Histoplasmosis

Clnica
The most common symptoms of disseminated
histoplasmosis are fever, fatigue, and weight loss.
Clnica en inmunocompromiso
Severely immunodeficient patients, may present
with overwhelming infection manifested by shock,
respiratory distress, hepatic and renal failure,
obtundation, and coagulopathy.
Patients with chronic infection often present with
pancytopenia, hepatosplenomegaly, hepatic enzyme
elevation, and oropharyngeal lesions. Other sites
include the skin, brain, and adrenal glands.
Diagnstico diferencial
The differential diagnosis includes malignancy,
infection (eg, tuberculosis, other fungal
diseases), and inflammatory diseases (eg,
inflammatory bowel disease, sarcoidosis)
Abordaje diagnstico
-Tests for antigen in urine and serum should be
performed in patients with suspected disseminated
histoplasmosis.
-Blood cultures should be performed in all
suspected cases.
- Among patients who have isolated meningitis, the
diagnosis may be based upon detection of antigen
or antibody in the cerebrospinal fluid (CSF)
Tratamiento
-One of the lipid formulations of amphotericin B is
recommended in patients who are sufficiently ill to
require hospitalization. Itraconazole is not
recommended for initial therapy in such patients since
it does not eradicate fungemia as rapidly as
amphotericin.
-Itraconazole is the treatment of choice for patients
who have mild to moderate symptoms and for step-
down therapy in those who have improved with initial
amphotericin B administration
Tratamiento
Most patients respond quickly to amphotericin B
and then can be transitioned to oral itraconazole.
The transition should occur after the patient
becomes afebrile (or at least demonstrates
consistent improvement in fever), no longer
requires blood pressure or ventilatory support or
intravenous fluids, and is able to take oral
medications
Sndrome hemofagoctico
Desencadenantes
Many patients with HLH have a predisposing
genetic defect, and/or an immunologic trigger,
which can include infection, malignancy,
rheumatologic disorder such as juvenile idiopathic
arthritis, or another disorder associated with
immune dysregulation.
Abordaje diagnstico
Complete blood count with differential
Coagulation studies, including PT, aPTT,
fibrinogen, D-dimer
Serum ferritin
Liver function tests, including ALT, AST,
GGT, total bilirubin, albumin, and LDH
Serum triglycerides
Abordaje diagnstico
Cultures of blood, bone marrow, urine, cerebrospinal fluid, and
other potentially infected body fluids; and viral titers and
quantitative polymerase chain reaction testing for EBV, CMV,
adenovirus, and other suspected viruses.
Bone marrow evaluation
Electrocardiograph, chest radiography, and an echocardiogram.
Cerebrospinal fluid analysis. The cerebrospinal fluid is abnormal in
over half of patients with HLH, with findings of cellular pleocytosis,
hemophagocytosis, and elevated protein.
Computed tomography scans of neck, chest, abdomen, and pelvis
to evaluate for possible malignancy.
Abdominal ultrasound, if the physical examination for
splenomegaly is inconclusive.
Diagnstico diferencial
The differential diagnosis of HLH includes
several multisystem illnesses characterized by
fever, hepatic failure, and neurologic
symptoms.
Criterios diagnsticos 5/8
Fever 38.5C
Splenomegaly
Peripheral blood cytopenia, with at least two of the following:
hemoglobin <9 g/dL (for infants <4 weeks, hemoglobin <10 g/dL);
platelets <100,000/microL; absolute neutrophil count
<1000/microL
Hypertriglyceridemia (fasting triglycerides >265 mg/dL) and/or
hypofibrinogenemia (fibrinogen <150 mg/dL)
Hemophagocytosis in bone marrow, spleen, lymph node, or liver
Low or absent NK cell activity
Ferritin >500 ng/mL (the author prefers to consider a ferritin
>3000 ng/mL as more indicative of HLH
Elevated soluble CD25 (soluble IL-2 receptor alpha) two
standard deviations above age-adjusted laboratory-specific norms
Anfotericina B
Mecanismo de accin
Mechanism of Action Binds to ergosterol altering cell
membrane permeability in susceptible fungi and
causing leakage of cell components with subsequent
cell death. Proposed mechanism suggests that
amphotericin causes an oxidation-dependent
stimulation of macrophages (Lyman, 1992).
Dosis en histoplasmosis
Histoplasmosis: Chronic, severe pulmonary or
disseminated: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8
mg/kg every other day (or 3 times/week) until total
dose of 10-15 mg/kg; may continue itraconazole as
suppressive therapy (lifelong for immunocompromised
patients)
-Meningitis: I.V.: 0.5-1 mg/kg/day for 7 days, then 0.8
mg/kg every other day (or 3 times/week) for 3 months
total duration; follow with fluconazole suppressive
therapy for up to 12 months
Administracin
-I.V.: May be infused over 4-6 hours.
- Bolus infusion of normal saline immediately
preceding, or immediately preceding and
following amphotericin B may reduce drug-
induced nephrotoxicity.
Reacciones adversas
Systemic:
>10%:
Cardiovascular: Hypotension, tachypnea
Central nervous system: Fever, chills, headache (less frequent with
I.T.), malaise
Endocrine & metabolic: Hypokalemia, hypomagnesemia
Gastrointestinal: Anorexia, nausea (less frequent with I.T.), vomiting
(less frequent with I.T.), diarrhea, heartburn, cramping epigastric
pain
Hematologic: Normochromic-normocytic anemia
Local: Pain at injection site with or without phlebitis or
thrombophlebitis (incidence may increase with peripheral infusion
of admixtures)
Neuromuscular & skeletal: Generalized pain, including muscle and
joint pains (less frequent with I.T.)
Renal: Decreased renal function and renal function abnormalities
including azotemia, renal tubular acidosis, nephrocalcinosis (>0.1
mg/mL)