Self-efficacy and self-management strategies in acute intermittent porphyria

Porphyrias are a group of rare, inherited metabolic disorders. Each is caused by reduced, or—in one disease—increased activity in one of the enzymes in the heme biosynthetic pathway and leads to symptoms in the form of acute neurovisceral attacks, skin lesions, or both [1]. Acute intermittent porphyria (AIP) is the most common of the acute porphyrias in most countries, with an estimated prevalence of 5.9 per million inhabitants in Europe [2]. The disease is characterized by acute attacks in the form of severe abdominal pain, in combination with pain in the back and thighs, polyneuropathy, nausea, vomiting and constipation [1, 3]. Tachycardia, hypertension, electrolyte disturbances and neurological and mental complications are also frequent. Attacks of AIP have by some patients been described as excruciatingly painful [4]. Though most patients experience only one or a few acute attacks during their lifetime, more severely affected patients report a reduced quality of life. They can experience major life event consequences such as failure to secure or loss of employment, impact on family size, increased anxiety, and depression [4‐6]. AIP is an autosomal dominant disease and is caused by mutations of the HMBS gene. Prevalence of mutations in the HMBS gene is probably underestimated in the healthy population [7, 8]. Clinical penetrance has been estimated to be about 10% [9], even lower in a recent population study [10]. Studies indicate that drug use including alcohol and hormonal changes are the most frequent inducers of acute attacks [11], with additional triggers being smoking, infections, physical and psychological stress, hunger and crash dieting [12, 13]. Avoidance of these triggers is recommended both to prevent HMBS mutation carriers not yet having symptoms from manifesting the disease, and to reduce the frequency and severity of attacks in patients who have already had symptoms of AIP. Among behavioral measures, avoiding the use of porphyrinogenic drugs is considered the single most important effort. In addition, a balanced diet with no prolonged fasting or crash dieting is generally recommended [14]. Smoking is also advised against, as smokers have been described to have more frequent acute attacks than non-smokers [12].

The Norwegian Porphyria Centre (NAPOS) offers genetic counseling of both symptomatic patients with AIP and healthy at-risk relatives, and genetic counseling is mandatory prior to predictive genetic testing. Genetic counseling usually comprises providing information about the disease with regard to genetic and biochemical mechanisms, symptoms, treatment and self-management recommendations. Additionally, if in the setting of predictive testing, the consequence of a decision to test, or not to test, is discussed. From a clinical point of view, one of the main benefits of predictive genetic testing for AIP is the possibility of choosing a lifestyle that reduces the risk of manifest disease and allows for awareness of potential long-term complications. Several drugs and behavioral factors are potential attack inducers and prevention of the disease by avoiding known triggers is by many porphyria experts a reason to recommend genetic testing in healthy at risk relatives. However, the points of view of patients with AIP on the effect of genetic testing have been investigated only poorly. Studies evaluating health behavior after genetic testing for other diseases indicate that genetic risk assessment is unlikely to lead to changes [15]. A qualitative study investigating the experiences of young adults with AIP diagnosed as minors found that early diagnosis was perceived as advantageous, but finding motivation for changes in behavior was difficult [16].

Perceived self-efficacy is considered an important factor used to explain differences in health behavior. Self-efficacy refers to a person’s degree of optimistic and self-confident view of own abilities to deal with certain life stressors [17]. Individuals with strong self-efficacy tend to make healthier lifestyle choices [18, 19]. Genetic counseling has the potential to provide AIP patients and their families with information about self-management strategies that might help reduce the risk of developing manifest disease. However, there is lack of knowledge on whether receiving an AIP diagnosis and counseling have an impact on behavior and whether this is associated with self-efficacy in patients with AIP. This information is important to improve the quality of genetic counseling and to learn how to best provide appropriate follow-up and care for persons with AIP.

In some patients, AIP is a chronic and debilitating disease with severe, recurrent acute attacks and low quality of life [25], while in the majority of patients, acute attacks are sporadic and infrequent. However, in both symptomatic AIP patients and genetically predisposed HMBS mutation carriers, life-long adherence to preventive measures is required and the disease carries the risk of severe acute attacks and serious long-term complications.

Self-efficacy is described as self-confidence in coping with various difficulties in life. High self-efficacy is related to higher motivation and a greater effort to solve such difficulties [26]. Having high self-efficacy is likely to be important to individuals with AIP, as lifestyle changes require self-drive and personal initiative. In our study, participants reported a high belief in their own ability to cope and exert control in general. No difference in self-efficacy was found between those self-classified with asymptomatic AIP compared with symptomatic disease. Almost all participants in our study had in some way made changes in their behavior, consistent with the high degree of self-efficacy found among them. Almost all participants reported that they were aware of the risk of using medications listed as porphyrinogenic, which is similar to the results of Andersen et al. [16].

With the exception of avoiding porphyrinogenic medications, recommendations for patients with AIP are in line with general health recommendations, namely sustaining a balanced diet, reducing alcohol and tobacco consumption, and avoiding infections and stress. Therefore, some of the preventive actions reported by the participants might also have been motivated by a desire for a healthier lifestyle in general [16]. Irrespective of the motives, this effort in trying to have a healthier lifestyle might be helpful in preventing acute attacks.

Respondents with self-reported symptomatic AIP reported changes in behavior to a greater extent than the asymptomatic group. It is natural that patients with symptoms they ascribe to their disease would perceive preventive actions as being important [25]. At the same time, experiencing one or several acute attacks could make patients lose their motivation to continue preventive efforts; however, it seems that this is not the case.

That the asymptomatic group reported having made changes in their behavior can be used as an argument for offering predictive testing. By taking preventive measures, the risk of experiencing an acute attack is expected to be reduced. At the same time, it is important to be aware that testing might also lead to some unnecessary worries and pathologising. The list of possible symptoms in AIP is long and can be difficult for the patient to distinguish from more common illnesses [16]. In our study 38/140 (27%) participants reported to experience porphyria-related complaints the present week, which is a very high percentage. Further, 34 participants self-classified as symptomatic reported that they had received genetic counseling (Fig. 1). Patients diagnosed with manifest AIP at NAPOS are offered genetic counseling at the time of diagnosis; however, most genetic counseling sessions are provided in a setting of predictive genetic testing, which in Norway has been mandatory since 2003 [27]. We expect that most of the respondents reporting attending genetic counseling have had predictive genetic testing performed as healthy at-risk relatives. Nevertheless, according to the motives for genetic testing results (Fig. 3), 45% of the study participants reported that symptoms was one of the reasons for testing. It is understandable that patients assume that a possible HMBS mutation could explain present symptoms, and our experience is that this often is a challenge in genetic counseling for AIP. Considering the low clinical penetrance for AIP [9, 10], it is unlikely that 34 out of 51 study participants who had attended genetic counseling have symptomatic disease. It is more likely that they have experienced symptoms that they ascribe to their genetic predisposition for AIP. An acute attack is verified by standardized criteria, including the demonstration of increased concentrations of porphobilinogen (PBG) in urine [28]. For instance, when AIP patients are experiencing abdominal pain, which is a common symptom in the general population, AIP is often perceived as the cause, without measurements to demonstrate increased PBG concentrations [14, 29]. It is recommended that symptomatic patients and high-excretors are assessed yearly including measurements of ALA and PBG in urine being performed [14]. It is important to educate patients on the importance of submitting a urine sample for ALA and PBG analysis when they experience symptoms that they consider likely to be related to AIP. It is not beneficial for the patient that symptoms are uncritically attributed to AIP, as it can lead to medicalization, worry, and other serious illnesses might be overlooked.

The least frequently reported change in behavior was avoidance of physical strain. Physical strain is not listed as a triggering factor in several larger studies on acute porphyrias [11, 30] but was reported as a triggering factor, particular in men, in a Northern-Swedish study on 145 manifest AIP patients [12]. It is well known that physical activity has both physical and psychological benefits, including reducing stress levels [31] and psychological stress was reported to be an important attack inducer in an American study of patients with AIP who were experiencing recurrent attacks [25]. Though there are reports that physical strain may be a triggering factor, moderate physical activity is beneficial. To distinguish physical activity from physical strain might however be difficult for the patients, and this should be addressed when counseling this group.

The patients who attended genetic counseling reported satisfaction with all three components of the sessions investigated using the SCS (Table 3). High levels of satisfaction with genetic counseling have also been shown for patients with other diagnoses [32, 33]. For the majority of participants in our study, the counseling sessions took place several years ago. Therefore, the results might not apply to today’s clinical practice, but are still of interest. Satisfied patients are more likely to make use of health services and to carry out medical recommendations [34]. In the decision-making process regarding genetic testing, information provided from the genetic counselor was not experienced as being of great importance. This is perhaps not surprising, as most individuals attending genetic counseling for predictive genetic testing of AIP had made the initiative themselves and it is thus likely that they already had made the decision to undergo testing. Their starting point was usually having a family member with manifest disease, so this is naturally reported as the most important motive (Fig. 3). Respondents also reported that they wanted to clarify their own situation to be able to prevent activation of the disease, which is in line with what they reported to be doing when answering questions about lifestyle changes. It is of interest that concern for developing the disease is reported as a less strong motive for testing than their motivation to be able to prevent the disease. This could be influenced by the fact that 45% reported already having symptoms they ascribed to their likely genetic predisposition, but also with their high self-efficacy, they were focused on the possibilities of avoiding trigger factors to avoid symptomatic disease. The concern for risk in children was also a frequently reported motive.

When patients are diagnosed with AIP at NAPOS, both the physician and the patient receive information about the diagnosis and guidelines for follow-up and treatment, and are informed that NAPOS offers personal counseling, patient courses, identity cards and telephone and e-mail support. It is likely that this information, in addition to the provided counseling, has contributed to study participants’ knowledge on triggering factors and enabled their changes in behavior (Fig. 2). In the self-reported symptomatic group, the respondents who had received genetic counseling reported both a higher level of education and they had more frequently secured employment compared to the group who had not received genetic counseling (Table 1). It is likely that resourceful patients more easily make use of what the health care system has to offer. That attending a specialist porphyria clinic providing advice, management, and counseling can be beneficial in terms of behavioral adjustments has been shown by others [5]. In addition, information about rare diseases is increasingly available, e.g. online. By being informed and experiencing more understanding and competence from health professionals, patients might feel more in control and better looked after.

This study indicated high levels of self-efficacy in Norwegian HMBS mutation carriers. This positive self-reliance is probably important to apply self-management strategies and might aid in reducing the severity of and/or preventing acute attacks. The respondents reported several preventive measures and behavioral changes after being diagnosed with AIP, the self-reported symptomatic cases to a greater extent than the asymptomatic. The possibility to prevent the disease and to consider the risk for children was important when the respondents decided to be genetically tested. They were highly satisfied with the genetic counseling they had received. Our study indicates that Norwegian HMBS mutation carriers have both the knowledge and the self-motivation to make good choices that might aid in preventing activation of the disease. Therefore, providing information, counseling, and education is worthwhile in AIP.