most drug hypersensitivity reactions are accompanied by cutaneous manifestations. Fever, mucous membrane involvement, large blisters, facial oedema, pustulosis and visceral involvement are clinical features that lead to suspicion of severe adverse drug reactions. Severe cutaneous adverse drug reactions (SCARs) include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash eosinophilia and systemic symptoms, acute generalized exanthematous pustulosis. Serum sickness like reactions, drug induced vasculitis and generalized bullous fixed drug eruptions are less severe clinical entities. SCARs are uncommon but associated with significant morbidity and mortality. Physician should be aware of specific red flags and danger signs to immediately identify these reactions. Immediate drug withdrawal is mandatory. Early diagnosis and appropriate treatment significantly affect the prognosis of the disease. The purpose of our review is to discuss clinical phenotypes of severe cutaneous drug hypersensitivity reactions.

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Genetic susceptibilities and prediction modeling of carbamazepine and allopurinol-induced severe cutaneous adverse reactions in Vietnamese

Pharmacogenomics ◽

10.2217/pgs-2019-0146 ◽

2020 ◽

Author(s):

Dinh van Nguyen ◽

Hieu Chi Chu ◽

Christopher Vidal ◽

Richard B Fulton ◽

Nguyet Nhu Nguyen ◽

...

Keyword(s):

Adverse Reactions ◽

Surrogate Marker ◽

Hypersensitivity Syndrome ◽

Stevens Johnson Syndrome ◽

Strongly Correlated ◽

Drug Induced ◽

Johnson Syndrome ◽

Severe Cutaneous Adverse Reactions ◽

Systemic Symptoms ◽

Cutaneous Adverse Reactions

Aims: To determine genetic susceptibility markers for carbamazepine (CBZ) and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese. Methods: A case control study was performed involving 122 patients with CBZ or allopurinol induced SCARs and 120 drug tolerant controls. Results: HLA-B*58:01 was strongly associated with allopurinol-induced SCARs and strongly correlated with SNP rs9263726. HLA-B*15:02 was associated with CBZ-induced Stevens–Johnson syndrome/toxic epidermal necrolysis but not with drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms. No association was found between HLA-A*31:01 and CBZ-induced SCARs. HLA-B*58:01 and rs3909184 allele A with renal insufficiency were shown to increase the risk of allopurinol-induced SCARs. Conclusion: HLA-B*58:01 and HLA-B*15:02 confer susceptibility to allopurinol-induced SCARs and CBZ-induced SJS/TEN in Vietnamese. Single nucleotide polymorphism rs9263726 can be used as a surrogate marker in identifying HLA-B*58:01.

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A Review of Adverse Cutaneous Drug Reactions Resulting from the Use of Interferon and Ribavirin

Canadian Journal of Gastroenterology ◽

10.1155/2009/651952 ◽

2009 ◽

Vol 23 (10) ◽

pp. 677-683 ◽

Cited By ~ 42

Author(s):

Nisha Mistry ◽

Jonathan Shapero ◽

Richard I Crawford

Keyword(s):

Side Effects ◽

Drug Reactions ◽

Drug Induced ◽

Common Cause ◽

Injection Site Reactions ◽

Drug Eruptions ◽

Fixed Drug ◽

Life Threatening ◽

Cutaneous Drug Reactions ◽

Systemic Drug

Drug-induced cutaneous eruptions are named among the most common side effects of many medications. Thus, cutaneous drug eruptions are a common cause of morbidity and mortality, especially in hospital settings. The present article reviews different presentations of drug-induced cutaneous eruptions, with a focus on eruptions reported secondary to the use of interferon and ribavirin. Presentations include injection site reactions, psoriasis, eczematous drug reactions, alopecia, sarcoidosis, lupus, fixed drug eruptions, pigmentary changes and lichenoid eruptions. Also reviewed are findings regarding life-threatening systemic drug reactions.

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Major Aspects of Detection and Monitoring of Adverse Reactions Associated with Cephalosporin Antibiotic Treatment

Safety and Risk of Pharmacotherapy ◽

10.30895/2312-7821-2021-9-1-34-42 ◽

2021 ◽

Vol 9 (1) ◽

pp. 34-42

Author(s):

E. Yu. Demchenkova ◽

G. I. Gorodetskaya ◽

I. A. Mazerkina ◽

M. V. Zhuravleva ◽

A. S. Kazakov ◽

...

Keyword(s):

Adverse Events ◽

Adverse Drug Reactions ◽

Patient Information ◽

Adverse Reactions ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Patient Information Leaflets ◽

Information Leaflets ◽

Spontaneous Reports ◽

Cephalosporin Antibiotics

Widespread use of cephalosporin antibiotics in clinical practice calls for greater attention to the risk of adverse drug reactions. Information on serious or unexpected adverse events reported during post-marketing experience is submitted to national and international pharmacovigilance databases. Analysis of these reports helps to identify new adverse drug reactions.The aim of the study was to analyse the safety profile of cephalosporin antibiotics based on spontaneous reports in the international VigiBase database.Materials and methods: the analysis of the adverse reaction profile of cephalosporin antibiotics was based on MedDRA system organ classes and included spontaneous reports submitted to VigiBase from the moment of its creation until August 2020.Results: the authors identified the most clinically significant adverse reactions for different cephalosporin generations. They compared and analysed information on adverse events in VigiBase and in patient information leaflets of medicinal products authorised in the Russian Federation. It was demonstrated that some serious events described in VigiBase spontaneous reports for V-generation cephalosporins are not included in the “Side effects” section of the patient information leaflets. According to VigiBase, the use of ceftaroline was associated with the development of generalised exfoliative dermatitis, Stevens–Johnson syndrome, tubulointerstitial nephritis, while the use of ceftolozane was associated with acute kidney injury, renal insufficiency, sepsis, pneumonia, and respiratory insufficiency.Conclusion: reporting of unexpected and serious adverse drug reactions to cephalosporin antibiotics is an important task of healthcare practitioners. Availability of information on class-specific and generation-specific serious adverse reactions will help predict and prevent their development.

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Overlapping DRESS and Stevens-Johnson Syndrome: Case Report and Review of the Literature

Case Reports in Dermatology ◽

10.1159/000475802 ◽

2017 ◽

Vol 9 (2) ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Aneline Casagranda ◽

Mariano Suppa ◽

Florence Dehavay ◽

Véronique del Marmol

Keyword(s):

Diagnostic Criteria ◽

Adverse Reactions ◽

Stevens Johnson Syndrome ◽

Drug Induced ◽

Johnson Syndrome ◽

Systemic Symptoms ◽

The Right ◽

Exanthematous Pustulosis ◽

Cutaneous Adverse Reactions

Drug-induced severe cutaneous adverse reactions (SCARs) include acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), and epidermal necrolysis (Stevens-Johnson syndrome [SJS], toxic epidermal necrolysis). The identification of the causal drug is crucial in order to avoid further exposure, but making the right differential diagnosis of the type of SCAR is equally important since treatment, follow-up, and prognosis of different SCARs are not the same. These syndromes are distinct entities with different clinical, biological, and histological patterns, but sometimes the early distinction between 2 SCARs can be extremely challenging, and overlapping conditions could therefore be taken into consideration, although true overlapping SCARs are very rare when using strict diagnostic criteria (described by the RegiSCAR group). Only a better understanding of the physiopathology of the SCARs could possibly explain these ambiguities and overlaps. We report a case of SCAR in an 86-year-old patient probably induced by allopurinol and simultaneously fulfilling the diagnostic criteria for DRESS and SJS, thus considered as an overlapping case of SCARs.

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HLA Association with Drug-Induced Adverse Reactions

Journal of Immunology Research ◽

10.1155/2017/3186328 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 17

Author(s):

Wen-Lang Fan ◽

Meng-Shin Shiao ◽

Rosaline Chung-Yee Hui ◽

Shih-Chi Su ◽

Chuang-Wei Wang ◽

...

Keyword(s):

Adverse Drug Reactions ◽

Antithyroid Drug ◽

Human Leukocyte ◽

Stevens Johnson Syndrome ◽

Drug Reactions ◽

Drug Induced ◽

Hla Association ◽

Hla Genes ◽

Johnson Syndrome ◽

Life Threatening

Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI). In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.

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Severe Cutaneous Adverse Drug Reactions in Bangladesh: A Review in a Tertiary Level Hospital

Journal of Armed Forces Medical College Bangladesh ◽

10.3329/jafmc.v12i2.41098 ◽

2016 ◽

Vol 12 (2) ◽

pp. 71-75

Author(s):

Md Niamul Gani Chowdhury ◽

Mohammad Enamul Hoque ◽

Md Abdul Latif Khan ◽

Md Shirajul Islam Khan

Keyword(s):

Adverse Drug Reactions ◽

Armed Forces ◽

Stevens Johnson Syndrome ◽

Military Hospital ◽

Case Report Form ◽

Drug Reactions ◽

Female Ratio ◽

Medical College ◽

Johnson Syndrome ◽

Systemic Symptoms

Introduction: The Severe Cutaneous Adverse Drug Reactions (SCADRs) are rare but life-threatening as these encompass drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and acute generalized exanthematous pustulosis (AGEP). Objective: To estimate the incidence of SCADRs and to find out the cause in Bangladesh. Materials and Methods: 50 patients with SCADRs were studied over a period of 1 year from January 2015 to December 2015 in the Department of Dermatology, Combined Military Hospital, Dhaka. Data were collected from the informant and recorded in structured Case Report Form. Quantitative data were expressed as mean and standard deviation and qualitative data as frequency and percentage. Results: Clinical diagnosis of the study subjects recognized 46.0% cases as SJS, 28(19.0%) as TEN, 16.0% as DRESS and 10.0% as AGEP. The maximum incidence (46%) was seen in the age group of 31-50 years; mean age of the patient was 37.42+5.3 years. Male and female ratio was 2.84:1. Anticonvulsant group of drugs could give rise to maximum incidence of SCADRs. Carbamazepine was responsible in 22.0% cases of SCADRs, followed by Phenytoin in 16.0% patients and Phenobarbital in 14.0% cases. Conclusion: SCADRs were seen mostly with the anticonvulsant drugs belonging to Carbamazepine and Phenytoin group. SCADRs deserve continuous monitoring to plan preventive strategies. Journal of Armed Forces Medical College Bangladesh Vol.12(2) 2016: 71-75

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