1. CASE PRESENTATION ``Heroes`` Isabel Alonzo-Proulx, CCFP(EM)

2. Case 19 y.o.,female c/o diarrhea and vomiting Sudden onset, profuse for last 8-10 hrs Some diffuse abdo pain Presents to ED in evening: BP 100/65 P 95 T 37.8b Looks anxious,feels weak, has been tolerating PO for last hour

3. Case cont... HPI: Ø prodrome Ø antibiotics in last 6 months Ø pregnant: started n menses 3 days ago Travel: came back from Costa Rica 3 weeks ago, lived in families, has not been sick since PMHx: Ø previous Sx Never pregnant

4. Case cont... O/E: Mucous are dry CV n Pneumo n Abdomen: slightly distended, BS+, diffuse tenderness, no guarding, no rebound CVA equivocal bilat Skin n

5. Case cont... Staff comes in... Looks sick Asks for rectal T: 40 Orders: IV: 1L NS bolus CBC, SMA-7, LFT’s, blood cultures X2 U/A and culture B-HCG Stool cultures x2, parasites, and C.Diff

6. Case cont... Results: WBC 13 500 U/A : RBC ++++, 1-5 leukos Creat 86 Hb 139 Platelets 190 Urinary B-HCG -

7. Case cont... Dx Pyelonephritis? Started on Cipro Observed in ER 4 hrs later, weakness and syncope BP: 90/40, obtunded Non-pitting edema of face and neck Sent to ressuc Volume ressucitated

8. Case cont... Hypothesis? DDX ?

9. Case cont... LABs repeated: Creat 86, now 100 Hb 139 now 90 Platelets 190 now 100 U/S abdomen and pelvis: splenomegalia 16 cm mesenteric adenitis n otherwise

10. Case cont... DDx: Acute pyelonephritis? Septic shock? PID? HUS? Leptospirosis? Gastroenteritis? Tick Typhus?

11. And now... Pt develops a rash:

14. Case cont... DDX : Kawasaki disease? Reye syndrome? Erythema multiforma? Rocky Mountain spotted fever?

15. Staphyloccocal Toxic Shock Syndrome Staph TSS

16. Staphylococcus Gram positive cocci:

17. S.Aureus - Pathologies Local invasion and tissular destruction: Impetigo Cellulitis Endocarditis... Toxin mediated TSS Staphyloccocal exfoliation syndrome Food poisoning

18. S. Aureus - Epidemiology Reservoir – Human Asymptomatic carriers: Naso-pharynx Rectum Perineum: 98% of women w TSS compared w control subjects Cutaneous colonisation – brief, repetitive Transmission – person to person

19. S. Aureus – Carrier rate Population General population HD patients DB insulin Desensitivation therapy patients IV drug users Carrier rate (%) 25 75 50 40

20. STSS - Historical 1978 – Todd and Fishaut first describe STSS Acute febrile illness in 7 children Development of shock Association w staphylococcus aureus 1981 –US epidemic TSS identified in 941 pts 812 menstrual cases; otherwise healthy women Association w hyperabsorbant tampons use Drastic drop in incidence since 1980 Now 50% of case are nonmentrual

21. Toxic shock syndrome and tampons : the risk remains US: annual incidence STSS: 1-5 cases per 100 000 women in menstruation > 90% in female 15-19y Mortality 3.3% Therapeutic Product Directorate: TPD-Web

22. STSS – Risk factors Menses Tampons : increased risk 33 times in susceptible women Nasal packing Young age Previous STSS Vaginal – postpartum or following abortion Surgical wounds: hernia repair, mammoplasty, arthroscopy Septorhinoplasty Influenza or influenza-like illness

23. STSS – Pathogenesis Toxic shock syndrome toxin-1 (TSST-1) 90-100% of mentrual-related cases (MRTSS) 40-60% of nonmenstrual cases (NMTSS) Enterotoxin B: 23% Enterotoxin C: 2% Enhanced production: Neutral vaginal pH Increase in vaginal pO2 and pCO2 Synthetic fibers in tampon composition

24. STSS – Pathogenesis TSST-1 & enterotoxins = Superantigens: Nonspecific T-lymphocyte stimulation without normal antigenic recognition Ad 20% Result: massive production of cytokines Release of IL-1, IL-2, TNF, interferon

26. STSS – Pathogenesis Immunitary response from host plays an important role in pathogenesis 70-80% of 18 y.o. have antibodies to TSST-1 90-95% at 40 y.o. Pts who dev STSS are unable to produce antibodies Frequent recidival

27. STSS – Clinical presentation Sx on presentation: Tachycardia 80% Fever 70-81% Hypotension 44-65% Confusion 55% Localized erythema 44-65% Scarlatin-like rash 4%

28. STSS – Clinical presentation Rapid onset of sx: Day 3-4 of menses Day 2 post-operative

29. STSS – Clinical presentation

31. STSS – Dx criteria CDC 1990: Clinical manifestations Fever >38.9 Rash – diffuse macular erythrodema Desquamation – 1-2 after onset, palms and soles Hypotension (SBP<90 mmHg) Multisystem involvement(3+): GI (V, diarrhea, abdo pain) Muscular (myalgias, CK X 2) Mucous membrane (vagnal, conjunctival hyperemia) Renal (CreatX2 or sterile pyuria) Hepatic (bili or ALTX2) Hemato (plt <100 000) CNS (disorientation and alteration in consciousness)

32. STSS – Dx criteria CDC 1990: Laboratory criteria Negative results on the following tests, if obtained: Serologic test for Rocky Mountain spotted fever, leptospirosis, measles Blood, throat, CSF cultures - (blood cultures may be + for Staph aureus)

33. STSS – Dx criteria CDC 1990: Case classification Definite case: all 6 criterias Probable case: 5 on 6 criterias In the absence of clinical markers, strict application is warranted Excludes subclinical cases Self-limited

35. STSS – Dx Isolation of Staphyloccocus aureus productor of exotoxins in a pt w compatible clinical picture Not necessary for dx Help in suspected cases RARELY isolated in blood

36. Case cont... Our patient: T> 38.9 Diffuse rash Hypotension Multisystem involvement: Diarrhea, V Alteration in consciousness Renal but not sufficient to meet the criteria Plts 100 000 Desquamation? Others tests – ? Probable case

37. Case cont... Our patient: Blood cultures – Monotest – Vaginal swab + for staph aureus Urine culture – C. Diff – in stools Specific toxins search at Winnipeg. Results pending.

38. STSS - Treatment Treatment of support: Agressive fluid support w isotonic NS or colloids: ad 10-20 L/24 hres Vasopressor/inotrope infusion as necessary Surgical treatment: Removal of foreign objects: Tampons Nasal packing Surgical debridement of scars: even if wound doesn’t look bad I & D if abcess

39. STSS - Treatment Therapy guided at stopping toxin production Antimicrobial agents: Have not been shown to affect outcome IN VITRO: Clindamycin inhibits protein synthesis – inhibition of TSST-1 Anti-staph peni, cephalosporin may promote TSST-1 production No clinical studies

40. STSS - Treatment Therapy guided at stopping toxin production Antimicrobial agents: Recommandation: Clindamycin 900 IV q8 +/- cloxacillin 2g IV q12 Clindamycin 900 IV q8 +/- vancomycin 1g IV q12 for MRSA

41. STSS - Treatment Additional therapies: Consider Intravenous immunoglobulin (IVIG): If patients remains unstable Contains antibodies to TSST-1 Sporadicaly reported to have salutary effect; controlled trials are incomplete Corticosteroids: May accelerate clinical improvement and diminish neuro sequelae Experimental agents

42. Case: evolution Tx: Cloxacillin + tazocin IV X 2 d then cloxacillin IV x 4 d then Keflex PO x 4 d Hemodynamic stabilisation w 4 L NS and 2 L of Pentaspan the first night No need for inotropes or additionnal therapies Progressive improvement of general condition