Talaromycosis

What is talaromycosis?

Talaromycosis is an infection caused by the thermally dimorphic fungus Talaromyces marneffei. The condition was originally called penicilliosis after the organism was called Penicillium marneffei; the fungus was reclassified in 2011.

Who gets talaromycosis?

Talaromycosis is seen almost exclusively in immunocompromised children and adults. Infection was initially identified in HIV/AIDS patients in tropical areas of Southeast Asia in the late 1980s and 1990s. Talaromycosis was classified as an AIDS-defining infection and one of the HIV clinical stage 4 conditions. It has also been reported to develop during the immune-reconstitution syndrome (IRIS).

Endemic countries include Vietnam, Thailand, the Philippines, Taiwan, Hong Kong, southern China, and India. Travellers have presented with talaromycosis in many non-endemic countries including Australia, the United States, Europe, and the United Kingdom.

With antiretroviral treatment (HAART), talaromycosis is now increasingly recognised in HIV-negative patients. Infected adults may have known associated conditions including:

• Autoimmune conditions, such as systemic lupus erythematosus and mixed connective tissue disease, are associated with impaired cell-mediated immunity
• Autoimmune conditions treated with immunosuppressants include primary biliary cirrhosis and autoimmune haemolytic anaemia
• Haematological conditions (eg, non-Hodgkin lymphoma, Waldenström macroglobulinaemia) and following haematological stem cell transplant
• Solid organ transplant, particularly renal transplants
• Adult-onset immunodeficiency syndrome due to neutralising anti-interferon gamma autoantibodies
• Treatment with biological agents, specifically kinase inhibitors (eg, ruxolitinib, sorafenib) and anti-CD30 monoclonal antibodies (eg, rituximab, obinutuzumab).

HIV-negative children with talaromycosis should be suspected to have an underlying immunodeficiency syndrome if secondary immunosuppression has been excluded. Talaromycosis has been reported in children with:

• Hyper-IgM syndrome
• Hyper-IgE syndrome (Job syndrome)
• Severe combined immunodeficiency disease (SCID)
• Congenital neutropenia
• Common variable immunodeficiency disease (CVID).

It has been suggested there may be a genetic susceptibility to infection with HLA-associations reported particularly in people of Southeast Asian descent.

What causes talaromycosis?

Talaromycosis is caused by Talaromyces marneffei, a fungus found in wild bamboo rats, their faeces, and the soil around their burrows. Infection of humans mainly occurs in the rainy season following inhalation of conidia from agricultural soil. Acute infection has an incubation period of 1–3 weeks, but reactivation of latent infection may present years later.

What are the clinical features of talaromycosis?

Talaromycosis can present as a local or disseminated infection. It is primarily a lung infection where it may remain localised.

Systemic features of disseminated talaromycosis include:

• Non-specific symptoms of fever, weight loss, and fatigue
• Respiratory symptoms such as shortness of breath and cough
• Enlarged lymph nodes, liver, and/or spleen
• Gastrointestinal disturbance such as diarrhoea
• Altered mental state, confusion, agitation, or reduced consciousness.

How does talaromycosis present in the skin?

Skin lesions are common in HIV/AIDS-associated talaromycosis (70%) and are often the presenting sign. The characteristic lesions are papules with central necrosis or umbilication scattered over the head and upper chest. Nodules, subcutaneous abscesses, pustules, cysts, and ulcers may occur.

The skin lesions are often atypical in IRIS-associated talaromycosis with verrucous (warty) lesions, red papules, or plaques seen.

In non-HIV-associated talaromycosis, the skin is involved in 40% of cases and may present with reactive rashes such as Sweet syndrome.

Skin lesions are uncommon in HIV-negative children with talaromycosis.

Facial nodules with talaromycosis 

What are the complications of talaromycosis?

Diagnosis of talaromycosis is often delayed, particularly in HIV-negative patients from non-endemic countries. The disease course is rapidly progressive once infection has disseminated.

Disseminated talaromycosis can involve the bone marrow, causing anaemia and thrombocytopenia, and the bones and joints, resulting in osteolytic lesions. In HIV-positive patients, talaromycosis is often associated with other opportunistic infections, such as tuberculous and non-tuberculous mycobacteria, which may obscure and delay diagnosis.

How is talaromycosis diagnosed?

General screening blood tests typically show a leukocytosis with neutrophilia, anaemia, thrombocytopaenia, and elevated C-reactive protein (CRP) and ESR. Liver enzymes may be disturbed.

Chest X-ray may show pleural effusions, nodules, infiltrates, and cavitation.

Diagnosis of talaromycosis requires demonstration of the organism. This can be achieved in the following ways.

• Culture is the gold standard. Blood, bone marrow, or skin can yield the organism. Culture however is slow, taking 2–4 weeks. The colonies are characteristic, and the dimorphism of the fungus can be demonstrated by changing the temperature of culture.
• Yeasts may be seen on microscopy of peripheral blood, skin or lymph node biopsy touch smears, or histology. Skin biopsy shows a granulomatous suppurative reaction. Special stains such as PAS and Grocott methamine silver, are required to demonstrate the round or oval yeast in and around macrophages and histiocytes.
• Rapid diagnostic tests using PCR or monoclonal antibodies are being developed but these usually require a clinical suspicion of the diagnosis.

Once talaromycosis has been confirmed, investigations should be directed at identifying an underlying predisposing cause if not already apparent.

What is the differential diagnosis for talaromycosis?

The differential diagnosis of the skin lesions of talaromycosis depends on the lesion morphology.

• Umbilicated papules are seen in molluscum contagiosum and other fungal infections, such as histoplasmosis and cryptococcosis.
• A subcutaneous nodule may be an epidermoid cyst, lipoma, mycetoma, or other deep atypical infection.
• Verrucous lesions may be viral warts, cutaneous tuberculosis, sporotrichosis, or chromoblastomycosis.

Intracellular fungi on histology may be confused with histoplasmosis.

What is the treatment for talaromycosis?

Systemic antifungal drugs are required to treat talaromycosis, with initial high dose therapy followed by prolonged maintenance over many months. Amphotericin B, itraconazole, and voriconazole are the usual agents prescribed.

Prophylactic treatment should be considered for high-risk individuals planning to travel to endemic countries.

What is the outcome for talaromycosis?

Talaromycosis can be rapidly progressive with a high mortality rate if untreated. Even with treatment, it is often fatal; children 55%, HIV-negative adults 30%, and HIV-positive adults 20%.