Blood and stool tests that assist in the diagnosis and treatment of inflammatory bowel diseases are essential tools for physicians. Often, when patients complain of abdominal pain and mild diarrhea, which are mostly caused by functional disorders such as irritable bowel syndrome, lactose intolerance, or temporary intestinal infections, doctors must determine whether to refer these patients for invasive tests such as colonoscopy and gastroscopy to rule out inflammatory bowel diseases like Crohn's disease and ulcerative colitis. The decision depends on the level of clinical suspicion.
These diseases sometimes manifest with atypical symptoms, leading to delayed diagnosis and treatment. Research has shown that the time to diagnose Crohn's disease can be around a year or even longer.
Blood tests measuring inflammatory markers, mainly C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR), are indirect indicators of inflammation but are not entirely accurate on their own. About a quarter of patients with mild inflammation in their inflammatory bowel diseases will have entirely normal blood test results (especially for ulcerative colitis). Assessing the precise level of inflammation in the intestines remains challenging, even in known cases of the disease.
Additional tests, such as calprotectin in stool and serology in blood, play a crucial role in evaluating inflammatory bowel diseases. Calprotectin is a protein released by inflamed cells in the intestines, and its level in stool can provide better insights than blood tests into the presence and severity of inflammation. Calprotectin is stable and can be measured in a stool sample kept refrigerated or frozen. In recent years, there has been a significant increase in the use of this test worldwide, even in Israel.
Calprotectin testing can serve three main purposes during diagnosis: first, it helps identify patients with gastrointestinal complaints who require further evaluation (e.g., colonoscopy or imaging). Second, it distinguishes between ulcerative colitis and Crohn's disease in cases of atypical inflammation in the large intestines (IBD-unclassified). Third, it can predict disease severity, where positive serological results in the blood may indicate a more aggressive disease course, with an increased risk of surgeries and hospitalizations. However, the test is not used for this purpose alone, as accurately estimating the risk and translating it into clinical practice for treatment decisions is still challenging.
Regarding serology in blood, there are specific markers such as ANCA (anti-neutrophil cytoplasmic antibodies) that are associated with ulcerative colitis and ASCA (anti-Saccharomyces cerevisiae antibodies) associated with Crohn's disease. While these tests are not highly accurate, positive results can aid in the diagnosis.
In summary, calprotectin and serology tests are valuable diagnostic tools in the hands of healthcare providers. When combined with other laboratory, radiological, and endoscopic tools, along with comprehensive clinical assessment, they help build a more comprehensive picture of the presence and severity of inflammation in the intestines, assisting in accurate diagnosis and personalized treatment decisions for each patient.
Tests for administering thiopurines (Imuran and Purinethol):
What is it?
Imuran and Purinethol are medications that suppress the activity of the immune system, thereby reducing excessive immune response in the gut. These drugs start working after 2-4 months of intake, and their effectiveness is mainly seen in maintaining remission rather than inducing it. They break down in the body into two main substances: 6TG, which is the active component but can cause side effects such as a decrease in blood cell count, and 6MMP, which is an inactive substance and can lead to liver function issues. The levels of these substances, among others, are determined by an enzyme called TPMT. After starting the medication, frequent blood tests are necessary to ensure treatment safety. It's important to emphasize that in most cases, the drug's efficacy in controlling the disease outweighs the risk of possible side effects. TPMT enzyme activity can be checked before starting treatment to predict some of the risk for side effects. This can be assessed through genetic testing or enzymatic activity testing. Genetic markers can be tested at various medical centers, but in Jews, only about a third of those with low activity will test positive for the genetic markers. Additionally, the enzymatic activity test, as opposed to genetics, allows the identification of patients with too high enzyme activity, which may indicate that the drug could be ineffective or cause liver function impairment. After initiating treatment, the levels of 6TG and 6MMP in the blood can be measured to determine whether the dosage should be increased, or decreased, or if the drug is not suitable for the patient.
When is it advisable to undergo this test?
Routine TPMT testing is done in the US before starting treatment with Imuran or Purinethol, but it is not mandatory in Israel and is not covered by the health basket. In European countries, the frequency of this test varies from one country to another, with some countries making it a routine practice and others less so. The results help in determining the dosage, deciding on the optimal treatment, and establishing the frequency of blood tests after treatment initiation. Regarding the measurement of drug levels (6TG and 6MMP), it can be particularly helpful in cases where there is a suspicion of side effects (such as unexplained liver function impairment, decreased blood cell count, or different clinical manifestations like hair loss) or when the clinical effect of the drug is only partial and one wants to directly assess the level of active substance in the body. The test can also identify patients who are not taking the medication regularly.
Is it reliable?
Genetic TPMT testing is reliable when positive but not when negative (since only about a third of cases of low enzyme activity are associated with a positive genetic response). The advantage of genetic testing is that it is not affected by drug administration and can be performed even while the patient is taking Imuran/Purinethol (unlike enzymatic testing). On the other hand, the enzymatic testing of TPMT activity identifies additional populations at risk and detects excessively high enzyme activity. It is essential to emphasize that a valid result does not completely eliminate the risk of side effects, and close medical and laboratory follow-up is necessary. Measurement of drug levels (6TG and 6MMP) is reliable when abnormal results are obtained. In such cases, the results can be relied upon for treatment planning.
Tests for guiding treatment with biological drugs of the TNF inhibitors class (Remicade and Humira):
What is it?
Remicade and Humira are artificial antibodies designed to neutralize an inflammatory molecule called TNF. The treatment is somewhat similar to a guided missile that targets a specific objective without affecting parallel processes. These biologics are considered highly effective both in inducing and maintaining remission in conditions like Crohn's disease and ulcerative colitis and can also promote inflammation resolution in the gut and encourage growth in children. However, there are cases where the medication becomes less effective over time, mostly due to the body breaking down the drug as it recognizes it as a foreign protein (the drug is a foreign antibody to the body). The drug level and the presence of antibodies against the drug can be measured in real-time, just before giving the medication. The drug levels can help determine the dosage and whether it is appropriate to switch to an alternative treatment. This test is carried out at several centers, such as Tel Hashomer, Ichilov, and Rambam.
When is it advisable to undergo this test?
There is evidence that drug levels provide a higher likelihood of predicting response to treatment over time. If the drug level is found to be low, increasing the dosage may prevent the loss of response. We primarily request this test in cases where there is no satisfactory clinical improvement or when there was improvement initially but it was lost over time. Over time, the use of these tests is gradually increasing as the information regarding drug levels may assist in optimal treatment planning, even during remission.
Is it reliable?
The test is relatively reliable, especially when obtaining a clear abnormal result (e.g., the absence of the drug in the blood and the presence of large amounts of antibodies).