Lékové hypersenzitivní reakce představují problematiku s celosvětově narůstající incidencí. Nežádoucí účinek podání léků podaného pro diagnostické a terapeutické účely může významně ovlivnit kvalitu života pacienta, stejně tak náklady na jeho léčbu. Prvotní projevy lékových hypersenzitivních reakcí jsou ve většině případů vázány na kožní povrch. Známe akutní lékové kopřivky, angioedémy či pozdní lékové kožní erupce charakteru makulo-papulárních exantémů, pozdních kopřivek atd. Objevit se však mohou i závažné komplikace pod obrazem anafylaktické reakce či těžkých pozdních lékových hypersenzitivit, jakou je například Steven-Jonesův syndrom. Předmětem tohoto přehledového sdělení je současný pohled na klinické projevy, diagnostiku a management lékových hypersenzitivních reakcí.
Drug hypersensitivity reactions are a healthcare problem with rising incidence. Adverse events diagnostic or therapeutical drugs could negatively affect patients' quality of life and increase healthcare costs. The first signs of drug hypersensitivity reactions involve skin or mucosal surfaces. Skin symptoms like acute urticaria or angioedemas and delayed reaction with maculopapular eruptions are well described. Those conditions could be the initial step to life-threatening reactions like anaphylaxis or severe cutaneous adverse reactions - Steven-Jones Syndrome, for example. This summary brings the current view on drug hypersensitivity symptoms, diagnostics and management.
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Publikace se zaměřuje na různé aspekty toxické epidermální nekrolýzy (Stevensova-Johnsonova syndromu) a souvisejících bulózních nemocí kůže. Určeno odborné veřejnosti.
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- dermatovenerologie
- alergologie a imunologie
- NLK Publikační typ
- kolektivní monografie
Stevens-Johnsonův syndrom a toxická epidermální nekrolýza (Lyellův syndrom) jsou vzácně se vyskytující onemocnění charakterizovaná rychlým vznikem puchýřů s následnou rozsáhlou kožní a slizniční exfoliací doprovázenou celkovými příznaky. Hlavním spouštěčem bývají ve většině případů léky, etiopatogeneze onemocnění však není zcela objasněna. Lyellův syndrom je spojen s vysokou letalitou, v průměru udávanou kolem 35 %, proto je naprosto klíčová včasná diagnostika vyžadující těsnou mezioborovou spolupráci. Diagnóza stanovená na základě klinického obrazu a podrobné farmakologické anamnézy by měla být potvrzena histopatologickým vyšetřením kožního vzorku, vč. vyšetření přímou imunofluorescencí.
Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell syndrome) are rare diseases characterized by rapid blistering followed by extensive skin and mucosal exfoliation and constitutional symptoms. In most cases, drugs are the main triggers, but the etiopathogenesis of the diseases is not fully understood. Lyell syndrome is associated with a high mortality rate, reported to be around 35%. Therefore, early diagnosis requiring close interdisciplinary cooperation is essential. The diagnosis based on the clinical picture and a detailed pharmacological history should be confirmed by histopathological examination of the skin specimen, including analysis by direct immunofluorescence.
BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.
- MeSH
- konsensus MeSH
- kůže MeSH
- lidé MeSH
- progrese nemoci MeSH
- Stevensův-Johnsonův syndrom * komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- atopická dermatitida klasifikace komplikace terapie MeSH
- benigní pemfigoid sliznice diagnóza klasifikace komplikace patologie terapie MeSH
- blefaritida diagnóza farmakoterapie MeSH
- diferenciální diagnóza MeSH
- keratokonjunktivitida diagnóza farmakoterapie MeSH
- konjunktivitida farmakoterapie klasifikace MeSH
- lidé MeSH
- nemoci očních víček etiologie terapie MeSH
- nemoci rohovky MeSH
- nemoci spojivky etiologie farmakoterapie MeSH
- oční symptomy * MeSH
- rosacea diagnóza komplikace patofyziologie terapie MeSH
- Stevensův-Johnsonův syndrom farmakoterapie klasifikace komplikace patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Importance: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug reactions associated with a high rate of mortality and morbidity. There is no consensus on the treatment strategy. Objective: To explore treatment approaches across Europe and outcomes associated with the SJS/TEN disease course, as well as risk factors and culprit drugs. Design, Setting, and Participants: A retrospective pan-European multicenter cohort study including 13 referral centers belonging to the ToxiTEN ERN-skin subgroup was conducted. A total of 212 adults with SJS/TEN were included between January 1, 2015, and December 31, 2019, and data were collected from a follow-up period of 6 weeks. Main Outcomes and Measures: Risk factors for severe acute-phase complications (acute kidney failure, septicemia, and need for mechanical ventilation) and mortality 6 weeks following admission were evaluated using a multivariable-adjusted logistic regression model. One tool used in evaluation of severity was the Score of Toxic Epidermal Necrolysis (SCORTEN), which ranges from 0 to 7, with 7 the highest level of severity. Results: Of 212 patients (134 of 211 [63.7%] women; mean [SD] age, 51.0 [19.3] years), the mean (SD) body surface area detachment was 27% (32.8%). In 176 (83.0%) patients, a culprit drug was identified. Antibiotics (21.2%), followed by anticonvulsants (18.9%), nonsteroidal anti-inflammatory drugs (11.8%), allopurinol (11.3%), and sulfonamides (10.4%), were the most common suspected agents. Treatment approaches ranged from best supportive care only (38.2%) to systemic glucocorticoids (35.4%), intravenous immunoglobulins (23.6%), cyclosporine (10.4%), and antitumor necrosis factor agents (3.3%). Most patients (63.7%) developed severe acute-phase complications. The 6-week mortality rate was 20.8%. Maximal body surface area detachment (≥30%) was found to be independently associated with severe acute-phase complications (fully adjusted odds ratio [OR], 2.49; 95% CI, 1.21-5.12; P = .01) and SCORTEN greater than or equal to 2 was significantly associated with mortality (fully adjusted OR, 10.30; 95% CI, 3.82-27.78; P < .001). Cyclosporine was associated with a higher frequency of greater than or equal to 20% increase in body surface area detachment in the acute phase (adjusted OR, 3.44; 95% CI, 1.12-10.52; P = .03) and an increased risk of infections (adjusted OR, 7.16; 95% CI, 1.52-33.74; P = .01). Systemic glucocorticoids and intravenous immunoglobulins were associated with a decreased risk of infections (adjusted OR, 0.40; 95% CI, 0.18-0.88; P = .02). No significant difference in 6-week mortality was found between treatment groups. Conclusions and Relevance: This cohort study noted differences in treatment strategies for SJS/TEN in Europe; the findings suggest the need for prospective therapeutic studies to be conducted and registries to be developed.
- MeSH
- cyklosporin terapeutické užití MeSH
- dospělí MeSH
- intravenózní imunoglobuliny terapeutické užití MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- retrospektivní studie MeSH
- Stevensův-Johnsonův syndrom * diagnóza epidemiologie etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.
Toxic epidermal necrolysis (TEN) represents a rare drug-induced autoimmune reaction with delayed-type hypersensitivity that initiates the process of developing massive keratinocyte apoptosis, dominantly in the dermoepidermal junction. Although the etiopathophysiology has not yet been fully elucidated, the binding of Fas ligand (FasL, CD95L) to the Fas receptor (CD95) was shown to play a key role in the induction of apoptosis in this syndrome. The knowledge of the role of immunoglobulin G (IgG) in inhibition of Fas-mediated apoptosis contributed to the introduction of i.v. Ig (IVIg) in the therapy of TEN patients. Despite great enthusiasm for this therapy at the end of the 1990s, subsequent studies in various populations and meta-analyses could not unequivocally confirm the efficacy of the IVIg-based treatment concept. Today, therefore, we are faced with the dilemmas of how to adjust therapy of TEN patients most effectively, which patients could benefit from IVIg therapy and what dose of the preparation should be administrated. The ground-breaking question is: do the host genetic profiles influence the responsiveness and side-effects of IVIg therapy in TEN patients? Based on recent pharmacological, immunological and genetic findings, we suggest that the variability of IVIg therapy outcomes in TEN patients may be related to functional variants in Fas, FasL and Fc-γ receptor genes. This novel concept could lead to improved quality of care for patients with TEN, facilitating personalized therapy to reduce mortality.
Kožní polékové exantémy po systémové terapii představují jednu z nejčastějších nežádoucích reakcí. Podle mechanismu je dělíme na farmakologické a idiosynkratické, do kterých spadá i alergie, zejména po opakovaném podání. Rozčleňujeme ji na 4 typy, IV. typ je nejčastější. Do něho také řadíme nejtěžší formy (např. syndrom epidermální nekrolýzy).
Skin exanthema represents one of the most frequent adverse drug reactions. Pharmacologic and idiosyncratic (including allergic reaction especially after repeated exposition) reactions according to mechanisms are mentioned. Four types of allergic reactions are distinguished - the IV. type is the most frequent (including the most severe epidermal necrolysis). The first step in patient´s management is withdrawing of the drug. Topical dermatological treatment depends on type of exanthema. Systemic therapy (antihistamins, steroids, immunosuppressives, IVIG, biologics) is used in severe cases. The records to the patients documentation (allergy pass) are crucial for prevention of repeated adverse events.
- MeSH
- alergie imunologie klasifikace patofyziologie MeSH
- autoimunitní nemoci chemicky indukované MeSH
- kožní nemoci chemicky indukované farmakoterapie imunologie MeSH
- kožní testy metody MeSH
- léková alergie * diagnóza komplikace MeSH
- léková dermatitida * diagnóza farmakoterapie MeSH
- lékový hypersenzitivní syndrom diagnóza imunologie patofyziologie MeSH
- lidé MeSH
- nežádoucí účinky léčiv diagnóza farmakoterapie imunologie MeSH
- Stevensův-Johnsonův syndrom diagnóza imunologie patofyziologie MeSH
- Check Tag
- lidé MeSH
