Fungal Infections in HIV-patients Hail M. Al-Abdely, MD Consultant, Infectious Diseases

Fungal Infections in HIV-patients Cutaneous Seborrheic dermatitis Onychomycosis Skin dermatophyte infection Muco-cutaneous Candidiasis Invasive Cryptococcosis Histoplasmosis Aspergillosis Penicilliosis (Geographically restricted) Coccidioidomycosis Blastomycosis

Immunologic Status and Fungal Infections Thrush Dermatophyte CD4 Seborrhea Cryptococcosis Histoplasmosis Aspergillosis Penicilliosis

Cutaneous Fungal Infections More common More extensive Relatively more difficult to treat

Cutaneous candidiasis involving the moist skinfolds under the breasts Cutaneous candidiasis involving the moist skinfolds under the breasts. The lesions are very red, and there are small red satellite lesions surrounding the main area of involvement. The typical location and the presence of satellite lesions make the gross image highly suggestive of cutaneous candidiasis. There is little tendency for deep tissue invasion with this type of lesion. (From Fitzpatrick et al.

Systemic Treatment of Cutaneous Fungal Infections   Fluconazole (Diflucan) Itraconazole (Sporanox) Terbinafine (Lamisil) Tinea corporis     and cruris 150 mg once a     week     3-4 weeks 200 mg qd     1-2 weeks 250 mg qd     2 weeks Tinea capitis 50 mg qd     3 weeks 3-5 mg/kg/day     4-6 weeks 125 mg qd     (3-6 mg/kg/day)     4 weeks Onychomycosis 150 mg once a     week     9 months 200 mg qd     Fingernails -6 weeks     Toenails - 12 weeks Pulse dosing     200 mg bid--    1 week on,     3 weeks off,     Toenails  3-4 months,     Fingernails     2-3 months 250 mg qd     Fingernails         6 weeks     Toenails         12 weeks Tinea pedis 150 mg once a week     3-4 weeks 400 mg qd 4 weeks 250 mg qd 6 weeks Tinea versicolor 400 mg single     dose 200 mg qd     5 or 7 days Studies ongoing

Extensive pharyngeal candidiasis involving the soft palette and uvula of a patient with AIDS. Oral pharyngeal candidiasis can be a marker of T-cell immunosuppression. T cells are required to control candida growth on the mucosal surfaces. However, adequate neutrophil number and function are enough to prevent deep invasion, and there is surprisingly little tendency to develop disseminated candidiasis in patients who are T-cell deficient. (From Fitzpatrick et al.

Oro-pharyngeal Candidiasis 90% of HIV-patients develop OPC during their lifetime. Candida appears as part of the mouth flora in more than 80% of HIV-positive patients. Actual predisposing factors for progression from colonization to disease are not well characterized.

Treatment of OPC Topical agents Systemic agents Clotrimazole, nystatin, Ampho B Systemic agents Fluconazole Itraconazole (Capsule, liquid) Ampho B

Treatment of OPC Systemic treatment Strategies Fluconazole is the most common agent. Faster action and less relapse than topical Rx. Major problem with increasing resistance. Higher dose. Switch to other agents. Strategies Treat each episode Continuous therapy

Esophageal Candidiasis Reported in 20% to 40% of all AIDS patients. Characterized by pseudomembranes, erosions and ulcers. Presentation is mainly with odynophagia and dysphagia

Esophageal Candidiasis Treatment Commonly empiric therapy. Endoscopy is indicated if the patient is not responding to antifungal therapy Drugs Fluconazole Itraconazole (Capsule, liquid) Ampho B

Candidiasis and HAART Since the advent of HAART, the incidence of new Candida infections has decreased by as much as 60% to 80%

Vaginal Candidiasis Vulvo-vaginal candidiasis occurs in approximately 30% to 40% of HIV-infected women. ? Candidiasis more common in women with HIV infection when other important risk factors for vaginal infection (sexual activity, racial and ethnic background). HIV infection influences the severity and persistence of vulvo-vaginal Candida infection.

Cryptococcosis Cryptococcus neoformans is an encapsulated yeast. 5% of HIV-infected patients in the Western World develop disseminated cryptococcosis CD4+ lymphocyte counts, less than 50 cells/mm3.

Cryptococcal Meningitis Cryptococcosis typically presents as a subacute meningitis Cryptococcal meningitis rarely presents as an obvious meningitis. Initial symptoms are commonly more subtle and may just include fever and headache.

Symptoms of Cryptococcal Meningitis

Diagnosis of Cryptococcal Meningitis Symptoms and Signs. 70% of patients with cryptococcal meningitis have positive blood cultures Serum cryptococcal antigen is a useful screening test. 1:8 is regarded as evidence of cryptococcal infection. India ink (CSF): 50% sensitive, needs experience. CSF cryptococcal antigen is rapid, sensitive and specific. Histopathological stains CSF culture.

Treatment of Cryptococcal Meningitis Induction amphotericin B, 0.7 mg/kg IV daily for 14 days or equivalent consider 5-flucytosine (5-FC) 25 mg/kg PO q6 hours measure opening pressure; consider means to reduce pressure if raised (>25 cms/water)

Treatment of Cryptococcal Meningitis Consolidation fluconazole, 400 mg PO bid for 2 days, then daily for 8 weeks; or itraconazole, 200 mg PO tid for 3 days, then bid for 8 weeks (appears to be slightly less active) repeat lumbar puncture, with measurement of opening pressure, if patients remain symptomatic (especially persistent headache)

Treatment of Cryptococcal Meningitis Maintenance fluconazole 200-400 mg daily amphotericin B 1 mg/kg/week (less effective than fluconazole) itraconazole 100-200 mg PO bid (less effective than fluconazole) there is no value to routine measurement of serum cryptococcal antigen

Treatment of Cryptococcal Meningitis Mild presentation Fluconazole + 5-flucytosine High dose fluconazole 800 mg QD Close monitoring

Complications of Cryptococcal Meningitis Acute mortality happens due to cerebral edema, which may be diagnosed by a raised opening pressure of the CSF. Hydrocephalus

Dimorphic Fungi (Endemic Mycoses) Histoplasmosis Coccidioidomycosis Penicilliosis marnefiei Blastomycosis Sporotrichosis

Histoplasmosis Coccidioidomycosis Penicilliosis

Characteristics of the Endemic Mycoses   Histoplasmosis Coccidioidomycosis Penicilliosis Appearance of organism on biopsy 1-5 mcm round to oval 30-80 mcm round spherules containing 2-5 mcm endospores 1-8 mcm pleomorphic elongated Method of duplication Budding Fission Clinical Features:   Fever 95% 99%   Weight loss 90% 60% 75%   Anemia 70% 50%   Pulmonary disease   Lymphadenopathy 20% 10% 40-50%   Skin lesions 5-10% 5%   Hepatosplenomegaly 25% 10-20%   Meningitis <1% Very rare

Aspergillosis Tends to occur in the very late stages of HIV infection, typically in patients with a history of other AIDS-defining illnesses. Two main presentations respiratory tract disease central nervous system infection

Conclusion Fungal infections remain an important cause of morbidity and mortality in patients with HIV disease. Epidemiology is changing with the advent of HAART. High index of suspicion is important to make a diagnosis of some of the invasive mycoses. Multiple opportunistic fungal infections can exist in the same patient on presentation.