Botryomycosis or bacterial pseudomycosis is an uncommon chronic bacterial infection with a global distribution. The term was coined by Rivolta in 1870 and refers to the grape-like granules (Gr. botryo = grapes) and the erroneously presumed fungal aetiology (Gr. mykes = fungus). The bacterial origin became clear after 1919, when Staphylococcus aureus was cultured from lesions. Staphylococcus aureus causes the majority of infections, followed by Pseudomonas aeruginosa and a number of other bacteria, including Actinobacillus lignieresii, Escherichia coli, Proteus species, and several anaerobic bacteria including Streptococcus intermedius. Pathogenesis is not clear but experimental data suggest that it is related to bacterial strain, virulence, inoculum of bacteria, presence of foreign bodies, and probably host immune response. Most individuals have impaired immunity of one sort or another, including diabetes mellitus, steroid use, post-transplantation, chronic granulomatous disease, HIV and HTLV-1 infection.

Botryomycosis is a chronic bacterial granulomatous disease often involving the skin and subcutaneous tissues. Clinically, there are one or more chronic dirty, pus-discharging infected skin ulcers, with infiltration of the underlying tissues, forming nodules or suppurative plaques. Underlying osteomyelitis should be excluded. Botryomycosis mimics clinical and histological both mycetoma and actinomycosis. These are much more frequent infections and also present with suppurative draining lesions with granules in the pus. Botryomycosis may appear like pyoderma vegetans. It was proposed that pyoderma vegetans and cutaneous botryomycosis should be classified together.

Up to one-third of cases of botryomycosis present with only deep visceral involvement, usually in immunodepressed, debilitated patients. General malaise, fever and leukocytosis can be present. Pulmonary botryomycosis is a chronic suppurative bacterial infection of the lung, which results in chronic cough and intermittent haemoptysis. This condition forms an important curative differential diagnosis for lung cancer. A retained foreign body should also be excluded. Rectal botryomycosis can mimic a carcinoma, and localisations in the kidney can mimic a renal kidney tumor. Other locations (eye, tongue, uterus, colon, liver, …) are possible.

For diagnosis, a deep wedge surgical biopsy or a fine-needle aspiration of the material is performed. Culture will usually show the presence of Staphylococcus aureus. Culture of anaerobic bacteria is not problem-free. Microscopically the organisms appear to be encapsulated in granules, which are thought to protect them from the effects of standard courses of antibiotics. There is surrounding granulomatous inflammation with occasional extension into muscle or bone. Biopsy of a lesion can show one or more large granules together with scattered micro-abscesses with pus and sinuses. There will be a central mass of bacteria within an area of pus. A high power view will often show an acidophilic ring or border (so-called Splendore-Hoeppli phenomenon). This eosinophilic structure (thick eosinophilic rings or radiating spokes) is seen in a variety of fungal and parasitic infections (especially around helminths such as schistosomes) and is particulary striking in actinomycosis, mycetoma and botryomycosis. It is also seen around silk sutures. The eosinophilic deposits are probably antigen-antibody and complement deposits, with a contribution from macrophages, lymphocytes and eosinophils (eosinophilic granule major basic protein).

Granules have to be distinguished from artifacts. A haematoxylin-eosin and May-Grünwald-Giemsa staining of a smear is performed. If the lesion would be an eumycetoma, one would expect to see distinct hyphae inside the granules. An eumycetoma will stain brownish with haematoxylin-eosin and black-greenish with May-Grünwald-Giemsa. A Gomori methenamine silver or periodic acid-Schiff stain is also used to demonstrate hyphae. An actinomycetoma stains homogenously eosinophilic with haematoxylin-eosin stain. With May-Grünwald-Giemsa, it will be blue in the center with pink filaments in the periphery. A Ziehl stain of an actinimycetoma shows branching filamentous acid fast bacteria. A Gram stain shows fine, Gram-positive, branching filaments within the actinomycetoma grain.

The most obvious differential diagnosis is mycetoma (eumycetoma and actinomycetoma). Other differential diagnoses include tuberculosis, infections with atypical mycobacteria (Mycobacterium marinum, M. kansasii, M. chelonae, M. avium-intracellulare), nocardiosis, cat-scratch disease, syphilis, deep fungal infection (especially Blastomyces dermatitidis, but also Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis), sporotrichosis, dematiaceous fungi (chromomycoses), bromoderma, giant keratoacanthomas, and tularaemia. For lesions in the anal, genital and inguinal areas, lymphogranuloma venereum (Chlamydia trachomatis, LGV) should be considered. Carcinoma should be excluded.

Botryomycosis usually requires surgical intervention for cure. Major surgery is often required for patients, because the infection is usually unresponsive to seemingly appropriate medical therapy. Any foreign body should be removed. Specific evaluation for immunodepression should be performed and treatment should be accordingly.