Date: 26 November 2013
History : A 20 yr old female with cystic fibrosis complicated by CF-related Diabetes mellitus (diagnosed at age 12 years) & ABPA (diagnosed at
15 years ). She was fairly stable until last 9 months, when she started to experience frequent pulmonary exacerbations, which have prompted intensive therapies.
Her serum IgE at the time of diagnosis was 5060 IU/L, skin prick test for aspergillus was positive, and serum was positive for precipitating antibodies to Aspergillus. She was treated with oral prednisone (1 mg/kg/day) for first two weeks followed by prednisone at 0.5 mg/kg every other day for at least 6 months with some clinical and serologic improvement. Over the following 5 years, she presented with a pattern of repeated episodic exacerbations with wheezing and crackles, increases in IgE and need to increase prednisone dosage. In an attempt to control her frequent ABPA relapses, itraconazole was added at 200mg twice a day, with some clinical & serologic improvement.
2-3 weeks prior to the scans and X rays, she developed severe protracted coughing spells associated with minor hemoptysis, low grade intermittent fever, and weight loss. Her FEV1 declined in a 3 months period from 56% to 33%.
A chest-x ray (Fig 3) did not reveal any new changes when compared to the one obtained almost a year before. A CT scan of the chest Figs 1 and 2- lateral view), however shows an ovoid soft tissue density within an ectatic bronchi in the anterior basal segment of the LLL, felt to be an aspergilloma.
She was started on oral voriconazole (3 months after the above scans and X-rays) which is better absorbed in CF patients than itraconazole, at 200mg twice a day. Her prednisone was gradually reduced to 5 mgs/day and her FEV1 increased to 46% of predicted (03/31/10), her IgE level was 1167 kU/L (previously in January 2009, her IgE level was 3053 kU/L)and her weight has plateaued.
Since she was not fit enough for surgery at that time, removing the aspergilloma by flexible bronchoscopy was unsuccessful. The aspergilloma can be seen at bronchoscopy in Fig 4.
Go to follow up 12 months later
Copyright:
Kindly donated by Dr N Turcios, Director of pediatric pulmonology/cystic fibrosis in Somerville, NJ.
Notes: n/a
Images library
-
Title
Legend
-
Itraconazole rash – macropopular rash after 7 days treatment with Itraconazole, in a patient with AIDS
-
A 72 year-old male patient had been in treatment for many years for severe asthma with relatively good exercise tolerance. Over the past two years he had increasing problems of shortness of breath, cough and productive sputum. There was no history of chest pain, haemoptysis or fever. His total IgE was 680.0 IU/l, and specific IgE against Aspergillus fumigatus was 14.6 IU/l. Precipitins against A. fumigatus were weakly positive (titre 1/2), and there was no eosinophilia. Computed tomography revealed marked emphysema but only mild bronchiectasis. Based on these results he was diagnosed with severe asthma with fungal sensitisation (SAFS) and itraconazole was started (SporanoxTM 200mg bds). Itraconazole dosage was reduced to 200 mg daily one month later due to progressive bilateral ankle oedema. Itraconazole levels by bioassay were 17.5 mg/l at that time (normal range 5-15 mg/l). Despite showing improvement on his chest symptoms, peripheral oedema became a major negative impact on patient’s quality of life. There were no signs of heart failure. Figure 1 was taken 2 months after itraconazole was started, when drug levels were 9.8 mg/l. Itraconazole was replaced by voriconazole. Concomitant medications included furosemide (80 mg daily) and spironolactone (100 mg daily). After discontinuing itraconazole, the oedema quickly subsided.
Ankle oedema is an uncommon complication of therapy with itraconazole. It has occurred in about 4% of patients treated in clinical trials involving this drug. This complication seems to be more frequent in patients concomitantly receiving calcium channel blockers, which was not the case for our patient. The mechanism is unknown. It usually does not represent cardiac failure, another reported side effect of itraconazole, but this must be excluded. Marked oedema requiring drug suspension is a rare phenomenon, and has not been previously reported in association with itraconazole.
, 
, 
-
The insert shows the size of the discs. These discs dissociate after infusion to release amphotericin B preferentially into the reticuloendothelial system and lung. This form of amphotericin B is marketed as either Amphotec or Amphocil, depending on the country.
