Aspergillosis

Aspergillosis

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Aspergillosis is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Pulmonary Aspergillosis

Disorder Subdivisions

  • Bronchopulmonary Allergic Aspergillosis
  • Pulmonary Mycetoma
  • Aspergilloma
  • Invasive Aspergillosis
  • Endocarditis
  • Madu'ra Foot
  • Mycetoma

General Discussion

Aspergillosis is a fungal infection caused by Aspergillus, a species of mold that is found all over the world. More than 300 different types of Aspergillus have been identified and more are continuing to be identified. Most of these molds are harmless, however, some types can cause a variety of diseases in humans ranging from simple allergic reactions to life-threatening invasive disease. Collectively, this group of diseases is referred to as aspergillosis and is broadly broken down into three categories - allergic, chronic and invasive. Four main clinical types of aspergillosis are usually identified - allergic bronchopulmonary aspergillosis, aspergilloma, invasive aspergillosis, and chronic necrotizing aspergillosis. Aspergillosis rarely develops in healthy individuals; it is much more likely to develop in individuals with asthma, cystic fibrosis, diabetes mellitus, and lung disease or in individuals who have a weakened immune system, who take corticosteroid drugs or who have had a bone marrow or organ transplant. In most cases, aspergillosis develops when susceptible individuals breathe in (inhale) Aspergillus spores.

Symptoms

The symptoms of aspergillosis vary depending upon the specific form of the disorder present. The lungs are usually affected in individuals with aspergillosis. Aspergillosis can present as an allergic reaction, an isolated finding affecting a specific area of the body (e.g., the lungs, sinuses or ear canals), or as an invasive infection that spreads to affect various tissues, mucous membranes or organs of the body.



Allergic Bronchopulmonary Aspergillosis

This form of aspergillosis usually occurs in individuals with long-standing asthma or cystic fibrosis. It is an allergic reaction to the breathing in (inhalation) of the fungi spores. These spores set off an improper response from an individual's immune system. Initial symptoms usually include fever, wheezing, shortness of breath (dyspnea), and a general feeling of poor health (malaise). Allergic bronchopulmonary aspergillosis may also cause chest pain, a cough that brings up blood or brown-colored globs (plugs) of mucus, and an excess of certain white blood cells (eosinophilia). The infection usually does not spread to other areas, but can cause to chronic widening (dilation) of the bronchial tubes (bronchiectasis).



Aspergilloma

The most common form of aspergillosis is the development of a fungal ball known as an aspergilloma. These growths consist of a tangled mass of fungus fibers, mucus, tissue debris, inflammatory cells, and blood clotting protein (fibrin). Aspergillomas form in air pockets or cavities found within the lungs that may have been formed from previous lung disease (e.g., tuberculosis or emphysema). Affected individuals may not have any apparent symptoms (asymptomatic) for years. Symptoms that can develop include wheezing, shortness of breath, chest pain, a chronic cough, fatigue, a cough that brings up blood (mild hemoptysis), and weight loss. Fever is rare unless individuals also have a bacterial infection. In some cases, hemoptysis can become severe, potentially causing suffocation (asphyxiation). An aspergilloma usually remains the same size, but can shrink or resolve without treatment. In rare cases, an aspergilloma may gradually grow larger, but usually does not spread to other areas. An aspergilloma may also be known as pulmonary aspergilloma.



Chronic Necrotizing Aspergillosis

This form of aspergillosis, also known as semi-invasive aspergillosis is characterized by infection of the lungs. Unlike an aspergilloma, it can spread to affect surrounding tissue. Chronic necrotizing aspergillosis shows a chronic, slowly progressive process that, unlike invasive aspergillosis, does not spread to other organ systems or the blood vessels (vascular invasion). In some affected individuals, an aspergilloma (fungal ball) may develop in a cavity created by the destruction of lung tissue by the original infection. Chronic necrotizing aspergillosis most often affects middle-aged and elderly individuals. General symptoms associated with this form of aspergillosis include fever, night sweats, a cough that brings up sputum and unintended weight loss for a period of 1-6 months.



Invasive Aspergillosis

Invasive aspergillosis is the most severe form of aspergillosis and usually affects individuals with weakened immune systems or those who have received bone marrow or solid organ transplants. It is characterized by infection that starts in the lungs and then rapidly travels through the bloodstream to affect various organs of the body potentially including the brain, kidneys, heart and skin. The specific symptoms associated with invasive aspergillosis vary based upon the organ system(s) involved. Affected individuals often develop fever, chills headaches, a cough that brings up blood (mild hemoptysis), shortness of breath (dyspnea), and chest pain. Severe life-threatening complications can develop including shock, delirium, massive bleeding from the lungs, and inflammation of the trachea and bronchi (tracheobronchitis), which may cause airway obstruction. Organ failure (e.g., liver or kidney) can occur. If the infection spreads to the brain, seizures, intracranial bleeding, or inflammation of the membranes surrounding the brain (meningitis) can occur.



Additional Forms of Aspergillosis

Aspergillosis may occur as an isolated infection of individual areas such as the nail beds, eyes, skin, sinuses or ear canals. Infection of the ear canals can cause itchiness, pain and the drainage of fluid from the ears. Infection of the sinuses may cause a stuffy nose, congestion, fever, facial pain and headache. An aspergilloma may form in the sinuses or the infection may spread to other areas including the brain. Aspergillosis of the sinuses is sometimes associated with bone loss of the facial bones.



Infection with Aspergillus may cause inflammation of the thin membrane (endocardium) lining the heart, a condition called endocarditis. This condition occurs when heart tissue is directly infected by Aspergillus during cardiac surgery (post-operative aspergillosis). Cases of aspergillosis affecting the site of surgery have also been reported following eye (ophthalmologic) and dental surgery.



As researchers learn more about aspergillosis, new clinical entities (e.g., severe asthma with fungal sensitization [SAFS]) are being identified. More research is necessary to clearly define and separate these diseases from existing forms of Aspergillus infection.

Causes

Aspergillosis is an infectious disease that occurs when susceptible individuals breathe in (inhale) fungal spores of the Aspergillus species of mold. Approximately 300 different species of Aspergillus have been identified, but only a few are known to cause diseases in humans. The most common of these are Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger. Aspergillus spores are found all over the environment both indoors and outdoors especially in decaying vegetation. It is also found in the soil, airborne dust, air vents, foods, spices, humidifiers, and potted plants.



It is not known why most people resist infection with this common fungus, while others appear more susceptible to developing infection. Individuals with a compromised or weakened immune system and those who have received a transplant, especially a bone marrow transplant, are at a greater risk of developing infection. Some individuals may have an improper immune system response to the fungal spores. Aspergillosis may also occur with greater frequency in individuals with diabetes mellitus, cystic fibrosis, asthma, AIDS, cancer or with low white blood cell counts (neutropenia). Individuals who take corticosteroid drugs are also at a greater risk of developing aspergillosis.



Some researchers believe that genetics plays a role in the development of aspergillosis. Researchers speculate that certain, as yet unidentified genes, may make some individuals more likely to develop an infection with Aspergillus (genetic predisposition). Researcher is underway to determine what affect genetics plays in the development of the various forms of aspergillosis.



Researchers have recently mapped the genomes for a few specific types of Aspergillus. A genome is the complete genetic make up of an organism and researchers hope that the genomes will lead them to novel treatment options and to a better understanding of the various differences betweens different species of Aspergillus.

Affected Populations

Aspergillosis affects males and females in equal numbers. The exact incidence rate in the general population is unknown. Allergic bronchopulmonary aspergillosis occurs with greater frequency in individuals with asthma or cystic fibrosis. Invasive aspergillosis occurs with greater frequency in individuals who have received an organ transplant, especially a bone marrow transplant. One estimate suggests that 5-13 percent of individuals who have received a BMT have developed invasive aspergillosis. Aspergilloma may occur in individuals with chronic lung disease in which lung damage has left open spaces or cavities.

Standard Therapies

Diagnosis

A diagnosis of aspergillosis is made based upon a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests such as bronchoscopy with biopsy, x-rays, antigen skin tests or blood tests.



During a bronchoscopy, a physician inserts a metal tube called a cannula through the mouth and down an affected individual's throat and obtains a sample of tissue to be analyzed (biopsy). X-rays of the chest are taken because to detect characteristic findings such as the presence of an aspergilloma in a lung cavity or the buildup (accumulation) of Aspergillus fungi in the lungs. During an Aspergillus antigen skin test, a physician will inject a needle into a specific area of the body. If the area becomes inflamed or irritated with 48-72 hours, the person has been exposed to the Aspergillus fungus. A physician may also perform a blood test to determine whether any aspergillosis antibodies are present. Antibodies, also known as immunoglobulins, are produced by the body to combat invading microorganisms, toxins, or other foreign substances.



Some forms of aspergillosis are easier to diagnose than others. For example, an aspergilloma is usually seen (often incidentally) on a chest x-ray. A diagnosis of invasive aspergillosis, however, is much more difficult. Researchers are studying ways to better and more rapidly diagnose aspergillosis.



Treatment

The treatment of aspergillosis varies depending upon the specific type of aspergillosis present and may include observation with no treatment, drug therapy or surgery.



In individuals with an aspergilloma who do not exhibit symptoms, no therapy may be necessary. Physicians will monitor an affected individual to detect any complications (massive hemoptysis) that may require treatment. This observation period may be known as watch and wait or watchful waiting. Most anti-fungal medications have not been effective in treating aspergillomas, although some individuals have responded to long-term treatment with oral itraconazole. Surgery to remove an aspergilloma may be performed. Unfortunately, some individuals with underlying lung disease may not be candidates for surgical intervention or may be high-risk surgical candidates.



Anti-fungal medications are used to treat individuals with invasive aspergillosis. For years, amphotericin B was the drug of choice; however, recently a newer anti-fungal drug known as voriconazole is now preferred because it has proven more effective with fewer side effects. The Food and Drug Administration (FDA) has approved voriconazole (Vfend®) for the treatment of acute invasive aspergillosis. Vfend is marketed by the pharmaceutical company Pfizer.



Another anti-fungal drug, caspofungin, has been approved by the FDA for the treatment of individuals with invasive aspergillosis who have not responded to other treatments (refractory) or are not candidates for conventional therapy. In some cases, individuals with invasive aspergillosis may be treated with a combination of several different anti-fungal medications. Surgery may be used to treat certain complications including massive hemoptysis or to treat localized infection that fails to respond to anti-fungal medications.



Individuals with allergic bronchopulmonary aspergillosis are treated with oral corticosteroids such as prednisone (inhaled steroids are ineffective). Corticosteroids suppress the immune system's improper response to the Aspergillus infection. Some individuals may receive an anti-fungal medication such as itraconazole along with corticosteroids.



Chronic necrotizing aspergillosis is treated with anti-fungal medications. For years, amphotericin B was used, but itraconazole has been demonstrated to be an effective therapy and less toxic.



Endocarditis caused by Aspergillus infection is treated by the surgical removal of the affected heart valves.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Berkow R., ed. The Merck Manual-Home Edition. 2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:311-2, 1149.



Stevens DA. Aspergillosis. In: Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co;1996:1830-32.



JOURNAL ARTICLES

Blyth CC, Palasanthiran P, O'Brien TA. Antifungal therapy in children with invasive fungal infections: a systemic review. Pediatrics. 2007;119:772-84.



Segal BH, Walsh TJ. Current approaches to diagnosis and treatment of invasive aspergillosis. Am J Respir Crit Care Med. 2006;173:707-17.



Pasqualotto AC, Denning DW. Post-operative aspergillosis. Clin Microbiol Infect. 2006;12:1060-76.



Ronning CM, Fedorova ND, Bowyer P, et al. Genomics of Aspergillus fumingatus. Rev Iberoam Micol. 2005;22:223-8.



Soubani AO, Chandrasekar PH. The clinical spectrum of pulmonary aspergillosis. Chest. 2002;121:1988-99.



Hoffman HL, Rathbun RC. Review of the safety and efficacy of voriconazole. Expert Opin Investig Drugs. 2002;11:409-29.



Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408-15.



Denning DW, Ribaud P, Milpied M, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis. 2002;34:563-71.



Granier F. Invasive fungal infections. Epidemiology and new therapies. Presse Med. 2000;29:2051-56.



Stevens DA, Schwartz HJ, Lee JY, et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med. 2000;342:756-62.



FROM THE INTERNET

Harman EM. Aspergillosis. Emedicine Journal, September 25, 2006. Available at: http://www.emedicine.com/med/topic174.htm Accessed on: July 20th, 2007.



Mayo Clinic for Medical Education and Research. Aspergillosis. May 3, 2007. Available at: http://www.mayoclinic.com/health/aspergillosis/DS00950 Accessed On: July 20th, 2007.

Resources

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