These are systemic fungal infections - either endemic or opportunistic, generally only infecting those who are immunocompromised.^1,2 See also the separate article on fungal lung infections.

Endemic fungal infections

Histoplasmosis

Histoplasmosis is linked to exposure to bird and bat droppings especially along the Ohio and Mississippi river valleys in the USA. It usually occurs as an atypical pneumonia, in the acute form appearing in epidemics with prostration, fever, and respiratory symptoms.

• Progressive disseminated histoplasmosis - fever, dyspnoea, cough, loss of weight and prostration with hepatosplenomegaly. Usually fatal within 6 weeks.
• Chronic progressive pulmonary histoplasmosis is usually seen in older patients with chronic obstructive pulmonary disease (COPD).
• Disseminated disease when seen in the immunocompromised is usually due to reactivation of prior infection often seen in HIV infection.

Management: itraconazole; amphotericin B in severe cases or for those who fail on itraconazole.

Coccidioidomycosis

Coccidioidomycosis is caused by a mould that grows in the soil in Southwestern USA, Mexico, and Central and South America. <1% of immunocompetent affected people suffer dissemination, but in these cases mortality is high. 40% of primary infections are symptomatic, usually presenting with respiratory tract symptoms plus fever, with pleuritic pain. There may be arthralgia with swelling (often knees and ankles).
Management: intravenous (IV) amphotericin B; in mild cases oral fluconazole³ or itraconazole continued for 6 months or longer. May need surgery to drain cavities or abscesses.

Pneumocystosis

See separate article Pneumocystis Jirovecii Pneumonia. It is very rarely symptomatic in immunocompetent patients⁴ but, in immunocompromised patients (especially HIV^5,6,7), there can be abrupt onset of fever, tachypnoea, shortness of breath and nonproductive cough. If untreated, there is rapid deterioration to death.^8,9

Start treatment on clinical suspicion but confirm before continuing: co-trimoxazole, nebulised pentamidine. Also, adjuvant steroids.¹⁰ Co-trimoxazole is given prophylactically when CD4 count falls.

Opportunistic infections

• Aspergillosis:¹¹ this is usually caused by Aspergillus fumigatus; occasionally, chronic sinusitis and colonisation of existing pulmonary cavities to form aspergilloma in immunocompetent patients may be seen - patients with very advanced HIV are particularly at risk, mostly with pulmonary disease leading to severe necrotising pneumonia.
  
  
  
  
  
• Mucormycosis: this includes zygomycosis and phycomycosis found in patients with predisposing conditions such as diabetic ketoacidosis, chronic renal failure and immunosuppressant drugs.
• Mycetoma:¹² this includes maduromycosis and actinomyecetoma, which is a slowly progressive locally destructive infection beginning in subcutaneous tissues often after trauma and spreading to contiguous structures (see separate article Mycetomas (Madura Foot))^13,14. A maduromycosis is a mycetoma caused by true fungi. It may start as a papule, nodule or abscess and it progresses over months or years to form multiple abscesses and sinus tracts reaching deep into the tissue.
• Blastomycosis: this usually occurs in men working outdoors in certain areas of South, Central and Midwestern USA and Canada; it usually affects the lung but can disseminate to the skin, bones and urogenital tract. Symptoms include cough, fever, dyspnoea and chest pain. It may resolve or progress with bloody, purulent sputum, pleurisy, fever, chills, loss of weight and prostration. In disseminated form, there are raised verrucous skin lesions with an abrupt, downward-sloping border often seen.
• Paracoccidioidomycosis: South American blastomycosis is only found in patients who have lived in South or Central Africa or Mexico and initially affects the upper respiratory tract. It usually appears with ulceration of the upper respiratory tract. Ulcers can coalesce to destroy the epiglottis, vocal cords and uvula. Eating and drinking are very painful. There may be skin lesions on the face.
• Sporotrichosis: this occurs when the organism is inoculated into the skin during gardening. It usually causes a skin infection - a hard, nontender, subcutaneous nodule which later ulcerates. Similar nodules then appear along the lymphatics draining the area.
• Chromoblastomycosis: this is a mainly tropical skin infection, usually affecting agricultural workers and causing skin infections. It begins as a papule or ulcer, usually on a lower extremity, and enlarges over months or years to become a papillomatous, verrucous nodule.
• Cryptococcus neoformans: see separate article Cryptococcosis. This is a yeast found in soil and dried pigeon droppings. Infection is usually transmitted by inhalation. Immunodeficient patients develop progressive lung disease and dissemination. It can involve any organ but mainly the central nervous system. It often presents with meningitis. It may progress to confusion, cranial nerve abnormalities, nausea and vomiting. Treatment is with oral fluconazole, IV amphotericin B.
• Candidiasis:¹⁵ this is normally associated with predisposing factors, e.g. neutropenia, antibiotic use, indwelling lines and abdominal surgery. It can cause candidaemia and disseminated candidiasis; also, deep focal candidiasis, in which it infects the peritoneum or meninges, is often implanted following dialysis or surgery. It can also cause candidal endocarditis and urinary tract candidiasis. Treat with amphotericin B, fluconazole, and consider adding flucytosine in severe cases.

Document references

1. Hay RJ in Oxford Textbook of Medicine, 4th Edition. Eds; Warrell DA et al. OUP 2003
2. Current Medical Diagnosis & Treatment 2003. Eds. Tierney LM et al. Lange Medical Books.Pp 101-102
3. Goa KL, Barradell LB; Fluconazole. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic use in major superficial and systemic mycoses in immunocompromised patients. Drugs. 1995 Oct;50(4):658-90. [abstract]
4. Miller RF; Pneumocystis carinii infection in non-AIDS patients. Curr Opin Infect Dis. 1999 Aug;12(4):371-7. [abstract]
5. Clinical Evidence, 2004. Pneumocystis pneumonia in people with HIV; Needs registration
6. Boyton R. Infectious lung complications in patients with HIV/AIDS. Curr Opin Pulm Med, 2005: 11: 203-207
7. Azoulay E, Parrot A, Flahault A, et al; AIDS-related Pneumocystis carinii pneumonia in the era of adjunctive steroids: implication of BAL neutrophilia. Am J Respir Crit Care Med. 1999 Aug;160(2):493-9. [abstract]
8. Tasci S, Ewig S, Burghard A, et al; Pneumocystis carinii pneumonia. Lancet. 2003 Jul 12;362(9378):124.
9. Bennett NJ et al; Pneumocystis (carinii) jiroveci Pneumonia, eMedicine, Aug 2010
10. Gallant J, Chaisson R, Moore R; The effect of adjuvant corticosteroids for the treatment of Pneumocystis pneumonia on mortality and subsequent complications. Chest, 1998; 114: 1258- 1263.
11. Brakhage AA; Systemic fungal infections caused by Aspergillus species: epidemiology, infection process and virulence determinants. Curr Drug Targets. 2005 Dec;6(8):875-86. [abstract]
12. Ania BJ et al; Mycetoma, eMedicine, Aug 2008
13. Corr P; Clinics in diagnostic imaging (26). Madura foot (or mycetoma). Singapore Med J. 1997 Jun;38(6):268-9. [abstract]
14. Lexier R, Walmsley SL; Successful treatment of Madura foot caused by Pseudallescheria boydii with Escherichia coli superinfection: a case report. Can J Surg. 1999 Aug;42(4):307-9.
15. Kalyoussef S et al; Candidiasis, eMedicine, Jul 2010

Acknowledgements