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Drug Hypersensitivity

Drug Hypersensitivities


Presentation

  • It may present in different clinical forms. We present a case of acute generalized exanthematous pustulosis occurring as a manifestation of AHS.[ncbi.nlm.nih.gov]
  • Predictors of DHRs against asparaginase and other biological agents relate to antigen presentation (HLA-DRB1 and HLA-A alleles, respectively).[ncbi.nlm.nih.gov]
  • This article presents the case of a 44-year-old Asian male who developed features of both TEN and DHS approximately one week after initial ingestion of moxifloxacin.[ncbi.nlm.nih.gov]
  • The clinical presentation of this syndrome comprises a diverse spectrum, ranging from mild to fulminating organ failure.[ncbi.nlm.nih.gov]
  • The clinical presentation of drug hypersensitivity reactions ranges from mild cutaneous reactions to life-threatening symptoms including anaphylaxis.[ncbi.nlm.nih.gov]
Generalized Lymphadenopathy
  • Alf Björnberg and Rolf Holst, GENERALIZED LYMPHADENOPATHY AS A DRUG REACTION TO HYDANTOIN, Acta Neurologica Scandinavica, 43, 3, (399-402), (2009).[dx.doi.org]
Fever
  • It is characterized by rash, fever, and internal organ involvement. It may present in different clinical forms. We present a case of acute generalized exanthematous pustulosis occurring as a manifestation of AHS.[ncbi.nlm.nih.gov]
  • The syndrome is a triad of fever, skin eruption, and internal organ involvement. Prompt identification and discontinuation of the offending drug with symptomatic treatment of toxic effects is the mainstay of therapy for DHS.[ncbi.nlm.nih.gov]
  • Two weeks after starting therapy, the patient had fever, joint pain, a cutaneous eruption, and hypereosinophilia (1,358 cells/mm(3)). These symptoms resolved after drug withdrawal but reappeared upon reintroduction of the drug.[ncbi.nlm.nih.gov]
  • Diagnosis of AIN should be considered in any case of rapidly progressive renal failure occurring during drug therapy, especially when fever, skin rash, arthralgias, macroscopic hematuria, and blood or urinary eosinophilia are present.[ncbi.nlm.nih.gov]
  • In addition, she had fever, abnormal liver function tests, eosinophilia, and atypical lymphocytosis. Laboratory tests indicated no elevation of antibody titers against cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6.[ncbi.nlm.nih.gov]
Infectious Mononucleosis
  • Minocycline is able to elicit a drug hypersensitivity syndrome that can resemble infectious mononucleosis. This drug reaction can be treated effectively by cessation of exposure to this drug and steroid therapy.[ncbi.nlm.nih.gov]
  • Tindle, Pathology of Infectious Mononucleosis, Infectious Mononucleosis, 10.1007/978-1-4684-6376-7_11, (126-141), (1989). T. Maeda, N. Sano, K. Togei, M. Shibata, K.[dx.doi.org]
  • With more common morbilliform maculopapular exanthems, as seen when amoxycillin is administered concurrently with a viral infection (eg, infectious mononucleosis), the exact mechanism is not clear, but may be due to viral infection altering the immune[mja.com.au]
Malaise
  • The most common presentations in patients with DHS are fever, which ranges from 38 C to 40 C and occurs in 85% of cases, malaise, pharyngitis, and cervical lymphadenopathy.[mdedge.com]
  • The syndrome may be mild (with arthralgias, fever, and rash) or fairly dramatic (with serositis, high fevers, and malaise), but it tends to spare the kidneys and CNS. The antinuclear antibody test is positive.[msdmanuals.com]
  • As with serum sickness, the rash is usually preceded by a prodromal phase consisting of fever, malaise, and lymphadenopathy. Viral infections must be ruled out, as they can mimic SSLR.[uspharmacist.com]
  • SJS/TEN manifest with an “influenza-like” prodromal phase (malaise, fever), followed by painful cutaneous and mucous membrane (ocular, oral, and genital) lesions, and other systemic symptoms.[doi.org]
Candidiasis
  • Oral candidiasis, bronkovesikuler respiratory sounds, rales at the apex of the left lung.[omicsonline.org]
Aphthous Stomatitis
  • Doxycycline is also effective at controlling non-infectious, inflammatory skin and mucosal diseases, including: Acne Rosacea Perioral dermatitis Hidradenitis suppurativa Recurrent aphthous stomatitis Bullous pemphigoid Granulomatous disorders such as[dermnetnz.org]
Arthralgia
  • Diagnosis of AIN should be considered in any case of rapidly progressive renal failure occurring during drug therapy, especially when fever, skin rash, arthralgias, macroscopic hematuria, and blood or urinary eosinophilia are present.[ncbi.nlm.nih.gov]
  • The syndrome may be mild (with arthralgias, fever, and rash) or fairly dramatic (with serositis, high fevers, and malaise), but it tends to spare the kidneys and CNS. The antinuclear antibody test is positive.[msdmanuals.com]
  • Additionally, hypotension, bleeding, interstitial nephritis, arthralgia, arthritis, myositis, thyroiditis, pneumonitis, respiratory distress syndrome, pericarditis, myocarditis, pancreatitis, colitis, orchitis, encephalitis, and aseptic meningitis have[mdedge.com]
  • Other non-cutaneous manifestations may include unexplained pyrexias, arthralgia, myalgia, eosinophilia or other haematological abnormalities, and derangement of liver function.[mja.com.au]
  • […] antibodies directed at drug-hapten coated cells Hemolytic anemia, neutropenia, thrombocytopenia Variable Type III (immune complex) Tissue deposition of drug-antibody complexes with complement activation and inflammation Serum sickness, fever, rash, arthralgias[aafp.org]
Urticaria
  • The present study aimed to investigate the relationship between NH and chronic urticaria, rhinitis/rhinosinusitis, and asthma in an effort to identify NH phenotypes.[ncbi.nlm.nih.gov]
  • SRs and CIs were further classified as NSAID-induced urticaria/angioedema (n 8), NSAID-exacerbated cutaneous disease (n 6) and NSAID-exacerbated respiratory disease (n 1) and single NSAID-induced urticaria/angioedema and/or anaphylaxis (n 11).[ncbi.nlm.nih.gov]
  • Fifteen patients (75%) were classified as having single-NSAID-induced urticaria and/or angioedema, three patients were classified as having NSAID-induced urticaria and/or angioedema, one patient was classified as having NSAID-exacerbated respiratory disease[ncbi.nlm.nih.gov]
  • SRs and CIs were further classified as single NSAID-induced urticaria/angioedema and/or anaphylaxis (n 13), NSAID-induced urticaria/angioedema (n 7), NSAID-exacerbated cutaneous disease (n 2) and NSAID-exacerbated respiratory disease (n 1).[ncbi.nlm.nih.gov]
  • Six of these were classified as "single NSAID-induced urticaria/angioedema or anaphylaxis" and 3 were classified as "NSAIDs-exacerbated respiratory disease."[ncbi.nlm.nih.gov]
Exanthema
  • Since then, many different types of exanthemas from the mild macular-papular forms to the severe life-threatening bullous exanthemas such as toxic epidermal necrolysis have been observed from numerous drugs.[ncbi.nlm.nih.gov]
  • METHODS: Forty patients, including 19 patients with Stevens-Johnson syndrome and toxic epidermal necrolysis and 21 patients with maculopapular exanthema, and 21 healthy donors were recruited into the study. Clinical data of patients were obtained.[ncbi.nlm.nih.gov]
  • Activation of T cells with a particular function seems to lead to a specific clinical picture (for example, bullous or pustular exanthema).[annals.org]
  • The second DHR includes exanthema, erythroderma, DRESS, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hepatitis, and agranulocytosis. The eliciting drugs can be identified by positive skin or in vitro tests.[ncbi.nlm.nih.gov]
  • Maculopapular exanthema (MPE) and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have quite distinct T cell infiltrating patterns.[ncbi.nlm.nih.gov]
Pruritus
  • This is a case of a young person who initially presented with a dramatic episode of unilateral arm swelling after injuring a finger, with subsequent episodes of recurrent localized edema without pruritus throughout their body, including episodes of gut[imrespdx.com]
  • Treat acute reactions supportively with antihistamines for pruritus, NSAIDs for arthralgias, corticosteroids for severe reactions (eg, exfoliative dermatitis, bronchospasm), and epinephrine for anaphylaxis.[msdmanuals.com]
  • Off‐target ADRs may or may not be associated with immunological memory, although they can manifest with a variety of shared clinical features, including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus and bronchospasm[doi.org]
  • Pruritus, burning, and pain are common, and if the itching is not treated, fissures and thickened skin with crusting areas will develop. 10,15 The rash will resolve if the offending agent is avoided.[uspharmacist.com]
  • Drug Hypersensitivity Reactions Immune reaction Mechanism Clinical manifestations Timing of reactions Type I (IgE-mediated) Drug-IgE complex binding to mast cells with release of histamine, inflammatory mediators Urticaria, angioedema, bronchospasm, pruritus[aafp.org]
Photosensitivity
  • Photosensitivity: The most common photosensitivity reaction is phototoxicity, which appears as an exaggerated sunburn on sun-exposed skin.[uspharmacist.com]
  • […] reaction - Long-term use of voriconazole causes significantly increased photosensitivity, resulting in some patients developing squamous cell carcinoma [26] and melanoma. [27] Recent studies have shown dose-dependent increased risk for squamous cell[emedicine.medscape.com]
  • These include: Drug hypersensitivity syndrome Autoimmune reactions Dizziness and headache After prolonged use, blue pigmentation of skin and nails Minocycline is less likely than doxycycline to cause photosensitivity.[dermnetnz.org]
  • Wijaya Martanto and Jiun Yit Pan, Severe DRESS syndrome secondary to sulfamethoxazole/trimethoprim complicated by hyperthyroidism, photosensitivity, anhidrosis, and juvenile idiopathic arthritis, Dermatologica Sinica, 33, 1, (33), (2015).[doi.org]
Chronic Urticaria
  • The present study aimed to investigate the relationship between NH and chronic urticaria, rhinitis/rhinosinusitis, and asthma in an effort to identify NH phenotypes.[ncbi.nlm.nih.gov]
  • Fujisawa D, Kashiwakura J, Kita H, Kikukawa Y, Fujitani Y, Sasaki-Sakamoto T, Kuroda K, Nunomura S, Hayama K, Terui T, Ra C, Okayama Y: Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria[doi.org]
Headache
  • Two weeks following therapy, the patient developed fever, skin rash, nausea, and headache. The next day, the patient became anuric. There was no family history of renal or hepatic disease.[mdedge.com]
  • These include: Drug hypersensitivity syndrome Autoimmune reactions Dizziness and headache After prolonged use, blue pigmentation of skin and nails Minocycline is less likely than doxycycline to cause photosensitivity.[dermnetnz.org]
  • […] pressure Lung disease, causing shortness of breath and cough ( interstitial pneumonitis , pleuritis, pneumonia and acute respiratory distress syndrome ) Neurological involvement, which may lead to meningitis and, encephalitis , polyneuritis, causing headache[dermnetnz.org]
  • Fever experienced since one week, especially at night, no chills, no seizures and no headache. No nausea and vomiting, loss of appetite three days before entering the hospital.[omicsonline.org]
  • Neurological manifestations of the DRESS syndrome include headache seizure, coma, and motor dysfunction due to meningitis or encephalitis.[en.wikipedia.org]

Workup

  • In this study, we aimed to assess the frequency of confirmed NSAID hypersensitivity in children with a previous reported reaction to NSAID in order to investigate the role of the drug provocation test (DPT) in the diagnostic workup and to explore the[ncbi.nlm.nih.gov]
  • However, only a few of these reactions can be confirmed as allergic after a diagnostic workup.[ncbi.nlm.nih.gov]
  • See this previous report for the differential of bilateral lower extremity edema. 2) C3 and C4 complement levels can be used in a workup of vasculitis to help distinguish pauci-immune vasculidities (they are normal). 3) Hereditary angioedema is an extremely[imrespdx.com]
  • It should be given to patients only after full allergy workup.[ncbi.nlm.nih.gov]
  • Workup for atrial fibrillation included echocardiogram that showed normal left ventricle (LV) ejection fraction without pericardial effusion or wall motion abnormalities.[ncbi.nlm.nih.gov]

Treatment

  • Considering that treatment for tuberculosis requires long-term management with several drugs, it is important to refrain from administering drugs that can cause DIHS during tuberculosis treatment.[ncbi.nlm.nih.gov]
  • Her ongoing exposure to minocycline was stopped, and treatment with oral prednisolone was begun. Her signs, symptoms, and laboratory abnormalities then began to resolve.[ncbi.nlm.nih.gov]
  • It is the only effective procedure that enables sensitized patients to receive the full treatment dose safely, thus representing an important advance in the patients' treatment and prognosis.[ncbi.nlm.nih.gov]
  • Systemic corticosteroid treatment of those with DHS testing positive for HHV6 has been speculated to prolong the duration of disease.[ncbi.nlm.nih.gov]
  • MEK inhibitors are being evaluated in clinical trials for treatment of different malignant neoplasms; trametinib dimethyl sulfoxide was approved by the US Food and Drug Administration for melanoma in 2013.[ncbi.nlm.nih.gov]

Prognosis

  • The clinical recognition that GCM may be a manifestation of an adverse drug reaction is important, since the prognosis and treatment of this entity may be different from that of other forms of myocarditis.[ncbi.nlm.nih.gov]
  • It is the only effective procedure that enables sensitized patients to receive the full treatment dose safely, thus representing an important advance in the patients' treatment and prognosis.[ncbi.nlm.nih.gov]
  • Samter's triad include asthma, aspirin sensitivity, and nasal/ethmoidal polyposis: ASP irin A sthma S ensitivity to aspirin P olyps T T oxic epidermal necrosis (TEN) T hirty percent of the skin (SJS less than 10%) " T errible" prognosis Management of[allergycases.blogspot.com]
  • The effect of corticosteroids on prognosis is unknown as controlled clinical trials are lacking. 2 Beware of cross-reactions and family predisposition Cross-hypersensitivity reactions are common between the three main aromatic anticonvulsants (i.e. phenytoin[medsafe.govt.nz]
  • Furthermore, other nongenetic factors such as renal impairment are also found to be an important factor resulting in allopurinol-induced SCARs of greater severity and poorer prognosis.[doi.org]

Etiology

  • Inpatient vancomycin use is increasing and appears to be emerging as an important etiology of DRESS syndrome. This study highlights the importance of vancomycin as a cause of DRESS syndrome.[doi.org]
  • […] is associated with reactivation of inactive Herpesviridae family viruses, including human herpesvirus 6 (HHV6), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) ( Arch Dermatol 2001;137:301, Br J Dermatol 2006;155:344, Arch Dermatol 2009;145:1030 ) Etiology[pathologyoutlines.com]
  • Diagnosis of DRESS syndrome is difficult to establish, and it requires a high level of suspicion as well as ruling out other etiologies. Multi-system involvement and febrile skin eruption makes the list of differential diagnoses quite extensive.[ncbi.nlm.nih.gov]
  • Drug reactions can be classified into immunologic and nonimmunologic etiologies ( Table 1 ) .[aafp.org]
  • Aisenberg, Hodgkin's Disease — Prognosis, Treatment and Etiologic and Immunologic Considerations, New England Journal of Medicine, 270, 10, (508), (1964). Esther Kaletzky, C.R. Proctor and T.P.[doi.org]

Epidemiology

  • We review the epidemiology of severe drug hypersensitivity reactions with a particular focus on severe cutaneous adverse reactions (SCARs).[ncbi.nlm.nih.gov]
  • This study presents an up-to-date review on epidemiology, clinical spectrum, diagnostic tools, and current management of DH in children. A new general algorithm for the study of these reactions in children is proposed.[ncbi.nlm.nih.gov]
  • The prevalence of DH in children remains not well defined as epidemiologic studies in children are lacking, and the most of those take into account adverse drug reactions (ADR) without a systematic allergy work-up to confirm or exclude hypersensitivity[ncbi.nlm.nih.gov]
  • This will further enhance a systematized framework for translating epidemiological, clinical and immunopathogenetic advances into preventive efforts and improved outcomes for patients.[doi.org]
  • […] lymphocytes, plasma cells, eosinophils and histiocytes Terminology Drug induced lymphadenopathy Hydantoin lymphadenopathy Pseudolymphoma syndrome Drug induced hypersensitivity syndrome (DIHS) Drug reaction with eosinophilia and systemic symptoms (DRESS) Epidemiology[pathologyoutlines.com]
Sex distribution
Age distribution

Pathophysiology

  • Drug hypersensitivity reactions still remain one of the most challenging problems in allergology due to their manifold clinical manifestations and their very diverse pathophysiology.[ncbi.nlm.nih.gov]
  • […] is unknown The underlying mechanisms causing DHS are poorly understood. 1 Defective detoxification of reactive oxidative metabolites 1 and a genetic predisposition 4 have been implicated in the pathophysiology of this syndrome, as has slow acetylator[medsafe.govt.nz]
  • […] syndrome Drug induced hypersensitivity syndrome (DIHS) Drug reaction with eosinophilia and systemic symptoms (DRESS) Epidemiology Uncommon Pediatric population Sites Predominantly cervical but all lymph node groups can be affected Can be generalized Pathophysiology[pathologyoutlines.com]
  • A significant proportion of these reactions lack immunological memory and current data are informative for these ADRs with regard to disease pathophysiology, therapeutic targets and biomarkers which may identify patients at greatest risk.[doi.org]
  • These insights have unveiled pathophysiological features that shift the existing paradigms and emphasize the autoinflammatory nature of skin pustular disorders.[doi.org]

Prevention

  • HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation.[ncbi.nlm.nih.gov]
  • Articles in this issue include: Drug allergy diagnosis; Principles of drug allergy management: acute drug reactions, individual preventive measures, desensitization, general preventive measures; Antibiotics allergy; Non-steroidal anti-inflammatory drugs[books.google.com]
  • There is a need to develop novel methodologies to evaluate how the in vitro mechanisms relate to the in vivo situation and how the highly consistent genetic findings with different HLA alleles can be more consistently used for both prediction and prevention[ncbi.nlm.nih.gov]
  • Abstract Due to the increase in utilization of chemotherapies and antibodies, drug hypersensitivity reactions have increased dramatically worldwide, preventing the use of first-line therapies and impacting patients' survival and quality of life.[ncbi.nlm.nih.gov]
  • DHR to those agents prevented their use and promoted the use of second line therapies to protect patients' hypersensitive reactions and anaphylaxis.[ncbi.nlm.nih.gov]

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