Steroids control paradoxical worsening of Mycobacterium ulcerans infection following initiation of antibiotic therapy

Lessons from Practice patients present outside endem by the long incubation period o BU is characterised by slowl with local necrosis, destruction ingly little systemic inflammatio infection is the result of its mycolactone, an immunomodu necrosis of host tissues and can responses and the recruitmen yc ca loc (BU). The M obacterium ulcerans infection is a geographilly restricted infection often referred to by its al name as Daintree, Buruli or Bairnsdale ulcer disease occurs in sub-Saharan Africa and within discrete regions of Australia, predominantly coastal Victoria and northern Queensland. Significant diagnostic delays, which place patients at risk of more extensive disease, are common. A recent review identified a mean duration of 42 days of symptoms before diagnosis (range, 2–270 days).3 These delays often occur when ic areas, a factor affected f 4–7 months.4 y progressive skin lesions of lipocytes and surprisn. This unusual pattern of unique virulence factor latory toxin that induces limit initiation of immune t of inflammatory cells.5 Following the increased use of antibiotics in BU, there have been descriptions of worsening clinical condition after an initial response to therapy.6 Such deteriorations (referred to as paradoxical reactions) are most common in patients with extensive disease and can take a variety of forms including increased ulcer size, ulceration of previously non-ulcerative papules or the development of new lesions not detectable before antibiotics.7 It is particularly important that paradoxical reactions are not misinterpreted as antibiotic failure, as the vast majority of lesions will resolve without a change in antibiotic regimen. Paradoxical reactions may be the result of antibioticinduced suppression of mycolactone synthesis, leading to decreased mycolactone concentrations and thus a reversal of macrophage and neutrophil dysfunction with renewed immune surveillance and response.7 There are many parallels to the paradoxical reactions described with Mycobacterium tuberculosis in HIV co-infected patients who initiate antiretroviral therapy. In that setting, the reaction likely represents an increased inflammatory response secondary to antiretroviral-induced immune reconstitution. As with M. tuberculosis, paradoxical reactions to BU commonly occur 4–8 weeks after therapy commences.7 In our case, the deterioration 4 weeks into therapy at the time that mycobacterial cultures became sterile indicates that this was not a failure of antibiotics but an unmasked immune phenomenon. Although our patient did receive a short course of intravenous antibiotics at the time of initiation of steroid therapy, the rapidity of his response and lack of identification of a new bacterial Clinical record