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This 49 yr old gentleman with a history of hyper IgE syndrome, cavitary bronchiectasis, primary TB, intestinal TB is on antibiotic and antifungal prophylaxis (itraconazole). In early 2006, he developed progressive consolidation which failed to respond to antibiotics. Aspergillus fumigatus was eventually grown from the second BAL. He subsequently commenced oral voriconazole but soon developed side effects, namely myopathy and visual disturbance. He was switched back to oral itraconazole but symptoms did not resolve and if anything they progressed. Treatment with voriconazole was resumed but was associated with further deterioration and an elevated CK (with readings up to 600 iu/L). In January 2007 he commenced on posaconazole. He tolerates this medication well and his chest disease improved with objective improvement in CT scans. However, in November 2007 the muscle symptoms recurred on posaconazole and his CK increased further (up to 800iu/L) and is unable to get up from a chair, hence it was discontinued. He starts to culture aspergillus fumigatus on a regular basis from sputum samples from December 2007 and in January 2008 his clinical condition deteriorated. A CT scan (see image) shows increasing mucoid impaction and possible areas of ground glass shadowing. He is admitted for intravenous amphotericin and subsequently caspofungin (due to an increase in his creatinine), with good clinical effect. He started on terbinafine but his muscle symptoms recur rapidly, with increased CK and muscle necrosis confirmed on biopsy. He also started on nebulised amphotericin, which he tolerated well although at lower doses than usual.
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Diagnosis:
The patient has evidence of subacute invasive aspergillosis as seen by growth of Aspergillus fumigatus in his sputum and BAL, and CT findings of subpleural based, multiloculated cavity in right upper lobe and multi-focal consolidation in both lungs, which failed to respond to antibiotics. He also has ABPA as suggested by sputum plugs containing aspergillus, grade 5 RAST, positive skin prick test to aspergillus. This was further confirmed by response to amphotericin, caspofungin and posaconazole with objective improvement in CT scans after treatment.
Response to antifungal therapy:
There is poor response to triazole anti-fungals namely, itraconazole and voriconazole, and terbinafine, but good transient response to posaconazole, intravenous amphotericin and caspofungin. Unfortunately, the patient developed significant side effects to triazole anti-fungals and terbinafine namely myopathy, myositis, visual disturbance and rigors and hence they had to be discontinued. He tolerated nebulised amphotericin well at lower than normal dose.
Outcome:
Patient is unable to take triazole anti-fungal agents or terbinafine due to side effects and develops recurrent exacerbations of aspergillosis needing intravenous amphotericin or caspofungin. But, fortunately, is able to tolerate nebulised amphotericin. Possible future therapeutic options for anti-fungal prophylaxis are surgery to resect aspergillus focus and interferon gamma.
Kindly presented by Dr Bryan Fernandes, Wythenshawe Hospital, Southmoor Rd, Manchester M23 9LT, UK and Dr. Alison Condliffe, Consultant in Respiratory Medicine, Addenbrooke’s Hospital. (PT PH)
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