Key Research Findings

Histoplasmosis is a systemic fungal infection endemic to the American continent, potentially lethal to individuals living with HIV/AIDS. 5 Currently available treatments for histoplasmosis are limited, expensive, and highly toxic. 5 Due to the time-consuming and costly nature of developing new drugs, drug repositioning presents an advantageous strategy for uncovering new therapeutic options. 5 Histoplasmosis can cause life-threatening disseminated infection in adults with untreated HIV. 10 Unlike immunocompetent individuals, solid organ transplant recipients with post-transplant histoplasmosis (PTH) often present with widespread disease and experience an attributable mortality rate of approximately 10%. 19 The simultaneous infection of histoplasmosis and miliary tuberculosis is rare, primarily affecting individuals with severe immunosuppression and presenting with diverse clinical forms similar to other infectious and neoplastic conditions. 14 Histoplasmosis is a dimorphic fungal infection, uncommon outside endemic pockets in North, Central, and South America, Asia, and Africa. 7 Histoplasmosis can be challenging to diagnose, and is widely underrecognized. 16 The treatment of histoplasmosis includes liposomal amphotericin B for severe cases and itraconazole for mild to moderate cases. 10 While itraconazole is the preferred azole for histoplasmosis, voriconazole is increasingly used; it exhibits in vitro activity against Histoplasma capsulatum and has shown success in case reports and small case series, but it may have a lower barrier to resistance. 12 Fluconazole therapy for histoplasmosis is only moderately effective and should be reserved for patients who cannot take itraconazole. 1 Histoplasmosis, an uncommon opportunistic infection in HIV-positive children, is often characterized by persistent fever and failure to thrive. 11 In dogs, histoplasmosis affects various breeds, with working and herding breeds predominantly presenting with disseminated histoplasmosis, and toy breeds primarily exhibiting the gastrointestinal form. 21 Treatment with liposomal amphotericin B (AMB-L) for at least 1 month, followed by itraconazole for at least 1 year, results in survival among the majority of individuals with CNS histoplasmosis. 20 A case report demonstrated successful endobronchial treatment of a non-healing tracheoesophageal fistula resulting from a previous Histoplasmosis capsulatum infection using decellularized porcine urinary bladder matrix. 17 For moderate to severe histoplasmosis associated with AIDS, the deoxycholate formulation of amphotericin B has been the preferred treatment. 2 However, serious side effects are associated with the use of amphotericin B. 2 Treatment of disseminated histoplasmosis in advanced HIV using itraconazole with increased bioavailability has shown success. 18 Histoplasmosis of the upper extremities is extremely rare and there is no consensus in its management, but a combined approach of surgery and medical treatment is recommended for optimal outcomes. 15 Evidence suggests that single, high-dose liposomal amphotericin B (LAmB) is effective in HIV-associated cryptococcal meningitis and histoplasmosis. 4 The use of chemotherapy in addition to standard antifungal therapy has proven successful in treating haemophagocytic lymphohistiocytosis (HLH) due to disseminated histoplasmosis. 13 Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is limited due to the high drug and hospitalization costs of the conventional long regimens. 3 Histoplasmosis of the Larynx is a very rare anomaly and is usually not seen in an immunocompetent individual. 6 Intravitreal antivascular endothelial growth factor injections (IVI), alone or in combination with verteporfin photodynamic therapy (IVI/PDT), have proven effective in managing choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome (POHS). 8

Treatment Summary

Histoplasmosis treatment options vary depending on the severity of the infection and the patient's individual characteristics. Liposomal amphotericin B is the preferred choice for severe cases, while itraconazole is recommended for mild to moderate cases. 10 Itraconazole is the preferred azole for histoplasmosis. 12 Fluconazole is only moderately effective and should be reserved for patients who cannot take itraconazole. 1 In severe cases associated with AIDS, the deoxycholate formulation of amphotericin B has been the preferred treatment. 2 However, amphotericin B can have serious side effects. 2 Treatment with itraconazole with increased bioavailability has shown success in treating disseminated histoplasmosis in advanced HIV. 18 A combination of surgery and medical treatment is recommended for optimal outcomes in cases of histoplasmosis of the upper extremities. 15 For individuals with CNS histoplasmosis, treatment with liposomal amphotericin B (AMB-L) for at least 1 month, followed by itraconazole for at least 1 year, results in survival for the majority of patients. 20 A successful endobronchial treatment using decellularized porcine urinary bladder matrix for a non-healing tracheoesophageal fistula caused by Histoplasmosis capsulatum has been reported. 17 Single, high-dose liposomal amphotericin B (LAmB) has shown effectiveness in treating HIV-associated cryptococcal meningitis and histoplasmosis. 4 The combination of chemotherapy and standard antifungal therapy has proven successful in treating haemophagocytic lymphohistiocytosis (HLH) caused by disseminated histoplasmosis. 13 Intravitreal antivascular endothelial growth factor injections (IVI), alone or in combination with verteporfin photodynamic therapy (IVI/PDT), have been shown effective in managing choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome (POHS). 8

Benefits and Risks

Benefit Summary

Effective treatment options for histoplasmosis exist, such as liposomal amphotericin B and itraconazole. 10 These treatments have the potential to improve survival rates for patients with histoplasmosis. 20 Intravitreal antivascular endothelial growth factor injections (IVI) have proven effective in managing choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome (POHS). 8

Risk Summary

Amphotericin B, a common treatment for histoplasmosis, can have serious side effects. 2 Voriconazole, another treatment option, may have a lower barrier to resistance. 12

Research Comparisons

Commonalities

Histoplasmosis poses a significant threat to individuals with compromised immune systems, particularly those with HIV/AIDS. 10 Diagnosing histoplasmosis can be challenging due to its diverse clinical presentations. 7 The infection can occur even in areas outside its endemic pockets. 7

Differences

The symptoms and treatment approaches for histoplasmosis vary depending on the geographical location and individual patient characteristics. 20 Research on histoplasmosis has encompassed a range of subjects, including children, dogs, and transplant recipients. 9 21 19

Consistency and Contradictions

While numerous treatments for histoplasmosis exist, not all are effective for every patient. 10 Treatment of histoplasmosis presents challenges such as potential drug side effects and the development of resistance. 12

Real-Life Implications

Individuals living in endemic areas and those with weakened immune systems should be particularly cautious about histoplasmosis. 10 If you experience symptoms associated with histoplasmosis, seek immediate medical attention. 10 Histoplasmosis can be contracted through exposure to bird or bat guano or by inhaling aerosolized soil in endemic regions. 10

Current Research Limitations

Research on histoplasmosis remains inadequate. 16 Further development of effective treatments for histoplasmosis is still underway. 12

Future Research Directions

Future research should focus on understanding the pathogenesis and treatment approaches for histoplasmosis, as well as developing new therapeutic options. 5

Conclusion

Histoplasmosis is a serious fungal infection that requires prompt and appropriate treatment. 10 Individuals at risk of developing histoplasmosis should take preventive measures. 10 Seek immediate medical attention if you experience symptoms associated with histoplasmosis. 10

Treatment List

Liposomal amphotericin B, itraconazole, fluconazole, voriconazole, intravitreal antivascular endothelial growth factor injections (IVI), etoposide chemotherapy, and decellularized porcine urinary bladder matrix