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Aspergillus otomycosis
Chronic otitis externa is often complicated by fungal infection. Aspergillus niger is the most common cause, with occasional cases caused by A.flavus and A.fumigatus (Than et al, 1980; Mugliston & o'Donaghue, 1985, Paulose et al, 1989; Lucente, 1993). It is usually unilateral. Experiments in volunteers showed that infection could be transferred from the affected ear to the unaffected ear by simple transfer of material and that epithelial damage increased the likelihood of infection (Yamashita, 1956; Sood et al, 1967).
The most important aspect of initial management is thorough cleaning of the external ear canal (Patow, 1995). This often requires a otomicroscope. Topical therapy with antifungal agents or other antimicrobial agents also necessary. Choices include amphotericin B (3%), flucytosine (10%), econazole cream, clotrinazole cream or powder, thiomersal (merthiolate) or cresyl acetate solution. Salicylic acid, griseofulvin and ketoconazole are less effective.
If there is a concurrent perforation of the tympanic membrane, and particularly if otalgia is a prominent feature, suppurative otitis media caused by Aspergillus or other fungi should be considered (Tiwari et al, 1995; Ibekwe et al, 1997). In immunocompromised patients (and rarely normal people), invasive external otitis may develop.
Prepared by D.W. Denning June, 1998
---
Aspergillus keratitis
Aspergillus has been documented as a frequent cause of post-traumatic keratitis (Thomas, 1994; Panda et al, 1997). Time between injury and recognition of fungal keratitis is a major determinant of success in treatment of Aspergillus keratitis.
Principles in the management of keratitis include:
Aspergillus keratitis can be treated with amphotericin 0.15-1.0% . Higher concentrations cause stromal oedema and so 0.15% is often used, with a 27% response rate if administered hourly (Thomas & Rajasekaran, 1988). Natamycin (primaricin) 5% ophthalmic solution is of value for superficial infections but does not penetrate well enough into the cornea for deep penetrating disease. Clotrimazole 1% solution is partially effective for Aspergillus and Candida infections but not Fusarium keratitis. Econazole local solution is also effective.(Thomas, 1994). The azoles can be prepared in arachis oil at 1% and gamma irradiated. In the USA miconazole 1% solution is available and is partially effective.
The use of oral itraconazole, 200-400mg/day is also effective in 75% of cases of Aspergillus keratitis (and superior to ketoconazole and topical amphotericin B) (Thomas et al, 1988, Heidemann 1995) although this is not a universal experience (Rosa, Jr, 1994). Topical itraconazole is less effective. (Thomas 1994, Oxford et al, 1995). When no other preparation is available 2% silver sulphadiazine solution may be better than nothing.
Surgery is sometimes required in the management of cases of mycotic keratitis which fail to respond to medical therapy or where there is a threat of ocular perforation or the formation of a descemetocoele. If possible surgery should be preceded by medical therapy for as long as possible. Relevant surgical procedures include debridement or lamellar keratectomy, formation of a conjunctival flap over a severely ulcerated area of the cornea (in an attempt to save the eyeball) or penetrating keratoplasty if a donor cornea is available. If malignant glaucoma occurs, or to restore drainage of aqueous humour, iridectomy, lens excision or anterior vitrectomy may be necessary (Thomas, 1994).
Prepared by D.W. Denning, April 1998
---
Allergic Aspergillus sinusitis
Images
Allergic Aspergillus sinusitis has many features in common with saprophytic sinusitis. It differs in that the sinus is filled with eosinophil-rich mucin which often contain Charcot-Leyden crystals. The pathogenesis is obscure.
It was first described by Katzenstein in 1983. Management consists of aeration of the affected sinus, usually a Caldwell-Luc procedure. Although both local and systemic steroids have been used in conjunction with surgery, there is no convincing evidence of benefit. Antifungal agents are unnecessary.
Prepared by D.W. Denning, April 1998
--
Aspergillus fungal ball of sinuses (Saprophytic sinus aspergillosis)
Images
Paranasal saprophytic aspergillosis is an uncommon cause of chronic or recurrent sinusitis. One series showed that 5% of 414 children treated for sinusitis had fungi only isolated and another 24% had bacteria and fungi isolated together (Laskownicka et al, 1978). In 600 adults treated for maxillary sinusitis, 14% revealed fungi, mostly A.fumigatus (Grigoriu et al, 1979). However most ear, nose and throat surgeons identify cases at surgery only every few years. The criteria for operation vary substantially and most patients with chronic sinusitis are not operated on. Most cases are in young to middle-aged adults.
It is likely that anatomical variation accounts for some cases (Stammberger, 1985). A common clinical finding is a bent middle turbinate with its convexity facing laterally instead of medially. Distortion of the osteomeatal complex, e.g. anatomical variation of the uncinate process will interfere with maxillary and frontal sinus drainage. Recurrent bacterial sinusitis leads to swelling of the ethmoidal air cells, further occluding the maxillary ostium. It is the combination of these factors that leads to most cases of paranasal saprophytic aspergillosis. In addition certain dental produces on the upper premolars and molars may introduce zinc oxide into the maxillary sinus which in turn creates favourable conditions for the growth of Aspergillus.
Usually discovered accidentally at surgery, prior symptoms are typical of chronic sinusitis; nasal congestion, facial discomfort or mild anterior headache, or post nasal dip. Most patients have previously received multiple courses of antibiotics, usually with at least a partial clinical response. Radiographs of the sinus demonstrate complete opacification of, usually, the maxillary sinus but occasionally of the sphenoid or rarely the frontal sinus. Usually only one sinus is involved radiologically and no bone erosion or extension of the soft tissue mass into adjacent structures. Endoscopic or CT examination of the nose usually demonstrates however, ethmoid involvement in addition to maxillary and/or sphenoid involvement (Stammberger, 1985).
Surgical aeration of the sinuses almost always cures the problem. Typically this is done via a Caldwell-Luc procedure and the sinus if found to contain a cheese-like, rubbery or friable soft tissue mass. The colour varies from green, brown to black and may be malodorous. The underlying mucosa is usually oedematous and may contain polyps. Most surgeons remove the mucosa and create a large antrostomy into the nose. Surgeons with extensive experience of the disease also maintain that the ipsilateral ethmoids should be explored and drained either endoscopically or surgically via a nasal approach (Stammberger, 1985). Relapse may occur otherwise. The role of nasal packing with amphotericin B or another antifungal agent is not established.
Prepared by D. W. Denning, June 1998
---
Aspergilloma
The vast majority of fungal balls in the lungs are due to Aspergillus with rare cases due to Pseudallescheria boydii or Mucorales. This discussion will focus on aspergillomas. The risk of developing an aspergilloma within a cavity of =2cm in diameter is 15-20% Approximately 10% of aspergillomas resolve spontaneously making uncontrolled observations in small numbers of patients difficult to interpret. Distinguishing chronic invasive aspergillosis from genuine aspergillomas is important because the former require systemic antifungal therapy. In the recent report of aspergillomas in AIDS (Addrizzo-Harris et al, 1997), progression of aspergillomas over time was seen with considerable morbidity and some mortality. This probably reflects invasion of cavity walls by Aspergillus rather than simple colonisation of Pneumocystis cavities by Aspergillus.
Several therapeutic strategies have been used in treating aspergillomas. Systemic antifungal therapy with ketoconazole is ineffective. Itraconazole 200mg daily is of marginal symptomatic benefit and little radiological benefit (Campbell et al, 1991). This probably reflects, at least in part, the lack of delivery of drug to the fungus ball and the chronic fibrotic/inflammatory changes in the surrounding lung. In addition, a dose of 400mg daily would have been more appropriate.
Many patients with aspergillomas are corticosteroid-dependent because of other pulmonary or systemic diseases. Steroids in patients with aspergillomas carry a slightly greater risk of the development of chronic invasive aspergillosis. Whether systemic antifungal therapy would prevent this is unclear.
Instillation of nystatin and amphotericin B has been tried with some benefit in some cases (especially with amphotericin B). Early data consisted of single instillations through a metal needle. Recently flexible plastic catheters have been used. Repeated instillations are usually necessary (in one study daily for 15 days (Lee, 1993)). Communication between the cavity and the airways is usual so the instilled agent usually leaks into the airways. Repeated instillations are labour intensive and not very effective for complex and/or bilateral aspergillomas. Recently described is the incorporation of amphotericin B in gelatin or glycerin that solidifies at 37oC (Giron, et al, 1993; Munk et al, 1993). This type of approach deserves further evaluation. Details of how to make up this preparation is given below.
Surgery is often appropriate for patients with haemoptysis. Surgical removal of aspergillomas is fraught with difficulty because of the very vascular, adherent pleura and because the remaining chest cavity may become infected with Aspergillus (Daly et al, 1986). The table shows the high risks of such an approach in patients with complex aspergillomas. Surgical removal of pleural aspergillomas and thoracoplasty is also prone to many complications and should be avoided if possible (Massard et al, 1992). In addition, many patients have underlying respiratory insufficiency and removal of a lobe of the lung would leave them unacceptably breathless. However, in those patients with major haemoptysis and simple aspergillomas, surgery offers an 84% five year survival compared with a 41% survival with conservative therapy (Jewkes, 1983). More recent series have substantially lower mortality rates, particularly if patients are selected carefully (El-Oakley-R et al, 1997; Chen,et al, 1997).
In patients with haemoptysis who are not fit to undergo surgery , embolisation may be appropriate. In most instances of haemoptysis abnormal and novel vascular connections to the systemic circulation are implicated. Usually this is the bronchial circulation but it may be any of the other arteries supplying the chest, e.g. internal or external mammary arteries etc. Aspergillomas also lead to an extensive network of small vessels. Several abnormal connections may exist in a single patient. The objective of embolisation is to permanently occlude these vessels. Patients with a communication between an intercostal and the anterior spinal artery can only be embolised safely if the catheter is introduced well past the anterior spinal artery. These patients require a skilled interventional radiologist for these difficult procedures.
If surgery is precluded, or the aspergilloma is complex, worsening haemoptysis is an appropriate indication for embolisation. The patient has to be able to lie still for 3-4 hours during the procedure which can be a major limiting factor. Each case has to be assessed on its merits. Depending on the radiologist, approximately 50-70% of embolisation procedures are successful (Remy & Jardin, 1990). However a relapse rate of 50% is typical.
Many patients with aspergillomas are elderly have significant underlying disease, including severe respiratory compromise in addition to the aspergilloma. Thus, many patients die with an aspergilloma rather than of it. However many die directly as a result of complications, e.g. haemoptysis or surgery and in other cases the fibrosis and additional respiratory embarrassment of the aspergilloma contributes to death (Jewkes et al, 1983).
Mortality from aspergilloma in 85 patients # (Jewkes, 1983)
Deaths Outcome
A)
Respiratory
17 (20)
Acute pneumonia
6
Chronic suppurative pneumonia
5
Respiratory failure
6
B)
After surgery for aspergilloma
7 (8)
Pulmonary resection
3
Cavernostomy*
4
C)
Haemoptysis
3
(3.5)
D)
Non-respiratory causes
9
(10.5)
E)
Not known
5
# outcome over 5 years or until death in 85% of cases studied
* evacuation of aspergilloma and instillation of antifungal agents (44% mortality) in contrast to pulmonary resection (7% mortality).
Prepared by D.W. Denning, April 1998
---
Allergic bronchopulmonary aspergillosis
First reported in detail in 1952 from the London Chest Hospital (Hinson et al, 1952) allergic bronchopulmonary aspergillosis (ABPA) is classified into five stages. These are acute remission, exacerbation, corticosteroid-dependent, asthma and fibrotic (Patterson et al, 1982). ABPA complicates asthma and cystic fibrosis (CF). Clearly the staging system has less meaning in cystic fibrosis because of progressive deterioration in respiratory status over many years. Precipitating antibodies to Aspergillus are common in adult cystics and in most cases ABPA is not present. Criteria for defining ABPA in CF are unclear.
Patients in remission require no therapy. Acute exacerbations are best treated with systemic corticosteroid therapy, usually a daily dose of 40-60 mg prednisolone for 7-10 days. Response to therapy can be gauged both clinically and serologically; serum IgE levels should fall and radiological infiltrates should clear. There is no useful data available on whether corticosteroids and/or antifungal agents slow the progression of the ABPA to pulmonary fibrosis which generally occurs between 5 and 11 years after the diagnosis. Long term corticosteroids may be necessary in those who deteriorate after steroid withdrawal (Greenberger, 1994).
In patients with frequent exacerbations, inhaled corticosteroids are useful in reducing the frequency of attacks. Probably this also lowers the risk of fibrosis in later years which is frequent otherwise. Many of these patients, however, require continuous systemic corticosteroid therapy to sustain remission.
For steroid-dependant patients a number of different antifungal strategies have been tried. Oral ketoconazole is ineffective (Shale et al, 1987; Fournier, 1987). In the first controlled trial of antifungal therapy in this condition, inhaled natamycin twice daily was also ineffective (Currie, 1990). There have been occasional anecdotal reports of the more commonly used polyene (amphotericin B) showing some benefit given by inhalation. The release of the new azole itraconazole yielded an alternative therapeutic avenue for ABPA. Itraconazole 200-400 mg/d has shown benefit in four open studies. In one open study of six patients who were corticosteroid dependent (3 with CF and 3 with asthma) five of the six patients responded (Denning et al, 1991). One patient with a low serum itraconazole concentration did not. In another series, as part of an international open-labelled compassionate use program several patients responded but the stage of disease and measurement of response was not well characterised (de Beule et al, 1988). Two other open studies have been published. One study of 16 patients with ABPA and cystic fibrosis demonstrated fewer exacerbations and a reduction in oral corticosteroid dose (Pacheco et al, 1993). Another compared a 2 year period before introduction of itraconazole with that on 200mg daily of itraconazole in 14 patients with ABPA and asthma (Salez et al, 1999). Compared with the reference period, blood eosinophilia, total IgE and Aspergillus precipitating antibody decreased, although Aspergillus specific IgE did not. Respiratory function as measured by FEV1, and FEF25-75 improved on itraconazole. Corticosteroid dose (prednisolone) was reduced from a mean of 22 to 6.5mg daily.
Recently a controlled trial of oral itraconazole versus placebo was completed and there was a clear benefit of itraconazole over placebo. (Stevens et al, 2000). In this study in asthmatic patients with ABPA, itraconazole 200mg twice daily was compared to placebo for 16 weeks and then all patients received 16 weeks of 200mg daily. Response was defined as 3 components - at least a 50% reduction in steroid dose and at least a 25% reduction in total IgE and either an increase by at least 25% increase in exercise tolerance or pulmonary function tests or an absence of pulmonary infiltrates. The study was conducted in the USA in 57 patients, typically about 50 years old of whom 25 had bronchietasis as determined on chest X-rays. In the first phase of the study, 13 of 28 (46%) of patients receiving itraconazole responded compared with 5 or 27(19%) receiving placebo (p=0.04). Patients older than 50 were more likely to respond (p=0.045), as were those without bronchietasis as determined on chest X-rays. No relapses occurred on the lower dose in the second phase of the study in those who responded, and an additional 12 (36%) patients responded, 8 of whom had received placebo previously. Only a few isolates of Aspergillus were collected. Those that were resistant (MIC 6.25g/ml) or tolerant (MIC
Aspergillus otomycosis
Chronic otitis externa is often complicated by fungal infection. Aspergillus niger is the most common cause, with occasional cases caused by A.flavus and A.fumigatus (Than et al, 1980; Mugliston & o'Donaghue, 1985, Paulose et al, 1989; Lucente, 1993). It is usually unilateral. Experiments in volunteers showed that infection could be transferred from the affected ear to the unaffected ear by simple transfer of material and that epithelial damage increased the likelihood of infection (Yamashita, 1956; Sood et al, 1967).
The most important aspect of initial management is thorough cleaning of the external ear canal (Patow, 1995). This often requires a otomicroscope. Topical therapy with antifungal agents or other antimicrobial agents also necessary. Choices include amphotericin B (3%), flucytosine (10%), econazole cream, clotrinazole cream or powder, thiomersal (merthiolate) or cresyl acetate solution. Salicylic acid, griseofulvin and ketoconazole are less effective.
If there is a concurrent perforation of the tympanic membrane, and particularly if otalgia is a prominent feature, suppurative otitis media caused by Aspergillus or other fungi should be considered (Tiwari et al, 1995; Ibekwe et al, 1997). In immunocompromised patients (and rarely normal people), invasive external otitis may develop.
Prepared by D.W. Denning June, 1998
---
Aspergillus keratitis
Aspergillus has been documented as a frequent cause of post-traumatic keratitis (Thomas, 1994; Panda et al, 1997). Time between injury and recognition of fungal keratitis is a major determinant of success in treatment of Aspergillus keratitis.
Principles in the management of keratitis include:
Aspergillus keratitis can be treated with amphotericin 0.15-1.0% . Higher concentrations cause stromal oedema and so 0.15% is often used, with a 27% response rate if administered hourly (Thomas & Rajasekaran, 1988). Natamycin (primaricin) 5% ophthalmic solution is of value for superficial infections but does not penetrate well enough into the cornea for deep penetrating disease. Clotrimazole 1% solution is partially effective for Aspergillus and Candida infections but not Fusarium keratitis. Econazole local solution is also effective.(Thomas, 1994). The azoles can be prepared in arachis oil at 1% and gamma irradiated. In the USA miconazole 1% solution is available and is partially effective.
The use of oral itraconazole, 200-400mg/day is also effective in 75% of cases of Aspergillus keratitis (and superior to ketoconazole and topical amphotericin B) (Thomas et al, 1988, Heidemann 1995) although this is not a universal experience (Rosa, Jr, 1994). Topical itraconazole is less effective. (Thomas 1994, Oxford et al, 1995). When no other preparation is available 2% silver sulphadiazine solution may be better than nothing.
Surgery is sometimes required in the management of cases of mycotic keratitis which fail to respond to medical therapy or where there is a threat of ocular perforation or the formation of a descemetocoele. If possible surgery should be preceded by medical therapy for as long as possible. Relevant surgical procedures include debridement or lamellar keratectomy, formation of a conjunctival flap over a severely ulcerated area of the cornea (in an attempt to save the eyeball) or penetrating keratoplasty if a donor cornea is available. If malignant glaucoma occurs, or to restore drainage of aqueous humour, iridectomy, lens excision or anterior vitrectomy may be necessary (Thomas, 1994).
Prepared by D.W. Denning, April 1998
---
Allergic Aspergillus sinusitis
Images
Allergic Aspergillus sinusitis has many features in common with saprophytic sinusitis. It differs in that the sinus is filled with eosinophil-rich mucin which often contain Charcot-Leyden crystals. The pathogenesis is obscure.
It was first described by Katzenstein in 1983. Management consists of aeration of the affected sinus, usually a Caldwell-Luc procedure. Although both local and systemic steroids have been used in conjunction with surgery, there is no convincing evidence of benefit. Antifungal agents are unnecessary.
Prepared by D.W. Denning, April 1998
--
Aspergillus fungal ball of sinuses (Saprophytic sinus aspergillosis)
Images
Paranasal saprophytic aspergillosis is an uncommon cause of chronic or recurrent sinusitis. One series showed that 5% of 414 children treated for sinusitis had fungi only isolated and another 24% had bacteria and fungi isolated together (Laskownicka et al, 1978). In 600 adults treated for maxillary sinusitis, 14% revealed fungi, mostly A.fumigatus (Grigoriu et al, 1979). However most ear, nose and throat surgeons identify cases at surgery only every few years. The criteria for operation vary substantially and most patients with chronic sinusitis are not operated on. Most cases are in young to middle-aged adults.
It is likely that anatomical variation accounts for some cases (Stammberger, 1985). A common clinical finding is a bent middle turbinate with its convexity facing laterally instead of medially. Distortion of the osteomeatal complex, e.g. anatomical variation of the uncinate process will interfere with maxillary and frontal sinus drainage. Recurrent bacterial sinusitis leads to swelling of the ethmoidal air cells, further occluding the maxillary ostium. It is the combination of these factors that leads to most cases of paranasal saprophytic aspergillosis. In addition certain dental produces on the upper premolars and molars may introduce zinc oxide into the maxillary sinus which in turn creates favourable conditions for the growth of Aspergillus.
Usually discovered accidentally at surgery, prior symptoms are typical of chronic sinusitis; nasal congestion, facial discomfort or mild anterior headache, or post nasal dip. Most patients have previously received multiple courses of antibiotics, usually with at least a partial clinical response. Radiographs of the sinus demonstrate complete opacification of, usually, the maxillary sinus but occasionally of the sphenoid or rarely the frontal sinus. Usually only one sinus is involved radiologically and no bone erosion or extension of the soft tissue mass into adjacent structures. Endoscopic or CT examination of the nose usually demonstrates however, ethmoid involvement in addition to maxillary and/or sphenoid involvement (Stammberger, 1985).
Surgical aeration of the sinuses almost always cures the problem. Typically this is done via a Caldwell-Luc procedure and the sinus if found to contain a cheese-like, rubbery or friable soft tissue mass. The colour varies from green, brown to black and may be malodorous. The underlying mucosa is usually oedematous and may contain polyps. Most surgeons remove the mucosa and create a large antrostomy into the nose. Surgeons with extensive experience of the disease also maintain that the ipsilateral ethmoids should be explored and drained either endoscopically or surgically via a nasal approach (Stammberger, 1985). Relapse may occur otherwise. The role of nasal packing with amphotericin B or another antifungal agent is not established.
Prepared by D. W. Denning, June 1998
---
Aspergilloma
The vast majority of fungal balls in the lungs are due to Aspergillus with rare cases due to Pseudallescheria boydii or Mucorales. This discussion will focus on aspergillomas. The risk of developing an aspergilloma within a cavity of =2cm in diameter is 15-20% Approximately 10% of aspergillomas resolve spontaneously making uncontrolled observations in small numbers of patients difficult to interpret. Distinguishing chronic invasive aspergillosis from genuine aspergillomas is important because the former require systemic antifungal therapy. In the recent report of aspergillomas in AIDS (Addrizzo-Harris et al, 1997), progression of aspergillomas over time was seen with considerable morbidity and some mortality. This probably reflects invasion of cavity walls by Aspergillus rather than simple colonisation of Pneumocystis cavities by Aspergillus.
Several therapeutic strategies have been used in treating aspergillomas. Systemic antifungal therapy with ketoconazole is ineffective. Itraconazole 200mg daily is of marginal symptomatic benefit and little radiological benefit (Campbell et al, 1991). This probably reflects, at least in part, the lack of delivery of drug to the fungus ball and the chronic fibrotic/inflammatory changes in the surrounding lung. In addition, a dose of 400mg daily would have been more appropriate.
Many patients with aspergillomas are corticosteroid-dependent because of other pulmonary or systemic diseases. Steroids in patients with aspergillomas carry a slightly greater risk of the development of chronic invasive aspergillosis. Whether systemic antifungal therapy would prevent this is unclear.
Instillation of nystatin and amphotericin B has been tried with some benefit in some cases (especially with amphotericin B). Early data consisted of single instillations through a metal needle. Recently flexible plastic catheters have been used. Repeated instillations are usually necessary (in one study daily for 15 days (Lee, 1993)). Communication between the cavity and the airways is usual so the instilled agent usually leaks into the airways. Repeated instillations are labour intensive and not very effective for complex and/or bilateral aspergillomas. Recently described is the incorporation of amphotericin B in gelatin or glycerin that solidifies at 37oC (Giron, et al, 1993; Munk et al, 1993). This type of approach deserves further evaluation. Details of how to make up this preparation is given below.
Surgery is often appropriate for patients with haemoptysis. Surgical removal of aspergillomas is fraught with difficulty because of the very vascular, adherent pleura and because the remaining chest cavity may become infected with Aspergillus (Daly et al, 1986). The table shows the high risks of such an approach in patients with complex aspergillomas. Surgical removal of pleural aspergillomas and thoracoplasty is also prone to many complications and should be avoided if possible (Massard et al, 1992). In addition, many patients have underlying respiratory insufficiency and removal of a lobe of the lung would leave them unacceptably breathless. However, in those patients with major haemoptysis and simple aspergillomas, surgery offers an 84% five year survival compared with a 41% survival with conservative therapy (Jewkes, 1983). More recent series have substantially lower mortality rates, particularly if patients are selected carefully (El-Oakley-R et al, 1997; Chen,et al, 1997).
In patients with haemoptysis who are not fit to undergo surgery , embolisation may be appropriate. In most instances of haemoptysis abnormal and novel vascular connections to the systemic circulation are implicated. Usually this is the bronchial circulation but it may be any of the other arteries supplying the chest, e.g. internal or external mammary arteries etc. Aspergillomas also lead to an extensive network of small vessels. Several abnormal connections may exist in a single patient. The objective of embolisation is to permanently occlude these vessels. Patients with a communication between an intercostal and the anterior spinal artery can only be embolised safely if the catheter is introduced well past the anterior spinal artery. These patients require a skilled interventional radiologist for these difficult procedures.
If surgery is precluded, or the aspergilloma is complex, worsening haemoptysis is an appropriate indication for embolisation. The patient has to be able to lie still for 3-4 hours during the procedure which can be a major limiting factor. Each case has to be assessed on its merits. Depending on the radiologist, approximately 50-70% of embolisation procedures are successful (Remy & Jardin, 1990). However a relapse rate of 50% is typical.
Many patients with aspergillomas are elderly have significant underlying disease, including severe respiratory compromise in addition to the aspergilloma. Thus, many patients die with an aspergilloma rather than of it. However many die directly as a result of complications, e.g. haemoptysis or surgery and in other cases the fibrosis and additional respiratory embarrassment of the aspergilloma contributes to death (Jewkes et al, 1983).
Mortality from aspergilloma in 85 patients # (Jewkes, 1983)
Deaths Outcome
A)
Respiratory
17 (20)
Acute pneumonia
6
Chronic suppurative pneumonia
5
Respiratory failure
6
B)
After surgery for aspergilloma
7 (8)
Pulmonary resection
3
Cavernostomy*
4
C)
Haemoptysis
3
(3.5)
D)
Non-respiratory causes
9
(10.5)
E)
Not known
5
# outcome over 5 years or until death in 85% of cases studied
* evacuation of aspergilloma and instillation of antifungal agents (44% mortality) in contrast to pulmonary resection (7% mortality).
Prepared by D.W. Denning, April 1998
---
Allergic bronchopulmonary aspergillosis
First reported in detail in 1952 from the London Chest Hospital (Hinson et al, 1952) allergic bronchopulmonary aspergillosis (ABPA) is classified into five stages. These are acute remission, exacerbation, corticosteroid-dependent, asthma and fibrotic (Patterson et al, 1982). ABPA complicates asthma and cystic fibrosis (CF). Clearly the staging system has less meaning in cystic fibrosis because of progressive deterioration in respiratory status over many years. Precipitating antibodies to Aspergillus are common in adult cystics and in most cases ABPA is not present. Criteria for defining ABPA in CF are unclear.
Patients in remission require no therapy. Acute exacerbations are best treated with systemic corticosteroid therapy, usually a daily dose of 40-60 mg prednisolone for 7-10 days. Response to therapy can be gauged both clinically and serologically; serum IgE levels should fall and radiological infiltrates should clear. There is no useful data available on whether corticosteroids and/or antifungal agents slow the progression of the ABPA to pulmonary fibrosis which generally occurs between 5 and 11 years after the diagnosis. Long term corticosteroids may be necessary in those who deteriorate after steroid withdrawal (Greenberger, 1994).
In patients with frequent exacerbations, inhaled corticosteroids are useful in reducing the frequency of attacks. Probably this also lowers the risk of fibrosis in later years which is frequent otherwise. Many of these patients, however, require continuous systemic corticosteroid therapy to sustain remission.
For steroid-dependant patients a number of different antifungal strategies have been tried. Oral ketoconazole is ineffective (Shale et al, 1987; Fournier, 1987). In the first controlled trial of antifungal therapy in this condition, inhaled natamycin twice daily was also ineffective (Currie, 1990). There have been occasional anecdotal reports of the more commonly used polyene (amphotericin B) showing some benefit given by inhalation. The release of the new azole itraconazole yielded an alternative therapeutic avenue for ABPA. Itraconazole 200-400 mg/d has shown benefit in four open studies. In one open study of six patients who were corticosteroid dependent (3 with CF and 3 with asthma) five of the six patients responded (Denning et al, 1991). One patient with a low serum itraconazole concentration did not. In another series, as part of an international open-labelled compassionate use program several patients responded but the stage of disease and measurement of response was not well characterised (de Beule et al, 1988). Two other open studies have been published. One study of 16 patients with ABPA and cystic fibrosis demonstrated fewer exacerbations and a reduction in oral corticosteroid dose (Pacheco et al, 1993). Another compared a 2 year period before introduction of itraconazole with that on 200mg daily of itraconazole in 14 patients with ABPA and asthma (Salez et al, 1999). Compared with the reference period, blood eosinophilia, total IgE and Aspergillus precipitating antibody decreased, although Aspergillus specific IgE did not. Respiratory function as measured by FEV1, and FEF25-75 improved on itraconazole. Corticosteroid dose (prednisolone) was reduced from a mean of 22 to 6.5mg daily.
Recently a controlled trial of oral itraconazole versus placebo was completed and there was a clear benefit of itraconazole over placebo. (Stevens et al, 2000). In this study in asthmatic patients with ABPA, itraconazole 200mg twice daily was compared to placebo for 16 weeks and then all patients received 16 weeks of 200mg daily. Response was defined as 3 components - at least a 50% reduction in steroid dose and at least a 25% reduction in total IgE and either an increase by at least 25% increase in exercise tolerance or pulmonary function tests or an absence of pulmonary infiltrates. The study was conducted in the USA in 57 patients, typically about 50 years old of whom 25 had bronchietasis as determined on chest X-rays. In the first phase of the study, 13 of 28 (46%) of patients receiving itraconazole responded compared with 5 or 27(19%) receiving placebo (p=0.04). Patients older than 50 were more likely to respond (p=0.045), as were those without bronchietasis as determined on chest X-rays. No relapses occurred on the lower dose in the second phase of the study in those who responded, and an additional 12 (36%) patients responded, 8 of whom had received placebo previously. Only a few isolates of Aspergillus were collected. Those that were resistant (MIC 6.25g/ml) or tolerant (MIC
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Lääkärin ohjeen mukaan. Yleensä otetaan 2-3 tippaa liuosta kahdesti vuorokaudessa. Hoito kestää tavallisesti enintään 10 vuorokautta.
Lääkkeen ottaminen
Ennen lääkkeen ottamista korvakäytävä puhdistetaan ja kuivataan huolellisesti. Tippoja pudotetaan korvakäytävään muovipulloa kevyesti puristamalla. Tippoja on helpointa antaa, jos ne ovat suunnilleen kehonlämpöisiä. Pulloa voikin lämmittää hetken aikaa kämmenessä ennen lääkkeen ottamista. Tiputtelun jälkeen on hyvä pitää hoidettava korva ylöspäin parin minuutin ajan, jolloin lääke leviää korvakäytävään. Tippoja voi viedä korvakäytävään myös tampoonin avulla. Pullon tiputuskärki ei saisi koskettaa ihoa, eikä tippoja saisi joutua silmiin. Mikäli tärykalvo on saattanut puhjeta, Locacorten-Vioform korvatippoja ei tule käyttää.
Haittavaikutukset
Haittavaikutuksia ei useinkaan esiinny. Joskus hoidettava alue ärtyy, jolloin ilmaantuu kutinaa, ihottumaa tai polttavaa tunnetta. Valmiste voi värjätä hiuksia, vaatteita ja vuodevaatteita.
Raskaus ja imetys
Lääkkeen käyttämisestä raskauden aikana ja imetyksen yhteydessä kannattaa neuvotella lääkärin kanssa.
Säilytys
Huoneenlämmössä, 15- 25 asteessa. Kelpoisuusaika pakkauksessa.
ATC-koodi
S02CA02
Tuotetiedot päivitetty
03.06.2004
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Sain lääkäriltä reseptin (joka käskettiin syödä, hih, no ei vaiskaan) Tippoja korviin.
Katotaan lähteekö tulehdus ja kutina viimein pois korvista!