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drug reaction with eosinophilia and systemic symptom
- 2. Objectives of today ◉Define DRESSDIHS ◉Causes and risk factors ◉Clinical manifestation ◉Diagnostic criteria ◉Investigations ◉Pathophysiology ◉Differential diagnosis ◉Treatment and prevention ◉Complications
- 3. 1definition
- 4. Drug hypersensitivity syndrome ◉severe, unexpected reaction to a medicine(s) ◉which affects several organ systems at the same time.
- 5. Cont. ◉ It most commonly causes the combination of a high fever, a morbilliform skin rash and inflammation of one or more internal organs including the liver, kidneys, lungs and/or heart. ◉It generally starts two to eight weeks after taking the responsible medicine. ◉1.2 to 6 per million person annually
- 7. Cont. Drugs that commonly induce DRESS syndrome include ◉Anti-Epilepsy Drugs: -Phenobarbital. - Carbamazepine. -Phenytoin. - Lamotrigine.
- 9. Risk factors ◉associated with individual susceptibility ◉type of antiepileptic drug used (more common with aromatic drugs) ◉ titration rate ◉concomitant medications
- 10. 3manifestation
- 11. Cont. ◉ Fever, lymphadenopathy. ◉ Skin rash: - Facial edema - Infiltrated papules - Generalized exanthematous rash / Exfoliate dermatitis.
- 13. Organs . ◉ Organ Involvement: - Hepatitis. - Nephritis. - Myocarditis. - Pneumonitis
- 14. Signs and Symptoms of DRESS ◉Symptoms: -Symptoms may be severe and involve many different organs: Percent of patients with involvement Organ 80%Liver 40%Kidney 33%Pulmonary 15%Cardiac/muscular 5%Pancreas Percent of patients with abnormality Abnormality 63%Atypical Lymphocyte 52%Eosinophilia 45%Lymphocytopenia 25%Thrombocytopenia 25%Lymphocytosis
- 15. 4Criteria
- 16. A criteria is there ◉ Diagnostic criteria for DIHS established by a Japanese consensus group ◉ The diagnosis is confirmed by the presence of the seven criteria above (typical DIHS) or of five of the seven (atypical DIHS).
- 17. Cont. ◉Maculopapular rash developed 3 weeks after starting with a limited number of drugs ◉Prolonged clinical symptoms after discontinuation of the causative drug ◉Fever (38°C) ◉liver abnormalities (ALT100U/L)*
- 20. 5Investigations
- 21. investigation ◉Skin biopsy, mild spongiosis, lymphocytic infiltrate in SD eosinophil's and DE ◉Patch test: Six weeks to six months after the complete resolution of rash.
- 22. Cont. ◉Liver function tests alkaline phosphatase greater than 1.5 times the upper limit of normal values on at least two different dates indicate liver involvement. ◉If Liver function tests were positive Serology for viral hepatitis
- 23. Cont. ◉Serum creatinine and urinalysis A moderate increase in creatinine level, low grade proteinuria, and abnormal urinary sediment with occasional eosinophil's indicate kidney involvement ◉High creatinine = darker color = kidney problem = sign of DRESS
- 25. 6pathophysiology
- 26. Cont. ◉The pathogenesis of DRESS syndrome is not well understood and is hypothesized to consist of a complex interaction between two or more of the following:
- 27. Cont. ◉A genetic deficiency of detoxifying enzymes leading to an accumulation of drug metabolites. The metabolites covalently bind to cell macromolecules causing cell death or inducing secondary immunological phenomena. Eosinophilic activation as well as activation of the inflammatory cascade may be induced by interleukin-5 release from drug-specific T-cells.
- 28. Cont. ◉Genetic associations between human leukocyte antigen (HLA) associations and drug hypersensitivity may occur. These include HLA-B*1502, associated with carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis
- 29. Cont. ◉A possible virus-drug interaction associated with viral reactivation may also exist. This phenomenon has been previously observed for herpes viruses (notably Epstein-Barr virus [EBV]).The clinical manifestations appear to be a result of an expansion of virus-specific and nonspecific T cells.
- 32. Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) ◉usually starts 4 to 28 days after drug exposure ◉Severe mucosal involvement with erosions and bleeding on at least two sites occurs in over 90 percent of cases of SJS/TEN ◉mucosal involvement occurs in approximately 50 percent of patients with DRESS, usually involves a single site (most often the mouth or pharynx), and does not progress to erosion ◉Eosinophilia and atypical lymphocytosis are not observed in SJS/TEN ◉whereas leukopenia is frequent and lymphopenia is nearly constant
- 33. Acute generalized exanthematous pustulosis (AGEP) ◉In contrast to DRESS, AGEP usually starts less than three days after drug exposure. Although pustules occasionally can occur in patients with DRESS ◉AGEP is characterized by hundreds or thousands pinpoint non- follicular pustules disseminated over the body surface ◉Internal organ involvement is rare ◉Complete blood cell count shows leukocytosis with neutrophilia (>7000/microL)
- 34. Hypereosinophilic syndromes ◉The hypereosinophilic syndromes (HES) are associated with marked peripheral eosinophilia (≥1500/microL) ◉involvement of multiple organs such as the heart, gastrointestinal tract, lungs, brain, and kidneys, without an alternative explanation for the organ damage ◉Skin manifestations of HES include eczema ◉erythroderma, lichenification, dermographism, recurrent urticaria, and angioedema
- 35. Sézary syndrome ◉Sézary syndrome typically presents with generalized erythroderma ◉The diagnosis is based upon the finding of Sézary cells in the peripheral blood (absolute Sézary count of at least 1000 cells/microL) ◉or increased number of CD4+ lymphocytes in the peripheral blood with a CD4/CD8 ratio ≥10
- 37. Treatment ◉Drug withdrawal. ◉Supportive measures (antihistamines). ◉Patients without severe organ involvement. -Topical steroids. ◉Patients with severe organ involvement. -Systemic corticosteroids.
- 38. prevention ◉Carry identification of alert bracelet. ◉Patients should be educated about the need for a strict avoidance of the offending drug.
- 39. 9Complications
- 40. Cont. ◉Most patients recover completely after drug withdrawal and appropriate therapy. ◉ However, some patients with DRESS syndrome suffer from chronic complications and approximately 10% die, primarily from visceral organ compromise
- 41. LET’S REVIEW SOME CONCEPTS What is it ? What cause it ? How can you see it ? How does it happen ? How can you treat it? How can you prevent it?
- 43. THANKS!
Editor's Notes
- Drug hypersensitivity syndrome is sometimes also called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), and Drug-Induced Hypersensitivity Syndrome (DIHS).
- is a kind of arthritis. It can cause an attack of sudden burning pain, stiffness, and swelling in a joint, usually a big toe. Sulfonamides group antibiotics Allopurinol reduces the production of uric acid in your body. Uric acid buildup can lead to gout or kidney stones. Minocycline (INN) is a broad-spectrum tetracycline antibiotic This medication is used to treat certain mental/mood disorders This medication can decrease hallucinations and help you to think more clearly and positively about yourself, feel less agitated, and take a more active part in everyday life.
- Mononucleosis = atypical lymphocyte
- https://www.med.or.jp/english/journal/pdf/2009_05/347_352.pdf
- This can be replaced by other organ involvement, such as renal involvement.
- Leukocyte abnormalities (at least one present) a. Leukocytosis (11*10*9/L) b. Atypical lymphocytosis (5%) c. Eosinophilia (1.5*10*9/L)
- Serum creatinine and urinalysis A moderate increase in creatinine level, low grade proteinuria, and abnormal urinary sediment with occasional eosinophils indicate kidney involvement Skin biopsy The histologic findings of mild spongiosis and a lymphocytic infiltrate in the superficial dermis, predominantly perivascular, with eosinophils and dermal edema, although not specific, supports the diagnosis of DRESS
- Liver function tests • Serum alanine aminotransferase (ALT) greater than twice the upper limit of normal values • and/or alkaline phosphatase greater than 1.5 times the upper limit of normal values on at least two different dates indicate liver involvement. If Liver function tests were positive Serology for viral hepatitis (hepatitis A IgM antibody, hepatitis B surface antigen, hepatitis B core IgM antibody, hepatitis C viral RNA) may be useful in excluding acute viral hepatitis . 25
- (TEN)8; HLA-B*1508, associated with allopurinol induced SJS/TEN9; and many others.10–13 It was also observed that the association of HLA-B*1502 and CBZ- induced SJS/TEN could be ethnicity-specific as observed in Chinese populations.14,15 Furthermore, the association of CBZ-induced drug hypersensitivity reactions seems to be phenotype-specific.
- In fact, drug-specific T-cells have been isolated from the blood and skin of patients in whom DRESS syndrome was induced by lamotrigine and CBZ.17–19 Shiohara et al20 reviewed the latest evidence regarding the association of viral infections and drug rashes as well as the mechanisms of how viral infections can induce drug rashes. They observed that sequential reactivations of several herpes viruses (HHV- 6, HHV-7, EBV, and cytomegalovirus) can be detected coincident with the clinical symptoms of drug hypersensitivity reactions.20 The pattern of the herpes virus re-activation was noted to be similar to that observed in graft-versus-host disease (GVHD),21,22 thus suggesting that DRESS may resemble GVHD in the sense that antiviral T-cells can cross-react with the drugs and do not only arise from the oligoclonal expansion of drug-specific T-cells. Kano et al16Review due also studied whether immunosuppressive conditions that allow HHV-6 reactivation could be specifically detected in the setting of anticonvulsant hypersensitivity syndrome (AHS). In order to test this idea, they performed serological tests for antibody titers for various viruses and found that serum immunoglobulin G (IgG) levels and circulating B-cell counts in patients with AHS were significantly decreased at onset compared with control groups (P<0.001 and P=0.007, respectively). These alterations returned to normal levels on the patient’s recovery. Additionally, they observed that the reactivation of HHV-6 measured by a greater than fourfold increase in HHV-6 IgG titers was exclusively detected in patients with AHS who had decreased IgG levels and B-cell counts. These findings suggest an association between the severity of AHS and possibly DRESS syndrome.
- http://www.uptodate.com/contents/drug-reaction-with-eosinophilia-and-systemic-symptoms-dress#H27761085
- viral exanthem
- Erythroderma (also known as "Exfoliative dermatitis, Lichenification" refers to a thickening of the epidermis seen with exaggeration of normal skin lines dermographism (or dermatographism) literally means writing on the skin. Firm stroking of the skin produces an initial red line Urticaria (from the Latin urtica, "nettle" from urere, "to burn"), commonly referred to as hives, is a kind of skin rash notable for pale red, raised, itchy bumps angioedema is the swelling of deep dermis, subcutaneous, or submucosal tissue due to vascular leakage.