H&P 46 yo woman with fever and tachypnea. 46 yo woman with fever and tachypnea. Hx of TAH for leiomyoma; path revealed leiomyosarcoma. Repeat surgery 3 wks PTA with BSO, omentectomy and evidence of intraperitoneal spread. Hx of TAH for leiomyoma; path revealed leiomyosarcoma. Repeat surgery 3 wks PTA with BSO, omentectomy and evidence of intraperitoneal spread. 2 days PTA presented to OSH with fever, headache and body ache. 2 days PTA presented to OSH with fever, headache and body ache.

H&P At OSH blood and urine Cx were obtained and LP performed. At OSH blood and urine Cx were obtained and LP performed. On DOA pt re-presented to OSH with persistent fever and tachypnea. CT C/A/P performed at that time--remarkable for fluid collections in the pelvis c/w lymphocele. On DOA pt re-presented to OSH with persistent fever and tachypnea. CT C/A/P performed at that time--remarkable for fluid collections in the pelvis c/w lymphocele. Transferred to UW on Gyn-Onc service; started on Levofloxacin/Flagyl and norepinephrine for persistent hypoTN. Transferred to UW on Gyn-Onc service; started on Levofloxacin/Flagyl and norepinephrine for persistent hypoTN. On HD#2 MICU service consulted for consideration of transfer. On HD#2 MICU service consulted for consideration of transfer.

H&P PMH: TAH with path c/w leiomyosarcoma. CT pre-operatively showed two small masses in the right anterior abdominal wall & enlarged periaortic lymph node  ex lap w/previously noted findings. PMH: TAH with path c/w leiomyosarcoma. CT pre-operatively showed two small masses in the right anterior abdominal wall & enlarged periaortic lymph node  ex lap w/previously noted findings. S/P appendectomy S/P appendectomy Meds: none Meds: none SH: Single. 10 cigs/day. Denies EtOH/drugs. Owns beauty parlor in Walla 2 SH: Single. 10 cigs/day. Denies EtOH/drugs. Owns beauty parlor in Walla 2

H&P PE: / % on 2L PE: / % on 2L Alert, tachypneic. Anicteric. OP-moist Alert, tachypneic. Anicteric. OP-moist No lymphadenopathy. No lymphadenopathy. Chest: clr. Cor: rrr Chest: clr. Cor: rrr Abd: well healed midline scar; NABS, sl tender s r/g/r. GU: wnl. Ext: 1+ edema, L UE PICC. Abd: well healed midline scar; NABS, sl tender s r/g/r. GU: wnl. Ext: 1+ edema, L UE PICC. Skin: erythema face/chest/ abdomen. Skin: erythema face/chest/ abdomen. Neuro: A&Ox3. Neuro: A&Ox3.

H&P Labs: Labs: 132| 111 | > < | 10 | 1.6 (bl 0.8) PMN w/bandemia 3.9 | 10 | 1.6 (bl 0.8) PMN w/bandemia TB 1.8 alb 1.6 TB 1.8 alb 1.6 Viral DFA neg Viral DFA neg C. diff toxin A and Ag neg C. diff toxin A and Ag neg 7.27/23/82/10 on 2L NC

Hospital Course Pt transferred to MICU service. Pt transferred to MICU service. Abx broadened. Abx broadened.

Hospital Course-day 3 Remained febrile (103.4) with increasing hypotension and oxygen requirements. By morning of HD 3 on NE/AVP/phenylephrine, anuric and requiring 100% oxygen. Remained febrile (103.4) with increasing hypotension and oxygen requirements. By morning of HD 3 on NE/AVP/phenylephrine, anuric and requiring 100% oxygen. All Cx remain NGTD. All Cx remain NGTD. Cr  3.6, Tbili  2.8, plt  53 Cr  3.6, Tbili  2.8, plt  53

Hospital Course CT of C/A/P showed diffuse bilateral infiltrates c/w ARDS; pelvic fluid collections s change compared to outside CT. CT of C/A/P showed diffuse bilateral infiltrates c/w ARDS; pelvic fluid collections s change compared to outside CT.

Hospital Course Pt had sampling of pelvic fluid collections. Surgical wound was opened to fascia (clean appearance) and swabs sent for Cx. Pt had sampling of pelvic fluid collections. Surgical wound was opened to fascia (clean appearance) and swabs sent for Cx. Cx from wound 1+ MSSA; all other Cx’s remained negative. Cx from wound 1+ MSSA; all other Cx’s remained negative. Pt given IVIg x 3 days Pt given IVIg x 3 days Started on HD Started on HD Pressors d/c’d Pressors d/c’d

Toxic Shock Syndrome First described in 1978; became widely known following association with highly absorbent tampons in First described in 1978; became widely known following association with highly absorbent tampons in TSS may be caused by S. aureus or Grp A strep species. TSS may be caused by S. aureus or Grp A strep species. Associated with various exotoxins and endotoxins. Associated with various exotoxins and endotoxins.

TSS S. aureus exotoxins are superantigens, able to activate large numbers of T cells at once  massive cytokine production including IL- 1,-2,TNF, IFN-gamma. S. aureus exotoxins are superantigens, able to activate large numbers of T cells at once  massive cytokine production including IL- 1,-2,TNF, IFN-gamma. These account for the high fevers, CPK elevation. These account for the high fevers, CPK elevation. TSST-1 producing S. aureus do not cause purulent response (TNF suppression of PMNs) TSST-1 producing S. aureus do not cause purulent response (TNF suppression of PMNs)

TSS Diagnostic Criteria: Diagnostic Criteria: T>38.9 T>38.9 Shock Shock Diffuse macular erythroderma (sun burn like appearance). Diffuse macular erythroderma (sun burn like appearance). Desquamation 1-2 wks after illness onset, esp palms/soles Desquamation 1-2 wks after illness onset, esp palms/soles Multisystem involvement of 3 or more organ systems incl: GI, CK elevation, mucosal hyperemia, ARF, hepatic dysfxn, thrombocytopenia or AMS. Multisystem involvement of 3 or more organ systems incl: GI, CK elevation, mucosal hyperemia, ARF, hepatic dysfxn, thrombocytopenia or AMS. Negative Cx’s and serologic tests for RMSF, lepto, measels. Negative Cx’s and serologic tests for RMSF, lepto, measels. May also see hypoNa/alb/Ca/PO May also see hypoNa/alb/Ca/PO

TSS Roughly ½ of S. aureus TSS cases assoc with menstruation Roughly ½ of S. aureus TSS cases assoc with menstruation Non-menstrual cases assoc with surgical, postpartum wound infxns, burns, cutaneous lesions, sinusitis, OM, etc. Non-menstrual cases assoc with surgical, postpartum wound infxns, burns, cutaneous lesions, sinusitis, OM, etc. Non-menstrual cases assoc with earlier onset rash, fever, increased renal/CNS complications and less myositis. Non-menstrual cases assoc with earlier onset rash, fever, increased renal/CNS complications and less myositis. Surgical wound sites that harbor toxin-producing s. aureus may be benign appearing. Surgical wound sites that harbor toxin-producing s. aureus may be benign appearing.

TSS treatment IVF, pressors IVF, pressors Search for foci of infection + surgical Tx Search for foci of infection + surgical Tx Antibiotic Tx to include clindamycin Antibiotic Tx to include clindamycin Suppression of protein synthesis based on theoretical/in vitro evidence. Suppression of protein synthesis based on theoretical/in vitro evidence. Mupirocin following recover to eliminate nasal carriage. Mupirocin following recover to eliminate nasal carriage.

TSS Treatment IVIG IVIG 70-80% of individuals develop Ab to TSST by teenage years; pts w/clinical TSS lack Ab to TSST-1. Some pts prone to relapse after 1 st episode TSS % of individuals develop Ab to TSST by teenage years; pts w/clinical TSS lack Ab to TSST-1. Some pts prone to relapse after 1 st episode TSS. 2 trials (methodologically weak) have looked at IVIG in GAS TSS and shown decreased mortality. 2 trials (methodologically weak) have looked at IVIG in GAS TSS and shown decreased mortality. In RCT (terminated early due to enrollment difficulties, 21 pts total) dose of IVIG 1g/kg on d1 and 0.5g/kg d2&3. In RCT (terminated early due to enrollment difficulties, 21 pts total) dose of IVIG 1g/kg on d1 and 0.5g/kg d2&3. Recent paper from same authors looked at dose IVIG required to neutralize supernatant; higher for SA than GAS. Recent paper from same authors looked at dose IVIG required to neutralize supernatant; higher for SA than GAS.

References Darenberg, J et al, “Intravenous Immunoglobulin G Therapy in Streptococcal Toxic Shock Syndrome: A European Randomized, Double-Blind, Placebo-Controlled Trial,” CID :333 Darenberg, J et al, “Intravenous Immunoglobulin G Therapy in Streptococcal Toxic Shock Syndrome: A European Randomized, Double-Blind, Placebo-Controlled Trial,” CID :333 Darenberg, J et al. “Differences in Potency of Intravenous Polyspecific Immunoglobulin G against Streptococcal and Staphylococcal Superantigens: Implications for Therapy of Toxic Shock Syndrome,” CID 2004, 38:836. Darenberg, J et al. “Differences in Potency of Intravenous Polyspecific Immunoglobulin G against Streptococcal and Staphylococcal Superantigens: Implications for Therapy of Toxic Shock Syndrome,” CID 2004, 38:836.