Histoplasmosis Reactivation from Previous Infection

Pathophysiology of Reactivation

Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum, which can remain dormant in tissues after primary infection, according to the Centers for Disease Control and Prevention 3, 4
Reactivation occurs primarily when cellular immunity wanes, such as when CD4+ T-lymphocyte counts fall below 150 cells/μL in HIV-infected individuals, as reported by the Centers for Disease Control and Prevention 4
During primary infection, dissemination from the lungs to other tissues likely occurs in all infected individuals during the first 2 weeks before specific immunity develops, but is usually controlled and becomes nonprogressive in immunocompetent hosts, as stated by the Infectious Diseases Society of America 5

CD4+ count <150 cells/μL in HIV-infected individuals is the most significant risk factor, according to the Centers for Disease Control and Prevention 4
History of previous exposure to Histoplasma capsulatum, especially in endemic areas, is a risk factor, as reported by the Centers for Disease Control and Prevention 3
Immunosuppression from organ transplantation, autoimmune disease treatments, or other causes is a risk factor, as stated by the European Society of Clinical Microbiology and Infectious Diseases 6
Residence in or travel history to endemic regions is a risk factor, though reactivation can occur years after leaving these areas, as reported by the Centers for Disease Control and Prevention 2

Disseminated histoplasmosis is the most common presentation of reactivated disease, according to the Centers for Disease Control and Prevention 3, 4
Prolonged fever is the most common presenting symptom in both adults and children, as reported by the Centers for Disease Control and Prevention 7, 8
Other common manifestations include weight loss, fatigue, and hepatosplenomegaly, as stated by the Centers for Disease Control and Prevention 3, 8
Respiratory symptoms, such as cough, chest pain, and dyspnea, occur in approximately 50% of patients, according to the Centers for Disease Control and Prevention 4
CNS involvement with meningitis and focal brain lesions can occur, particularly in severely immunocompromised patients, as reported by the Centers for Disease Control and Prevention 8

Detection of Histoplasma antigen in urine or serum is the most rapid and sensitive diagnostic method for disseminated disease, according to the Centers for Disease Control and Prevention 2, 8
Blood cultures using lysis-centrifugation technique are positive in >85% of AIDS patients with disseminated histoplasmosis, as reported by the Centers for Disease Control and Prevention 8
Histopathologic examination of tissue biopsies showing characteristic 2-4 μm budding yeast forms can diagnose the disease, according to the Centers for Disease Control and Prevention 2

Initial therapy with liposomal amphotericin B for 3-10 days until clinical improvement occurs is recommended for moderate to severe disseminated disease, as stated by the Centers for Disease Control and Prevention 2, 9
Liposomal amphotericin B is more effective than standard deoxycholate formulation, with more rapid response, lower mortality, and reduced toxicity, according to the Centers for Disease Control and Prevention 9
After initial improvement, transition to oral itraconazole to complete 12 weeks of treatment is recommended, as reported by the Centers for Disease Control and Prevention 2, 9
For mild to moderate disease, itraconazole capsules for 12 weeks are recommended, according to the Centers for Disease Control and Prevention 2, 9
Fluconazole 800 mg daily is an alternative if patients cannot tolerate itraconazole, but is less effective, as stated by the Centers for Disease Control and Prevention 1, 9

Lifelong suppressive therapy with itraconazole 200 mg twice daily is recommended for patients with severe disseminated or CNS infection and in patients who relapse despite appropriate therapy, according to the Centers for Disease Control and Prevention 1, 9
In HIV-infected patients who respond to antiretroviral therapy with sustained CD4+ counts >150 cells/μL, discontinuation of suppressive therapy may be considered, as reported by the Centers for Disease Control and Prevention 1
Suppressive therapy should be resumed if the CD4+ count decreases to <150 cells/μL, according to the Centers for Disease Control and Prevention 1