Home » Alpha-1 » What conditions can be associated with Alpha-1?
Through the years, there are a number of rare illnesses that have been identified as being associated with Alpha-1. In some cases, the relationship between a particular disease and Alpha-1 is not well established. Just because a rare disease occurs in one or two individuals with Alpha-1, this alone does not mean that Alpha-1 caused the disease.
Big Fat Reference Guide – AlphaNet
There are several other conditions that have been associated with Alpha-1. These include necrotizing panniculitis, a painful scarring skin condition; vasculitis, an inflammation of the blood vessels; granulomatosis with polyangiitis (formerly known as Wegener's Granulomatosis), an unusual type of vasculitis affecting the lungs; bronchiectasis, a distortion and destruction of the bronchial tubes leading to chronicA condition or illness that arises slowly over days or weeks and may or may not resolve with treatment. It is the opposite of acute. More infection; and hepatocellular carcinoma, a cancer of the liver cells. There is some statistical evidence of an association with certain types of arthritis. There may be other conditions associated with Alpha-1 that we haven't learned of yet.
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necrotizing panniculitis, a painful skin condition characterized by discoloration of the skin, large eruptions, and scarring. This condition appears to be related to an inflammation of the blood vessels under the skin leading to death of the overlying skin. This condition is classified as a "vasculitis," an inflammatory condition of the blood vessels. The condition is known to respond well to intravenous augmentation therapy.
Big Fat Reference Guide – AlphaNet
Read more about panniculitis here.
One of a number of diseases known as vasculitis or inflammation of the blood vessels. Wegener's granulomatosis is unique in that it primarily affects the lungs and the kidneys. In the lungs, it can cause inflammatory nodules known as granulomas. There is a growing appreciation that Alpha-1 may play a role in this condition.
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Another form of vasculitis associated with Alpha-1 is a condition called Granulomatosis with polyangiitis (formerly known as Wegener's Granulomatosis). Granulomatosis with polyangiitis causes nodules to develop in the lung and other parts of the body. It is not known whether augmentation therapy is beneficial in this condition.
Big Fat Reference Guide – AlphaNet
Is there a connection between Alpha-1 and bronchiectasis? When should patients with bronchiectasis be treated with antibiotics?
The connection between Alpha-1 and bronchiectasis is 1) statistical, and 2) biochemical. The statistical association is that, while virtually all non-Alpha-1 bronchiectasis has an identifiable cause (most commonly: severe childhood [or adult] lung infections, immune deficiency, congenital abnormalities, fungal infections of the airways), people with Alpha-1 seem to have a higher-than-expected incidence of bronchiectasis and, in many cases, have no other reason to explain why they have it. There is much written in medical literature regarding the association between bronchiectasis and Alpha-1.
The biochemical association is somewhat theoretical. Since we know that alpha-1 antitrypsin blocks some of the destructive enzymes of the body's white blood cells, and since we know these enzymes can damage the structural proteins of the bronchi, it is not a large leap to postulate that the reason people with Alpha-1 get bronchiectasis has to do with bronchial damage caused by white blood cell enzymes. Why some Alphas get bronchiectasis and others do not is an unanswered question. Perhaps it has to do with the number of bronchial infections that an Alpha gets during their life.
Since patients with symptomatic bronchiectasis generally always have infected sputum, the best way to decide whether it's time to treat with antibiotics is when there is a change in the clinical status of the patient (more short of breath, increased sputum, change in the color or consistency or odor of the sputum). The chronicA condition or illness that arises slowly over days or weeks and may or may not resolve with treatment. It is the opposite of acute. More use of prophylactic or suppressive antibiotics, especially by inhalation, has been advocated in patients with severe recurrent infections caused by bronchiectasis.
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Rapidly growing mycobacteria (RGM) are ubiquitous in the environment but cause lung disease in only a fraction of exposed individuals. This variable susceptibility to disease implies vulnerability to RGM infection due to weakness in host defense. Since most persons who contract RGM lung disease have no known host defense defect, it is likely that uncharacterized host deficiencies exist that predispose to RGM infection. Alpha-1-antitrypsin (AATalpha-1 antitrypsin More) is a host factor that may protect individuals from respiratory infections. Therefore, we assessed AATalpha-1 antitrypsin More protein anomalies as a risk factor for RGM lung disease. In a cohort of 100 patients with RGM lung disease, Mycobacterium (M.) abscessus was the most prevalent organism, isolated in 64 (64%) subjects. Anomalous AATalpha-1 antitrypsin More proteins were present in 27% of the cohort, which is 1.6 times the estimated prevalence of anomalous AATalpha-1 antitrypsin More proteins in the United States population (p=0.008). In in vitro studies, both AATalpha-1 antitrypsin More and a synthetic inhibitor of serine proteases suppressed M. abscessus infection of monocyte-derived macrophages by up to 65% (p<0.01). AATalpha-1 antitrypsin More may be an anti-RGM host-defense factor, and anomalous AATalpha-1 antitrypsin More phenotypes or AATalpha-1 antitrypsin More deficiency may constitute risk factors for pulmonaryMedical term referring to the lungs. More disease due to RGM.
Alpha-1-antitrypsin (AAT) anomalies are associated with lung disease due to rapidly growing mycobacteria and AAT inhibits Mycobacterium abscessus infection of macrophages – National Library of Medicine
There is recent evidence that individuals with Alpha-1 are more susceptible to infections caused by an unusual group of germs known as atypical mycobacteria. This type of germ is a relative of the organism that causes tuberculosis. Fortunately, these infections are clinically uncommon although many of us carry some of these germs in our lungs every day.
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A brief word about liver cancer needs to be included. There is a definite increased risk of primary cancer of the liver (hepatocellular carcinoma). This is a rare form of liver cancer that is rare even in individuals with Alpha-1-–it’s just not as rare in Alpha-1 as it is in the general population. This cancer happens at increased rates in all individuals who have scars in the liver. Cancers also are seen more frequently if the body is immune suppressed with transplant medications. The fastest growing hepatocellular carcinomas still do not grow very fast and they rarely metastasize out of the liver. The primary cure for this cancer is a surgery to remove the cancer nodule from the liver.
This surgery can be done if the cancer is small and does not involve critical structures inside the liver. For this reason, some experts recommend a liver ultrasound every 6 months to screen for a small cancer that can be cut out for a cure if found. Other liver experts would suggest that the right interval is yearly, and only if significant scar is present in individuals over age 50. Importantly, there is no study that has been done to define the best interval and each center may have different suggestions.
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Individuals with Alpha-1-related liver disease are at increased risk of developing a type of liver cancer known as hepatocellular carcinoma. This increased risk for hepatocellular carcinoma also is seen in individuals with other diseases that cause scar tissue in the liver. Therefore, this form of cancer is probably not caused by Alpha-1, but rather from having severe liver scarring.
Big Fat Reference Guide – AlphaNet
Other conditions that may be associated with Alpha-1 include rheumatoid arthritis and lupus erythematosus (an autoimmune disease). A clear relationship between Alpha-1 and these conditions has not been established, and it may well be that Alpha-1 does not lead to an increased risk for developing any one of these conditions. Instead, it may be that when an individual who happens to have Alpha-1 also develops one of these conditions, they may suffer more severe symptoms.
Big Fat Reference Guide – AlphaNet
PI MZ carriersAn Alpha-1 Carrier is a person who has one normal ATT gene (M) and one defective AAT gene (usually S or Z). It does NOT mean you cannot get sick. More have an increased incidence of gallstone disease34 and an increased susceptibility to immune disorders such as ANCA-associated vasculitis...
Although the mechanisms leading to lung or liver disease in PI MZ carriers are probably analogous to those identified in PI ZZ carriers, the factors leading to the increased incidence of gallstones in PI MZ carriers remain to be determined."
Alpha-1 Antitrypsin Deficiency - The New England Journal of Medicine
• Elastase is a pancreatic enzyme.
• Increased elastase due to alpha-1-antitrypsin deficiency can cause chronic pancreatitis.
• Chronic pancreatitis leads to steatorrhea, malabsorption, vitamin deficiency (A, D, E, K, B12), diabetes and weight loss.
Alpha-1 antitrypsin deficiency panniculitis - DermNet NZ
A lack of Alpha1-antitrypsin in patients with rheumatoid arthritis could allow inflammation to increase because of uninhibited lysosomal enzymes.
Mini Review: Alpha 1-antitrypsin and Its Involvement In Rheumatoid Arthritis
The genetic types of alpha1-antitrypsin (Pi types) were studied in 55 adults with classical or definite rheumatoid arthritis and 56 children with juvenile rheumatoid arthritis. A comparison was made with control groups of 211 healthy adults and 512 schoolchildren. Pi types MZ and SZ were significantly more prevalent in adults with rheumatoid arthritis than in the control adults. There was no difference between the patients with juvenile rheumatoid arthritis and the control children. Reduced concentrations of alpha1-antitrypsin, as associated with heterozygotes for the Z allele, may be a contributory factor to the development of rheumatoid arthritis or to the tissue destruction of rheumatoid arthritis.
Rheumatoid arthritis and alpha-1-antitrypsin - NCBI
PI MZ carriersAn Alpha-1 Carrier is a person who has one normal ATT gene (M) and one defective AAT gene (usually S or Z). It does NOT mean you cannot get sick. More have an increased incidence of gallstone disease and an increased susceptibility to immune disorders such as ANCA-associated vasculitis. Particularly high odds were reported for disorders associated with myeloperoxidase-reactive ANCA with perinuclear staining (p-ANCA) and those associated with proteinase 3–reactive ANCA with cytoplasmic staining (c-ANCA). ANCAassociated vasculitis can occur with other AATalpha-1 antitrypsin More variants such as the S allele and may represent a loss-of-function phenotype, since proteinase 3 is a target protease for AATalpha-1 antitrypsin More.
Alpha-1 Antitrypsin Deficiency - The New England Journal of Medicine
