Drug Reaction With Eosinophilia and Systemic Symptoms (Dress)
Upcoming SlideShare
Loading in...5
×
 

Like this? Share it with your network

Share

Drug Reaction With Eosinophilia and Systemic Symptoms (Dress)

on

  • 3,230 views

Drug Reaction With Eosinophilia and Systemic Symptoms (Dress)

Drug Reaction With Eosinophilia and Systemic Symptoms (Dress)

Presented by Theerapan Songnuy, MD.

Statistics

Views

Total Views
3,230
Views on SlideShare
3,225
Embed Views
5

Actions

Likes
0
Downloads
68
Comments
0

2 Embeds 5

http://www.pinterest.com 4
http://dresssyndrome.org 1

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

Drug Reaction With Eosinophilia and Systemic Symptoms (Dress) Presentation Transcript

  • 1. DRESS/DIHS (Drug Reaction With Eosinophilia and Systemic Symptoms/ DrugInduced Hypersensitivity Syndrome) Theerapan Songnuy
  • 2. Scope of The Presentation• Overview of SCARs• Definition of DRESS/DIHS• Epidemiology• Clinical Manifestations & Common Culprit Drugs• Pathogenesis• Diagnosis• Conclusion
  • 3. Severe Cutaneous Adverse Drug Reaction (SCAR)• DRESS• SJS• TEN• AGEP Severe cutaneous adverse reactions (SCARs) to drugs are groups of drug hypersensitivity reactions with a heterogeneous clinical presentation Roujeau JC. Clinical heterogeneity of drug hypersensitivity. Toxicology 2005;209 (2) 123- 129
  • 4. DRESS/DIHS• Definition : a drug-induced adverse reaction that is serious and well characterized. Patients exhibit skin eruption, fever, facial edema, poly-adenopathy, visceral involvement & blood abnormalities.• Previous names: - drug-induced pseudo-lymphoma* - drug hypersensitivity syndrome - drug rash with eosinophilia and systemic symptom ** *Saltzstein S. Ackerman L: Lymphadenopathy induced by anticonvulsant drugs and mimicking clinically and pathologically malignant lymphomas. Cancer 12:164-182, 1959**Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome ( drug rash with eosinophilia and systemic symptoms: DRESS ). Semin Cutan Med Surg 1996; 15: 250-7.
  • 5. Epidemiology• Incidence 1: 1,000 to 1: 10,000 of drug exposure• Case report or series• Most affected patients are adults and elderly Fiszenson-Albala F, Auzerie V , Mahe E, et al: A 6-month prospective survey of cutaneous drug reactions in a hospital setting. Br J Dermatol 149. 1018-1022. 2003.
  • 6. Clinical Manifestations• History of drug exposure• Usually has a late onset, 3 to 8 weeks after use of the culprit drug• Characterized by fever, skin eruption, prominent eosinophilia, lymphocyte activation, and multi-visceral involvement.• Wolf R, Orion E, Marcos B, Matz H. Life-threatening acute adverse cutaneous drug reactions. Clin Dermatol 2005;23 (2) 171- 181
  • 7. DRESS in Asian Population• A retrospective study• The National Taiwan University Hospital• Patients hospitalized between 1998 and 2008• Drug eruption with systemic involvement• Using the inclusion criteria proposed by the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR)• Clinical charts and sequential medical laboratory data obtained during hospitalization were reviewed.• Demographic data, medication history, clinical course, laboratory results, and pathologic findings of all cases were analyzed. Chen YC, Chiu HC & Chu CY. Drug Reaction With Eosinophilia and Systemic Symptoms: A Retrospective Study of 60 Cases . Arch Dermatol. 2010;146(12):1373-1379
  • 8. Patients• A total of 60 patients• 26 male and 34 female• The mean age was 51 years (age range, 6-90 years; median, 54.5 years)• Most patients were treated in internal medicine, dermatology, pediatric and neurology departments Chen YC, Chiu HC & Chu CY. Drug Reaction With Eosinophilia and Systemic Symptoms: A Retrospective Study of 60 Cases . Arch Dermatol. 2010;146(12):1373-1379
  • 9. Clinical Manifestations• The average drug reaction latency period was 20.7 days (range, 3-76 days)• Fever (temperature >38°C (87%)• Lymphadenopathy (31%)• Twenty-nine patients were reported to have lesions in at least 1 mucosal area (48%), always including the oral mucosa.• All patients revealed a diffuse exanthematous eruption some with typical facial edematous erythema ,some cases this was followed by exfoliative dermatitis (12%) or blistering or purpuric eruption (10%) Chen YC, Chiu HC & Chu CY. Drug Reaction With Eosinophilia and Systemic Symptoms: A Retrospective Study of 60 Cases . Arch Dermatol. 2010;146(12):1373-1379
  • 10. Clinical Images of Patient Affected by DRESS A, Diffuse erythematous exanthematous eruption B, Prominent facial edematous erythema C, Purpuric eruption Chen YC, Chiu HC & Chu CY. Drug Reaction With Eosinophilia and Systemic Symptoms: A Retrospective Study of 60 Cases . Arch Dermatol. 2010;146(12):1373-1379.
  • 11. LABORATORY EXAMINATION• Elevation of liver enzyme levels was the most common finding : 48 patients (80%) had levels double that of normal, with or without hyper-bilirubinemia.• Renal involvement (40%) was significantly higher in the allopurinol group than in the other patients (68% [n = 13] vs 33% [n = 10]) p< 0.02• The rates of lung (n = 20), cardiomuscular system (n = 9), and pancreas involvement (n = 3) were 33%, 15%, and 5%, respectively• Of 9 patients with cardiomuscular involvement, none was observed to have specific cardiac enzyme elevation. Chen YC, Chiu HC & Chu CY. Drug Reaction With Eosinophilia and Systemic Symptoms: A Retrospective Study of 60 Cases . Arch Dermatol. 2010;146(12):1373-1379.
  • 12. Effects on internal organs (A) and blood (B) of drugreaction with eosinophilia and systemic symptoms.Drug Reaction With Eosinophilia and Systemic Symptoms: A Retrospective Study of 60 CasesArch Dermatol. 2010;146(12):1373-1379. doi:10.1001/archdermatol.2010.198
  • 13. Common Culprit DrugsChen Y C,Chiu H C & Chu C Y. Drug Reaction With Eosinophilia and Systemic Symptoms: A RetrospectiveStudy of 60 Cases. Arch Dermatol. 2010;146(12):1373-1379
  • 14. Clinical &Common Culprit Drug in Children• Clinical manifestation: - median age 12 y ( 7 mo-17 y) - 6 boys, 5 girls - rash ( 100%) developed median day 17 ( 7-60 d) - facial edema ( 73%) - mucosa ( 73%) - high fever 38.7-40 c ( 91%)Pediatrics.aappublications.org. Experience and reason: Drug-Induced Hypersensitivity Syndrome in Pediatric Patients. Pediatrics.2001; 108(2): 485-492.
  • 15. Clinical &Common Culprit Drug in Children• Clinical manifestation: - lymphadenopathy ( 73%) - visceral involvement ( 91%) ; liver, lung etc. - Hematological abnormalities ( 73%) eosinophilia leukocytosis anemiaPediatrics.aappublications.org. Experience and reason: Drug-Induced Hypersensitivity Syndrome in Pediatric Patients. Pediatrics.2001; 108(2): 485-492.
  • 16. Clinical &Common Culprit Drug in Children• Diagnosis was done on median day 3 ( 0-18 d) after onset of symptoms• Drugs were administered for median day 25 ( 7-71 d)Pediatrics.aappublications.org. Experience and reason: Drug-Induced Hypersensitivity Syndrome in Pediatric Patients. Pediatrics.2001; 108(2): 485-492.
  • 17. Pathogenesis• Unknown 1. Drug detoxification : slow acetylation, reactive metabolite affects to immune mechanism - The persistence of minocycline in the plasma and/or in the skin of 7 out of 9 patients with skin phototypes V–VI. - The melanin-minocycline complex, which could explain the severe and prolonged DRESSMaubec E et al. Minocycline-Induced DRESS: Evidence for Accumulation of the Culprit Drug. Dermatology 2008;216:200–204
  • 18. Pathogenesis 2. Genetic factor - HLA-B * 5701 : abacavir hypersensitivity* - HLA-B * 5801 : allopurinol *** Mallal S et al. HLA-B*5701 Screening for Hypersensitivity to Abacavir. N Engl J Med 2008;358:568-79.** Hung SI, Chung WH, Liou LB et al. HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci USA 2005; 102: 4134-9.
  • 19. HLA-B*5701 screening for hypersensitivity to abacavir.• Abacavir : NTRI , major problem is immune-mediated hypersensitivity reaction 5-8%• Difficult to differential from infection, inflammatory disease & other adverse drug reaction• PREDICT-1 : study group performed Prospective, Randomized Evaluation of DNA Screening in Clinical TrialMallal S et al ; PREDICT-1 Study Team NEJM. 2008 Feb 7;358(6):568-79.
  • 20. HLA-B*5701 screening for hypersensitivity to abacavir• Patients & Method - 265 centers, 19 countries - From April- September 2006 - Participants: HIV-1 patient who was assessed to take abacavir with unknown HLA-B* 5701 - Random to two groups then take abacavir & follow up for 6 wk.• Mallal S et al ; PREDICT-1 Study Team NEJM. 2008 Feb 7;358(6):568-79 .
  • 21. HLA-B*5701 screening for hypersensitivity to abacavir 1956 enrolled 980 screening gr. 976 control gr. 55 positive 925 negative 847 clinically assess HLA-B*5701 HLA-B*5701 hypersensitivity reaction 54 no take 858 take Abacavir Abacavir 803 clinically assess hypersensitivity reaction 802 immune-mediated 842 immune-mediated assess hypersensitivity assess hypersensitivity reaction reactionMallal S et al ; PREDICT-1 Study Team NEJM. 2008 Feb 7;358(6):568-79.
  • 22. HLA-B*5701 screening for hypersensitivity to abacavir• Results - Prevalence HLA-B * 5701 : 5.6% -Screening reduced immuno-mediated hypersensitivity reaction ( 0% vs 2.7% , p<0.001 - NPV= 100% PPV= 48% - Total hypersensitivity reaction = 93 from screening gr. 3.4% from control gr. 7.8% ( p<0.001) In conclusion: pharmaco-genetic prevent hypersensitivity reactionMallal S et al ; PREDICT-1 Study Team NEJM. 2008 Feb 7;358(6):568-79
  • 23. Pathogenesis 3. Reactivation of viral infections: HHV 6, HHV 7 EBV & CMV - A case had clinical manifestations lab abnormalities, PCR for HHV-6 positive, & confirmed by skin biopsy* - HHV-6 reactivation as evidenced by the rise in HHV-6 IgG titres and HHV-6 DNA levels commonly occurs 2–3 weeks after onset***Ichiche M, Kiesch N & Bels DD. DRESS syndrome associated with HHV-6 reactivation. European Journal of Internal Medicine.14( 2003) 495-500.** Shiohara T, Inaoka M, Kano Y. Drug-induced hypersensitivity syndrome(DIHS): a reaction induced by a complex interplay among herpesviruses and antiviral and antidrug immune responses. Allergol Int 2006; 55:1–8.
  • 24. Pathogenesis3. Reactivation of viral infections: HHV 6, HHV 7 EBV & CMV - Adults in dermatologic centers, France - Nov 2002-Dec 2005 - 40 patients were enrolled - Using the REGISCAR criteria, follow up on day 0, 15, 30, 90, 180, 360 - Skin biopsy was done in all patients at DRESS onset - Control gr. ( 50): taking drug without rashPicard et al. Drug Reaction with Eosinophilia andSystemic Symptoms ( DRESS) : A Multiorgan Antiviral T Cell Response. Sci Transl Med 25 August 2010;2(46): 46-62.
  • 25. Pathogenesis3. Reactivation of viral infections: HHV 6, HHV 7 EBV & CMV -Reactivation was found at early onset of DRESS - EBV-specific CD8+ T lymphocyte found in blood, skin, liver & lungPicard et al. Drug Reaction with Eosinophilia andSystemic Symptoms ( DRESS) : A Multiorgan Antiviral T Cell Response. Sci Transl Med 25 August 2010;2(46): 46-62
  • 26. Diagnosis• RegiSCAR• European Registry of Severe Cutaneous Adverse Reaction ( SCAR)• Include admitted patients• History of drug exposure
  • 27. Diagnosis• The RegiSCAR study group: large multinational registry Patient has to have 3 from4 clinical symptoms - Acute skin rash - Fever greater than 38 degree C - Two or more sites of enlarged lymph nodes - At least one internal organ involvementKardaun SH, Sidorrff A, Valeyrie-Allanore L et al.Variability in the clinical pattern of cutaneous side effect of drug with systemic symptoms: does a DRESS syndrome really exist? Response Br J Dermatol 2007;156: 609-10.
  • 28. Diagnosis-Hematologic abnormalities lymphocytosis or lymphopenia Eosinophilia Thrombocytopenia
  • 29. DiagnosisJapanese Consensus Group 1. MP rash after 3 wk. of drug exposure 2. Symptoms persisted longer than 2 wk. after drug cessation 3. Fever higher than 38 degree selcius 4. At least one abnormalities of WBC - Leukocytosis > 11,000 / cumm. - Atypical lymphocytosis ( > 5 %) - Eosinophilia ( > 1500 / cumm>) 5. Liver abnormalities ( alanine aminotransferase > 100 U/L) 6. Enlarged lymph nodes 7. HHV 6 reactivationAtypical DIHS : clinical symptoms from 1-5 Shiohara T, Iijima M, Ikezawa Z, Hashimoto K. The D iagnosis of DRESS syndrome has been sufficienctly established on the basis of typical clinical feutures and viral reactication s. Br J Dermatol 2007; 156: 1045-92.
  • 30. Conclusion• DRESS/DIHS is a severe drug reaction• Common culprit drugs : anticonvulsant (aromatic group), antibiotic ( sulfonamide)• Clinical manifestations : fever, skin rash, lymphadenopathy, hematologic abnormalities & internal organs involvement• Onset 2-10 wk. after start drug• Differential diagnosis• HLA screening if test available• Prompt treatment• Patient education
  • 31. Differential Diagnosis• Other drugs reactions : serum sickness-like, SJS/TEN• Viral infections : EBV, Hepatitis A, B• Kawasaki disease• Lymphoma• Etc.
  • 32. Treatment• Drug cessation ( suspected drug)• Symptomatic & Supportive - Antipyretic - Antihistamine - Fluid & Electrolyte imbalance - Prevent infection
  • 33. Treatment• Systemic Corticosteroid - prednisolone 1-2 MKD until internal organ improvement, then tapper in 2-4 wk. - relapse may be present
  • 34. Treatment• Patient Education - drug hypersensitivity card - counseling
  • 35. Prognosis• Mortality rate 10 %• Most common from liver failure