Autoimmunity

Autoimmune lung disease

There are multiple causes of lung disease in individuals with PI including infection, malignancy, and autoimmunity. Differentiating between these can be difficult. In most cases of lung disease, the autoimmunity is not due to formation of an antibody, but an abnormal accumulation of white blood cells in the lung tissues, causing inflammation and damage.

Sometimes white blood cells accumulate in a specific part of the lung known as the interstitium, which is the site where oxygen is taken up from the lung to the bloodstream. Too many white blood cells in the interstitium can cause a disease called interstitial lung disease, in which the ability of oxygen to be absorbed into the bloodstream is impaired.

Some individuals with certain types of PI develop clusters of immune cells in the lung, called granulomas. Granulomas are sometimes formed in an attempt to contain an infection that cannot be resolved, or because the immune cells are not being regulated properly, a situation that sometimes occurs in PI. Two types of PI that often have granulomas in the lung are chronic granulomatous disease (CGD) and CVID.

Individuals with CVID sometimes develop both interstitial lung disease and granulomas in the lung. This disease is called granulomatous lymphocytic interstitial lung disease (GLILD). Recent studies show GLILD can also occur in other rare forms of PI that are similar to CVID.

Occasionally, individuals with ataxia-telangiectasia or APECED will develop a different type of interstitial lung disease, which can also decrease the ability of the lung to absorb oxygen. Without proper treatment, the inflammation caused by interstitial lung disease can be so severe that it will cause scarring (fibrosis) of the lung and permanently impair the ability of the lung to absorb oxygen.

Symptoms of autoimmune lung disease

In most cases, the symptoms of interstitial lung disease develop slowly over time. Individuals with CGD can develop symptoms more quickly due to an infection causing lung inflammation. Individuals may notice a decrease in their endurance with every day activities. They may find themselves having to cut back on exercise, such as biking or running. These changes are often attributed to other causes, which may delay the diagnosis of the lung disease.

Individuals often complain of a cough, which is usually non-productive (i.e., brings up no phlegm). Enlargement and rounding of the toenails and fingernails, termed clubbing, is not specific to PI or to lung damage, but they are a clue that the lungs should be evaluated. In some cases, the lung damage can lead to a severe lowering of blood oxygen causing individuals to have a bluish tint to their skin or mucous membranes. This is known as cyanosis. Fever is not a typical finding, unless infection is also present.

On the lung exam, a healthcare provider may hear abnormal breath sounds such as crackles, wheezes, or a decrease in the amount of air moving in and out of the lung with breathing. Often these symptoms lead to the incorrect diagnosis of asthma or a lung infection by physicians not familiar with autoimmune lung diseases in PI.

Diagnosing autoimmune lung disease

Chest X-rays are useful for diagnosing infections (pneumonia). A chest X-ray can sometimes be normal, however, even when there is still significant lung disease present. A chest CT scan is a much better test to detect lung abnormalities even when the chest X-ray is normal. In individuals with CVID and GLILD, changes on the chest CT scan will often appear before the patient has symptoms.

Breathing tests, called pulmonary function tests (PFTs), can demonstrate how well the lungs are working. Changes in PFTs can be found in interstitial lung disease and other types of lung disease. However, individuals often must lose a significant amount of lung function to show symptoms that lead to ordering of the PFTs.

In some cases, a lung biopsy is needed to make the correct diagnosis and define the correct treatment course. A lung biopsy is a surgical procedure usually done by making a small incision in the chest and inserting a small scope and instruments to obtain a piece of lung tissue. The lung biopsy is evaluated by a pathologist, a doctor who performs a variety of tests on the lung tissue, including a microscopic examination. The tests performed by the pathologist can determine the specific type of lung disease that is present, such as cancer, infection, interstitial lung disease, or granuloma.

Treating autoimmune lung disease

Inflammatory changes in the lung are usually treated with drugs that suppress or alter the immune system. The most common medicine used is corticosteroids (like prednisone), which can be given through an inhaler, by mouth, or intravenously (IV). Steroids can be effective but may not provide long-term improvement. Steroids can also cause side effects such as high blood pressure, high blood sugar, osteopenia (weak bones), hyperlipidemia (high cholesterol), and stress on the kidney and eyes if used for a long period of time.

Other immune suppressive medicines, such as cyclosporine and sirolimus, are sometimes helpful. Some types of lung disease respond to one type of immunosuppressant medication but not another. IVIG, in addition to other drugs, can sometimes improve the inflammation in the lungs.

Without treatment, interstitial lung disease can progress and cause permanent lung damage. Fibrosis cannot be reversed. It is very important that your doctor has the correct diagnosis of your specific lung disease and expertise in treating the disorder in order to ensure the best outcome.

Diagnosing gastrointestinal disease

The diagnosis of gastrointestinal disorders in PI often requires a combination of approaches. Individuals will undergo a physical exam, laboratory tests on blood and stool, and radiology tests. Physical exam findings may include oral or anal ulcers, abdominal tenderness, fluid in the abdomen (ascites), enlargement or tenderness of the liver, cracks or fissures around the anus, weight loss, and poor growth for children.

Laboratory tests include a complete blood count and an examination of the stool to determine whether the individual may be losing blood through the stomach or intestines. Lab tests will measure inflammation with a C reactive protein (CRP) and erythrocyte sedimentation rate (ESR); albumin and pre-albumin levels as a rough measure of nutritional status; and AST, ALT, and bilirubin levels as a measure of liver irritation.

To evaluate for a bowel infection, testing of the stool is performed to identify bacteria or viruses. Samples of stool are also stained and evaluated under the microscope for the presence of specific parasites or other organisms.

Radiologic tests that may be helpful include an abdominal X-ray, abdominal and liver ultrasounds, and a CT scan of the abdomen after contrast material has been swallowed. Sometimes, the only way to make a diagnosis of either bowel or liver inflammation is to obtain a piece of tissue that can be evaluated under the microscope by a pathologist. For certain conditions, the physician may want to pass a scope into the esophagus, stomach, and intestines to directly see those areas. They may also perform biopsies and other tests in the liver. This is done by obtaining a small piece of liver tissue with a biopsy needle inserted through the skin and into the liver. Both of these procedures are typically done by a gastroenterologist, a doctor who specializes in the treatment of intestinal disorders.

Treating autoimmune gastrointestinal disease

In general, immunosuppressant medications are used to treat autoimmune or inflammatory disorders of the bowel in most individuals with PI. The treatment plan has to balance the risks of the treatment against the risks of the disease. It may be helpful to work with a nutritionist to provide advice about an appropriate diet and vitamins. In some cases, including the bowel disease associated with CVID or CGD, steroids are often the first line of therapy, and in many cases, they may be sufficient to control symptoms. In contrast, the severe bowel disease associated with IPEX syndrome or Omenn syndrome typically requires stronger immunosuppressive medications. For individuals with PI who have significant gastrointestinal symptoms, it is essential to have a gastroenterologist involved to assist with diagnostic testing and directing treatment.

Diagnosing endocrine complications

Diagnosis of thyroid autoimmunity is typically made by a series of blood tests to identify abnormal levels of thyroid hormone. The identification of specific autoantibodies in the blood is helpful in confirming that the process is autoimmune in nature.

T1D is typically diagnosed by checking the urine for the presence of glucose (sugar) and checking the blood for elevated glucose levels. If these do not decrease as expected after eating or if they are high even when a patient is fasting, then diabetes may have developed. Identification of autoantibodies directed against the islet cells can help confirm that the process is autoimmune.

Treating autoimmune endocrine disease

In general, most autoimmune endocrine disease leads to a deficiency of very important hormones that are supposed to be made by the endocrine organs. Treatment typically involves administering replacement hormone to try to achieve normal levels. For hypothyroidism, additional thyroid hormone can be taken as a pill. Treatment of T1D typically involves giving insulin either via shots or an insulin pump. Even though T1D is autoimmune-mediated, it is not yet clear whether the use of immunosuppressive drugs early in the course of disease changes the need for insulin treatment or not.

In the case of the thyroid, autoimmunity can also cause increased function, which requires removal or destruction of at least part of the gland to correct the problem. This may require surgical removal of part of the thyroid, radiation treatment to the thyroid gland, or use of other drugs. This is always done under the direction of an endocrinologist.

Living with autoimmunity

Significant autoimmune or inflammatory disease is common among individuals with PI. Early recognition and treatment of these symptoms is critical for optimizing quality of life and decreasing complications associated with PI. This requires that individuals and their healthcare providers be aware of signs and symptoms that may suggest an autoimmune disease, and that appropriate diagnostic testing and treatment be initiated in a timely fashion.

Maintaining a balance between the immunosuppression used to control the autoimmune process, while avoiding compounding the immune deficiency of the underlying PI, requires close cooperation between the individual with PI (and/or their caregiver) and the various specialists involved in their care. Treatment may require frequent dosage adjustments or changes in overall approach to reach the desired balance.