Botryomycosis (Bacterial pseudomycosis, Granular bacteriosis, Staphylococcic actinophytosis)
Are You Confident of the Diagnosis?
Characteristic findings on physical examination
Most cases of botryomycosis present with one or more exophytic, grouped and indurated nodules surmounted by draining sinus tracts or fissures (
Typical lesions of botryomycosis.
Most cases are localized to a single anatomic area, but the disease may spread widely over the cutaneous surface. Although they may be painful or tender to the touch, lesions are typically asymptomatic, and patients are usually afebrile. While the vast majority of botryomycosis lesions do not extend deeper than the subcutis, cases involving the underlying muscles and bones (periostitis to true osteomyelitis) have been reported.
Expected results of diagnostic studies
Aside from a compatible morphology, three confirmatory diagnostic steps may be taken. Direct examination of the granules will disclose non-filamentous lobules that stain with Gram stain (either gram positive or negative, depending upon the etiologic bacterium). Bacterial culture will reveal the precise causative organism, as well as the antibiotic susceptibility pattern of that organism. It should be noted that both aerobic and anaerobic cultures should be performed due to the rare case of botryomycosis due to anaerobic microbes.
Finally, a biopsy will show a mixed-cellular inflammatory infiltrate surrounding lobular granules with a basophilic center and eosinophilic periphery. Tissue Gram stain (Brown-Brenn stain) will highlight bacteria on and near the granules: singly, in pairs and packed tightly together in clumps. Unlike fungal diseases, which may have a similar appearance, the granules will not stain with GMS (silver) stain. When deep extension is suspected, routine radiography, magnetic resonance imaging or bone scanning may be required for verification.
Differential diagnosis includes most prominently: mycetoma (both eumycetoma due to fungi and actinomycotic mycetoma due to Nocardia) and actinomycosis. All of these diseases share the feature of a discharge containing granular material. These lesions are best distinguished from one another by the differing results obtained utilizing a combination of the three confirmatory steps outlined above.
Whenever an exudate specimen from a suspected case of botryomycosis is sent for bacterial culture, a simultaneous fungal culture should also be requested. Biopsy specimens should be routinely examined with a battery of stains (PAS, GMS, Brown-Brenn and Ziehl-Neelsen). Small lesions of botryomycosis might also resemble sporotrichosis, North American blastomycosis, and the various forms of tuberculosis cutis. Culture and histology would lead to the proper diagnosis in these cases.
Who is at Risk for Developing this Disease?
There is a wide age range associated with botryomycosis: 9 months to 80 years of age. There is a slight predominance of men over women, with a 3:2 ratio.
While some totally normal individuals have developed botryomycosis, most of those affected have some disease or disorder that is predisposing. In general, patients with depressed cellular immunity are at high risk. Thus, many recent cases have been described in HIV-positive hosts. Diabetics, alcoholics and the debilitated and malnourished are also at increased risk. Individuals receiving chronic corticosteroid therapy for unrelated illnesses are prone to botryomycosis. Cystic fibrosis patients have a notably increased risk, probably due to concomitant thick secretions, repeated lung infections, and altered respiratory tract immune status.
As noted previously, trauma (presumably resulting in inoculation) to the affected area may be a known antecedent event.
What is the Cause of the Disease?
Based on a retrospective literature meta-analysis, Staphylococcus aureus is responsible for just over 40% of botryomycosis cases, while Pseudomonas aeruginosa causes about 20% of cases. Other bacteria commonly (2% to 7% of cases) isolated from botryomycosis lesions include alpha-hemolytic Streptococci, Staphylococcus epidermidis, Micrococcus pyogenes, Escherichia coli and Proteus vulgaris. About 2% of cases are due to anaerobic or microaerophilic bacteria, such as Bacteroides species. In some cases, more than one microbe may be isolated and, under these circumstances, it is impossible to discern if one organism is more important than the other in disease genesis.
The exact etiopathogenesis is uncertain. Botryomycosis is most often associated with defects of cellular immunity, both overt and subtle. A decreased total lymphocyte count, and a depressed T-cell count in particular, is often present. However, these patients rarely exhibit overwhelming, life-threatening complications. Thus, it is felt that this disease represents a balance between relatively low-virulence bacteria, introduced into the skin in modest numbers, most comonly by minor trauma, and a depressed but still functional immune system. This concordance of events leads to a sort of symbiotic relationship and, thus, a localized and chronic bacterial infection.
Systemic Implications and Complications
Botryomycosis typically is a localized, cutaneous infection. However, ever since the first classification schema was proposed in 1959, visceral botryomycosis has been recognized. Involvement of the internal organs most often occurs following surgical interventions or in more severely immunocompromised patients. Most visceral botryomycosis affects the lung; involvement of the liver, brain, kidneys, gastrointestinal tract, prostate and pericardium has also been noted in isolated case reports.
The treatment of choice for botryomycosis consists of prolonged (2 weeks to 2 months) antibiotic administration. The exact duration of therapy depends solely upon clinical response. The selection of antibiotic used is based upon the culture results and associated sensitivity studies. Almost every imaginable antibiotic has been successfully employed, particularly penicillin G, erythromycin, trimethoprim-sulfamethoxazole and minocycline. In the unlikely but not unheard of event of antibiotic failure, complete surgical extirpation of the affected area may be entertained. There is no place for physical modalities in the management of botryomycosis.
Optimal Therapeutic Approach for this Disease
Most lesions will respond to antibiotic therapy directed against the microbes isolated from lesions, and based upon antibiotic susceptibility testing. Responses should occur within 2 weeks to 2 months. Orally administered antibiotics have been the rule. Should underlying tissue be involved, particularly the bone, parenteral antibiotics should be entertained. Visceral involvement, though rare, is treated with intravenous antibiotics.
The patient should be followed about every 2 weeks to monitor for lesional clearance. Re-culture (with repeat antibiotic sensitivity) can be considered in lesions showing no or minimal response in 1 month. Follow-up radiographs and scans should be obtained when indicated due to muscle, osseous or visceral disease. Once clinically cured, there is no need for ongoing therapy.
Unusual Clinical Scenarios to Consider in Patient Management
Pain out of proportion to the clinical lesion should suggest muscle and/or bone involvement. When appropriate antibiotic administration has been accomplished and the patient judged to be adherent to the regimen prescribed, then complete surgical removal has been performed when clinical success proves elusive. Partial amputation has been suggested as treatment when a limb is involved and medical treatment fails. When other antimicrobials have failed, however, dapsone (100mg daily) has proven effective and is worth trying in lieu of deforming major surgery.
What is the Evidence?
Winslow, DJ. "Botryomycosis". Am J Pathol. vol. 35. 1959. pp. 153-76.(The first and still the most comprehensive attempt at classifying botryomycosis. Provides abundant evidence for visceral disease.)
Waisman, M. "Staphylococcic actinophytosis". Arch Dermatol. vol. 86. 1962. pp. 525-9.(Despite appropriate antibitoic therapy, surgical intervention was required. Perhaps today our larger spectrum of available antibiotics would make this quite unlikely.)
Kansky, A. "Botryomycosis". Acta Derm Venereol. vol. 44. 1964. pp. 369-76.(Early recognition that immune alterations, such as diabetes, may predispose to this unusual infection.)
Brunken, RC, Lichon-Chao, N, van den Broek, H. "Immunologic abnormalities in botryomycosis". J Am Acad Dermatol. vol. 9. 1983. pp. 428-34.(A case report highlighting immunologic aberrations in botryomycosis, and also a nice review or previous immune deficiency states [except AIDS] reported in conjunction with this infection.)
Neafie, RC, Marty, AM. "Unusual infections in humans". Clin Microbiol Res. vol. 6. 1993. pp. 34-56.(Aside from a good discussion of the differential diagnosis of botryomycosis, some wonderful examples of the spectrum of unusual infectious diseases that can affect human beings.)
Mehregan, DA, Su, WPD, Anhalt, JP. "Cutaneous botryomycosis". J Am Acad Dermatol. vol. 24. 1991. pp. 393-96.(Not really a summary, but a collection of case reports that clearly highlight the clinical variability in morphology among cases of botryomycosis.)
Bonifaz, A, Carrasco, E. "Botryomycosis". Int J Dermatol. vol. 35. 1996. pp. 381-8.(The best summary/review article on the subject. Also a detailed retrospective analysis of the causative organisms reported up to that date.)
Karthikeyan, K, Thappa, DM, Jeevankumar, B. "Cutaneous botryomycosis in an agricultural worker". Clin Exp Dermatol. vol. 26. 2001. pp. 456-7.(Despite heroic efforts at treatment, a case of botryomycosis is presented where amputation seems destined to happen.)
de Vries, HJC, van Noesel, CJM, Hoekzema, R, Hulsebosch, HJ. " Botryomycosis in an HIV-positive subject". J Eur Acad Dermatol Venereol. vol. 17. 2003. pp. 87-90.(Nice contemporary example of botryomycosis associated with HIV.)
Meissner, M, Spieth, K, Wolter, M, Gille, J, Boehncke, WH, Thaci, D. "Cutaneous botryomycosis: A rarely diagnosed bacterial infection of the skin". Hautarzt. vol. 58. 2007. pp. 966-8.(Beautiful color rendition of the classic botryomycosis histology.)
Rubenstein, E, Krulig, E, Cardenas, V, Kerdel, FA. "Botryomycosis-like pyoderma in the genital region of a human immunodeficiency virus (HIV)-positive man successfully treated with dapsone". Int J Dermatol. vol. 49. 2010. pp. 842-3.(Example of dapsone as a therapeutic alternative in resistant cases.)
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