Medicine II Homework January 6, 2010 Subsection B4 Facilitator: Remedios F. Coronel, M.D.

Patho-mechanisms for Cytopenia in Active SLE Anemia – Auto-antibodies to red cells as part of the auto- immunity – Impaired erythropoietin production by kidneys involved in the SLE – Gastrointestinal blood loss from anti-inflammatory therapy – Increased red cell destruction from hypersplenism – Drug-induced immune phenomenon Lam SKLam SK, Quah TC. Anemia in systemic lupus erythematosus. J Singapore Paediatr Soc. 1990;32(3-4):132-6.Quah TC

Patho-mechanisms for Cytopenia in Active SLE Leukopenia specifically lymphopenia – Cytotoxic activity against allogeneic and autologous 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 systemic lupus erythematosus. Rheumatology (7): P. Stastny and M. Ziff. Antibodies against cell membrane constituents in systemic lupus erythematosus and related diseases. I. Cytoxic effect of serum from patients with systemic lupus erythematosus (SLE) for allogenic and for autologous lymphocytes. Clin Exp Immunol April; 8(4): 543–550.

Febrile Neutropenia A medical emergency marked by fever and an abnormally low neutrophil count that could be fatal in a matter of hours Infectious Disease Society of America 2002 – Temperature of 38.5°C associated with a ANC of 0.5x10 9 /L or a temperature of 38°C for 1 hour – ANC <1.0x 10 9 /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 Systemic Candidiasis Candidemia – Associated with several days of fever unresponsive to antimicrobials, prolonged IV catheterization, multi organ infection – others: intravascular catheter-related candidiasis, suppurative thrombophlebitis, endocarditis Disseminated Candidiasis – Frequently associated with multiple deep organ infections or may involve single organ infection – Candida osteomyelitis, arthritis, endocarditis, pericarditis, and meningitis, requires prolonged antifungal therapy for at least 4-6 weeks – The history of a patient with presumptive disseminated candidiasis reveals a fever unresponsive to broad- spectrum antimicrobials and negative results from blood culture Systemic Candidiasis: Two Primary Syndromes

Antimicrobial Agents DRUGINDICATIONREMARKS Azole - Fluconazole (IV/oral) - Drug of choice in most cases of candidemia and disseminated candidiasis (in non- neutropenic and hemodynamicaly stable patients - Lower nephrotoxicity rates (<2%) and ease of use because of the high degree of bioavailability and the long half-life of the drug - Voriconazole (IV/Oral) - If additional mold coverage is desired - Used in neutropenic and hemodynamicaly unstable patients Echinocandins (Capsofungin IV) - Recommended for candidemia in most patients with neutropenia - Caspofungin is a broad- spectrum - An effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non-albicans Candida species

- Recommended for candidemia in most patients with neutropenia; A broad-spectrum sem-isynthetic echinocandin; An effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non-albicans Candida species such as C glabrata - An effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non-albicans Candida species such as C glabrata; Can be initiated as a 70mg loading dose, followed by 50 mg/d intravenously to complete a minimum of 2 weeks of antifungals after improvement and after blood cultures have cleared Anudilafungin IV - Anidulafungin is a broad- spectrum echinocandin; An effective alternative for severe mucosal infections and systemic infections due to candida - Be initiated as a 200mg loading dose, followed by 100mg intravenously to complete a minimum of 2 weeks of antifungals after improvement and after blood cultures have cleared Micafungin IV - Has been shown to be an effective alternative for severe mucosal infections and systemic infections due to Candida, especially those due to non- albicans Candida species - Administered at 100 mg/d intravenously to complete a minimum of 2 weeks of antifungals after improvement and after blood cultures have cleared

Sepsis and Septic Shock Systemic inflammatory response syndrome (SIRS) – Two or more of the following conditions: (1) fever (oral temperature >38°C) or hypothermia ( 24 breaths/min); (3) tachycardia (heart rate >90 beats/min); (4) leukocytosis (>12,000/L), leukopenia ( 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 <90 mmHg systolic, or 40 mmHg less than the normal blood pressure of the patient) for at least 1 hour despite adequate fluid resuscitation – Need for vasopressors to maintain systolic blood pressure 90 mmHg or mean arterial pressure 70 mmHg

References Harrison’s Principles of Internal Medicine 17 th Edition Lam SK, Quah TC. Anemia in systemic lupus erythematosus. J Singapore Paediatr Soc. 1990;32(3-4): P. Stastny and M. Ziff. Antibodies against cell membrane constituents in systemic lupus erythematosus and related diseases. I. Cytoxic effect of serum from patients with systemic lupus erythematosus (SLE) for allogenic and for autologous lymphocytes. Clin Exp Immunol April; 8(4): 543–550.