Transcript Pathomechanisms for Cytopenia in Active SLE

Clinical Case Conference #5
Amaro - Aribon
Pathomechanisms for Cytopenia
in Active SLE
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)
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.
Define Ferbrile Neutropenia
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.
Risk Factors for Candidiasis
Risk factors for Candidiasis
• General
– Conditions causing a compromised host defense
• Neutropenia
• Glucocorticoid therapy
• Malnutrition
Reference:
http://www.harrisonspractice.com/practice
/ub/view/Harrisons%20Practice/141100/0/
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:
http://www.harrisonspractice.com
/practice/ub/view/Harrisons%20Pr
actice/141100/0/Candida
Risk factors for Candidiasis
• Vulvovaginal candidiasis
– Third trimester of pregnancy
– Antibiotic use
Reference:
http://www.harrisonspractice.com/practice
/ub/view/Harrisons%20Practice/141100/0/
Risk factors for Candidiasis
• Cutaneous candidiasis
– Macerated skin
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Diapered area of infants
Under pendulous breasts or pannus
Hands constantly in water
Hands covered by occlusive gloves
Reference:
http://www.harrisonspractice.com/practice
/ub/view/Harrisons%20Practice/141100/0/
Risk factors for Candidiasis
• Esophageal candidiasis
– HIV infection
• Uncommon until CD4+ counts fall below 50/μL
Reference:
http://www.harrisonspractice.com/practice
/ub/view/Harrisons%20Practice/141100/0/
Risk factors for Candidiasis
• Invasive candidiasis
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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:
http://www.harrisonspractice.com/practice
/ub/view/Harrisons%20Practice/141100/0/
Antimicrobial treatment of
systemic candidiasis
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
Caspofungin
70 mg (loading dose)
50 mg/d
IV, at least 2 weeks *
Anidulafungin
200 mg (loading dose)
100 mg/d
IV, at least 2 weeks *
Echinocandins
Micafungin
Voriconazole
100 mg/d
IV, at least 2 weeks *
6 mg/kg IV or orally 2x/d
(loading dose)
3 mg/kg orally twice per day
or 200 mg orally twice per
day
Amphotericin B deoxycholate
0.5-0.7 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.