Case

1. NOON CONFERENCE
L A U R E N B O N O M O , T Y I N T E R N

2. HOSPITAL COURSE
2/17: Admitted to SCH with Dx of DIHS/DRESS
- Stopped lamotrigine and listed as allergy
- Attempted topical steroids and cetirizine for pruritus
2/18: Developed new edema of face, neck, hands
2/19: Worsening labs, still febrile
- LFTs trending up (now low 100s)
- WBC spike to 67k, now 13% eos
- Started IV methylpred 1.5 mg/kg
2/20-21: Significant clinical improvement!
- LFTs and WBC decreased
- PO intake and UOP increased

3. 2/22: Developed new 2L O2 requirement overnight
- In AM, found to be tachypneic with subcostal retractions, CBG WNL
- No improvement after Lasix x1
- RRT called, transferred to PICU
- Ultimately required CPAP for acute hypoxemic respiratory failure
2/23: AST/ALT > 200, HHV-6 PCR now 47 million (from 610)
- Steroids increased to 2 mg/kg, added IVIG
2/24: Last true fever after 2nd IVIG infusion
2/27: CPAP discontinued, weaned off supplemental O2, completed 3rd IVIG
3/1: Discharged home from PICU after being SORA x 3d
HOSPITAL COURSE

4. DIHS (A.K.A. DRESS)
DIHS = Drug-Induced Hypersensitivity Syndrome
• Still more commonly called DRESS (Drug Reaction with Eosinophilia
and Systemic Symptoms)
• Severe, multi-system reaction with fever, rash, and visceral involvement
• Hepatitis, myocarditis, nephritis, pneumonitis (at risk for ARDS)
• Typically 2-6 weeks after drug initiation
• Most common in adults without sex prediliction
• Eosinophilia and atypical lymphocytes in estimated 30% of cases
• Allopurinol, anticonvulsants, and sulfonamides are the most common
agents
• Underlying mechanisms poorly understood
• Particular serotypes of HLA-A, HLA-B, HLA-C have an increased risk of
developing DRESS in response to specific medications
• A role of viral co-infection also suspected (specifically, HHV-6
reactivation)

5. REGISCAR SCORE
If yes, more points
for:
• > 50% BSA
• Presence of
edema,
purpura, scaling
• Skin Bx c/w
DRESS

6. REGISCAR SCORE

7. BUT WAIT…
This patient with > 4 days of fever has cervical LAD, red tongue, diffuse
rash, swelling and peeling of hands… what about Kawasaki Disease?
• Patient actually met SCH criteria for incomplete KD on presentation!
• Eventually met criteria for complete KD after peeling/swelling of hands
• We did obtain TTE because of this, but it was fortunately completely
normal
• Ultimate clinical picture more consistent with DIHS
• Missing nonpurulent conjunctivitis
• Oral erythema but not classic “strawberry tongue”
• >5 years old
• Recent use of drug strongly associated with DIHS
• Impressively high HHV-6 viral load
• Pulmonary involvement

9. MANAGEMENT
• Majority of patients do well after cessation of the offending agent
• Can treat symptomatically with strong topical steroids, anti-histamines
• But mortality is 2-10%!
• If visceral involvement -> prednisone at least 1 mg/kg/day or equivalent
• Transaminases >5x ULN or renal/pulmonary/cardiac involvement
• Multiple reports of high-dose IVIG (1 g/kg) used as adjuvant
• Thought helpful because it supports protection against HHV-6
• Recommended in all patients with life threatening signs (BM failure,
encephalitis, liver/renal/respiratory failure)
• French study of 6 patients with DRESS did not support use of IVIG
monotherapy
• 4 out of 6 ultimately required steroids
• Other proposed therapies: CsA, cyclophosphamide, interferons, MMF,
rituximab, N-AC, valgancyclovir

10. OUR PATIENT
• Encouraging progress, but not out of the woods
• Long-term sequelae of DIHS include:
• Thyroiditis
• Myocarditis
• Pancreatitis
• Will need close follow up with continued lab monitoring, strict return
precautions
• Steroid dose adjustment PRN, but plan for long and slow taper (next 6
weeks)
• Expect rash to resolve in cephalad to caudad fashion
• Lamotrigine and aromatic anticonvulsants are now absolutely
contraindicated

11. QUESTION 1
A 62-year-old gentleman with a history of bipolar disorder, obesity, HTN, HLD,
and gout presents to the ED with fever and diffuse morbilliform rash x 4 days.
On further workup, he is found to have leukocytosis with eosinophilia as well
as elevated transaminases.
The patient has been on a stable dose of lamotrigine since 2016. Last November,
he started taking celecoxib for pain and swelling of his right great toe that was
ultimately diagnosed as gout. He began taking daily allopurinol in January.
Two days ago, he completed a course of levofloxacin for PNA.
Which of the following should be discontinued and immediately added to patient’s
allergy list?
• A) Lamotrigine (and all aromatic anticonvulsants)
• B) Celecoxib
• C) Allopurinol
• D) Levoflocxacin

12. QUESTION 1
A 62-year-old gentleman with a history of bipolar disorder, obesity, HTN, HLD,
and gout presents to the ED with fever and diffuse morbilliform rash x 4 days.
On further workup, he is found to have leukocytosis with eosinophilia as well
as elevated transaminases.
The patient has been on a stable dose of lamotrigine since 2016. Last November,
he started taking celecoxib for pain and swelling of his right great toe that was
ultimately diagnosed as gout. He began taking daily allopurinol in January.
Two days ago, he completed a course of levofloxacin for PNA.
Which of the following should be discontinued and immediately added to patient’s
allergy list?
• A) Lamotrigine (and all aromatic anticonvulsants)
• B) Celecoxib
• C) Allopurinol
• D) Levoflocxacin
Note: It would not be unreasonable to add fluoroquinolones to allergy list too. That said, LVQ
a much rarer cause of DRESS, and time course would be very unusual. You could consider
patch testing after resolution of symptoms.

13. QUESTION 2
A 28-year-old man presents with fever, malaise, and rash x 8 hours. 10 days ago,
he was started on TMP-SMX for MRSA infection. His last dose was this
morning. He takes no other meds and has no allergies.
On exam: T38.6, HR 110, other VS WNL. There are erythematous, urticarial,
targetoid plaques over his shoulders that are studded with small, tense
blisters. You also note erythematous targetoid lesions on his palms. There are
small vesicles and crusts of the upper and lower lips and a small erosion of
the soft palate. CBC, CMP, and ESR are WNL.
Which of the following is the most likely diagnosis?
• A) Acute generalized exanthematous pustulosis (AGEP)
• B) Drug-induced hypersensitivity syndrome
• C) Red man syndrome
• D) Stevens-Johnson syndrome

14. QUESTION 2
A 28-year-old man presents with fever, malaise, and rash x 8 hours. 10 days ago,
he was started on TMP-SMX for MRSA infection. His last dose was this
morning. He takes no other meds and has no allergies.
On exam: T38.6, HR 110, other VS WNL. There are erythematous, urticarial,
targetoid plaques over his shoulders that are studded with small, tense
blisters. You also note erythematous targetoid lesions on his palms. There are
small vesicles and crusts of the upper and lower lips and a small erosion of
the soft palate. CBC, CMP, and ESR are WNL.
Which of the following is the most likely diagnosis?
• A) Acute generalized exanthematous pustulosis (AGEP)
• B) Drug-induced hypersensitivity syndrome
• C) Red man syndrome
• D) Stevens-Johnson syndrome

15. REFERENCES
• Husain, Zain, Bobby Y. Reddy, and Robert A. Schwartz.
"DRESS syndrome: Part I. Clinical perspectives."
Journal of the American Academy of Dermatology 68,
no. 5 (2013): 693-e1.
• Kardaun, S. H., P. Sekula, L. Valeyrie‐Allanore, et al.
"Drug reaction with eosinophilia and systemic
symptoms (DRESS): an original multisystem adverse
drug reaction. Results from the prospective R egi
SCAR study." British Journal of Dermatology 169, no. 5
(2013): 1071-1080.
• Ginory, Almari, Michelle Chaney-Catchpole, Julie M. Demetree, Laura M. Mayol Sabatier, and Mathew
Nguyen. "Drug reaction with eosinophilia and systemic symptoms (DRESS) in an adolescent treated with
lamotrigine." The Journal of Pediatric Pharmacology and Therapeutics 18, no. 3 (2013): 236-240.
• Kuschel, Stephanie L., and Matthew S. Reedy.
"Cyclosporine treatment of drug reaction with
eosinophilia and systemic symptoms (DRESS)
syndrome: a case report and brief review of the
literature." Practical dermatology 2018 (2018): 41-43.