Current Opinion in Allergy and Clinical Immunology

doi: 10.1097/ACI.0000000000000557pmid: N/A

Blanca, Miguel;Whitaker, Paul

doi: 10.1097/ACI.0000000000000554pmid: 31169595

aAllergy Service, Hospital Infanta Leonor, Madrid, Spain bDepartment of Respiratory Medicine, Leeds Teaching Hospitals NHS Trust, Leeds, UK Correspondence to Miguel Blanca, Allergy Service, Hospital Infanta Leonor, 28031 Madrid, Spain. E-mail: [email protected]

Garvey, Lene H.;Savic, Louise C.

doi: 10.1097/ACI.0000000000000543pmid: 31247633

Purpose of review This review aims to describe current best practice and recent advances in the use of risk stratification as a tool for drug provocation testing (DPT). In particular, we focus on the testing of unsubstantiated penicillin allergy labels. Recent findings The inherent risks of DPT are mitigated through careful selection of patients. A detailed history will elicit features of a potentially severe index reaction, as well as significant patient comorbidities which may increase the risks associated with DPT. Such patients require skin testing and/or in vitro testing prior to consideration for a DPT. However, there is increasing evidence that patients without these features may be able to proceed directly to DPT. This has been demonstrated extensively with unsubstantiated penicillin allergy labels, and a variety of risk stratification models have been employed to identify the ‘low-risk’ patient. Improved outcomes and reduced cost have been demonstrated with such models without compromising patient safety. Summary Risk stratification tools may enable well-tolerated and effective ‘delabelling’ of low-risk patients, with less demand on already scarce resources. aDanish Anaesthesia Allergy Centre, Allergy Clinic, Department of dermatology and allergy, Copenhagen University Hospital Gentofte bDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark cAnaesthetic Department, Leeds Teaching Hospitals NHS Trust, Leeds, UK Correspondence to Lene H. Garvey, MD, Danish Anaesthesia Allergy Centre, Allergy Clinic, Department of dermatology and allergy, Copenhagen University Hospital Gentofte, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. E-mail: [email protected]

Peter, Jonny;Choshi, Phuti;Lehloenya, Rannakoe J.

doi: 10.1097/ACI.0000000000000545pmid: 31145192

Purpose of review Immune-mediated adverse drug reactions (IM-ADRs) are many times more common in HIV-infected patients. Usual offending drugs include antiretroviral and antiinfectives, but the burden of specific drug IM-ADRs is population-specific; changing as new and fixed dose combinations enter the market, and drug-resistance patterns demand. This review considers recent literature on epidemiology, mechanisms, clinical management and prevention of IM-ADRs amongst persons living with HIV/AIDS. Recent findings Epidemiological studies continue to describe high rates of delayed hypersensitivity to known offenders, as well as similar reactions in preexposure prophylaxis. IM-ADRs to oral and injectable integrase strand transfer inhibitors are reported with expanding use. The clinical spectrum and management of IM-ADRs occurring in HIV-infected populations is similar to uninfected; with exceptions such as a recently described severe delayed efavirenz DILI with high mortality. Furthermore, the context can be unique, such as the lower than expected mortality in a Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) cohort from a HIV/TB high burden setting. Programmatic data showing the near complete elimination of Abacavir drug hypersensitivity syndrome following implementation of HLA-B57:01 screening is a stellar example of how prevention is possible with mechanistic insight. Summary IM-ADRs remain a challenge in persons living with HIV. The complexities posed by polypharmacy, overlapping drug toxicities, drug interactions, overlap of IM-ADRs with other diseases, limited alternative drugs, and vulnerable patients with advanced immunosuppression with high mortality, necessitate increased use of drug provocation testing, treat-through and desensitization strategies. There is an urgent need for improved diagnostics and predictive biomarkers for prevention, or to guide treat-through, rechallenge and desensitization approaches. aDivision of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town bAllergy and Immunology Unit, University of Cape Town Lung Institute cCombined Drug Allergy Clinic, Groote Schuur Hospital dDivision of Dermatology, Department of Medicine, University of Cape Town, Cape Town, South Africa Correspondence to Professor Jonny Peter, Division of Allergy and Clinical Immunology, H52 Old Main Building, Groote Schuur Hospital, Observatory, 7925 Cape Town, South Africa. E-mail: [email protected]

Ardern-Jones, Michael R.;Mockenhaupt, Maja

doi: 10.1097/ACI.0000000000000546pmid: 31247634

Purpose of review Severe cutaneous adverse reactions (SCAR) are relatively uncommon but can be life-threatening. This review focuses on the nonanaphylactic (non-IgE-mediated) phenotypes of drug hypersensitivity, with specific reference to diagnosis and management of acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Recent findings Here, we review recent guidelines on optimal supportive care as well as publications of interventional treatment for SJS/TEN, including various immunomodulating therapies, and management strategies for severe ocular disease with the use of amniotic membrane transplantation. In DRESS, long-term autoimmune sequelae are increasingly recognized and modify strategies for treatment of the acute episode. If the causative drug is not apparent from careful inspection of the drug exposure history, in-vitro diagnostics, HLA testing and skin testing before drug challenge testing may be considered and we present an algorithm for investigation of complex cases. Summary Careful phenotypic analysis of the increasingly complex recognized patterns of SCAR facilitates the enhancement in our understanding of T-cell mediated drug hypersensitivity and allows the improvement of in-vitro diagnostic testing to minimize patient exposure to test substances in all but a very limited number of cases, thereby enhancing safety. aDepartment of Dermatology, Southampton General Hospital, University Hospitals Southampton NHS Foundation Trust bDermatoimmunology, Sir Henry Wellcome Laboratories, Clinical, Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK cDokumentationszentrum schwerer Hautreaktionen (dZh), Department of Dermatology, Medical Center and Medical Faculty, University of Freiburg, Freiburg, Germany Correspondence to Associate Professor Michael R. Ardern-Jones, LF76, South Academic Block (MP825), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. Tel: +44 2381 206594; e-mail: [email protected]

Gómez, E.;Ruano, M.;Somoza, M.L.;Fernández, J.;Blanca-López, N.

doi: 10.1097/ACI.0000000000000547pmid: 31135394

Purpose of review Nonimmediate drug hypersensitivity reactions (NI-DHR) constitute the most complex group of drug allergy, with many drugs involved. Both parent drugs and their reactive metabolites can be implicated. Although with some drugs the number of metabolites is limited, with others it is quite extensive and many still remain to be identified. The diagnostic approaches are insufficient for the diagnosis and realistic approaches that reproduce the pathological response are lacking. Recent findings A wider view has now been considered, with the inclusion of several mechanisms that may contribute to drug hypersensitivity reactions (DHR): the classical hapten hypothesis, the danger signal and the pharmacological interaction. Monitoring the acute response provides relevant information about the mechanisms involved, with the identification of a large number of genes that can be over-expressed or under-expressed in the acute phase of the response. Assessment of risk of developing reactions can be verified by HLA associations. Summary Further knowledge of these NI-DHR, including molecular genetics and transcriptomic analysis, has enabled a better understanding and management of these reactions. aRoche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland bGeneral University Hospital of Alicante cInfanta Leonor University Hospital, Allergy Service, Madrid, Spain Correspondence to E. Gómez, Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Brunngasse, 40. 4153. Reinach. BL., Switzerland. Tel: +41 76 321 40 37; e-mail: [email protected]

Lee, Youngsoo;Shin, Yoo Seob;Park, Hae-Sim

doi: 10.1097/ACI.0000000000000541pmid: 31107257

Purpose of review Nonsteroidal anti-inflammatory drug (NSAID) is one of the most frequently prescribed medications in the medical field, and hypersensitivity to NSAID is a common adverse drug reaction encountered. However, NSAID hypersensitivity presents a variety of symptoms caused by diverse pharmacological and immunological mechanisms. Recent findings Owing to the heterogeneity of the disease, a new concept for the classification of NSAID hypersensitivity has recently been proposed to diagnose and manage NSAID hypersensitivity for personalized treatment. Acute and delayed reactions were distinguished in this classification, and identification of symptoms and speculation of putative mechanisms help physicians make the right diagnosis. NSAID-exacerbated respiratory disease is a noticeable phenotype of NSAID hypersensitivity that involves upper airway comorbidities (chronic rhinosinusitis with nasal polyps) as well as asthmatic features. The cutaneous phenotypes of NSAID hypersensitivity occur, and cross-reactivity with other types of NSAID should be considered in establishing a proper diagnosis. Hypersensitivity to a single NSAID can present urticaria/angioedema and anaphylaxis, in which an IgE-mediated immune response is suggested to be a prime mechanism. Management of NSAID hypersensitivity reactions includes avoidance, pharmacological treatment following standard guidelines, and aspirin desensitization. Summary The classification, diagnosis, and management of NSAID hypersensitivity should be individually reached by identifying its phenotype. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea Correspondence to Hae-Sim Park, Department of Allergy and Clinical Immunology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Korea. Tel: +82 31 219 5150; fax: +82 31 219 5154; e-mail: [email protected]

Brockow, Knut;Pfützner, Wolfgang

doi: 10.1097/ACI.0000000000000548pmid: 31135396

Purpose of review Cutaneous drug hypersensitivity reactions (CDHRs) are a complicated area with multiple clinical manifestations and differential diagnoses, requiring differentiated diagnostic measurements and optimized therapeutic management. Recent findings Disseminated CDHRs to classical drugs can be classified by a simple algorithm, whereas chemotherapeuticals or biopharmaceuticals may show drug-specific and atypical clinical presentations. Controversies in drug hypersensitivity diagnosis exist about the benefit and accuracy of in-vitro tests. Although skin tests are the best means of detecting sensitization to drugs, methods have not been sufficiently standardized. The necessity for skin tests before performing drug provocation test (DPT) and of prolonged DPTs is discussed in selected patients. If a suspicion has been documented, β-lactam allergy should be excluded. The standard allergy diagnosis is done by an allergist. In case of urgent need because of an infection and low risk according to history, faster delabeling pathways have been developed. There is weak evidence that patients with mastocytosis may have a slightly increased risk of developing immediate-type drug hypersensitivity; however, if considerations are taken, drugs do not have to be withheld for this patient group. There is particular need for improved diagnostic measurements in patients with drug-induced severe cutaneous adverse reactions (SCARs), both identifying the offending drug and detecting individuals at risk. Further challenges encompass appropriate treatments during the acute as well as chronic phase of SCARs. Summary Recent literature has contributed to our understanding of clinical manifestations and existing controversies and future needs in this area. aDepartment of Dermatology and Allergology Biederstein, School of Medicine, Technical University of Munich, Munich bDepartment of Dermatology and Allergology, University Medical Center, Gießen and Marburg GmbH, Philipps Universität, Marburg, Germany Correspondence to Knut Brockow, Department of Dermatology and Allergology Biederstein, School of Medicine, Technical University Munich, Biedersteiner Str. 29, 80802 München, Germany. Tel:+ 0049 89 4140 3182; fax+: 0049 89 4140 3127; e-mail: [email protected]

Roesner, Lennart M.;Zeitvogel, Jana;Heratizadeh, Annice

doi: 10.1097/ACI.0000000000000553pmid: 31157635

Purpose of review This review summarizes the mode of action of IL-4 and IL-13 in skin allergy, upcoming therapeutics and depicts key outcomes of the latest clinical trials. Recent findings Atopic dermatitis is considered to be one of the most common inflammatory skin disease in industrialized countries. Accompanied by strong pruritus, atopic dermatitis has a significant impact on quality of life in severely affected individuals. Aside from unspecific immunosuppressant medications, therapeutics targeting the key cytokines IL-4 and IL-13 and their downstream mediators are under development or have been approved just recently with outstanding potential. Summary The recent development of several biologics and small compounds has the potential to revolutionize the treatment of atopic dermatitis, and applying this set of state-of-the-art drugs will provide a unique chance to gain insights into this skin disorder, patient subgroups, and key inflammatory mediators. Division of Immunodermatology and Allergy Research, Department of Dermatology, Allergy and Venereology, Hannover Medical School Hannover, Hannover, Germany Correspondence to Jana Zeitvogel, Division of Immunodermatology and Allergy Research, Department of Dermatology, Allergy and Venereology, Hannover Medical School, Hannover, Germany. Tel: +49 511 532 5074; e-mail. [email protected]

Lunjani, Nonhlanhla;Hlela, Carol;O’Mahony, Liam

doi: 10.1097/ACI.0000000000000542pmid: 31107258

Purpose of review The skin is home to a diverse milieu of bacteria, fungi, viruses, bacteriophages, and archaeal communities. The application of culture-independent approaches has revolutionized the characterization of the skin microbiome and have revealed a previously underappreciated phylogenetic and functional granularity of skin-associated microbes in both health and disease states. Recent findings The physiology of a given skin-niche drives the site-specific differences in bacterial phyla composition of healthy skin. Changes in the skin microbiome have consistently been associated with atopic dermatitis. In particular, Staphylococcus aureus overgrowth with concomitant decline in Staphylococcus epidermidis is a general feature associated with atopic dermatitis and is not restricted to eczematous lesions. Changes in fungal species are now also being described. Changes in the composition and metabolic activity of the gut microbiota are associated with skin health. Summary We are now beginning to appreciate the intimate and intricate interactions between microbes and skin health. Multiple studies are currently focused on the manipulation of the skin or gut microbiome to explore their therapeutic potential in the prevention and treatment of skin inflammation. aAPC Microbiome Ireland, University College Cork, Cork, Ireland bDepartment of Dermatology, University of Cape Town, Cape Town, South Africa cDepartment of Medicine and Microbiology, University College Cork, Cork, Ireland Correspondence to Liam O’Mahony, Office 450, 4th Floor Food Science and Technology Building, University College Cork, Cork, Ireland. Tel: +353 21 4901316; e-mail: [email protected]