What conditions can be associated with Alpha-1?

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.

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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.

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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