Background
Diabetic foot disease (DFD) includes an array of medical conditions, mainly resulting from diabetic peripheral neuropathy and arterial disease which can lead to foot ulceration. Diabetic foot ulceration may progress with wound infection, osteomyelitis and, ultimately, amputation. As a result, DFD burden is significant, resulting in major economic consequences for patients, their families and society. Limited evidence on the costs of treating diabetic foot is available, in particular in developing countries, where its burden is higher. 
Aim
To estimate the annual direct medical costs of outpatients with DFD in Brazil, in 2014. 
Method
 We conducted a cost-of-illness study, considering the perspective of the Brazilian Public Health Care System (SUS). The analytic horizon was one year (2014). Medical costs only were considered. Considering the range of syndromes included in the DFD spectrum, we developed four well-defined hypothetical DFD cases: 1) peripheral neuropathy without ulcer, 2) non-infected foot ulcer, 3) infected foot ulcer, 4) clinical management of amputated patients. We did not considered DFD conditions requiring hospitalization, i.e., osteomyelitis, and amputations. Considering National Guidelines for DFD management, we developed a standardized questionnaire in which resource utilization for the following healthcare components was assessed: imaging and laboratory exams; medications; procedures and non-medication therapies; and health professional. A panel of 12 experts in DFD from various reference centers in the country were invited to participate. Healthcare resources used were quantified, and then multiplied by unit costs. Unit costs of each resource was obtained from National Standardized SUS Pricing List (SIGTAP). We then extrapolated the costs to obtain the annual direct medical costs of DFD outpatients in Brazil as a whole, considering a decision tree, considered epidemiologic parameters obtained from the national literature. Parameters were prevalence of diabetes (6.2%), prevalence of diabetic foot disease among individuals with diabetes (9%), proportion of diabetic patients with ulcer (5.3%), proportion of these with infection (50%), and proportion of diabetics which required amputation (1.4%). The resulting number of cases in each of the segments of the analytic model was then multiplied by the estimated average cost per case, generating the total economic burden of DFD in the country. Costs were estimates in Brazilian Reais (BRL) and then converted to USD (1USD=2.66 BRL) and Int$ (1BRL=1.7477, World Bank) using official conversion rates for 2014. 
Results
We obtained responses of 8 (67%) panel members. The average annual direct medical costs were estimated at USD 225.8 (Int$ 343.7) for a case of peripheral neuropathy without ulcer, USD 268.2 (Int$ 408.1) for a case of non-infected foot ulcer, USD 1,062.5 (Int$ 1,617.1) for a case of infected foot ulcer, and USD 394.1 (Int$ 599.7) for the clinical management of an amputated patient. The most relevant cost component was healthcare professionals (16-38%), followed by the imaging exams (8-40%). As a result of the extrapolation the estimated number of diabetic individuals with diabetic foot disease (829,7 thousand), foot ulcers (43,726), infected ulcers (21,491), and amputated (11,284) resulted in an estimated total annual direct medical costs of USD 220.43 million (Int$ 335.49 million).
 
Discussion
Little evidence is available on the economic burden of DFD in Brazil. We identified significant resource utilization for the outpatient management DFD syndromes, particularly related to healthcare personnel. Costs were higher for more severe disease of complex management. DFD imposes a significant health and economic burden to the Brazilian Healthcare System, emphasizing the need for health policies targeting its improved prevention and care.

Annual direct medical costs of outpatients with diabetic foot disease in Brazil