SKIN REACTIONS WITH PSYCHOTROPICS: A SYSTEMATIC REVIEW

Transcription

1 SKIN REACTIONS WITH PSYCHOTROPICS: A SYSTEMATIC REVIEW *Anderson Isaac, PharmD Candidate, 2019 Pooja Patel, PharmD Candidate, 2019 Katelyn Thomasson, PharmD Candidate, 2019 Erika Tillery, PharmD, BCPP, BCGP Presbyterian College School of Pharmacy ACKNOWLEDGEMENT: REBECCA CONLEY, PHARMD & JESSICA HORTON, PHARMD *PRESENTING AUTHOR 1

2 OBJECTIVES 1. Define the skin reactions DRESS, SJS, and TEN, and review the clinical presentation and pathophysiology of the these cutaneous reactions. 2. Discuss the methods and outcomes of a systematic review that was conducted in order to assess the frequency of drug-induced skin reaction development with the administration of psychotropic medications (anticonvulsants, mood stabilizers, antipsychotics, and antidepressants). 2

3 DRESS Drug Reaction with Eosinophilia and Systemic Symptoms Also known as Hypersensitivity Syndrome Drug-Induced Hypersensitivity Syndrome (DIHS) Can occur up to 8 weeks post ingestion of offending agent Usually with first-time use of medication Can be life-threatening 10% mortality if not recognized and treated Diagnostic Criteria (3) Cutaneous drug eruption Hematological abnormalities Atypical lymphocytes on blood smear Eosinophilia Systemic involvement Lymphadenopathy Hepatitis Ben-Ari K, Goldberg I, Shirazi I, Amitay I, Sigler M, Brenner S. An unusual case of DRESS syndrome. Journal of Dermatological Case Reports. 2008;2(3): doi: /jdcr

4 DRESS Presentation Morbilliform rash (measleslike) Facial edema Pharyngitis Malaise Lymphadenopathy Hepatic Necrosis If anticonvulsants are the culprit, look for the triad 1. Fever 2. Generalized exanthema (rash) 3. Multi-organ failure Systems Affected Thyroid Lungs Liver Kidneys Labs Assessments TSH, T4 CBC LFTs SCr UA Lars Grimm. 15 Adverse Cutaneous Drug Reactions. Medscape. Pileri, A., et. al., DRESS. Divison of Dermatology Skonicki J, Warnock J. Drug eruptions: 6 dangerous rashes. Current Psychiatry April;7(4): Ben-Ari K, Goldberg I, Shirazi I, Amitay I, Sigler M, Brenner S. An unusual case of DRESS syndrome. Journal of Dermatological Case Reports. 2008;2(3): doi: /jdcr

5 SJS Stevens-Johnson Syndrome Also known as Erythema Major Definition SJS if less than 10% of TBSA is detached SJS/TEN if 10-30% of TBSA is detached Can be life threatening or altering Mortality rate: 5-15% Scarring, more pigmentation changes Blindness Prodromal symptoms are often seen prior to rash eruption Illustration copyright 2000 by Nucleus Communications, Inc. All rights reserved. Blahd W. WebMD. Rule of Nine. Lars Grimm. 15 Adverse Cutaneous Drug Reactions. Medscape. Skonicki J, Warnock J. Drug eruptions: 6 dangerous rashes. Current Psychiatry April;7(4):

6 SJS Presentation: Prodromal Symptoms High fever Asthenia Myalgia Arthralgia Vomiting Diarrhea Pharyngitis Cough Malaise Large, connected lesions Widespread & unraised Burning sensation Presentation: Rash Usually involves the trunk + at least 2 mucosal sites (eyes, mouth, esophagus, or genitalia) Has also been seen on face, hands, and feet. Firmansyah I. Stevens-Johnson Syndrome at a Glanced. Updated June 15, Accessed March 21, Y., Ocular SJS. Doheny Eye Institue, USC School of Medicine Lars Grimm. 15 Adverse Cutaneous Drug Reactions. Medscape. Skonicki J, Warnock J. Drug eruptions: 6 dangerous rashes. Current Psychiatry April;7(4): Pan, 6

7 TEN Toxic Epidermal Necrolysis Also known as Toxic Epidermal Necrosis Syndrome (TENS) Lyell s Syndrome Severe reaction, similar to SJS Definition SJS/TEN if there is 10-30% of TBSA detached TEN if there is greater than 30% of TBSA detached Can be life threatening Mortality rate: 30-40% Sepsis is the most common cause of death Staphylococcus aureus, Pseudomonas aeruginosa Lars Grimm. 15 Adverse Cutaneous Drug Reactions. Medscape. Widgerow AD. Toxic epidermal necrolysis - management issues and treatment options. International Journal of Burns and Trauma. 2011;1(1): Schwartz R, Avello E, Palisson F. Lamotrigine-Induced Toxic Epidermal Necrolysis Treated With Intravenous Immunoglobulin and Amniotic Membranes. Arch Dermatol. 2008;144(6): Skonicki J, Warnock J. Drug eruptions: 6 dangerous rashes. Current Psychiatry April;7(4): Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet Journal of Rare Diseases. 2010;5:39. doi: /

8 TEN Diffuse skin tenderness and erythema Resembles burns Usually starts at face and moves downward (2-3 days) Sparing the scalp Presentation Skin separates in sheets Large, semi-flat blisters Positive Nikolsky sign Skin detaches when pressure is applied Acute Complications Infection risk, loss of skin integrity Electrolyte abnormalities Dehydration Hypoalbuminemia Long Term Complications Eyelid malformations, ingrown lashes Lung diseases Pigmentation abnormalities, scarring Dystrophy of nails Joint contractures Lars Grimm. 15 Adverse Cutaneous Drug Reactions. Medscape. Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet Journal of Rare Diseases. 2010;5:39. doi: / Ly T. Toxic Epidermal Necrolysis.;

9 PATHOPHYSIOLOGY Proposed Hypotheses Immune response to antigenic complexes Genetic susceptibilities (HLA-B*5801, HLA- B*1502) Receptor-mediated apoptosis, Fas ligand Drug-specific cytotoxic T cells, release destructive proteins Mechanism Of Manifestation Sensitization: delayed presentation (1-3 weeks after) Exaggerated inflammatory response Cytokines and matrix metalloproteinases (MMPs) Apoptosis of keratinocyte cells causes epidermal necrolysis Extracellular matrix destruction, major fluid shifts, and SIRS Journal of the American Academy of Dermatology , e82- e83doi: ( /j.jaad ) French LE. Toxic epidermal necrolysis and Stevens Johnson syndrome: our current understanding. Posadas SJ, et al. Delayed reactions to drugs show levels of perforin, granzyme B, and Fas-L to be related to disease severity. J Allergy Clin Immunol. 2002;109(1): doi: /mai Abe R, Shimizu T, Shibaki A, Nakamura H, Watanabe H, Shimizu H. Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome Are Induced by Soluble Fas Ligand. The American Journal of Pathology. 2003;162(5):

10 ARE THERE ANY GUIDELINES FOR TREATING DRUG-INDUCED SKIN REACTIONS? 10

11 SYSTEMATIC REVIEW: METHODS Three independent investigators May 2017-December 2017 Databases: EBSCOHost and PUBMED Final search phrase utilized: Stevens Johnson Syndrome OR SJS OR Toxic Epidermal Necrolysis OR TENS OR Drug Reaction with Eosinophilia Systemic Symptoms OR DRESS AND psychiatric medications OR psychotropics AND psychotic disorders OR schizophrenia AND epilepsy Antiepileptic drugs: carbamazepine, oxcarbazepine, valproic acid, divalproex, lamotrigine, and phenytoin 11

12 SYSTEMATIC REVIEW: METHODS Inclusion Criteria publication Full text article English Language References available Scholarly Academic Journal Peer reviewed Case Studies 12

13 SYSTEMATIC REVIEW: RESULTS Article Type Resulting Number of Articles Case Reports 56 Letter to the Editor 3 Systematic Review 2 Review Articles 2 Post Marketing Surveillance 1 Case Control 1 Retrospective Analysis 1 Prospective Case Series 1 Tertiary Guidance Document 1 13

14 SYSTEMATIC REVIEW: RESULTS Prevelance of Drug Induced Skin Reaction Number of Cases Lamotrigine Phenytoin Carbamazepine Oxcarbazepine Valproic acid Clozapine Lithium Duloxetine Fluoxetine Offending Agent Levetiracetam 14

15 SYSTEMATIC REVIEW: RESULTS Pharmacotherapy Utilized for Treatment of SJS, DRESS, and TEN in Case Reports Topical Agents 11% Drug Therapy Not Specified 7% Systemic Steroids 38% Miscellaneous Drug Use 13% Antibiotics 13% Histamine Antagonist 18% 15

16 SYSTEMATIC REVIEW: DISCUSSION No guideline or algorithm in the United States UK Guidelines for the Management of Stevens-Johnsons Syndrome/Toxic Epidermal Necrolysis in Adults 2016 Practical Guidelines for the Management of Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome 2007 Dress Syndrome: Time to Define Treatment Guidelines? Lamotrigine, phenytoin, carbamazepine, and oxcarbazepine Limitations: Case reports vs meta-analysis and/or randomized controlled trials Lack of reports in the United States Variations in pharmacotherapy 1. Creamer D, et al. British Journal Of Dermatology [serial online]. June 2016;174(6): Fromowitz J, et al. International Journal Of Dermatology [serial online]. October 2007;46(10): Singh V, et al. National Journal Of Integrated Research In Medicine [serial online]. September 2014;5(5):

17 SYSTEMATIC REVIEW: CONCLUSION Future Plans Critique the evidence and apply interventions to existing patients who have active orders for anticonvulsants, mood stabilizers, antipsychotics, and/or antidepressant therapies. Design a treatment guideline for drug-induced skin reactions that could be implemented in institutions and be utilized by health-care providers. 17

18 TEST YOUR KNOWLEDGE Clinical symptoms of DRESS, SJS, and TEN is ONLY exhibited on the epidermis of the body? TRUE FALSE A patient is diagnosed with SJS and his entire left lower extremity is affected. What is the total body surface area percentage of the left lower extremity? 3% 10% 12% 9%

19 SKIN REACTIONS WITH PSYCHOTROPICS: A SYSTEMATIC REVIEW *Anderson Isaac, PharmD Candidate, 2019 Pooja Patel, PharmD Candidate, 2019 Katelyn Thomasson, PharmD Candidate, 2019 Erika Tillery, PharmD, BCPP, BCGP Presbyterian College School of Pharmacy ACKNOWLEDGEMENT: REBECCA CONLEY, PHARMD & JESSICA HORTON, PHARMD *PRESENTING AUTHOR 19