1. STUDENT CLINICAL
MEET
Sabari krishnan
31.07.2012

2. • Name : Mrs ML
• Age :50/m
• CR.NO:2541826
• D O A:27.05.2012
• D O D:12.06.2012
• Unit :IM2

3. PRESENTING COMPLIANTS
• Loose stools -15 days
• Fever -15 days
• Rash all over the body-14 days
• Decreased urine output-10 days

4. Significant back ground history
 History of knee joint pain for past 8 months
• Bilateral symmetrical
• No early morning stiffness
• History of increasing pain with squatting and walking
• Consulted private practitioner 4 weeks back, he was
prescribed Leflunomide 10 mg b.d, HCQ 200 mg hs,
considering rheumatoid arthritis, however clinical features
not s/o of any inflammatory arthritis.

5. History of presenting illness
• Loose stools-15 days
-7-8 episodes/day, watery, small volume stools
-not associated blood or mucus
-associated with vomiting,4-5 episodes/day, non projectile
containing food particles, associated with pain abdomen.
• Fever -15 days
- intermittent, high grade fever , documented upto 104 F
-not associated with chills and rigor, relived by antipyretics.

6.  Rash all over the body-15 days
-pruritic, maculopapular rash
-developed after taking medication,
-sparing oral mucosa, palms and soles,
- no h/o blister formation and scarring.
 Decreased urine output 10 days
-500-600ml/day, associated with dysuria, no hematuria.

7. past history
• No k/c/o DM,HT, TB, asthma, CAD, CVA.
• h/o cataract operation right eye 2 yrs back.
Personal history
• Chronic smoker-40 yrs, bidi 30-40/day, smoking index -1200 to
1600.
• Chronic alcoholic-20yrs,1-2 times /wk, for 20 yrs.
• Bladder and bowel habits normal.

8. General examination
Conscious, oriented
Vitals-PR-110/min, regular, normal volume, all peripheral pulse
felt, no RR or RF delay.
BP-116/80mmHg
RR-30/min
Temp-febrile
Spo2-92% on RA
No pallor, icterus, cyanosis, clubbing, lymphadenopathy.

9. Generalised erythematous scaly rash all over the body

10. Systemic examination
• RS-BAE present, no added sounds
• CVS-S1S2 present, no murmur
• Abdomen –soft, non tender, no organomegaly, no free
fluid, bowel sounds present.
• CNS-WNL

11. HEMOGRAM
28/5 30/5 31/5 04/6 05/6 6/06 11/06
Hb 12.6 12.7 12.9 11.3 10.2 9.8 9.7
TLC 29,600 26,000 26,500 32,600 29,200 19,300 9700
DC N35 L18 N41 L18 N71 L17 N40 L56 N68 N84 L12 N70 L24
M4 E45 M5 E27 M2 E10 M3 E01 L27 M2 E02 M4 E02
M3 E02
PLATELE 1,78,000 1,50,000 85,000 64,000 96,000 1,00000 1,45,000
TS
PBF RBC - AEC- Activated
N/N 7047/mm lymphocyte
present

12. Biochemistry
28/05 31/05 02/06 04/06 06/06 08/06 11/06
Na/k 145/ 144/ 139/ 143/3.7 144/ 143/ 146/
4.2 3.15 3.2 3.2 3.1 3.9
Urea/creatinine 206.7/ 73/ 58.3/ 67.1/ 54.7/ 28.4/ 34.8/
9.74 2.85 1.50 0.84 0.77 0.58 0.80
SGOT/SGPT 94.8/ 85.0 410/ 200 745/ 235/ 166.7/ 82.6/ 49.0/
379 294 227.6 149.8 86.7
ALP 379 679 500 591 632 567 465
TP/albumin 4.86/ 2.7 5.27/ 4.16/ 4.32/ 4.71/ 5.31/ 5.53/
2.7 2.1 1.8 2.0 2.5 2.8
bilirubin 0.5 1.30 3.2 6.1 4.9 3.3 2.2
calcium 7.62 7.9 6.19 _ _ _ 7.85
phosphorus 7.99 3.44 2.03 _ _ _ 2.74
magnesium 2.55 1.51 1.45 _ _ _ 1.82

13. Investigations
• AEC(absolute eosinophil count)- 7047
• Urine R/E- Sugar –nil
Albumin-+
• 24 hrs urine protein-80
urine creatinie-600
• Bence jones proteins-negative
• SERUM ELECTROPHORESIS-no M band seen, urine protein –nil.
• Urine c/s-negative
• Blood c/s-negative
• ANA and ANCA-negative
• Viral markers –negative
• USG ABDOMEN-Mild hepatomegaly with fatty liver.
- B/L early renal parenchymal disease.

15. Course and management

16. Units final diagnosis
Drug Rash with Eosinophilia and Systemic Symptoms
 Hepatitis
 renal involvement
-Acute interstitial nephritis
-Associated renal vasculitis (?drug
induced)

17. Topics for discussion
 DRESS syndrome
• Clinical features
• Pathophysiology
• Treatment
 Leflunomide induced vasculitis

18. DRESS
• Term DRESS introduced in 1996 by Bocquet to differentiate DIHS with
hemotological and visceral involvement from other types of drug sesnsitivity
• Dress syndrome is severe life threatening manifestation of drug reaction including
a
– severe skin eruption,
– fever,
– hematological abnormalities [eosinophilia or atypical lymphocytes] and
– internal organ involvement.
• Formerly called Hypersensitivity Syndrome (HSS), phenytoin hyper- sensitivity syndrome, drug
hypersensitivity syndrome, drug- induced hypersensitivity syndrome, and drug-induced delayed multiorgan
hypersensitivity syndrome.
Patrice et al The American Journal of Medicine (2011)124,588-597

19. Drugs causing DRESS

20. continued

22. Clinical features of DRESS
 Delayed onset, usually 2-6 wks, after initiation
of drug therapy.
 Persistence or aggravation of symptoms
despite the discontinuation of the culprit drug.
Typically presents with rash and fever (87%).

23.  severe systemic manifestations
lymphadenopathy (75%),
hepatitis (51%),
hematologic abnormalities (30%).
interstitial nephritis (11%),
arthralgia's,
 Other symptoms: pruritus, oliguria, hepato-renal syndrome,
and asthenia.
 Can affect any organ system (lungs, CNS, GI, etc.)

24. SKIN MANIFESTATION OF DRESS
 Classically generalised erythematous maculopapular rash.
 Periorbital, facial or neck edema with pinhead-sized
characterised feature at early stage. Rash often generalised
into severe exfoliative dermatitia.
shiohara et al allergology international 2006;55;1-8
Augusto J et al.
Nephrol. Dial.
Transplant.
2009;24:2940-2942

25. Hepatic involvement
 Mild transaminitis to fulminant hepatic failure.
 Increase in transaminases due to necrosis
 Usually anicteric, if icteric its poor prognosis
 Pathogenesis is due to eosinophilic infiltration
driven by interleukin 5.
shiohara et al allergology international 2006;55;1-8

26. Renal involvement
 Acute tubulointerstitial nephritis- the tubules and interstitium showed
marked interstitial edema with an intense inflammatory infiltrate of
lymphocytes and plasmocytes.
Kidney biopsy showing acute interstitial nephritis (PAS stain)
 Acute tubular necrosis - present
with an infiltrate of polynuclear
neutrophils and lymphocytes in the
tubules

27. Hematological abnormalities
shiohara et al allergology international 2006;55;1-8

28. PATHOPHYSIOLOGY
 Causative drug induces hypersensitivity as a result of
abnormalities in the production and detoxification of its
active metabolites.
 Genetic predisposition, as the risk is increased in patients
with a positive family history for DRESS syndrome, in slow
acetylators, and in blacks .
• Accepted hypothesis for sulfonamides and anticonvulsants..
Joint Bone Spine 72 (2005) 82–85

29. • DRESS syndrome induced by anticonvulsants
may be related to epoxide–hydrolase
deficiency, which leads to accumulation of
toxic metabolites known as arene oxides. The
toxic effects of these metabolites on cells may
trigger an immunological response

30. HHV 6
• HHV 6-recently incriminated as a cofactor in development of
DRESS.
• Acts as a trigger in patient with predisposing immunological
and genetic susceptibility
• It interfere with drug metabolism, by altering the enzymes
involved in drug detoxification
Tohyama M, et al. Arch Dermatology 2002;138:268-9

31. 1. Maculopapular rash developing > 3 weeks after starting suspect drug
2. Prolonged clinical symptoms 2 weeks after discontinuation of the suspected drug
3. Fever > 38° C
4. Liver abnormalities (ALT > 100 U/L) or other organ involvement
5. Lymphadenopathy
6. Human herpesvirus 6 reactivation
7. Leucocyte abnormality
Leukocytosis ( > 11 x 109/L)
Atypical lymphocytosis (>5%)
esinophilia .1.5 x 109/L

32. The RegiSCAR-Group Diagnosis Score for Drug Reaction
with Eosinophilia and Systemic Symptoms (DRESS)

33. Dress syndrome most common differential diagnoses

34. Treatment

35. Role of steroids
• The main stay of treatment is systemic corticosteroids.
• Rapid resolution of rashes and fever occur within days after starting
systemic steroids, usual dose is prednisolone 40-60mg/day
• Systemic steroids can reduce symptoms of delayed hypersensitivity
reactions.
• Systemic steroids needs to be tapered over 6-8 wks to prevent the relapse
of various symptoms of this syndrome.
shiohara et al allergology international 2006;55;1-
8

36. Other treatment modalities

39. The patient in this case developed a systemic
illness characterized by fever, skin rash, diffuse
lymphadenopathy, profound peripheral
eosinophilia, mild transaminitis, altered mental
status, and acute kidney injury following
reexposure to intravenous vancomycin. As seen
here, renal biopsy revealed a granulomatous
acute interstitial nephritis (AIN) (lower left)
with a cellular infiltrate consisting of numerous
eosinophils, lymphocytes, neutrophils, plasma
cells, and macrophages (lower right).
Lymph node biopsy was consistent with a
reactive lympadenitis. Vancomycin was
discontinued, and the patient received
intravenous methylprednisolone for 3 days
followed by oral prednisone tapered over 4
weeks, with complete resolution of the

40. TAKE HOME MESSAGE
 Early recognition of symptoms is vital to
minimize morbidity and mortality,
 Discontinuation of causative drug-immediate and
life long.
 All granulomatous vasculitis with eosinophilia,
are not chrug-strauss, it could be due to DRESS
also.

41. Further course of the patient
• Seen in nephrology OPD after 14 days of discharge, Cough
with expectoration, high grade fever, upper abdominal pain -2
days, admitted in ward.
• CT CHEST AND ABDOMEN -patchy consolidation with
ground glassing in lingula and b/l lower lobe, splenic infarct.
• UGIE- 2 deep ulcer 1 anterior and 1 posterior duodenal wall,
next day developed perforation peritonitis, modified graham’s
patch repair done.
• Patient died due to VAP, sepsis and MODS.

42. Overall diagnosis
 DRESS- Leflunomide induced
– Hepatitis
– Renal involvement
Nephritis
Associated vasculitis ?drug induced
 Duodenal ulcers with perforation peritonitis
– ?steroid related / exacerbated
– ?vasculitis associated with leflunamide
– Sepsis, MOD  Death