A paradoxical reaction in a mycobacterium ulcerans infection

A 63-year-old previously well male presented with a 3-month history of a slowly progressing, painless ulcer on his left calf. Histopathology demonstrated necrotising granulomata and Mycobacterium ulcerans’ PCR confirmed a diagnosis of Mycobacterium ulcerans infection. He was managed with Clarithromycin 500mg BD and Rifampicin 600mg daily. One month later, after initial improvement on antibiotics, he developed increasing erythema, swelling and exudate and eventually a second ulcer adjacent to the initial ulcer. Repeat biopsy showed active chronic ulceration with dermal necrosis, a heavy infiltrate of neutrophils and acid fast bacilli. Repeat culture was negative and PCR was not performed. The differential diagnosis of his clinical deterioration after initial improvement on antibiotics included microbiological failure or a paradoxical reaction. A trial of oral prednisolone 0.5mg/kg led to some improvement with reduction in erythema and size of the ulcer. Timolol 0.05% drops and hyperbaric oxygen were also used as adjuvant therapies. Antibiotics were continued for a further 12 weeks and at cessation, the second ulcer had completely healed and the primary ulcer had significantly improved.
Paradoxical reactions in Mycobacterium ulcerans infection were first recognised in 2009 on the Bellarine Peninsula of south-eastern Australia. The pathogenesis is thought to be due to antibiotic mediated reduction of mycolactone levels and reversal of the local immune-inhibitory state. Treatment options include systemic corticosteroids and surgery. Increased awareness of paradoxical reactions in M. ulcerans infections is required to ensure that appropriate treatment is administered which includes systemic corticosteroids as an option in severe reactions.

Dr. Priska McDonald