DRESS syndrome due to a cocktail of medications.

1. DRESS
SYNDROME
Presented By,
Reima Elizabeth Jacob
PharmD Intern

2. • Drug reaction with eosinophilia and systemic
symptoms (DRESS) is a severe adverse drug-induced
reaction.
• DRESS is rare, occurring in 1 : 1000 to 1 : 10000
patients prescribed anticonvulsant therapy. It can result
in a dreadful prognosis, with a mortality rate of 2 to
45%.
• Most commonly described after the introduction of
aromatic anticonvulsants, allopurinol, or antiretroviral
therapies

3. PATHOPHYSIOLOGY
• Abnormal immune response in a genetically
susceptible Individual - induced by the formation of
reactive metabolites OR reactivation of herpes viruses
6, 7 and Epstein-Barr virus .
• In the case of aromatic anticonvulsants, toxic
metabolites in the form of arene oxides are produced,
which lead to a type of IV hypersensitivity reaction .
• Lack of the enzyme epoxide hydrolase, involved in the
breakdown of the toxic metabolites.

4. SIGNS & SYMPTOMS
DRESS is characterized by
• Fever
• skin rash
• hematological abnormalities,
• systemic involvement such as hepatitis
• usually presents 2–6 weeks after drug initiation

5. DIAGNOSIS
• Physical examination
• Radiological findings
• Complete blood test
• In vitro interferon gamma release test - serum is
exposed to different drugs taken by the patient with a
subsequent increase in IFN-gamma demonstrated in the
offending drug.

6. TREATMENT
• Key element-early and permanent withdrawal of every
suspected medication.
• Use of strong topical steroids is sufficient for mild
cases.
• Severe cases-a systemic corticotherapy
(methylprednisolone 1-2mg/kg/d).
• Aggressive intravenous fluid hydration.

7. REAL CASE

8. SUBJECTIVE
• Demographic details:
Name: X Age: 27 years Sex: Female
Ward: General Ward II DOA: 22/01/2018
• C/O: Patient developed generalized weakness for last
5-6 days, loss of appetite and decreased sleep.
• Social History: Married 10 months ago
• Family history: Asthma
• Allergies: Nil

9. OBJECTIVE
Vital signs
• BP-130/60 mmHg
• PR-88 beats/min
• RR-22/min
• Temp- 101.6 F
• CNS-intermittently confused
• CVS- S1S2+ no murmurs
• RS- NVBS BL+
• P/A-soft, non tender, liver palpable

10. Past medical history: She was admitted at CMC Vellore
due to
• Insidious onset of high grade fever associated with
chills and rigors.
• Intermittent cough with minimal expectoration.
• Erythematous rash starting from her face and gradually
spreading to chest and abdomen.
• Generalized itching
• Blood and mucous in stool
• Weight loss (4 kg)
• Jaundice

11. She was diagnosed with Bipolar disorder since 13/12/17
• T. Lithium SR 450 mg BD +T. Oxcarbamezipine 300
mg BD from 13/12/17
• T. Risperidone 300 mg BD +T. Trihexphenydyl 2 mg
1-0-1 from 8/12/17
• T. Olanzepine 5 gm BD +T. Divalprox 250 mg BD for
5 days from 8/12/17 to 12/12/17
• T. Chlorpromazine 50 mg BD from 27/12/17 to
16/01/18
Personal History- Disturbed sleep, depression

12. • O/E: Patient conscious, oriented
• Icterus +, pedel edema up to the knee
• Lymphadenopathy +
• Dry skin with diffuse maculopapular rashes seen on the
face and trunk
• Skin peeling seen around the lips
• Asterixes +
• Traube’s space-dull ( indicates splenomegaly)
• Oral: Cheilitis, candida +
• Genitilia: matting and increased secretions +

13. • Lab investigations:
• AST- 143 U/L, ALT: 177 U/L, ALP: 367 U/L,
• GGT: 366
• Bilirubin-Total: 10.74 mg/dl
Direct: 9.72 mg/dL
• Total protein: 5.3 g/l, Globulin: 2.7 g/l
• Serum ammonia: 36 mcg/dL
• PT: 13.6 INR: 1.12
• WBC: 16,600 cells/mm3
• Na-125 mmol/L Bicarbonate: 14 mmol/L
• Eosinophils: 17%

14. • USG Findings:
• Hepatosplenomegaly with no focal leisons
• Multiple peripancreatic, porta hepatis and para-aortic
nodes
• Mild GB wall edema due to hypoalbuminemia
• Minimal ascites
• EEG report- generalized cortical dysfunction
• Negative viral titers

15. • Current medications
• IV Piperacillin Tazobactum 4.5 gm 1-1-1
• IV Hydrocortisone 75 mg 1-1-1-1
• IV Acetylcysteine 7 gm BD
• T. Udiliv 1-1-1
• T. Neurobion forte 1-0-1
• IV. Pantoprezole 40 mg 1-0-0
• Candid mouth paint 1-1-1
• Duphulac enema 30 ml BD
• IV NS 50 ml/hr
• Zyntec gel on local application
Withhold Bipolar
medications

16. ASSESSMENT
• Her clinical picture is consistent with DRESS
syndrome- to oxcarbazepine
• Her background history of a combination psychotropic
and anticonvulsant drug use may serve as a
predisposing factor through cytochrome P450 enzyme
inhibition, allowing the accumulation of antigenic
metabolites of a second drug metabolized via the same
cytochrome P450 subenzymes.
• RegiSCAR scoring: 6

18. MY PLAN
• IV Piperacillin Tazobactum 4.5 gm 1-1-1
• IV Hydrocortisone 75 mg 1-1-1-1
• IV Acetylcysteine 7 gm BD
• T. Udiliv 1-1-1
• T. Neurobion forte 1-0-1
• IV. Pantoprezole 40 mg 1-0-0
• Candid mouth paint 1-1-1
• Duphulac enema 30 ml BD
• IV NS 50 ml/hr
• Zyntec gel on local application

19. • Prednisolone 40 mg/day orally and gradually can be
tapered over 6 weeks.
• Levetiracetam can be initiated to a total daily dose of
2500 mg when the symptoms of DRESS subsides.

20. MONITORING
• Complete Blood Count
• Hepatic function
• Mental status
• Regarding levetiracetam : Emergence or worsening of
suicidal thoughts or behavior, depression, or any
unusual changes in mood or behavior
• Behavioral abnormalities, including psychiatric and
non-psychotic symptoms (eg, aggression, agitation,
anger)
• Further allergic reactions

21. PATIENT COUNSELING
• Due to the likelihood of genetic predisposition, first
degree relatives should avoid this class of drugs
• Emotional support from family members
• Psychotherapy
• Advice to report any hypersensitivity reaction to any
drugs.
• Counsel the importance of adhering to the medications
• Eat hygienic foods
• Get vaccinated before travelling to endemic areas
• Report immediately if similar reaction occurs again.

22. BRAND NAMES
Generic name Brand name
Prednisolone Acticort, Anisoline
Aceylcysteine Bronac, albunil
Pantoprezole Pan, Abipanta
Lactulose Duphulac, Abilax

23. REFERENCE
• S. H. Kardaun, A. Sidoroff, L. Valeyrie-Allanore et al.,“Variability in the
clinical pattern of cutaneous side-effects of drugs with systemic
symptoms: does a DRESS syndrome really exist?” British Journal of
Dermatology, vol. 156, no. 3, pp. 609–611, 2007.
• K. Ben-Ari, I. Goldberg, I. Shirazi et al., “An unusual case of DRESS
syndrome,” Journal of Dermatological Case Reports, vol.3, pp. 39–42,
2008.
• Bocquet H, Bagot M, Roujeau JC. Druginduced pseudolymphoma and
drug hypersensitivity syndrome (drug rash with eosinophilia and systemic
symptoms: DRESS).Semin Cutan Med Surg. 1996;15(4):250 –257

24. TAKE AWAY POINTS
• Naranjo Adverse Drug Reaction Probability scaling
can be used- to find likelihood of an ADR
• >9 Definite ADR; 5–8 probable ADR; 1–4 possible
ADR; <0 doubtful ADR.