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1
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Pichler WJ, Thoo L, Yerly D. Drug hypersensitivity and eosinophilia: The decisive role of p-i stimulation. Allergy 2023; 78:2596-2605. [PMID: 37395496 DOI: 10.1111/all.15795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 05/31/2023] [Accepted: 06/16/2023] [Indexed: 07/04/2023]
Abstract
Eosinophilia is a common finding in drug hypersensitivity reactions (DHR). Its cause is unclear, as neither antigen/allergen-driven inflammation nor clonal expansion is involved. Most delayed-DHRs are due to p-i (pharmacologic interaction of drugs with immune receptors). These are off-target activities of drugs with immune receptors that result in various types of T-cell stimulation, some of which involve excessive IL-5 production. Functional and phenotypic studies of T-cell clones and their TCR-transfected hybridoma cell lines revealed that some p-i-induced drug stimulations occur without CD4/ CD8 co-receptor engagement. The CD4/CD8 co-receptors link Lck (lymphocyte-specific protein tyrosine kinase) and LAT (linker for activation of T cells) to the TCR. Alteration of Lck or LAT can result in a TCR signalosome with enhanced IL-5 production. Thus, if a more affine TCR-[drug/peptide/HLA] interaction allows bypassing the CD4 co-receptor, a modified Lck/LAT activation may lead to a TCR signalosome with elevated IL-5 production. This "IL-5-TCR-signalosome" hypothesis could also explain eosinophilia in superantigen or allo-stimulation (graft-versus-host disease), in which evasion of CD4/CD8 co-receptors has also been described. It may open new therapeutic possibilities in certain eosinophilic diseases by directly targeting the IL-5-TCR signalosome.
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2
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Caro-Chang LA, Fung MA. The role of eosinophils in the differential diagnosis of inflammatory skin diseases. Hum Pathol 2023; 140:101-128. [PMID: 37003367 DOI: 10.1016/j.humpath.2023.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 03/27/2023] [Indexed: 04/03/2023]
Abstract
Eosinophils are known to be present in inflammatory skin diseases, but their diagnostic utility is not well established. Upon review of the published status of lesional eosinophils, several categories were identified. 1) Lesional eosinophils highly characteristic such that, in their absence, the pathologist may question the diagnosis. These include arthropod bite reactions and scabies, urticarial dermatitis, and other eosinophilic dermatoses. 2) Lesional eosinophils rare or absent, such that, in their presence, the pathologist may question the diagnosis. These include pityriasis lichenoides, graft versus host disease, and connective tissue disorders. 3) Lesional eosinophils variable and, while in some cases expected, are not required for diagnosis. These include drug reactions, atopic dermatitis and allergic contact dermatitis. 4) Lesional eosinophils variable and not expected but may be seen to a limited extent. These include lichen planus and psoriasis.
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3
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Abstract
Disorders of hyperpigmentation are common and challenging conditions which can arise due to a myriad of etiologic factors. Many of them can present across skin types but are more common in skin of color individuals with Fitzpatrick skin types III-VI. Facial hyperpigmentation, in particular, can have a significant impact on the quality of life of affected individuals due to its increased visibility. This article provides a comprehensive review of disorders of facial hyperpigmentation including epidemiology, pathogenesis, diagnostic considerations, and treatment approaches for these conditions.
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Affiliation(s)
- Nicole C Syder
- Department of Dermatology, Keck School of Medicine of University of Southern California, Keck School of Medicine, University of Southern California, 830 South Flower Street, Suite 100, Los Angeles, CA 90017, USA
| | - Claudia Quarshie
- Department of Dermatology, Keck School of Medicine of University of Southern California, Keck School of Medicine, University of Southern California, 830 South Flower Street, Suite 100, Los Angeles, CA 90017, USA
| | - Nada Elbuluk
- Department of Dermatology, Keck School of Medicine of University of Southern California, Keck School of Medicine, University of Southern California, 830 South Flower Street, Suite 100, Los Angeles, CA 90017, USA.
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4
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Someko H, Kataoka Y, Obara T. Drug fever: a narrative review. ANNALS OF CLINICAL EPIDEMIOLOGY 2023; 5:95-106. [PMID: 38504950 PMCID: PMC10944987 DOI: 10.37737/ace.23013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/21/2024]
Abstract
Drug fever is an adverse drug reaction accompanied by a febrile response and is a common problem among clinicians, hence an updated knowledge of drug fever is important. A consensus regarding the definition of drug fever is lacking. Thus, descriptions of drug fever in previous literature are often inconsistent. In this narrative review, we summarized various features of drug fever, including its definition, epidemiology, risk factors, clinical presentation, diagnosis, treatment and prognosis, based on the earliest literature. Recent advances in information technology have encouraged researchers to use pharmacovigilance databases for clinical and pharmacological research. We outlined how a pharmacovigilance database, along with recently developed research methods, could be used to research drug fever.
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Affiliation(s)
- Hidehiro Someko
- Department of General Internal Medicine, Asahi General Hospital
- Scientific Research WorkS Peer Support Group (SRWS-PSG)
| | - Yuki Kataoka
- Scientific Research WorkS Peer Support Group (SRWS-PSG)
- Department of Internal Medicine, Kyoto Min-iren Asukai Hospital
- Section of Clinical Epidemiology, Department of Community Medicine, Kyoto University Graduate School of Medicine
- Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine/Public Health
| | - Taku Obara
- Department of Pharmaceutical Sciences, Tohoku University Hospital
- Division of Molecular Epidemiology, Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University
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Abstract
Doctors-in-training often receive an inadequate dermatology education. Furthermore, studies have highlighted the under-representation of skin of colour (SOC) in dermatological teaching, learning resources and research. Our image-based questionnaire, distributed to all internal medicine trainees in southwest England, highlighted knowledge gaps regarding SOC among training physicians. It is intrinsically more challenging for clinicians to confidently formulate dermatological diagnoses in SOC. In this review, we provide guidance for physicians to help make the diagnostic process more straightforward. First, we outline how skin colour is determined and classified. We discuss how inflammation presents in SOC, with the typical 'erythema' that physicians often associate with inflammation being a less prominent feature in darker skin tones. We then summarise nine important conditions that we believe physicians working in all specialties should be able to identify in patients with SOC, covering both conditions encountered on the medical take and conditions disproportionately affecting individuals with SOC. The population of the UK is rapidly diversifying; thus, as physicians, we have a professional duty to educate ourselves on dermatological conditions in SOC to provide the best quality of care for all our patients, regardless of their skin type.
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Affiliation(s)
- Eliza Hutchison
- University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
| | - Rakeb Yoseph
- University of Bristol Medical School, Bristol, UK
| | - Hannah Wainman
- Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK
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6
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Ernst M, Lundgren M, Evans MD, Miller D, Giubellino A. The Mixed Spongiotic and Interface Reaction Pattern: A Study of Clinical and Histopathologic Findings. J Cutan Pathol 2022; 49:1051-1059. [PMID: 36445270 PMCID: PMC9709294 DOI: 10.1111/cup.14306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 07/12/2022] [Accepted: 08/01/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Categorization of biopsy specimens into inflammatory reaction patterns is central to dermatopathologic assessment. Mixed inflammatory patterns are poorly characterized and may represent clinicopathologic challenges. The purpose of this study was to identify clinical and histopathologic findings associated with the mixed spongiotic-interface dermatitis (SID) histopathologic pattern. METHODS Fifty-one institutional biopsy specimens of SID were identified over a 2-year period by retrospective natural language search. Histopathologic and clinical features were identified. RESULTS The most common histopathologic features associated with SID were mild spongiosis (51%), focal vacuolar interface change (72%), lymphocytic exocytosis (92%), and superficial-dermal lymphocytic infiltrate (94%) with variable eosinophils (61%). Clinically, 80% of subjects presented with a symmetric morbilliform eruption. Polypharmacy (94%), immunosuppression (47%), and history of malignancy (47%) were common. The most common diagnoses were drug reaction (37%), possible drug reaction (12%), and viral exanthem (12%). Drug reaction with eosinophilia and systemic symptoms represented 25% of all confirmed cutaneous adverse drug reactions (CADR). Average time from drug initiation to symptom initiation was 20 days (SD: 22.3, range: 0-90); median disease duration was 25.5 days. Spongiotic vesicles and Langerhans cells were less common in patients with a strong clinicopathologic diagnosis of drug reaction compared to non-drug eruptions (p = 0.04). CONCLUSIONS The mixed SID pattern is commonly encountered in CADR but may represent a more subacute course, implying consideration for inciting medication(s) started before the typical 7- to 14-day window.
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Affiliation(s)
- Madison Ernst
- University of Minnesota, Department of Laboratory Medicine and Pathology
- University of Minnesota, Department of Dermatology
| | - Mia Lundgren
- University of Minnesota, Department of Laboratory Medicine and Pathology
| | - Michael D. Evans
- University of Minnesota, Clinical and Translational Science Institute
| | | | - Alessio Giubellino
- University of Minnesota, Department of Laboratory Medicine and Pathology
- University of Minnesota, Masonic Cancer Center Minneapolis
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Histopathologic Features of Maculopapular Drug Eruption. Dermatopathology (Basel) 2022; 9:111-121. [PMID: 35466243 PMCID: PMC9036233 DOI: 10.3390/dermatopathology9020014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/23/2022] [Accepted: 03/28/2022] [Indexed: 12/19/2022] Open
Abstract
Background: Cutaneous adverse drug reaction (CADR) is common in both inpatient and outpatient clinical settings and has been associated with a large variety of medications. Drug reactions represent a significant burden to the healthcare system due to increased hospital stay durations and associated costs. Moreover, some of these reactions may be life-threatening. The most common clinical manifestation of a CADR is a maculopapular drug eruption (MDE). Due to its many clinical mimics and associations with a variety of histopathologic patterns, maculopapular drug eruption is difficult to definitively diagnose from both a clinical and histopathological perspective. Summary: We reviewed the clinical and histopathologic features of 327 cases of MDE from several studies in the literature and summarized characteristic histopathologic findings and their frequencies of occurrence. We found that the most common and suggestive histopathologic features of MDE were epidermal spongiosis, lymphocytic infiltrate, and occasional necrotic keratinocytes; interface change at the DEJ; superficial perivascular and interstitial lymphocytic infiltrate with or without eosinophils and neutrophils in the mid-to-deep dermis and mild papillary dermal edema; and dilation of superficial vessels. The presence of multiple histopathologic patterns within the same tissue specimen is also suggestive of MDE. This review and analysis suggest that a biopsy may improve the diagnostic accuracy by both establishing common and uncommon features associated with MDE and reviewing features that help to exclude other causes of maculopapular eruption. Key Message: Histopathologic criteria for the diagnosis of MDE, while not entirely specific, may aid in establishing a differential that includes a drug eruption. Thus, a biopsy can be a helpful diagnostic tool when MDE is suspected by demonstrating findings suggestive of MDE or by ruling out clinical mimics. However, biopsy results cannot be used in isolation as clinical-pathologic correlation is paramount in MDE.
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8
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Telemedicine in Drug Hypersensitivity. Immunol Allergy Clin North Am 2022; 42:323-333. [DOI: 10.1016/j.iac.2021.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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9
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Tsabouri S, Atanaskovic-Markovic M. Skin eruptions in children: Drug hypersensitivity vs viral exanthema. Pediatr Allergy Immunol 2021; 32:824-834. [PMID: 33621365 DOI: 10.1111/pai.13485] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 02/13/2021] [Accepted: 02/18/2021] [Indexed: 12/11/2022]
Abstract
Childhood rashes or exanthemas are common and are usually relatively benign. There are many causes of rash in children, including mainly viruses, and less often bacterial toxins, drugs, allergens and other diseases. Viral exanthema often appears while children are taking a medication in the course of a viral infection; it can mimic drug exanthema and is perceived as a drug allergy in 10% of cases. In the vast majority of cases, the distinction between virus-induced and drug-induced skin eruption during the acute phase is not possible. The drugs most commonly implicated are beta-lactams (BL) and non-steroidal anti-inflammatory drugs (NSAIDs). Viruses, commonly Epstein-Barr virus (EBV), human herpesvirus 6 (HHV6) and cytomegalovirus (CMV), and the bacterium, Mycoplasma pneumoniae, may cause exanthema either from the infection itself (active or latent) or because of interaction with drugs that are taken simultaneously. Determination of the exact diagnosis requires a careful clinical history and thorough physical examination. Haematological and biochemical investigations and histology are not always helpful in differentiating between the two types of exanthema. Serological and polymerase chain reaction (PCR) assays can be helpful, although a concomitant acute infection does not exclude drug hypersensitivity. A drug provocation test (DPT) is although considered the gold standard for the diagnosis and is not preferred by the patients. Skin tests are not well tolerated, and in vitro tests, such as the basophil activation test and lymphocyte transformation, are of low sensitivity and specificity and their relevance is debatable. Based on current evidence, we propose a systematic clinical approach for timely differential diagnosis and management of rashes in children who present a cutaneous eruption while receiving a drug.
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Affiliation(s)
- Sophia Tsabouri
- Child Health Department, Medical School, University of Ioannina, Ioannina, Greece
| | - Marina Atanaskovic-Markovic
- Faculty of Medicine, University of Belgrade, Belgrade, Serbia.,University Children's Hospital of Belgrade, Belgrade, Serbia
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10
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Neumayer DS, Rongisch R, Kästle J. [Emergencies in dermatology : From gonorrhea to angioedema]. Med Klin Intensivmed Notfmed 2020; 115:699-707. [PMID: 32910216 DOI: 10.1007/s00063-020-00723-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Revised: 05/24/2020] [Accepted: 05/25/2020] [Indexed: 11/30/2022]
Abstract
The spectrum of dermatological emergencies is diverse. Infections, in particular sexually transmitted infections, anaphylactic reactions, and cutaneous drug reactions are common causes for patients to present themselves to the dermatological emergency service. If a sexually transmitted infection is suspected, it is important for the physician to recognize which diseases need immediate treatment to avoid late complications. This requires a reliable diagnosis and knowledge of the appropriate therapy. Cutaneous drug reactions can take many forms. There is a spectrum of reactions that occur immediately after the administration of a medication (which manifest themselves as anaphylaxis), to those that can appear weeks after the initiation of a therapy. These reactions can be harmless and self-limiting, but also be life-threatening. It is essential for physicians in everyday clinical practice to recognize drug intolerances in time and to treat them appropriately.
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Affiliation(s)
- Daniela Stefanie Neumayer
- Institut für Dermatologie und Venerologie, Universitätsklinikum Köln, Kerpener Str. 62, 50937, Köln, Deutschland.
| | - Robert Rongisch
- Institut für Dermatologie und Venerologie, Universitätsklinikum Köln, Kerpener Str. 62, 50937, Köln, Deutschland
| | - Judith Kästle
- Institut für Dermatologie und Venerologie, Universitätsklinikum Köln, Kerpener Str. 62, 50937, Köln, Deutschland
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11
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Takenaka D, Nishizawa T. Morbilliform drug eruptions caused by trimethoprim–sulfamethoxazole. BMJ Case Rep 2020; 13:13/9/e238255. [DOI: 10.1136/bcr-2020-238255] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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12
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Deschaine MA, Lehman JS. The interface reaction pattern in the skin: an integrated review of clinical and pathological features. Hum Pathol 2019; 91:86-113. [DOI: 10.1016/j.humpath.2019.06.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 06/18/2019] [Accepted: 06/20/2019] [Indexed: 12/14/2022]
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13
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Kim TO, Shin HJ, Kim YI, Lim SC, Koh YI, Kwon YS. Cutaneous adverse drug reactions in patients with peripheral blood eosinophilia during antituberculosis treatment. Korean J Intern Med 2019; 34:1050-1057. [PMID: 30879290 PMCID: PMC6718751 DOI: 10.3904/kjim.2018.063] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2018] [Accepted: 07/25/2018] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND/AIMS Peripheral eosinophilia during tuberculosis (TB) treatment is common, but has not been fully evaluated. The aim of this study was to determine the prevalence and clinical significance of peripheral blood eosinophilia in patients undergoing anti-TB treatment. METHODS We retrospectively reviewed the clinical and laboratory data of patients who received anti-TB treatment and had peripheral blood eosinophilia (> 5% of the total white blood cell count) at the Chonnam National University Hospital between January 2010 and December 2014. RESULTS Of all 2,234 patients with TB who received anti-TB treatment, 397 (17.8%) had peripheral blood eosinophilia. Of the 397 with eosinophilia, we reviewed the data of 262 (66%), and cutaneous adverse drug reactions (CADRs) were observed in 161 (61.5%). Of the 161 with CADRs, itching (47.2%) and skin rash (47.8%) were common. Older age, abnormal liver function, and higher peak blood eosinophil percentage were associated with CADRs in multivariate analysis. There was a significant relationship between increased peak eosinophil counts and the degree of severity of CADRs. CONCLUSION Peripheral blood eosinophilia is a relatively common occurrence during anti-TB treatment. Peripheral blood eosinophil counts were higher according to the degree of severity of CADRs.
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Affiliation(s)
- Tae-Ok Kim
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea
| | - Hong-Joon Shin
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea
| | - Yu-Il Kim
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea
| | - Sung-Chul Lim
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea
| | - Young-Il Koh
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea
| | - Yong-Soo Kwon
- Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Korea
- Correspondence to Yong-Soo Kwon, M.D. Department of Internal Medicine, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 61469, Korea Tel: +82-62-220-6575 Fax: +82-62-225-8578 E-mail:
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14
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Samuelov L, Nathan A, Slutsky E, Fruchter D, Gat A, Sprecher E, Goldberg I. Nested case–control study investigating the diagnostic role of tissue eosinophilia in adverse cutaneous drug reactions. J Eur Acad Dermatol Venereol 2019; 33:1152-1157. [DOI: 10.1111/jdv.15509] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2018] [Accepted: 01/18/2019] [Indexed: 12/21/2022]
Affiliation(s)
- L. Samuelov
- Department of Dermatology Tel Aviv Sourasky Medical Center Affiliated with Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
| | - A. Nathan
- Department of Dermatology Tel Aviv Sourasky Medical Center Affiliated with Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
| | - E. Slutsky
- Department of Dermatology Tel Aviv Sourasky Medical Center Affiliated with Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
| | - D. Fruchter
- Department of Dermatology Tel Aviv Sourasky Medical Center Affiliated with Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
| | - A. Gat
- Institute of Pathology Tel Aviv Sourasky Medical Center Affiliated with Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
| | - E. Sprecher
- Department of Dermatology Tel Aviv Sourasky Medical Center Affiliated with Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
| | - I. Goldberg
- Department of Dermatology Tel Aviv Sourasky Medical Center Affiliated with Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
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15
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Dermatologic Conditions of the Early Post-Transplant Period in Hematopoietic Stem Cell Transplant Recipients. Am J Clin Dermatol 2019; 20:55-73. [PMID: 30298481 DOI: 10.1007/s40257-018-0391-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Hematopoietic stem cell transplants (HSCTs) are used to treat a variety of conditions, including hematologic malignancies, bone marrow failure syndromes, and immunodeficiencies. Over 60,000 HSCTs are performed annually worldwide, and the numbers continue to increase. Indeed, as new conditioning regimens develop, more and more individuals, including those of older age, will be eligible for transplants. Nevertheless, although HSCTs are clearly a life-saving and necessary treatment for thousands of patients per year, there is still substantial morbidity and mortality associated with the procedure. Of note, skin eruptions in the post-HSCT period are frequent and often significantly reduce quality of life in recipients. Moreover, these cutaneous findings sometimes herald an underlying systemic condition, presenting possible opportunities for timelier intervention. Dermatologists therefore play a vital role in distinguishing life-threatening conditions from benign issues and prompting recognition of critical complications earlier in their course. This article aims to review the major dermatologic conditions occurring in the early post-HSCT period.
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16
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Ortonne N. [Histopathology of cutaneous drug reactions]. Ann Pathol 2017; 38:7-19. [PMID: 29279184 DOI: 10.1016/j.annpat.2017.10.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2017] [Accepted: 10/26/2017] [Indexed: 12/17/2022]
Abstract
There are many different types of cutaneous adverse reactions. The most classical reactions are driven by T lymphocytes that specifically react towards a drug, with an individual genetic susceptibility linked to certain type I major histocompatibility complex alleles. These reactions are characterized by a wide variety of clinical and histopathological presentations, and a wide range of severity. The most frequent entity is the maculopapular rash, while the most aggressive forms are the Steven-Johnson syndrome and toxic epidermal necrolysis (SJS-TEN). The histopathological alterations associated to each of these syndromes have been better described in the literature during the past 10 years, encompassing non-specific lesions, as in most drug induced maculopapular rashes, to more specific inflammatory patterns. The finding of confluent apoptotic keratinocytes with epidermal detachment is the prototypical aspect of SJS-TEN. There are however numerous pitfalls, and a similar aspect to those observed in each cutaneous drug reactions entities can be found in other diseases. DRESS syndrome can indeed present with dense and epidermotropic T-cell infiltrate, sometimes with nuclear atypias, and thus can be difficult to distinguish from a primary or secondary cutaneous T-cell lymphoma. The diagnosis of cutaneous adverse reactions relies on a clinical-pathological confrontation and requires an accurate evaluation of drug imputability.
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Affiliation(s)
- Nicolas Ortonne
- Département de pathologie, hôpital Henri-Mondor, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil, France.
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17
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Singh S, Khandpur S, Arava S, Rath R, Ramam M, Singh M, Sharma VK, Kabra SK. Assessment of histopathological features of maculopapular viral exanthem and drug-induced exanthem. J Cutan Pathol 2017; 44:1038-1048. [DOI: 10.1111/cup.13047] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Revised: 09/10/2017] [Accepted: 09/11/2017] [Indexed: 12/19/2022]
Affiliation(s)
- Sanjay Singh
- Department of Dermatology and Venereology; All India Institute of Medical Sciences; New Delhi India
| | - Sujay Khandpur
- Department of Dermatology and Venereology; All India Institute of Medical Sciences; New Delhi India
| | - Sudheer Arava
- Department of Pathology; All India Institute of Medical Sciences; New Delhi India
| | - Ramashankar Rath
- Department of Centre for Community Medicine; All India Institute of Medical Sciences; New Delhi India
| | - M. Ramam
- Department of Dermatology and Venereology; All India Institute of Medical Sciences; New Delhi India
| | - Manoj Singh
- Department of Pathology; All India Institute of Medical Sciences; New Delhi India
| | - Vinod K. Sharma
- Department of Dermatology and Venereology; All India Institute of Medical Sciences; New Delhi India
| | - Sushil Kumar Kabra
- Department of Paediatrics; All India Institute of Medical Sciences; New Delhi India
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18
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Wang F, Zhao YK, Li M, Zhu Z, Zhang X. Trends in culprit drugs and clinical entities in cutaneous adverse drug reactions: a retrospective study. Cutan Ocul Toxicol 2017; 36:370-376. [PMID: 28423957 DOI: 10.1080/15569527.2017.1301947] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Fang Wang
- Department of Dermatology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China,
| | - Yu-Kun Zhao
- Department of Dermatology, Eastern Hospital of First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, and
| | - Minyi Li
- Department of Dermatology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China,
| | - Zhe Zhu
- Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Xingqi Zhang
- Department of Dermatology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China,
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19
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Abstract
The term "drug reactions" is relevant to dermatology in three categories of reactions: cutaneous drug reactions without systemic features, cutaneous drug reactions with systemic features, and systemic drugs prescribed by the dermatologist with systematic adverse effects. This article uses examples from each of these categories to illustrate several important principles central to drug reaction diagnosis and management. The information presented will help clinicians attain the highest possible level of certainty before making clinical decisions.
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Affiliation(s)
- Stephen E Wolverton
- Department of Dermatology, Indiana University, 545 Barnhill Drive, Emerson Hall 139, Indianapolis, IN 46202, USA.
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20
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Dodiuk-Gad RP, Chung WH, Shear NH. Adverse Medication Reactions. CLINICAL AND BASIC IMMUNODERMATOLOGY 2017. [PMCID: PMC7123512 DOI: 10.1007/978-3-319-29785-9_25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Cutaneous adverse drug reactions (ADRs) are among the most frequent adverse reactions in patients receiving drug therapy. They have a broad spectrum of clinical manifestations, are caused by various drugs, and result from different pathophysiological mechanisms. Hence, their diagnosis and management is challenging. Severe cutaneous ADRs comprise a group of diseases with major morbidity and mortality, reaching 30 % mortality rate in cases of Toxic Epidermal Necrolysis. This chapter covers the terminology, epidemiology, pathogenesis and classification of cutaneous ADR, describes the severe cutaneous ADRs and the clinical and laboratory approach to the patient with cutaneous ADR and presents the translation of laboratory-based discoveries on the genetic predisposition and pathogenesis of cutaneous ADRs to clinical management guidelines.
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21
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Abstract
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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Affiliation(s)
- Merin Kuruvilla
- Department of Internal Medicine, Division of Allergy & Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - David A Khan
- Department of Internal Medicine, Division of Allergy & Immunology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
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22
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Weinborn M, Barbaud A, Truchetet F, Beurey P, Germain L, Cribier B. Histopathological study of six types of adverse cutaneous drug reactions using granulysin expression. Int J Dermatol 2016; 55:1225-1233. [DOI: 10.1111/ijd.13350] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 03/07/2016] [Accepted: 03/20/2016] [Indexed: 01/26/2023]
Affiliation(s)
- Marie Weinborn
- Department of Dermatology; Nancy University Hospital; Brabois Hospital; Vandoeuvre-les-Nancy France
| | - Annick Barbaud
- Department of Dermatology; Nancy University Hospital; Brabois Hospital; Vandoeuvre-les-Nancy France
| | - Francois Truchetet
- Department of Dermatology; Metz-Thionville Regional Hospital; Thionville France
| | | | - Lucie Germain
- Department of Clinical Epidemiology and Evaluation; Nancy University Hospital; Nancy France
| | - Bernard Cribier
- Department of Dermatology; Strasbourg University Hospital; Strasbourg France
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23
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Skowron F, Bensaid B, Balme B, Depaepe L, Kanitakis J, Nosbaum A, Maucort-Boulch D, Bérard F, D'Incan M, Kardaun S, Nicolas JF. Comparative histological analysis of drug-induced maculopapular exanthema and DRESS. J Eur Acad Dermatol Venereol 2016; 30:2085-2090. [DOI: 10.1111/jdv.13832] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 05/17/2016] [Indexed: 11/30/2022]
Affiliation(s)
- F. Skowron
- Department of Dermatology; CH de Valence; Valence France
| | - B. Bensaid
- Drug Allergy Unit-CCR2A; Department of Allergy and Clinical Immunology; CHU Lyon-Sud; Pierre-Bénite France
| | - B. Balme
- Department of Dermatopathology; CHU Lyon-Sud; Pierre-Bénite France
| | - L. Depaepe
- Department of Dermatopathology; CHU Lyon-Sud; Pierre-Bénite France
| | - J. Kanitakis
- Department of Dermatology; Groupement Hospitalier Edouard Herriot; Lyon France
| | - A. Nosbaum
- Drug Allergy Unit-CCR2A; Department of Allergy and Clinical Immunology; CHU Lyon-Sud; Pierre-Bénite France
- INSERM U1111 - CIRI; av T Garnier; Lyon France
| | | | - F. Bérard
- Drug Allergy Unit-CCR2A; Department of Allergy and Clinical Immunology; CHU Lyon-Sud; Pierre-Bénite France
- INSERM U1111 - CIRI; av T Garnier; Lyon France
| | - M. D'Incan
- Department of Dermatology; CHU Estaing; Clermont-Ferrand France
| | - S.H. Kardaun
- Department of Dermatology; Reference center for cutaneous adverse reactions; University Medical Center of Groningen; Groningen the Netherlands
| | - J.-F. Nicolas
- Drug Allergy Unit-CCR2A; Department of Allergy and Clinical Immunology; CHU Lyon-Sud; Pierre-Bénite France
- INSERM U1111 - CIRI; av T Garnier; Lyon France
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24
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Botelho LF, Porro AM, Enokihara MM, Tomimori J. Adverse cutaneous drug reactions in a single quaternary referral hospital. Int J Dermatol 2015; 55:e198-203. [DOI: 10.1111/ijd.13126] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Revised: 05/30/2015] [Accepted: 06/15/2015] [Indexed: 11/29/2022]
Affiliation(s)
| | - Adriana M. Porro
- Department of Dermatology; Federal University of São Paulo; São Paulo Brazil
| | | | - Jane Tomimori
- Department of Dermatology; Federal University of São Paulo; São Paulo Brazil
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25
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Abstract
Dermatology consultation can improve diagnostic accuracy in the hospitalized patient with cutaneous disease. Dermatology consultation can streamline and improve treatment plans, and potentially lead to cost savings. Dermatology consultants can be a valuable resource for education for trainees, patients, and families. Inpatient consultative dermatology spans a breadth of conditions, including inflammatory dermatoses,infectious processes, adverse medication reactions, and neoplastic disorders, many of which can be diagnosed based on dermatologic examination alone, but when necessary, bedside skin biopsies can contribute important diagnostic information.
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Affiliation(s)
- Lauren K Biesbroeck
- Division of Dermatology, University of Washington School of Medicine, 1959 Northeast Pacific Street BB-1353, Box 356524, Seattle, WA 98195-6524, USA
| | - Michi M Shinohara
- Division of Dermatology, University of Washington School of Medicine, 1959 Northeast Pacific Street BB-1353, Box 356524, Seattle, WA 98195-6524, USA.
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26
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Abstract
Cutaneous drug reactions are common adverse effects that occur in about 2-3% of the hospitalized patients. They have both immunologic and non-immunologic underlying mechanisms. These reactions are clinically and histologically similar to dermatoses. Their significant clinical indicators include: history of drug intake, atypical clinical features and improvement after cessation of the offending drugs. Their diagnostic histological clues include the presence of mixed histological patterns, apoptotic keratinocytes, eosinophils (dermis and epidermis), papillary dermal edema and extravasations of erythrocytes. However, no single clinical or histological feature is specific of drug eruptions. This work attempts to classify the histomorphologic reactions to various drugs in defined categories for assistance in morphologic diagnosis.
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27
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Ortonne N, Valeyrie-Allanore L, Bastuji-Garin S, Wechsler J, de Feraudy S, Duong TA, Delfau-Larue MH, Chosidow O, Wolkenstein P, Roujeau JC. Histopathology of drug rash with eosinophilia and systemic symptoms syndrome: a morphological and phenotypical study. Br J Dermatol 2015; 173:50-8. [DOI: 10.1111/bjd.13683] [Citation(s) in RCA: 83] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/25/2015] [Indexed: 01/29/2023]
Affiliation(s)
- N. Ortonne
- Département de Pathologie; Assistance Publique - Hôpitaux de Paris (AP-HP); Hôpital Henri-Mondor; 94010 Créteil Cedex France
- INSERM U955 équipe 9; Hôpital Henri-Mondor; 94010 Créteil Cedex France
- Université Paris Est Créteil (UPEC); Faculté de Médecine, LIC EA4393; 94010 Créteil Cedex France
| | - L. Valeyrie-Allanore
- Université Paris Est Créteil (UPEC); Faculté de Médecine, LIC EA4393; 94010 Créteil Cedex France
- Service de Dermatologie; Assistance Publique - Hôpitaux de Paris (AP-HP); Hôpital Henri-Mondor; 94010 Créteil Cedex France
| | - S. Bastuji-Garin
- Université Paris Est Créteil (UPEC); Faculté de Médecine, LIC EA4393; 94010 Créteil Cedex France
- Service de Santé-Publique; Assistance Publique - Hôpitaux de Paris (AP-HP); Hôpital Henri-Mondor; 94010 Créteil Cedex France
| | - J. Wechsler
- Département de Pathologie; Assistance Publique - Hôpitaux de Paris (AP-HP); Hôpital Henri-Mondor; 94010 Créteil Cedex France
| | - S. de Feraudy
- Département de Pathologie; Assistance Publique - Hôpitaux de Paris (AP-HP); Hôpital Henri-Mondor; 94010 Créteil Cedex France
| | - T.-A. Duong
- Université Paris Est Créteil (UPEC); Faculté de Médecine, LIC EA4393; 94010 Créteil Cedex France
- Service de Dermatologie; Assistance Publique - Hôpitaux de Paris (AP-HP); Hôpital Henri-Mondor; 94010 Créteil Cedex France
| | - M.-H. Delfau-Larue
- INSERM U955 équipe 9; Hôpital Henri-Mondor; 94010 Créteil Cedex France
- Université Paris Est Créteil (UPEC); Faculté de Médecine, LIC EA4393; 94010 Créteil Cedex France
- Service d'Immunologie Biologique; Assistance Publique - Hôpitaux de Paris (AP-HP); Hôpital Henri-Mondor; 94010 Créteil Cedex France
| | - O. Chosidow
- Université Paris Est Créteil (UPEC); Faculté de Médecine, LIC EA4393; 94010 Créteil Cedex France
- Service de Dermatologie; Assistance Publique - Hôpitaux de Paris (AP-HP); Hôpital Henri-Mondor; 94010 Créteil Cedex France
| | - P. Wolkenstein
- Université Paris Est Créteil (UPEC); Faculté de Médecine, LIC EA4393; 94010 Créteil Cedex France
- Service de Dermatologie; Assistance Publique - Hôpitaux de Paris (AP-HP); Hôpital Henri-Mondor; 94010 Créteil Cedex France
| | - J.-C. Roujeau
- Université Paris Est Créteil (UPEC); Faculté de Médecine, LIC EA4393; 94010 Créteil Cedex France
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28
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Kim JT, Jeong HW, Choi KH, Yoon TY, Sung N, Choi YK, Kim EH, Chae HB. Delayed hypersensitivity reaction resulting in maculopapular-type eruption due to entecavir in the treatment of chronic hepatitis B. World J Gastroenterol 2014; 20:15931-15936. [PMID: 25400481 PMCID: PMC4229562 DOI: 10.3748/wjg.v20.i42.15931] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2014] [Revised: 05/25/2014] [Accepted: 07/25/2014] [Indexed: 02/07/2023] Open
Abstract
Several clinical trials have demonstrated the potent antiviral efficacy of entecavir (ETV), and this relatively new nucleoside analogue drug has rapidly become a frequently prescribed therapy for chronic hepatitis B (CHB) worldwide. While the studies have also shown a good overall safety profile for ETV, adverse drug reactions (ADRs) in patients with advanced cirrhosis have been reported and represent a broad spectrum of drug-induced injuries, including lactic acidosis, myalgia, neuropathy, azotemia, hypophosphatemia, muscular weakness, and pancreatitis, as well as immune-mediated responses (i.e., allergic reactions). Cutaneous ADRs associated with ETV are very rare, with only two case reports in the publicly available literature; both of these cases were classified as unspecified hypersensitivity allergic (type I) ADR, but neither were reported as pathologically proven or as evaluated by cytokine release analysis. Here, we report the case of a 45-year-old woman who presented with a generalized maculopapular rash after one week of ETV treatment for lamivudine-resistant CHB. The patient reported having experienced a similar skin eruption during a previous three-month regimen of ETV, for which she had self-discontinued the medication. Histopathological analysis of a skin biopsy showed acanthotic epidermis with focal parakeratosis and a perivascular lymphocytic infiltrate admixed with interstitial eosinophils in the papillary and reticular dermis, consistent with a diagnosis of drug sensitivity. A lymphocyte stimulation test showed significantly enhanced IL-4, indicating a classification of type IVb delayed hypersensitivity. The patient was switched to an adefovir-lamivudine combination regimen and the skin eruption resolved two weeks after the ETV withdrawal. This case represents the first pathologically and immunologically evidenced ETV-induced delayed type hypersensitivity skin reaction reported to date. Physicians should be aware of the potential, although rare, for cutaneous ADRs associated with ETV treatment.
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MESH Headings
- Antiviral Agents/adverse effects
- Biopsy
- Cells, Cultured
- Cytokines/metabolism
- Drug Eruptions/blood
- Drug Eruptions/diagnosis
- Drug Eruptions/etiology
- Drug Eruptions/immunology
- Drug Substitution
- Female
- Guanine/adverse effects
- Guanine/analogs & derivatives
- Hepatitis B, Chronic/diagnosis
- Hepatitis B, Chronic/drug therapy
- Humans
- Hypersensitivity, Delayed/blood
- Hypersensitivity, Delayed/chemically induced
- Hypersensitivity, Delayed/diagnosis
- Hypersensitivity, Delayed/immunology
- Leukocytes, Mononuclear/drug effects
- Leukocytes, Mononuclear/immunology
- Leukocytes, Mononuclear/metabolism
- Middle Aged
- Skin/drug effects
- Skin/immunology
- Skin/pathology
- Time Factors
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29
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Drug Reaction Patterns. Dermatopathology (Basel) 2014. [DOI: 10.1007/978-1-4471-5448-8_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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30
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Drug-induced exanthems: Correlation of allergy testing with histologic diagnosis. J Am Acad Dermatol 2013; 69:721-728. [DOI: 10.1016/j.jaad.2013.06.022] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Revised: 06/03/2013] [Accepted: 06/06/2013] [Indexed: 11/20/2022]
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31
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Liippo J, Pummi K, Hohenthal U, Lammintausta K. Patch testing and sensitization to multiple drugs. Contact Dermatitis 2013; 69:296-302. [DOI: 10.1111/cod.12076] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Revised: 01/21/2013] [Accepted: 02/09/2013] [Indexed: 12/17/2022]
Affiliation(s)
- Jussi Liippo
- Department of Dermatology; Turku University Hospital; 20521 Turku Finland
| | - Kati Pummi
- Department of Dermatology; Turku University Hospital; 20521 Turku Finland
- Department of Pathology; Turku University Hospital; 20521 Turku Finland
| | - Ulla Hohenthal
- Department of Internal Medicine; Turku University Hospital; 20521 Turku Finland
| | - Kaija Lammintausta
- Department of Dermatology; Turku University Hospital; 20521 Turku Finland
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32
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Schwartz RA, McDonough PH, Lee BW. Toxic epidermal necrolysis: Part II. Prognosis, sequelae, diagnosis, differential diagnosis, prevention, and treatment. J Am Acad Dermatol 2013; 69:187.e1-16; quiz 203-4. [PMID: 23866879 DOI: 10.1016/j.jaad.2013.05.002] [Citation(s) in RCA: 197] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Revised: 05/06/2013] [Accepted: 05/10/2013] [Indexed: 02/01/2023]
Abstract
Toxic epidermal necrolysis (TEN) is a life-threatening, typically drug-induced, mucocutaneous disease. TEN has a high mortality rate, making early diagnosis and treatment of paramount importance. New but experimental diagnostic tools that measure serum granulysin and high-mobility group protein B1 (HMGB1) offer the potential to differentiate early TEN from other, less serious drug reactions, but these tests have not been validated and are not readily available. The mainstay of treatment for TEN involves discontinuation of the offending drug, specialized care in an intensive care unit or burn center, and supportive therapy. Pharmacogenetic studies have clearly established a link between human leukocyte antigen allotype and TEN. Human leukocyte antigen testing should be performed on patients of East Asian descent before the initiation of carbamezapine and on all patients before the initiation of abacavir. The effectiveness of systemic steroids, intravenous immunoglobulins, plasmapheresis, cyclosporine, biologics, and other agents is uncertain.
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Affiliation(s)
- Robert A Schwartz
- Dermatology, Preventive Medicine, and Pathology, Rutgers University New Jersey Medical School, Newark, New Jersey 07103-2714, USA.
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33
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Turk BG, Gunaydin A, Ertam I, Ozturk G. Adverse cutaneous drug reactions among hospitalized patients: five year surveillance. Cutan Ocul Toxicol 2012; 32:41-5. [PMID: 22812902 DOI: 10.3109/15569527.2012.702837] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
CONTEXT Cutaneous Adverse Drug Reactions (CADRs) are observed in 2-3% of hospitalized patients. The clinical presentation of the CADRs varies among different populations. OBJECTIVE To study the CADRs in hospitalized patients and their outcome. MATERIALS AND METHODS Patients hospitalized at our department between 2005 May and 2010 May were retrospectively reviewed for the diagnosis of CADRs. RESULTS A total of 94 patients (3.3%) were diagnosed with CADR among 2801 hospitalized patients. Of them, 56 patients were female (59.6%) and 38 patients were male (40.4%). The culprit drugs were antibiotics (24.5%), non-steroid anti-inflammatory drugs (NSAID) (22.4%), anticonvulsants (13.8%), antihypertensive agents (8.5%), paracetamol with or without pseudoephedrine or phenylephrine (6.4%), intravenous contrasts (3.2%), terbinafine (2.1%), biologic agents (2.1%) and various other medications (17.0%). The most common clinical type of CADRs was morbilliform exanthemas in 59.6% of the patients, followed by erythroderma (6.4%), drug reactions with eosinophilia and systemic symptoms (6.4%), lichenoid drug reaction (5.3%), urticaria and angioedema (4.3%), acute generalized exanthematous pustulosis (4.3%), drug-induced vasculitis (3.2%), drug induced psoriasis (2.1%), Stevens-Johnson syndrome/toxic epidermal necrolysis overlap (2.1%), psoriasiform drug reaction (2.1%). Fixed drug reaction, erythema multiforme, bullous drug reaction, drug induced panniculitis were observed in one each. No deaths occurred on the follow-up. Fever was observed in 35.1% of the patients. Eosinophilia was present in 51.1% of them. Latency period ranged between 0-15 days in 59 patients (62.8%), 15-30 days in 19 patients (20.2%), 30-90 days in 13 patients (13.8%), 90-120 days in three of them (3.2%). The latency for anticonvulsant drugs was statistically longer than the other group of drugs (p: 0.027). DISCUSSION AND CONCLUSIONS CADRs were more common in women and most of them were caused by antimicrobial agents followed by NSAIDs and anticonvulsants. Latency period of anticonvulsants were longer than the other groups.
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Affiliation(s)
- Bengu Gerceker Turk
- Ege University Medical Faculty, Department of Dermatology, Bornova, Izmir, Turkey.
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34
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Heinzerling LM, Tomsitz D, Anliker MD. Is drug allergy less prevalent than previously assumed? A 5-year analysis. Br J Dermatol 2012; 166:107-14. [PMID: 21916887 DOI: 10.1111/j.1365-2133.2011.10623.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Rashes are a frequent conundrum in clinical practice as they may be reactive, drug induced or disease specific. Identification of the culprit drug is important as re-exposure may be harmful or even life-threatening and unnecessary avoidance of 'innocent' drugs leads to limitations of treatment options. OBJECTIVE To objectify the cause of suspected cutaneous drug reactions in a large patient population. METHOD Over 5years (2006-10), 612 patients with suspected cutaneous drug reactions were evaluated. Histology was assessed. About 200 patients were invited for complete work-up with skin tests (prick/intracutaneous testing and scratch/patch as indicated) and, if necessary, lymphocyte transformation tests (LTT). In special cases, drug provocation tests were conducted. RESULTS A total number of 141 cases with suspected drug reaction underwent full work-up (age 6-86years; 75% female, 25% male). In 107 cases (76%) a drug was identified whereas 34 (24%) were reactive rashes or had other causes. Mostly, cutaneous drug reactions were maculopapular rashes, urticaria/angio-oedema; less frequently, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, systemic drug-related intertriginous and flexural exanthema, toxic epidermal necrolysis and fixed drug eruptions were present. Of all the cutaneous drug reactions investigated, 39·8% were caused by antibiotics, 21·2% by anti-inflammatories, 7·6% by contrast media and 31·4% by others (oral antidiabetics, antimycotics, antipsychotics, antiepileptics and others). CONCLUSION Clinical assessment overestimates the role of drug allergies in cutaneous reactions. Assessment of suspected drug reactions can be greatly improved by thorough evaluation including dermatological and allergological work-up with skin testing and assays such as LTT.
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Affiliation(s)
- L M Heinzerling
- Department of Dermatology and Allergies, Cantonal Hospital, St Gallen, Switzerland Department of Dermatology, University Hospital Erlangen, 91054 Erlangen, Germany.
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35
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Gavini A, Telang GH, Olszewski AJ. Generalized purpuric drug exanthem with hemorrhagic plaques following bendamustine chemotherapy in a patient with B-prolymphocytic leukemia. Int J Hematol 2012; 95:311-4. [DOI: 10.1007/s12185-012-1012-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2011] [Revised: 01/18/2012] [Accepted: 01/19/2012] [Indexed: 10/14/2022]
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36
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Abstract
Many cutaneous conditions can mimic infection. If these lesions are not accurately recognized, they may be treated with antimicrobial agents, which adds cost, potential risk, and inconvenience to the patient and the healthcare system. The presenting signs and symptoms of many ulcerating, pustular, morbilliform, bullous, neoplastic, granulomatous, autoimmune, and neutrophilic conditions, as well as clinical vasculitis, cellulitis, folliculitis, and panniculitis, have been mistaken for infection. This review emphasizes the clinical presentation, physical exam, and diagnostic workup of many of these conditions to assist the clinician in ascertaining the correct diagnosis. In addition, general treatment options are provided for each disease category.
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Affiliation(s)
- Janelle R Ricketts
- Dermatology Department, University of CT Health Center, Farmington, CT 06030, USA.
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37
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Rouzaire P, Luci C, Blasco E, Bienvenu J, Walzer T, Nicolas JF, Hennino A. Natural killer cells and T cells induce different types of skin reactions during recall responses to haptens. Eur J Immunol 2011; 42:80-8. [PMID: 21968602 DOI: 10.1002/eji.201141820] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2011] [Revised: 08/25/2011] [Accepted: 09/20/2011] [Indexed: 11/07/2022]
Abstract
The role of T cells in contact hypersensitivity (CHS) to haptens has been well described. However, recent reports demonstrated that CHS-like reactions to experimental haptens could be induced in mice deficient in T cells and B cells, as a result of adaptive-like features of NK cells. Here, we compared hapten-specific inflammatory reactions induced by memory T cells or NK cells. Classical CHS protocols were applied to WT or T- and B-cell deficient mice. Adoptive transfers of hapten-specific T cells and NK cells were also performed. Liver NK cells from hapten-primed mice induced specific recall responses to haptens upon transfer in CD3ε-deficient mice, thus confirming the existence of "memory" NK cells in the liver. We investigated the nature of the inflammation generated in these transfer conditions and found that hapten-induced skin inflammation mediated by CD8(+) T cells or "memory" NK cells are different. Indeed, ear swelling induced by memory NK cells was transient and not associated with cellular infiltrate and inflammation markers, characteristic for T-cell-mediated responses. Thus, NK cells and T cells mediate distinct forms of skin inflammation. NK cell-mediated pathogenesis does not rely on cellular infiltrate and could be involved in atypical forms of adverse drug reactions.
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Son YM, Lee JR, Roh JY. Causality assessment of cutaneous adverse drug reactions. Ann Dermatol 2011; 23:432-8. [PMID: 22148009 PMCID: PMC3229935 DOI: 10.5021/ad.2011.23.4.432] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2010] [Revised: 03/03/2011] [Accepted: 04/26/2011] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Cutaneous adverse drug reactions (ADRs) are the most common adverse reactions attributed to drugs. A systematic and effective approach to a patient with suspected drug eruption allows for prompt recognition, classification and treatment of cutaneous ADRs. A standardized and effective approach for objective causality assessment is necessary to make consistent and accurate identification of ADRs. OBJECTIVE Although the Naranjo algorithm is the most widely used assessment tool, it contains many components which are not suitable for clinical assessment of ADRs in Korea. The purpose of this study is to compare correlations of the Naranjo algorithm and the Korean algorithm to evaluate usefulness of both algorithms in order to make a causal link between drugs and cutaneous ADRs. In addition, this study classifies the clinical types and causative agents of cutaneous ADRs. METHODS The authors retrospectively reviewed the clinical types and laboratory findings of patients who were diagnosed with cutaneous ADRs in the dermatology clinic at Gil hospital. One hundred forty-one patients were enrolled in this evaluation. The causal relationship of ADRs was assessed by using the Naranjo algorithm and Korean algorithm (version 2.0). RESULTS A cross-tabulation analysis was applied to the Naranjo algorithm and Korean algorithm (version 2.0). Simple correlation analysis and a Bland-Altman plot were used for statistical analysis. Correlation analysis confirmed that the two assessment algorithms were significantly correlated. Exanthematous eruptions (68.8%), Stevens- Johnson syndrome (10.6%), and urticaria (8.5%) were the most common types of cutaneoues ADRs. The most common causative agents were antibiotics/antimicrobials, antipyretics/non-steroidal anti-inflammatory drugs, and central nervous system depressants. CONCLUSION The Naranjo algorithm and Korean algorithm (version 2.0) were significantly correlated with each other, and thus reliable assessment methods to determine cutaneous ADRs.
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Affiliation(s)
- Young-Min Son
- Department of Dermatology, Gachon University of Medicine and Science, Gil Hospital, Incheon, Korea
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39
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Histopathologic Features of Exanthematous Drug Eruptions of the Macular and Papular Type. Am J Dermatopathol 2011; 33:695-704. [DOI: 10.1097/dad.0b013e31820a285d] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Weyers W, Metze D. Histopathology of drug eruptions - general criteria, common patterns, and differential diagnosis. Dermatol Pract Concept 2011; 1:33-47. [PMID: 24396718 PMCID: PMC3881081 DOI: 10.5826/dpc.0101a09] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2011] [Accepted: 05/18/2011] [Indexed: 02/06/2023] Open
Abstract
Drug eruptions are among the most common inflammatory diseases of the skin and also among those biopsied most often. Yet, the value of histopathologic examination of drug eruptions has often been disputed. One reason is that the spectrum of histopathologic changes in drug eruptions is broad. Nevertheless, each histopathologic pattern assumed by drug eruptions has a limited number of differential diagnoses, and numerous criteria and clues are available to distinguish drug eruptions from other diseases associated with those patterns. By recognition of common patterns, consideration of differential diagnoses, and attention to distinct clues, a histopathologic diagnosis of drug eruption can usually be made with confidence.
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Affiliation(s)
| | - Dieter Metze
- Department of Dermatology, University of Münster, Münster, Germany
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Huang HY, Luo XQ, Chan LS, Cao ZH, Sun XF, Xu JH. Cutaneous adverse drug reactions in a hospital-based Chinese population. Clin Exp Dermatol 2010; 36:135-41. [PMID: 20738322 DOI: 10.1111/j.1365-2230.2010.03922.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND Cutaneous adverse drug reactions (CADRs) are common skin adverse reactions associated with drugs. AIM To assess recent trends in CADRs and the drugs associated with them, using data from the past 5 years in the largest single database available on a hospital-based population in China. METHODS All clinical records of inpatients admitted with a diagnosis of CADR to the Dermatology Ward, Huashan Hospital from January 2004 to December 2008 were retrospectively studied. RESULTS In the 734 patients, the three most common types of CADRs were nonsevere reactions, erythema multiforme (EM)-like eruptions (n = 255), urticaria (n = 192) and exanthematous reactions (n = 159), followed by three severe reactions: Stevens-Johnson syndrome (n = 58), toxic epidermal necrolysis (n = 29) and exfoliative dermatitis (n = 22). The most common single drug associated with the development of all drug eruptions was allopurinol, followed by amoxicillin, cephalosporins, antiepileptic agents and antipyretic/analgesic agents. However, the most common single drugs associated with severe reactions were antiepileptic agents, followed by allopurinol, antipyretic/analgesic agents and cephalosporins. In contrast to patients with nonsevere reactions, patients with severe reactions were more likely to be male (P < 0.001) and to have a greater mean age of onset (P < 0.001), a longer latency period (P < 0.001) and a longer duration of hospitalization (P < 0.001). CONCLUSION In contrast to previous studies, we found allopurinol to be the most common single drug associated with CADRs followed by antibiotics (amoxicillin and cephalosporins), and antiepileptic, especially carbamazepine. A higher incidence of EM-like eruptions and urticaria was also seen.
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Affiliation(s)
- H-Y Huang
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
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Current world literature. Curr Opin Allergy Clin Immunol 2009; 9:482-8. [PMID: 19690478 DOI: 10.1097/aci.0b013e3283312f84] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Hogan DJ. Morbilliform drug eruptions. J Am Acad Dermatol 2009; 61:152. [PMID: 19539857 DOI: 10.1016/j.jaad.2009.01.024] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2009] [Revised: 01/13/2009] [Accepted: 01/15/2009] [Indexed: 11/28/2022]
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