Medicine IIHomeworkJanuary 6, 2010
Subsection B4
Facilitator: Remedios F. Coronel, M.D.
Patho-mechanisms for Cytopenia inActive SLE
•Anemia
–Auto-antibodies to red cells as part of the auto-immunity
–Impaired erythropoietin production by kidneysinvolved in the SLE
–Gastrointestinal blood loss from anti-inflammatorytherapy
–Increased red cell destruction from hypersplenism
–Drug-induced immune phenomenon
Patho-mechanisms for Cytopenia inActive SLE
•Leukopenia specifically lymphopenia
–Cytotoxic activity against allogeneic andautologous lymphocytes
–Direct lysis of lymphocytes by complement
•Thrombocytopenia
–Autoantibody-mediated (Anti-GPIIb/IIIa and anti-TPOR antibodies
M. Kuwana, J. Kaburaki, Y. Okazaki, H. Miyazaki and Y. Ikeda. Two types of autoantibody-mediated thrombocytopenia in patients with systemiclupus erythematosus. Rheumatology 2006 45(7):851-854
P. Stastny and M. Ziff. Antibodies against cell membrane constituents in systemic lupus erythematosus and related diseases. I. Cytoxic effect ofserum from patients with systemic lupus erythematosus (SLE) for allogenic and for autologous lymphocytes. Clin Exp Immunol. 1971 April; 8(4):543–550.
Febrile Neutropenia
•A medical emergency marked by fever and anabnormally low neutrophil count that could befatal in a matter of hours
•Infectious Disease Society of America 2002
–Temperature of 38.5°C associated with a ANC of0.5x109/L or a temperature of 38°C for 1 hour
–ANC <1.0x 109/L with a predicted decrease to <0.5
•If early neutropenia <10-14 days
Risk Factors for Candidiasis
•Use of antibacterial agents
•Indwelling intravascular catheters
•Hyperalimentation fluids
•Indwelling urinary catheters
•Parenteralglucocorticoids
•Respirators
•Neutropenia
•Abdominal and thoracic surgery
•Cytotoxic chemotherapy
•Immunosuppressive agents for organ transplantation
Antimicrobial Treatment for SystemicCandidiasis
•Candidemia
–Associated with severaldays of feverunresponsive toantimicrobials, prolongedIV catheterization, multiorgan infection
–others: intravascularcatheter-relatedcandidiasis, suppurativethrombophlebitis,endocarditis
•Disseminated Candidiasis
–Frequently associated withmultiple deep organinfections or may involvesingle organ infection
–Candida osteomyelitis,arthritis, endocarditis,pericarditis, and meningitis,requires prolonged antifungaltherapy for at least 4-6 weeks
–The history of a patient withpresumptive disseminatedcandidiasis reveals a feverunresponsive to broad-spectrum antimicrobials andnegative results from bloodculture
Systemic Candidiasis: Two Primary Syndromes
Antimicrobial Agents
DRUG
INDICATION
REMARKS
Azole
- Fluconazole (IV/oral)
- Drug of choice in mostcases of candidemia anddisseminated candidiasis (innon- neutropenic andhemodynamicaly stablepatients
- Lower nephrotoxicity rates(<2%) and ease of usebecause of the high degree ofbioavailability and the longhalf-life of the drug
- Voriconazole(IV/Oral)
- If additional mold coverageis desired
- Used in neutropenic andhemodynamicaly unstablepatients
Echinocandins(Capsofungin IV)
- Recommended forcandidemia in most patientswith neutropenia
- Caspofungin is a broad-spectrum
- An effective alternative forsevere mucosal infectionsand systemic infections due toCandida, especially those dueto non-albicans Candidaspecies
- Recommended for candidemia inmost patients with neutropenia; Abroad-spectrum sem-isyntheticechinocandin; An effectivealternative for severe mucosalinfections and systemic infectionsdue to Candida, especially thosedue to non-albicans Candidaspecies such as C glabrata
- An effective alternative forsevere mucosal infections andsystemic infections due toCandida, especially those due tonon-albicans Candida speciessuch as C glabrata; Can beinitiated as a 70mg loading dose,followed by 50 mg/d intravenouslyto complete a minimum of 2 weeksof antifungals after improvementand after blood cultures havecleared
Anudilafungin IV
- Anidulafungin is a broad-spectrum echinocandin; Aneffective alternative for severemucosal infections and systemicinfections due to candida
- Be initiated as a 200mg loadingdose, followed by 100mgintravenously to complete aminimum of 2 weeks of antifungalsafter improvement and after bloodcultures have cleared
Micafungin IV
- Has been shown to be aneffective alternative for severemucosal infections and systemicinfections due to Candida,especially those due to non-albicans Candida species
- Administered at 100 mg/dintravenously to complete aminimum of 2 weeks of antifungalsafter improvement and after bloodcultures have cleared
Sepsis and Septic Shock
•Systemic inflammatory response syndrome (SIRS)
–Two or more of the following conditions: (1) fever (oraltemperature >38°C) or hypothermia (<36°C); (2) tachypnea(>24 breaths/min); (3) tachycardia (heart rate >90beats/min); (4) leukocytosis (>12,000/L), leukopenia(<4,000/L), or >10% bands
–May have a non-infectious etiology
•Sepsis
–SIRS that has a proven or suspected microbial etiology
•Septic shock
–Sepsis with hypotension (arterial blood pressure <90mmHg systolic, or 40 mmHg less than the normal bloodpressure of the patient) for at least 1 hour despiteadequate fluid resuscitation
–Need for vasopressors to maintain systolic blood pressure90 mmHg or mean arterial pressure 70 mmHg
References
•Harrison’s Principles of Internal Medicine 17th Edition
•Lam SK, Quah TC. Anemia in systemic lupus erythematosus. JSingapore Paediatr Soc. 1990;32(3-4):132-6.
•P. Stastny and M. Ziff. Antibodies against cell membraneconstituents in systemic lupus erythematosus and relateddiseases. I. Cytoxic effect of serum from patients with systemiclupus erythematosus (SLE) for allogenic and for autologouslymphocytes. Clin Exp Immunol. 1971 April; 8(4): 543–550.
•P. Stastny and M. Ziff. Antibodies against cell membraneconstituents in systemic lupus erythematosus and relateddiseases. I. Cytoxic effect of serum from patients with systemiclupus erythematosus (SLE) for allogenic and for autologouslymphocytes. Clin Exp Immunol. 1971 April; 8(4): 543–550.