consenso histoplasmose
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consenso histoplasmose


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Mild to moderate Itra (200 mg twice daily for at least 12 months) A-II Longer treatment may be required in patients with persistent
immunodeficiencyc
CNS histoplasmosis Liposomal AmBa (5.0 mg/kg daily for 4\u20136 weeks), followed by
Itrab (200 mg 2\u20133 times daily for at least 12 months)
B-III High failure and relapse rates support aggressive therapy, but
whether less intensive therapy would suffice is unknown;
longer treatment may be required for patients with persistent
immunodeficiencyc
NOTE. AmB, amphotericin B; Itra, itraconazole.
With regard to prophylaxis, there are few studies on which to make evidence-based recommendations on the role of prophylaxis to prevent histoplasmosis in immunosuppressed patients. Prophylaxis is not used
routinely but is reserved for situations in which the rate of development of infection exceeds 10 cases per 100 patient-years. The optimal duration for prophylaxis is unknown, but health care providers should consider
the incidence of histoplasmosis in the community and the severity of immunosuppression. Itra (200 mg daily) is recommended when prophylaxis is prescribed.
With regard to pregnancy, all azoles are contraindicated because of the risk of teratogenicity. Otherwise, the indications for treatment are not different in pregnancy, and lipid formulations of AmB are preferred.
AmB deoxycholate is preferred for use in children, because it is effective, well tolerated, and less costly. The dosage of Itra for children is 5.0\u201310.0 mg/kg daily in 2 divided doses, not to exceed 400 mg daily. The
dosage of methyl-prednisolone is 2.0 mg/kg daily given intravenously, and the dosage of prednisone is 2.0 mg/kg daily given orally. Indomethacin (1.0\u20133.0 mg/kg daily, divided 3 times) is the nonsteroidal anti-
inflammatory agent of choice for pericarditis in children.
a Liposomal AmB (3.0 mg/kg daily) or AmB lipid complex (5.0 mg/kg daily) are recommended for 1\u20132 weeks, except in patients with meningitis, for whom the dosage of liposomal AmB is 5.0 mg/kg daily for 4\u2013
6 weeks. The deoxycholate formulation of AmB (0.7\u20131.0 mg/kg daily) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity.
b Itra should be given as a loading dose of 200 mg 3 times daily for the first 3 days, followed by 200 mg twice daily thereafter. Itra (200 mg once daily) may be sufficient in patients with less severe manifestations
of histoplasmosis. If used for prophylaxis, a dosage of 200 mg daily is recommended. Concentrations of Itra in serum should be monitored in patients being treated for chronic pulmonary, disseminated, or CNS
histoplasmosis; a random serum concentration 11.0 mg/mL should be sought. Drug monitoring is infrequently needed for patients receiving shorter courses of therapy for acute pulmonary histoplasmosis and its
complications.
c Chronic, potentially lifelong suppressive therapy with Itra is required for patients with AIDS who do not achieve immune reconstitution in response to antiretroviral therapy. Lifelong suppressive therapy may be
useful in patients with other immunosuppressive disorders in whom immunosuppression cannot be substantially reduced and in patients who experience relapse despite receipt of appropriate therapy.
818 \u2022 CID 2007:45 (1 October) \u2022 Wheat et al.
the right paratracheal region or the subcarinal area [52, 63].
Most patients are asymptomatic, and mediastinal granuloma is
found incidentally by imaging studies, but symptoms related
to compression of adjacent structures can occur. The caseous
center can spontaneously drain via a fistula or sinus tract to
the bronchus, skin, or esophagus; bacterial superinfection oc-
casionally develops when fistulae or sinus tracts are present
[64].
Itraconazole is appropriate for symptomatic cases, but there
are no controlled trials to prove its efficacy. The capsule is thin
(2\u20133 mm) and adherent, but it is not invasive, so surgical
removal or decompression with removal of the free wall and
contents is possible when involvement of the superior vena
cava or esophagus causes persistent symptoms (despite admin-
istration of antifungal therapy). There is no evidence that me-
diastinal granuloma evolves into mediastinal fibrosis. Thus,
treatment with either surgery or itraconazole should not be
used to prevent the development of mediastinal fibrosis [63,
64].
Mediastinal Fibrosis
Recommendations
19. Antifungal treatment is not recommended (A-III).
20. The placement of intravascular stents is recommended
for selected patients with pulmonary vessel obstruction (B-III).
21. Itraconazole (200 mg once or twice daily for 12 weeks)
is recommended if clinical findings cannot differentiate me-
diastinal fibrosis from mediastinal granuloma (C-III).
Evidence summary. Mediastinal fibrosis is characterized by
invasive fibrosis that encases mediastinal or hilar nodes and
that is defined by occlusion of central vessels and airways [65\u2013
68]. Occlusion of airways or vessels of both lungs occurs in
only a small proportion of cases (\u223c20%) but is usually fatal
[69]. Most patients have occlusion of the superior vena cava
or loss of function of only 1 lung, which may have significant
morbidity with chest pain or hemoptysis, but long-term sur-
vival is generally favorable [69].
Most authorities believe that neither antifungal nor anti-
inflammatory treatment ameliorates the outcome of medias-
tinal fibrosis [65, 66], but others have reported improvement
after antifungal therapy [70]. If the clinical findings are con-
sistent with a more inflammatory process rather than a chronic
fibrotic process, especially if complement fixation antibodies
for H. capsulatum are present and the erythrocyte sedimenta-
tion rate is elevated, treatment should be considered. A 12-
week course of itraconazole (200 mg once or twice daily) is
suggested if clinical and CT findings do not differentiate me-
diastinal fibrosis from mediastinal granuloma. Patients who
truly have mediastinal fibrosis are not expected to respond to
antifungal therapy. Corticosteroid therapy has not been helpful
when tried [66, 71, 72] and is discouraged.
Placement of intravascular stents has been helpful in some
patients with superior vena cava, pulmonary artery, or pul-
monary vein obstruction [73] and should be considered es-
pecially for patients who are at highest risk because of involve-
ment of both lungs. The placement of stents in obstructed
airways is not recommended because of the high risk of growth
of granulation tissue, leading to recurrent obstruction, but it
may be necessary in selected patients in whom interventional
airway experts find that no other treatment alternative is
feasible.
Surgery should be approached with great caution in patients
with mediastinal fibrosis and should be performed only for
those who are expected to die of the condition without inter-
vention. Surgeons experienced in the management of this con-
dition should be consulted [72].
Broncholithiasis
Recommendations
22. Antifungal treatment is not recommended (A-III).
23. Bronchoscopic or surgical removal of the broncholith
is recommended (A-III).
Evidence summary. Broncholithiasis is the erosion of calcified
lymph nodes into a bronchus, often causing hemoptysis and
inflammation. Spitting of small pieces of white chalk-like ma-
terial, termed \u201clithoptysis,\u201d may occur [52]. When stones of
substantial size are extruded, they may cause prolonged periods
of intense cough and hemoptysis, with localized wheeze and
distal obstructive pneumonitis. Diagnosis is made broncho-
scopically. Removal of the stones bronchoscopically or surgi-
cally is recommended.
Pulmonary Nodules (Histoplasmomas)
Recommendation
24. Antifungal treatment is not recommended (A-III).
Evidence summary. Lung parenchymal sites of infection may
contract and then persist indefinitely as lung nodules or his-
toplasmomas [74]. Calcification is usually found in the center
of a histoplasmoma or in concentric rings and is generally