Blastomycosis: causes, symptoms, diagnosis, and treatment

Blastomycosis, also known as North American blastomycosis, is a chronic, suppurative, granulomatous disease caused by Blastomyces dermatitidis. The primary infection site is often the lungs, and the infection can be disseminated to other tissues and organs, especially the skin and bone marrow.


Causes

Blastomyces dermatitidis is present as mold at room temperature and resides in soils rich in animal excrements and in moist, rotting environments containing acidic organic matters, usually near rivers. The inhaled spores transform into 15 - 20 μm in size, invasive yeasts in the lungs, forming large basal buds.


Signs and Symptoms

The disease is mainly manifested by suppurative granuloma, and thick-walled blastospores can be seen in the early abscesses and in the late giant cells or tissues.

Primary pulmonary blastomycosis

Inhalation of fungal spores from the respiratory tract causes alveolitis, macrophage infiltration, followed by neutrophil infiltration, abscesses, and granulomatous lesions, resembling primary tuberculosis or histoplasmosis. Symptoms include dry cough, chest pain, low fever, and dyspnoea. The disease is aggravated over time, often affecting both lungs, but cavitation is less common. Only hilar lymphadenopathy or primary pulmonary tuberculosis-like changes can be seen in X-ray examination. In the late stage, the manifestations may resemble tumors or other deep fungal infections. Most are self-healing, and few progresses into disseminated blastomycosis.

Chronic cutaneous and osseous blastomycosis

The disease is the most common extrapulmonary infection. Skin lesions are often in the exposed areas of the body such as hands, feet, head, and face, but the scalp, palms, and soles are less involved. Initial papules or pustules gradually expand peripherally, forming dark red verrucous patches or subcutaneous nodules with raised edges, containing many small abscesses, with pus discharge when squeezing. Central dark scabs can progress into ulcers. After the skin lesions heal, atrophic scars are remaining, and new skin lesions may occur on the scars. In addition, mucous membranes in the throat can also be invaded, but the nearby lymph nodes are often not enlarged. Subjective symptoms are generally absent, and occasionally low fever may be present. Good prognosis is present.

25% - 50% of patients may have osseous blastomycosis, mainly manifested by osteolysis or monoarthritis. The disease can occur in the spine, ribs, skulls, and long bones, and focal or diffuse osteomyelitis can be seen in the metaphysis, resembling tuberculous granuloma. When the joint is invaded, there are often fever, local swelling, suppuration, and sometimes exudative sinus tracts.

Systemic blastomycosis

The disease often results from hematogenous dissemination of primary lesions in the lungs, skin, and bones. The bones, lungs, and skin are mostly involved, and osseous lesions account for 2/3. The lesions in the ribs and spine are the most common. Bone destruction and hyperplasia can be seen in X-ray examination, and pulmonary hilar lymphadenopathy and cavities with a diameter of less than 1 cm can be seen in 95% of patients. The skin lesions are mainly multiple abscesses on the trunk. The liver, spleen, kidney, brain, and prostate can be infected. There are systemic lymph nodes enlargement, fever, emaciation, and asthenia.

Inoculated blastomycosis

If the hands or fingers come into contact with patients, refractory chancriform ulcers, lymphangitis, and local lymph nodes enlargement may occur, but can heal without expansion.


Histopathology

The histologic reaction of lung infection is acute purulent or chronic granulomatous, and lymph nodes can be involved. Focal or diffuse fibrosis may be seen in chronic patients.

Early skin lesions are dermal and subcutaneous microabscesses. Old skin lesions are abscesses and granuloma formation, with mild fibrosis. The epidermis presents pseudoepitheliomatous hyperplasia, resembling a tumor. There are unicellular, thick-walled, single budding spores in giant cells or abscesses, with a diameter of 8 - 15 μm, with wide bud neck. The cells are unevenly stained in HE stain, and the cytoplasm is separated from the cell wall, with gaps. PAS and GMS stain are more distinct.


Diagnosis

On the basis of clinical findings and single budding spores with a diameter 8 - 15 μm and with wide bud neck found in microscopy, the disease can be diagnosed.


Treatment

Untreated blastomycosis often progresses slowly and rarely causes death.

Treatment regimens depend on the severity of infection. Mild to moderate blastomycosis, can be treated by itraconazole 200mg orally tid for the first three days followed by 200mg qd or bid for 6 - 12 months. Fluconazole may be ineffective, but 400 - 800 mg orally once daily can be used to treat mild patients who cannot tolerate itraconazole. Intravenous amphotericin B is used for the treatment of severe blastomycosis, and is usually effective. After the condition improves, the medications should be switched to oral itraconazole.

Voriconazole and posaconazole have strong antifungal effects, but their value in the treatment of this disease has yet to be determined.