Fever, Rash, and Systemic Symptoms: Understanding the Role of Virus and HLA in Severe Cutaneous Drug Allergy

Pavlos, Rebecca; Mallal, S.; Ostrov, David A.; Pompeu, Y.A.; Phillips, Elizabeth

doi:10.1016/j.jaip.2013.11.005

Cited by 81 publications

(62 citation statements)

References 162 publications

(76 reference statements)

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“…89 Several insights of importance for diagnosis and potential future management of drug allergy were reported. HLA associations with adverse drug reactions are well described, 90 but Gueant et al 91 have now identified HLA-DRA variants predicting penicillin/amoxicillin allergy but not cephalosporin allergy. Insight into the mechanism of keratinocyte apoptosis in patients with toxic epidermal necrolysis (TEN) was noted in a study of microRNAs extracted from tissues and sera of patients and through supporting in vitro studies.…”

Section: Drug Allergymentioning

confidence: 99%

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014

Sicherer

Leung

2015

Journal of Allergy and Clinical Immunology

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This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin diseases that were reported in the Journal in 2014. Studies on food allergy suggest worrisomely high rates of peanut allergy and food-induced anaphylaxis-related hospitalizations. Evidence is mounting to support the theory that environmental exposure to peanut, such as in house dust, especially with an impaired skin barrier attributed to atopic dermatitis (AD) and loss of function mutations in the filaggrin gene, is a risk factor for sensitization and allergy. Diagnostic tests are improving, with early studies suggesting the possibility of developing novel cellular tests with increased diagnostic utility. Treatment trials continue to show the promise and limitations of oral immunotherapy, and mechanistic studies are elucidating pathways that might define the degree of efficacy of this treatment. Studies have also provided insights into the prevalence and characteristics of anaphylaxis and insect venom allergy, such as suggesting that baseline platelet-activating factor acetylhydrolase activity levels are related to the severity of reactions. Advances in drug allergy include identification of HLA associations for penicillin allergy and a microRNA biomarker/mechanism for toxic epidermal necrolysis. Research identifying critical events leading to skin barrier dysfunction and the polarized immune pathways that drive AD have led to new therapeutic approaches in the prevention and management of AD.

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Section: Drug Allergymentioning

confidence: 99%

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014

Sicherer

Leung

2015

Journal of Allergy and Clinical Immunology

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“…However, this system did not include HHV-6 reactivation, which is not a feature of other adverse drug reactions, making its detection a sensitive and specific marker for the diagnosis of DIHS. Based on this, an updated diagnostic tool with nine parameters was developed by a Japanese consensus group (J-SCAR), with the requirement of at least seven to identify DRESS [26] (Table 3).…”

Section: Statins-atorvastatinmentioning

confidence: 99%

Eosinophilic Drug Allergy

Kuruvilla

Khan

2015

Clinic Rev Allerg Immunol

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While peripheral or tissue eosinophilia may certainly characterize drug eruptions, this feature is hardly pathognomonic for a medication-induced etiology. While delayed drug hypersensitivity reactions with prominent eosinophilic recruitment have been typically classified as type IVb reactions, their pathophysiology is now known to be more complex. Eosinophilic drug reactions have a diversity of presentations and may be benign and self-limited to severe and life-threatening. The extent of clinical involvement is also heterogeneous, ranging from isolated peripheral eosinophilia or single organ involvement (most often the skin and lung) to systemic disease affecting multiple organs, classically exemplified by drug-reaction with eosinophilia and systemic symptoms (DRESS). The spectrum of implicated medications in the causation of DRESS is ever expanding, and multiple factors including drug metabolites, specific HLA alleles, herpes viruses, and immune system activation have been implicated in pathogenesis. Due to this complex interplay of various factors, diagnostic workup in terms of skin and laboratory testing has not been validated. Similarly, the lack of controlled trials limits treatment options. This review also describes other localized as well as systemic manifestations of eosinophilic disease induced by various medication classes, including their individual pathophysiology, diagnosis, and management. Given the multitude of clinical patterns associated with eosinophilic drug allergy, the diagnosis can be challenging. Considerable deficits in our knowledge of these presentations remain, but the potential for severe reactions should be borne in mind in order to facilitate diagnosis and institute appropriate management.

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“…HLA-B*5701, HLA-B*5801, HLA-B*1502, HLA-A*3101, HLA-A*0206, HLA-B*4403, HLA-A29, HLA-B12, HLA-DR7, and HLA-A2 are linked to SJS drug hypersensitivity reactions. [38][39][40][41] HLA-DQB1*0601, HLA-DQA1*0103, DQB1*0301, and HLA-A*0206 are linked to ocular manifestations in SJS. 42 Genetic influences can explain why SJS occurs in multiple family members even though it is a rare condition 43 or why it recurs in certain individuals.…”

Section: Genetic Predispositionmentioning

confidence: 99%

Stevens-Johnson Syndrome without Skin Lesions: A Rare and Clinically Challenging Disease in the Urgent Setting

Anders¹,

Taylor²,

Kravchuk³

et al. 2015

Emerg Med Open J

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Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme are life threatening diseases causing mucocutaneous eruptions and can be difficult to manage medically. When oral tissues are involved, airway management can be of critical importance. Fluid and electrolyte imbalance are common and protocols to prevent secondary infection are initiated. All three conditions are rapidly evolving. Stevens-Johnson syndrome is more commonly associated with Mycoplasma pneumoniae in the pediatric population and drug hypersensitivity in adults, whereas erythema multiforme is mostly associated with herpes simplex virus in the adult population. These diseases are T-cell-mediated immune reactions, thought to represent a spectrum of the same disease. Clinical and immunohistochemical techniques are capable of differentiating Stevens-Johnson syndrome from erythema multiforme and provide insight into the possible underlying pathology creating the disease. Rare cases of Stevens-Johnson syndrome without skin manifestations have been associated with Mycoplasma pneumoniae and predominantly occur in males. In-hospital management is recommended to provide airway support, maintain fluid intake, electrolyte balance, obtain multi-speciality consultation, and to perform diagnostic testing. We describe a case of a 14 year old male with atypical Stevens-Johnson syndrome and a review of the literature.

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Fever, Rash, and Systemic Symptoms: Understanding the Role of Virus and HLA in Severe Cutaneous Drug Allergy

Cited by 81 publications

References 162 publications

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014

Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2014

Eosinophilic Drug Allergy

Stevens-Johnson Syndrome without Skin Lesions: A Rare and Clinically Challenging Disease in the Urgent Setting

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