1. Clinical Case Conference #5
Amaro - Aribon

2. Pathomechanisms for Cytopenia in Active SLE

3. Cytopenia in SLE Most common hematologic manifestations of SLE:
Normochromic normocytic anemia
due to autoimmune hemolysis, aplastic anemia, and pure red cell aplasia
Leukopenia (<4000/uL) which usually consists of Lymphopenia (<1500/uL)
primarily due to a fall in absolute lymphocyte count
Thrombocytopenia (100,000/uL)
- autoimmune hemolysis, aplastic anemia, and pure red cell aplasia
- The decrease in WBC count is primarily due to a fall in absolute lymphocyte count accompanied by an increase in granulocyte percentage

5. Cytopenia in SLE
Pathogenic auto-antibodies , and immune complexes bind to target tissues with activation of complement and phagocytic cells.
Complement, and immune cells lead to release of chemotaxins, cytokines, chemokines, vasoactive peptides, and destructive enzymes. -

6. Define Ferbrile Neutropenia

7. Febrile Neutropenia
Refers to the clinical presentation of fever (one temperature ≥ 38.5 °C or three readings ≥38° C but ≤38.5 °C per 24 hrs) in a neutropenic patient with an uncontrolled neoplasm involving the bone marrow, or in a patient undergoing treatment with cytotoxic agents.
Braunwald, et al. Harrison’s Principles of Internal Medicine 17th ed.

8. Risk Factors for Candidiasis

9. Risk factors for Candidiasis
General
Conditions causing a compromised host defense
Neutropenia
Glucocorticoid therapy
Malnutrition
Reference:

10. Risk factors for Candidiasis
Oropharyngeal thrush
Diabetes mellitus
HIV infection
Common in acute HIV infection
Increasingly common late in disease as the CD4+ cell count falls
Dentures
Inhaled or oral glucocorticoids
Neonatal period
Iron deficiency
Reference:

11. Risk factors for Candidiasis
Vulvovaginal candidiasis
Third trimester of pregnancy
Antibiotic use
Reference:

12. Risk factors for Candidiasis
Cutaneous candidiasis
Macerated skin
Diapered area of infants
Under pendulous breasts or pannus
Hands constantly in water
Hands covered by occlusive gloves
Reference:

13. Risk factors for Candidiasis
Esophageal candidiasis
HIV infection
Uncommon until CD4+ counts fall below 50/μL
Reference:

14. Risk factors for Candidiasis
Invasive candidiasis
Use of broad-spectrum antibiotic therapy
Indwelling central venous catheter
Total parenteral nutrition
Perforation of the GI tract through trauma, surgery, or peptic ulceration
Mucosal damage due to cytotoxic agents used for cancer chemotherapy
Contamination of the hub or skin site of a catheter in an umbilical or central vein with secretions from the mouth, rectum, or vagina or with drainage from surgical wounds or tracheostomy sites
Intravenous drug abuse
Third-degree burns
Very low birth weight (in neonates)
Neutropenia
Glucocorticoid therapy
Reference:

15. Antimicrobial treatment of systemic candidiasis

16. Disseminated candidiasis with end organ infection
Triazole Antifungal Drug
Fluconazole
800 mg (loading dose)
400 mg/d
IV or oral, at least 2 weeks *
Voriconazole
6 mg/kg IV or orally 2x/d
(loading dose)
3 mg/kg orally twice per day or 200 mg orally twice per day
Echinocandins
Caspofungin
70 mg (loading dose)
50 mg/d
IV, at least 2 weeks *
Anidulafungin
200 mg (loading dose)
100 mg/d
Micafungin
Amphotericin B deoxycholate
mg/kg/d intravenously to achieve a minimum of 1- to 2-g total dose.
Liposomal preparations of amphotericin B
Doses between 3 and 5 mg/kg/d
* after a demonstrated negative blood culture result or clinical signs of improvement.

17. Define sepsis and septic shock

18. Sepsis
a serious medical condition that is characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) and the presence of a known or suspected infection

19. Septic Shock
State of sepsis with refractory arterial hypotension or hypoperfusion abnormalities in spite of aggressive fluid resuscitation (typically upwards of 6 liters or 40 ml/kg of crystalloid).
Signs of systemic hypoperfusion may be either end-organ dysfunction or serum lactate greater than 4 mmol/dL. Other signs include oliguria and altered mental status