In some patients, AIP is a chronic and debilitating disease with severe, recurrent acute attacks and low quality of life , 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 . 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. .
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 . 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 . 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 . 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 . 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 . 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 . 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 . It is well known that physical activity has both physical and psychological benefits, including reducing stress levels  and psychological stress was reported to be an important attack inducer in an American study of patients with AIP who were experiencing recurrent attacks . 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 . 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 . 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.
The design of this study does not allow any conclusions as to whether there is an association between general self-efficacy and the level of preventive actions reported by the participants. The grouping of the respondents into asymptomatic and symptomatic cases of AIP was based on self-reported and self-perceived AIP symptoms. The list of symptoms in AIP is long, and many of the symptoms are the same as those in other more common diseases or general health complaints. It is likely that patients classifying themselves with symptomatic disease attributed other health complaints as being AIP symptoms and in reality should have been classified as “asymptomatic”. Difficulties in separating AIP symptoms from subjective health complaints has been reported by others . Considering the high percentage of patients’ self- classifying as symptomatic in our study, we suspect that if this had been evaluated by standardized criteria including measurements of PBG in urine, fewer patients would have been classified as symptomatic. Also, the study had a retrospective design, which is suitable for studying rare cases with low incidence, but recall bias must always be taken in to consideration .
The present study had a response rate of 55%, which is a problem with regard to representability, however, it is in line with average response rates estimated at 53% . The non-responders’ reasons for not answering the questionnaire can only be speculated on, but if they had low self-efficacy and were not motivated for lifestyle changes this would have influenced the conclusions in this study, and can therefore be a limitation to the conclusions drawn. This, however, represents a constant problem in research where participating is based on informed consent.
Further investigations into what extent lifestyle contribute to a lower penetrance and expressivity of AIP could yield important knowledge. Continued research is warranted to better understand how counseling can be helpful to this patient group.