Consider the following case scenarios, discuss the biopsychosocial domains of the patient, and outline a management plan. Case Study Audrey is a 30-year-old lawyer with Crohn’s disease maintained in remission with Infliximab and azathioprine. She is 16 weeks pregnant. Her husband has ulcerative colitis in remission. They consult with you for information regarding the following: […]
The primary constituents of inflammatory bowel disease (IBD) are Ulcerative Colitis (UC) and Crohn’s Disease (CD). The incidence rates for CD and UC in Western countries have increased over the last four decades.1 The same trend has also been observed in developing countries, although it is less pronounced.1 Signs and symptoms that are common to both Crohn’s disease and ulcerative colitis include diarrhea, fever and fatigue, abdominal pain and cramping, blood in stool, reduced appetite, and unintended weight loss.6 The hallmark of IBD is chronic, uncontrolled inflammation of the intestinal mucosa, which can affect any part of the gastrointestinal tract.2 What distinguishes IBD from inflammatory responses seen in the normal gut is the inability to downregulate those responses- an individual with IBD lives in a state of chronic inflammation.2
Crohn’s disease is characterized in the literature as a progressive, systemic autoimmune disorder marked by abnormal inflammation of the GI tract. Any part of the GI tract can be affected, from the mouth to the anus.3 In patients with Crohn’s disease, the epithelial-lined mucosal layer often increases in permeability, allowing pathogens to permeate through to the mucosal layers beneath with less resistance. The ending result is an inflammatory response to the pathogens, which trigger antigen receptors.3
Ulcerative Colitis shares a similar pathology and inflammation profile to Crohn’s; however, it exclusively affects only the colon’s inner lining.5 Additionally, selective genetic subtleties can further distinguish the two. The number of genes differentially expressed is rather large; about 378 genes are unique to CD, 150 genes are unique to UC, and 122 genes are differentially expressed in both groups.
Safety of the medications during pregnancy and delivery:
Audrey mentioned that she was maintaining her Crohn’s disease with Infliximab and azathioprine. I’m glad that she has inquired about any potential contraindications because, at times, the consequences of taking a contraindicated drug during pregnancy can be grave. In her case, however, the biologic she is taking, Infliximab, is considered low risk with respect to pregnancy. Available evidence has suggested that infliximab carries low fetal risk and is compatible with use during conception and in the first two trimesters of
pregnancy.8 However, it has been established that infliximab readily crosses the placenta at high levels in the late second and third trimesters. This is important because while pregnant mothers commonly take Infliximab, and no fetal abnormalities have been observed in the literature, there is little data on the long-term implications and risk of early exposure on a child’s development.7,9 Because of this, doctors take extra precautions and are recommended to stop administering the drug after thirty weeks’ gestation.9 If necessary, the expectant mother can be bridged with steroids to control disease activity until delivery, and then she may return to her normal regimen.9 Azathioprine, an immunomodulator, is also considered low-risk during pregnancy when administered at its standard dose.6 Hopefully, this information will put Audrey at ease. Nonetheless, she must still discuss this topic with her doctor to ensure that she takes the safest precautions.
Can she breastfeed if she is taking these medications:
Breastfeeding plays a crucial role in a child’s health; it boosts immunity, reduces the risk of certain diseases, and promotes beneficial gut flora changes. Once again, I’m glad she asked this question, as most drugs pass into human milk, and the effect can be devastating to a young baby. With that said, the vast majority of medications can be taken without harm.
In this case, Infliximab has been established as generally safe to use in pregnancy, as it is not excreted in breast milk in any clinically significant amount.9 The clinical data shows no significant difference in pregnancy outcomes of patients exposed to infliximab during pregnancy compared to the healthy population.9
Azathioprine, on the other hand, has been contraindicated in breastfeeding women. The theoretical potential risks include bone marrow suppression, infection susceptibility, and the neonate’s pancreatitis.10 However, studies have shown conflicting results, so in this case, it is important to weigh the benefits and risks of breastfeeding and make an individualized decision based on the patient. This is definitely a conversation that Audrey should have with her physician.
The likelihood that their child will develop IBD in the future:
Epidemiological studies demonstrate that certain genetic factors influence susceptibility to IBD.2 It is possible, yet not inevitable, that a child of a parent with IBD will have it too. In this case, since both parents have IBD, the child’s chances may be as high as 36%.7 With that being said, the disease is genetically complex and cannot be explained by a single gene model alone.
The couple’s ethnicity can also suggest their child’s risk of developing this disease. Although Audrey and her husband did not provide this information, she should be aware that those of European Jewish (Ashkenazi) descent who have a first-degree relative with IBD are 3 to 5 times more likely to develop the disease than non-Ashkenazi Jews who also have a first-degree relative with IBD.3 This specific susceptibility has been established by various studies and could be useful information to the couple if they are of the same ethnicity.
It is critical for clinicians to examine and consider the psychosocial factors of disease when designing a holistic method of management that will optimally influence a patient’s quality of life. Biopsychosocial parameters are important determinants for overall well-being, health-care-seeking tendencies, and health-related quality of life, and there is a strong suggestion that the occurrence and development of diseases are associated with a patient’s
psychological status, and that physical health and mental health influence each other.
IBD can be completely debilitating- many symptoms, the most severe of which include abdominal cramping, bloody diarrhea, nausea, and fever.6 These symptoms have psychosocial implications impair quality of life in terms of physical, psychological, and social functioning, including school truancy, social isolation, and psychiatric problems such as anxiety, depression, and antisocial and dependent behavior.11 Additionally, certain direct and indirect costs are associated with these symptoms, which can financially debilitate the child’s family and might result in familial strife.
It seems that Audrey and her husband are both doing well, and their symptoms have been managed through chronic treatment. Their anxiety seems to mainly stem from their pregnancy and the possibility of their child developing IBD. If Audrey and her husband had both developed IBD at a young age, they’d probably experienced many negative symptoms and psychosocial issues arising from the disease. Understandably, they wouldn’t want their child to go through the same thing. Additionally, since the disease can be financially debilitating (from costs of medical treatment and treatment for other comorbidities/mental health), it is a fair assumption that these potential costs can cause worry.
Also, even though they have been largely established as safe, there are mixed opinions on the effects of the drugs Audrey takes during her pregnancy. I assume that this could be a major source of stress for Audrey, as she has to consider both her health and that of her child when considering whether to continue or culminate in her use of the drugs.
Furthermore, it is important to consider the psychosocial effects that stem from Audrey’s occupation. As a lawyer, she is likely subjected to immense stress in the workplace. A study published by Johns Hopkins University established that out of a study of 100 occupations, lawyers in the United States have the highest incidence of depression.12 I don’t have more information on her psychological well-being, but her doctor should follow up with her to see how she copes with the multiple stressors she faces.
Treatment Plan and Recommendations:
As I already discussed in the sections regarding the safety of the drugs Audrey is taking, I think it is appropriate for Audrey to continue with her current treatment plan, which involves using both infliximab and azathioprine to manage her Crohn’s disease. However, due to evidence that infliximab crosses the placenta at high levels in late pregnancy, I would advise her to stop taking the drug after thirty weeks’ gestation, as commonly recommended in the literature.9 The cessation of infliximab may induce painful and uncomfortable symptoms in Audrey, and if this is the case, she can be bridged with steroids to control disease activity until delivery, and then she may return to her normal regimen.9
To reiterate my point about Azathioprine, the benefits of her taking the drug outweigh the risks; this is illustrated by the fact that most gastroenterologists advise their patients to continue with treatment regardless of pregnancy.
Considering the psychosocial factors, Audrey is affected by, I would also recommend she join a support group consisting of other expectant mothers with IBD. Participation in a support group can arm her with better coping strategies so that she can
better manage the stress and anxiety she is faced with while connecting with others that can relate to her situation.
As a pharmacology student, I was drawn to this particular case because it would allow me to look into infliximab and azathioprine and review their pharmacokinetic and pharmacodynamic properties. The first thing we’re taught in the pharmacology program at McGill is that every single drug has adverse effects and that it is always essential to consider the risk-benefit profile associated with use. While my pharmacology classes have armed me with the knowledge to be critical of drugs in terms of their adverse physiological effects, this class has encouraged me to explore the psychosocial factors as well that can also largely influence the risk-benefit profile of using a particular drug. This has enlightened my understanding of multi-factorial decision-making when choosing what treatment plan to pursue. I’m thankful that this class has exposed me to this, but I wish my colleagues in my program that have not had the chance to explore the psychosocial factors of disease and medication would have the same opportunity. I think an emphasis should be placed on this paradigm in at least one of our required core pharmacology classes.
From studying the limitations of the drugs mentioned in this case and the degree of uncertainty that exists, there seems to be a lot of opportunity for further research on IBD. There is no definite cure, and I believe that we can do better. Much research has been done on the genetics associated with Ulcerative Colitis and Crohn’s disease. Investment should be made in drug development to increase the probability of remission.
Additionally, more analytical studies should be done in order to establish a diagnostic that can earlier predict the onset of the disease in high-risk individuals so that it can be most effectively managed.
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Published On: 01-01-1970