Diagnostic Procedures:
• Blood chemistry tests and cell counts.
• Analysis of urine, both chemistry and microscopic.
• Imaging tests such as x-ray, MRI, and CT scan, which show lung infiltrates or nodules typical of granulomatosis or vascular tissue damage.
• A CT virtual bronchoscopy can help identify stenosis and larynx problems.
• Digital subtraction angiograpy (DSA) may be useful in identifying stenosis or other abnormalities caused by vasculitis.
• Biopsy of the suspected granuloma and/or blood vessels or other affected tissues.
• Biopsies may be required of tissues where there is persistent inflammation problems in one or more of the following organs, as listed below starting with the most frequent:
Sinus, nose, ear, throat, lung, joints, fever, kidney, trachea, eye, skin, peripheral nerves, inflammation of the heart lining, central nervous system, and very rarely heart, pancreas, spleen, prostate, liver, testicles
Angiography:
Angiography is a way to produce X-ray pictures of the inside of blood vessels. When blood vessels are blocked, damaged or abnormal in any way, chest pain, heart attack, stroke or other problems may occur. Angiography helps your physician determine the source of the problem and the extent of damage to the blood vessel segments that are being examined.
Biopsy:
A biopsy is a small tissue sample that is examined by a pathologist for abnormalities. Some things to be aware of:
1. Biopsies are usually done under local anesthetic, excepting for open lung biopsies which require a general anesthesia.
2. Negative sinus biopsies are notoriously unreliable because it is such a problem to get the correct tissue sampled.
3. Kidney biopsies are generally rather trouble free and involve minimal intrusiveness if done by the guided-needle method.
4. Lung biopsies may be either by guided-needle or an open-lung surgical method. The open lung is major surgery and probably to be avoided if possible.
5. Some physicians insist on an open lung biopsy. It might be best to get a second opinion on the necessity for that method before proceeding.
6. More than once, a lung granuloma as been incorrectly identified as lung cancer. It may be prudent to have the tissue sample submitted to a different pathologist in a different hospital for evaluation.
Different types of blood tests are described in more detail at the links below.
ANCA Test: (Anti-Neutrophil Cytoplasmic Antibody test)
This test is highly specific for certain autoimmune diseases affecting blood vessels (Churg-Strauss Syndrome, Microscopic Polyangiitis and Wegener's Granulomatosis). It is done by separating out neutrophils (one type of white blood cell) and staining them with a dye that will fluoresce when exposed to ultra-violet light. The illuminated neutrophils are then examined by microscope to determine the character of the fluorescing granules in the neutrophils.
One of four findings may result from the ANCA tests:
1. A test result where the fluorescent granules are scattered in the cytoplasm of neutrophils (positive cytoplasmic or C-ANCA)
2. A test result where the fluorescent granules are mostly near the nucleus of neutrophils (positive perinuclear or P-ANCA).
3. A test result where the fluorescent granules are diffuse, both in the cytoplasm and near the nucleus (positive mixed ANCA).
4. A negative ANCA where so little fluorescence is present, it falls below the upper limit of normal.
Points to consider about ANCA:
1. The upper limit of normal C-ANCA ratio varies from lab to lab. The upper normal limit for the test result to be considered a negative may be about 1:16 or 1:32.
2. The C-ANCA test is about 90+% accurate for WG for serious cases, but only 50% or so for light cases).
3. Not all medical labs do the test, so frequently it is a 'send-out' test. A tentative diagnosis made by positive C-ANCA is often confirmed by biopsy.
4. The related P-ANCA test if positive may be an indicator for some other autoimmune diseases, e.g., microscopic polyarteritis (MPA), Churg-Strauss Syndrome (CSS), or crescentic glomerulonephritis.
5. In the case of mixed ANCA, it may require other tests and analysis of symptoms to determine if the cause of the abnormality is vasculitis or some other condition.
6. The C-ANCA and P-ANCA are immunofluorescent (IIF) tests requiring a human microscopic examination and interpretation. Results may vary if different individuals are doing the test. It is best to have these and other tests done at the same lab each time to reduce the possible variations.
7. While a positive C-ANCA is highly diagnostic for Wegener's, some small percentage of Wegener's patients test P-ANCA positive, rather than C-ANCA. Occasionally a Wegener's patient will switch at times from testing positive to one ANCA to the other.
8. ANCAs are titrated tests. Stained blood samples are diluted in steps, progressively until no fluorescence is detected. Results are reported as the dilution level at which fluorescence ceases. These are given as 1:256 or 1/256 for example. The higher the ANCA ratio, the more of the harmful antibodies are present in the patient's blood.
9. ANCA test results can be positive due to conditions other than autoimmune diseases. Amebiasis, ulcerative colitis, mesangiocapillary glomerulonephritis with crescents, improperly cleaned glassware, and both subacute and bacterial endocarditis have been shown to cause transient positive ANCAs.
10. ANCA test samples can show differing results if submitted to different labs. An effort to standardize these tests is underway in Europe by the EUVAS group. False positives or negatives can and do occur due to mishandling or misinterpretation or even effects of medications or other disease conditions.
11. In diagnosis both C-ANCA by immunofluorescence and anti-PR-3 by ELISA result in greater sensitivity than either test alone, and are often both are performed even if only the C-ANCA is ordered.
C Reactive Protein (CRP) :
C-reactive protein is a test that measures the concentration of a protein in serum that indicates acute inflammation.
Complete Blood Counts (CBC):
The complete blood count (CBC) is a very common blood test. It evaluates the three major types of cells in blood: red blood cells, white blood cells, and platelets.
Red Blood Cells (RBC) carry oxygen from the lungs to the rest of the body. Three tests measure red blood cell (RBC) count:
1. The red blood cell count is a measure of the number of RBCs in the body.
2. Hemoglobin is the oxygen-carrying protein in red blood cells. RBCs carry oxygen to all parts of the body.
3. MCV measures the average size of the red blood cells.
4. Other factors analyzed include the hematocrit (HCT), which is the percentage of red blood cells in the blood sample. If a child has anemia, the results for RBC, hemoglobin, and hematocrit will all be low.
White Blood Cells (WBCs) help the body fight infection. Also called leukocytes. These cells are bigger than red blood cells, and there are far fewer of them in the bloodstream. An abnormal white blood cell count may indicate that there is an infection, inflammation, or other stress in the body. For example, a bacterial infection can cause the WBC count to increase or decrease dramatically. There are five types of white blood cells: neutrophils, lymphocytes, eosinophils, basophils, and monocytes. Each has a different job.
1. Neutrophils and lymphocytes are the two major types of WBCs. Neutrophils play a key role in the body's defense against invading bacteria by destroying invading organisms. Someone with insufficient neutrophils is at risk for developing serious infections.
2. Lymphocytes produce antibodies, specific proteins that attack and help destroy specific germs. They are especially important in fighting viral infections, like colds and flu.
3. Eosinophils and basophils in the blood may be increased in allergic conditions. (Churg-Strauss patients have high #s of eosinophils.)
4. Monocytes, the largest white blood cells in the bloodstream, remove dead cells and organisms from the blood.
The Platelets are the smallest blood cells. They play an important role in blood clotting and the prevention of bleeding. When a blood vessel is damaged or cut, platelets clump together and plug up the hole until the blood clots. If the platelet count is too low, a person can be in danger of bleeding in any part of the body.
Erythrocyte (Red cell) Sedimentation Rate (ESR or SED):
ESR (erythrocyte sedimentation rate) is a nonspecific screening test for various diseases. This 1-hour test measures the distance (in millimeters) that red blood cells settle in unclotted blood toward the bottom of a specially marked test tube.
Bronchoscopy:
A bronchoscope is device used to see the lungs. It can be flexible or rigid. Usually, a flexible bronchoscope is used. The flexible bronchoscope is a tube less than 1/2 inch wide and about 2 feet long.
The scope is passed through your mouth or nose, and then into your lungs. Going through the nose is a good way to look at the upper airways. The mouth method allows the doctor to use a larger bronchoscope.
A rigid bronchoscope requires general anesthesia. You will be asleep. If a flexible bronchoscope is used, you will be awake. The doctor will spray a numbing drug (anesthetic) in your mouth and throat. This will cause coughing at first, which will stop as the anesthetic begins to work. When the area feels thick, it is sufficiently numb. Medications may be given through an IV to help you relax.
If the bronchoscopy is done through the nose, numbing jelly will be place into one nostril. Once you are numb, the tube will be inserted into the lungs. Then, the doctor sends saline solution through the tube. This flushes the lungs and allows the doctor to collect samples of lung cells, fluids, and other materials inside the air sacs. This part of the procedure is called a lavage.
Sometimes, tiny brushes, needles, or forceps may be passed through the bronchoscope and used to take tissue samples (biopsies) from your lungs. A doctor can also place a stent in the airway or view the lungs with ultrasound during a bronchoscopy.
Imaging Tests:
Imaging tests will be used to assess organ damage as well as lung infiltrates or nodules.
X-rays use electromagnetic radiation to make images of your bones, teeth and internal organs. Tests may be done for sinus, lungs, head, kidneys and others as required.
Computed Tomography (CT) scans are generally preferable to x-rays because of their considerably greater detail and diagnostic utility, and are not significantly more expensive than x-rays. There is greater radiation exposure so the number of CT scans should be only those required.
Magnetic Resonance Imaging (MRIs) may be done for soft tissues where x-rays and CT scans are not always useful and are particularly useful in identifying vascular inflammations in the brain.
Digital Subtraction Angiography may be useful in identifying and monitoring blood vessel abnormalities.
Videostroboscopy may be useful in imaging the trachea and glottus.
Pathergy Test:
The pathergy test is helpful in diagnosing Behcet's Disease although not 100% specific. It is a simple test in which the forearm is pricked with a small, sterile needle. Occurrence of a small red bump or pustule at the site of needle insertion, 1 to 2 days after the test, constitutes a positive test. Although a positive pathergy test is helpful in the diagnosis of Behçet's disease, only a minority of Behçet's patients demonstrate the pathergy phenomenon (i.e., have positive tests). Patients from the Mediterranean region are more likely to demonstrate a positive response to a pathergy test. However, only 50% of patients in Middle Eastern countries and Japan have this reaction. This reaction is even less common in the United States. In addition, other conditions can occasionally result in positive pathergy tests, so the test is not 100% specific.
Urine Chemistry Tests:
Your kidneys are bean-shaped organs, each about the size of your fist. They are located near the middle of your back, just below the rib cage. The kidneys are sophisticated reprocessing machines. Every day, your kidneys process about 200 quarts of blood to sift out about 2 quarts of waste products and extra water. Creatinine is a waste product in the blood created by the normal breakdown of muscle cells during activity. Healthy kidneys take creatinine out of the blood and put it into the urine to leave the body. When kidneys are not working well, creatinine builds up in the blood.
Urine chemistry is checked for:
Blood Component Normal Values**
Nitrite Negative
PH (Acid/Alkaline) 5.0 to 8.0
Protein # Negative
Glucose Normal or negative
Ketones Negative
Urobilinogen Normal or negative
Bili Qual Negative
Blood Negative
Red Blood Cells Less than 1 per HPF
White Blood Cells 2 per HPF
**Measured values can vary from normal due to disease, medications, or medication interactions.
Urine Microscopic Tests:
Urine is checked for the following:
Cell abnormalities
White blood cells
Red blood cells
Transitional epithelial cells
Squamous epithelial cells
Renal tubular epithelial cells
Fat Globules and Oval Fat Bodies
Microorganisms:
• Yeast
• Bacteria
• Trichomonas vaginalis
• Clinically Significant Casts
• Tamm-Horsfall protein
• Crystals (Most crystals are not clinically significant)
• Crystals may be counted if abnormal.
• Abnormal crystals may indicate pH problems
• Miscellaneous Elements and Artifacts
• Mucus
• Sperm
• Artifacts
X-rays:
X-rays are a form of electromagnetic radiation, just like visible light. In a health care setting, x-rays are emitted by a machine as individual "particles" (photons) that pass through the body and then get detected by a sensitive film.
Structures that are dense (such as bone) will block most of the photons, and will appear white on developed film. Structures containing air will be black on film, and muscle, fat, and fluid will appear as shades of gray. Metal and contrast media (intravenous or oral contrast) blocks almost all the photons and will appear bright white.
The basic science of x-ray generation and detection is the key behind general radiographs of the body, mammography, fluoroscopy (real-time imaging on video screens), and computed tomography (CT).