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Drug reaction with eosinophilia and systemic symptoms, drug hypersensitivity syndrome

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  • NOTE:DRASS also called Drug hypersensitivity syndromeEruption = طفح جلدي
  • You know that we have 4 type of hypersensitivity reactions. Anaphylaxis, cytotoxic, immune complex, delayed type . Interesting point and for you to remember these names if U take first later from each, you will end up with the word “acid”. So let’s go back to DRESS, which type of these that DRASS based on ?
  • 80% of cases are reported as a hypersensitivity reaction to certain drugs
  • The cause in the case was because of carbamazepine whichthe latency between drug exposure and onset of symptoms is considerably long may be reach more than 6 months
  • Which will affect the patient in one way or another because that will lead to changing of drug concentration in the body
  • may occur in children, but most cases occur in adults without sex predilectionsex predilection = with no susceptible gender more than the another
  • It have been believed that
  • Diagnose such a case is not easy, because the symptoms may relate to other conditions. So the investigations in DRESS depend on the aim of exclude other conditions and prove DRESS therefore the following test should be done.
  • Spongiosis is mainly intercellular edema (abnormal accumulation of fluid) in the epidermis
  • Testing for herpesvirus infection to avid farther complicationThe Epstein–Barr virus (EBV), Each test can support the diagnosis but not prove it ! And the combination of supportive results can be a strong evidence to diagnose a case with DRESS
  • The most useful test to determine which drug is

    1. 1. rug eaction osinophilia ystamic ymptoms Drug reaction with eosinophilia and systemic symptoms Done by: Bayan Al-Ghadeer Group ( 2) Block 1.2 King Faisal University College of Medicine
    2. 2. Learning Objectives Adverse drug reaction Diagnosis DRESS Overview Treatment Etiology and risk factors Complication Pathophysiology Prognosis Clinical presentation
    3. 3. Introduction to the topic Adverse drug reaction How to identify adverse drug reactions 3
    4. 4. What is Adverse drug reaction ? (ADR) is an unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use, which is suspected to be related to the drug. The reaction may be a known side effect of the drug or it may be new and previously unrecognized. 4
    5. 5. How to identify adverse drug reactions ? The patient may tell you about symptoms they have experienced since taking a new medicine. ADR criteria Abnormal clinical measurements while on drug therapy (e.g. temperature, pulse, blood pressure, blood glucose, body weight) Abnormal biochemical or haematological laboratory results while on drug therapy 5
    6. 6. Overview Definition Which type of hypersensitivity is it based on ? 6
    7. 7. What is DRESS ? is a rare, potentially life-threatening, drug-induced severe, unexpected hypersensitivity reaction that includes skin eruption, hematologic abnormalities (eosinophilia, atypical lymphocytosis), lymphadenopathy, and internal organ involvement (liver, kidney, lung) Drug hypersensitivity syndrome 7
    8. 8. Which type of hypersensitivity is DRASS ? 8
    9. 9. Delayed hypersensitivity reactions Or type IV hypersensitivity reactions. inflammatory reactions initiated a secondary cellular response by mononuclear leukocytes . Lymphocytes (T cells ) monocytes/macrophages 9
    10. 10. Etiology and risk factors Causes side effects of “ Carbamazepine (Tegretol)” side effects of “Diazepam” Who may develops DERSS ? 10
    11. 11. What could cause DRESS ? Antiepileptic agents e.g. carbamazepine drugs associated with DRESS 11
    12. 12. Carbamazepine Antiepileptic drug Common side effects may include: • • • • feeling dizzy drowsy, or unsteady Nausea vomiting • diarrhea • constipation • stomach pain 12
    13. 13. Cont… Serious side effect such as: • • • • • • • • • pale skin and skin pain feeling light-headed rapid heart rate, trouble concentrating Fever Chills sore throat mouth and throat ulcers easy bruising or bleeding, • • • • • • • • • severe tingling numbness pain and muscle weakness Confusion agitation vision problems hallucinations feeling short of breath swelling of your ankles or feet • urinating less than usual • Jaundice (yellowing of the skin or eyes) • severe skin reaction • swelling in face or tongue • burning in eyes • a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling. 13
    14. 14. Diazepam It is often used in stress and anxiety. Side effects: • drowsiness, tired feeling • memory problems • dizziness, spinning sensation • feeling restless or irritable • muscle weakness • nausea, constipation • blurred vision, double vision • mild skin rash, itching • loss of interest in sex • • • • new or worsening seizures weak or shallow breathing feeling like you might pass out muscle twitching, tremor • drooling or dry mouth, slurred speech 14
    15. 15. Carbamazepine Diazepam If the patient takes diazepam with tegretol decrease levels of diazepam by increasing the elimination of diazepam by liver enzymes. increase level of carbamazepine by decreasing the elimination of carbamazepine by liver enzymes. 15
    16. 16. Who may develops DRESS ? Children adults without sex predilection *most cases occur in adults 16
    17. 17. Pathophysiology 17
    18. 18. Pathophysiology pathophysiology of DRESS syndrome remains unclear A defect in the way the liver metabolizes drugs may be responsible. immunological imbalance Another theory is that co-infection with the human herpes virus 6 (HHV6) is important to initiate the syndrome. Genetic may play a role. Pharmacogenetic studies have found a relation between certain population and certain antiepileptic in developing DRESS 18
    19. 19. Clinical presentation Signs & symptoms 19
    20. 20. Signs & symptoms Symptoms and signs vary from mild to severe depending on the patient and drug Start up to 12 weeks or more after initiation of drug treatment and can occur after a dose increase . e.g. the onset of carbamazepine’s side effects considerably long and may be reach more than 6 months ! Symptoms may persist or recur for several weeks after stopping drug treatment. 20
    21. 21. Prominent eosinophilia Exanthema Hepatitis Lymphadenopathy 21
    22. 22. Facial swelling Fever Generalized edema Multi-organ failure 22
    23. 23. Diagnosis Investigations ( exclude & prove ) The most useful test 23
    24. 24. Investigations CBC with differential and peripheral blood smear • eosinophilia >700/microL suggests the diagnosis of DRESS. • In some patients, lymphocytosis • And/or the finding of atypical lymphocytes on peripheral smear also support the diagnosis of DRESS. 24
    25. 25. Cont... 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
    26. 26. Cont... 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. 26
    27. 27. Cont... Testing for herpes-virus infection The search for active infection with human herpes-virus testing for EBV, HHV-6, or HHV-7 is increasingly performed in patients with DRESS, since viral infection reactivation may be a marker of prolonged course and increased risk of complications Imaging studies In patients presenting with nonspecific symptoms of pulmonary involvement (eg, cough, tachypnea/dyspnea), chest radiograph or CT scan may provide evidence of interstitial pneumonitis and/or pleural effusion 27
    28. 28. Which drug is responsible ? Patch test • helps identify which substances may be causing a reaction in a patient. • A patch test relies on the principle of a type IV hypersensitivity reaction. • Allergic substance will exhibit inflammation in the skin • Useful for detecting an ADR with carbamazepine and other drugs but not all. 28
    29. 29. Treatment 29
    30. 30. How to treat DRESS? Stopping all doses of suspected medication causing the symptoms Keeping the symptoms under control follow up to avoid relapse Supportive therapy ( replacement of causative medication ) Antihistamine Corticosteroids epinephrine if needed 30
    31. 31. Complication & Prognosis 31
    32. 32. Prognosis & complication Most patients with DRESS recover completely in weeks to months after stop replace the drug Autoimmune diseases have been reported in some patients months or years after the resolution of the drug reaction. In rare cases, patients developed chronic renal failure and lymphoma. death 32
    33. 33. Adverse drug reaction Adverse drug reaction could be fatal and a special care should be provide for the patient. DRESS in detail If you as a doctor suspect of drug hypersensitivity reaction, it is important to take a proper medication history with considering the side effects. Summary 33
    34. 34. http://www.dermnetnz.org/reactions/drug-hypersensitivity-syndrome.html http://www.rxlist.com/tegretol-side-effects-drug-center.htm http://www.rxlist.com/valium-side-effects-drug-center.htm http://treato.com/Carbamazepine,Diazepam/?a=s http://www.uptodate.com/contents/drug-reaction-with-eosinophilia-and-systemicsymptoms-dress http://dermnetnz.org/reactions/drug-hypersensitivity-syndrome.html References 35
    35. 35. 36