University of Alabama at Birmingham

Gorgas Case 2015-08

Universidad Peruana Cayetano Heredia
The Gorgas Courses in Clinical Tropical Medicine are given at the Tropical Medicine Institute at Cayetano Heredia University in Lima, Perú. Each August we conduct one of our 2-week refresher courses for those with previous training in tropical medicine; currently in session is the Gorgas Advanced Course. There will be one more case next week to complete the 2015 case series.
The following patient was seen by the Gorgas Advanced Course participants in the outpatient clinic of the Tropical Medicine Institute in Lima.

History: 43 year-old male transferred from the Peruvian Cancer Institute after a negative work-up of a painful non-healing ulcerative lesion on the sole of the left foot. Illness began 3 years earlier and after 1 year the patient noticed progressive swelling on the sole that extended to the whole left foot in a matter of 6 months and has since significantly impaired his normal activities. Multiple papular lesions have developed that started to drain initially dark brown material and more recently yellow purulent material. The patient has squeezed the sinus tracts and very small white grains are extruded. The patient has received oral antibiotics with no improvement. No fever, lymphadenopathy, or systemic symptoms. No relevant past medical history.

Epidemiology: Born and lives in Nazca, a desert area south of Lima. He is a farmer, harvests corn and potato, and works mainly barefoot. No travel history.

Physical Examination: BP 125/85; temperature 37.2°C; HR 76, respirations 18. Marked swelling of the left foot involving the sole and dorsal aspects of the foot with multiple draining sinus tracts [Images A, B]. Normal sensation; no lymphadenopathy; rest of the exam was normal.

Laboratory Results: Hemoglobin 12.3 g/dl; WBC 5.1 with normal differential, platelets 254,000; glucose 96 mg/dl; creatinine 0.8 mg/dl; normal electrolytes; normal urine. X-ray with mild osteomyelitis of the 5th metatarsal bone of the left foot [Image C]. Negative serologies for HIV and HTLV-1.

Images ABC for Case 2015-08
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Diagnosis: Actinomycetoma with Osteomyelitis.
Images DE for Case 2015-08
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Discussion: Biopsy of the foot showed an inflammatory reaction surrounding a grain, and filamentous structures can be seen inside the grain [Image D]. Gram stain of an expressed white grain showed tiny branching Gram-positive filamentous bacteria [Image E] consistent with actinomycetoma; culture is pending. The granules of an actinomycete can be differentiated from a eumycetoma based on the width of its filaments (0.5–1 μm in actinomycetoma), whereas in eumycetoma these are several microns greater (2–6 μm). Direct KOH and culture for fungi were negative. Fine needle aspirations were negative for conventional or possibly super-infecting bacteria.

The clinical presentation here is that of a so-called Madura Foot. Actinomycetoma refers to a mycetoma with a bacterial cause usually due to Nocardia (white grains), Streptomyces (white/yellow grains), or Actinomadura (red grains).

The main and very important differential diagnosis in this case is eumycetoma, a mycetoma due to fungal causes [see Gorgas Case 2002-04] but which produces black grains. This common subcutaneous mycosis in the tropics, and by far the most common cause of this clinical presentation in Perú, is caused by a wide variety of fungal organisms but is usually due to Madurella mycetomatis. Clinical diagnosis is thus not sufficient in these cases and an exact agent must be ascertained. Osteomyelitis from eumycetoma however would be more unusual and takes much longer to develop. Eumycetoma, and in this case bacterial infection due to actinomycetoma, appear to be localized phenomena due to local inoculation without any potential for widespread dissemination.

Other clinical diagnoses in the differential include botryomycosis (chronic staphylococcal infection) [see Gorgas Case 2003-04], other causes of chronic bacterial osteomyelitis, and malignancy. Other subcutaneous mycoses where sinus tracts and grains would not be found include sporotrichosis [Gorgas Case 2008-01], chromomycosis and lobomycosis (lacaziosis) [Gorgas Case 2005-03], as well as subcutaneous zygomycosis.

Actinomycetoma is frequent in farm workers due to greater exposure to minor skin trauma by Acacia thorns and splinters present in the soil. Its greatest incidence is between the fourth and fifth decades of life. The legs are the most commonly affected site, but actinomycetoma can be present in most regions of the body. In Mexico, the second most frequent region affected is the back and chest, probably due to the habit of carrying wood and lying on the ground.

Knowing that the most likely cause of actinomycetoma in this case is Nocardia spp, the patient was started on two drugs, cotrimoxazole (8 mg/kg/d) and amikacin (15 mg/kg/D) given in 4 to 5 cycles of 5 weeks each [Clin Dermatol. 2012 Jul-Aug;30(4):372-81]. During the first 3 weeks the two drugs are combined, and during the remaining 2 weeks cotrimoxazole is used alone. The number of cycles is determined by the clinical evolution. Then, cotrimoxazole alone is continued for at least 1 year. Our patient has received 2 cycles so far with some improvement; less swelling is present, all sinus tracts are closed, and no more grains can be obtained. In contrast, eumycetomas are poorly responsive to medical therapy with anti-fungal agents and often require aggressive surgery or amputation.