Conclusion

In short, AIP does not occur merely due to genetic factor, it will only trigger in the presence of both genetic and environmental factor. The treatment depends on the symptoms of porphyria that the patients have. Although porphyria usually cannot be cured, certain lifestyle changes may help to manage it. Undeniably, in most cases, people with AIP are capable of leading a normal healthy life. Despite that, they should be persistent in controlling their lifestyle, alcoholism and smoking must be avoided. Based on the case studies, it shows that patients with AIP are able to recover and lead a normal life after receiving the treatments. As an individual become older, the chance of experiencing acute attack reduces. However, the acute attack will still remain with the person and will not disappear in one's whole life.

Application of Theory for Case Studies #2

In this case, the transtheoretical model can fit in to explain the case. There are five stages which are the precontemplation, contemplation, preparation, action and maintenance.

Based on the case, the patient undergoes the precontemplation stage where he was not aware of the disease and has no intention to receive treatment and change lifestyle.

Next, in the contemplation stage, the patient experience acute attack and has the intention to receive treatment.

In the preparation stage, he does research on Acute Intermittent Porphyria and later found out that he has a family history on this disorder. Thus, he plans to receive treatment and change his lifestyle.

Then, in the action stage, the patient with AIP receives two treatments which are glucose intravenous and heme treatment. 

Lastly, in the maintenance stage, the patient is very aware and careful about his lifestyle after the treatment in order to prevent the recurrent of acute attack. 

Figure 37. Transtheoretical model

Case Studies #2

Figure 36. Case study

One of the patients in the case study was 39-years-old male who diagnosed with Acute Intermittent Porphyria (AIP) in 1998. This patient reported that he suffered from abdominal pain and constipation. More importantly, he also took many examinations from doctors to diagnose the disease or disorders was, however the results were normal. At the end of the test result, his spot urine sample also used to diagnose, ALA, PBG and Proto-PBG was positive. This is because his family members were diagnosed and suffered from AIP. In other words, it was medical history of AIP had found among his family. Besides that, patient received two types of treatments after he had diagnosed with AIP. The first type of treatment was he administered the glucose orally and had been monitored within three days. Unfortunately, he suffered the acute attack of AIP after he recovered. Due to the glucose did not function during his fasting for Ramadhan. Therefore, heme treatment had been replaced from glucose administration as treatment of AIP. He had completely recovered from AIP within two days after received intravenous heme (injection into the bloodstream). After the recovered from AIP, he became more careful in his lifestyle, such as prescribed the drug carefully.

Application of Theory for Case Studies #1

Based on case study 1, behavioral theory can be applied to cope with patients who do not want to make changes in their lifestyle. Behavioral theory is suggested by Skinner, which he more specifically named it as operant conditioning. Behavioral theory focuses on the leading factor to an action and the result or consequences of performing the action (McLeod, 2015). Skinner believed that the consequences will largely affect one to repeat or not repeat the particular action or behavior. 

In this case, positive reinforcement can be applied. Positive reinforcement is referred to the strengthening of good behavior by rewarding a person (McLeod, 2015). When the patient refrains himself from smoking or drinking alcohol, the physician can award or praise him with the thing he like. The happiness of getting reward may be a motivation for him to stop smoking or drinking alcohol. 

Next, positive punishment can also be used. Punishment is used to reduce undesirable behavior. However, it is not encouraged because there might be negative side effects. For example, punishment can lead to aggression or delinquent behavior. 

Case Studies #1

Figure 35. Case study

A 39-year-old male, was diagnosed of suffering from Acute Intermittent Porphyria. His spot urine sample was used for diagnosis, which his urine acetone and urobilinogen was positive and the ALA level was 25mg. Furthermore, his urine color turned into black after exposed to the sun. According to Sezgin (2016), he had reported experienced of severe abdominal pain, cold sweats. progressive muscle weakness, as well as constipation. Due to his family history, which included two brothers and a sister were also struggle of AIP, thus genetic inheritance was the primary factors of causing his AIP. Besides, he did not follow the advice of the physician, he also continued cigarette smoking and alcohol assumption, which possibly in triggering the recurrent attack of AIP. Moreover, he also used of the outpatient medication. For treatment, he had received intravenous dextrose infusion when he was confirmed of having AIP. Whereas he received heme cure at the third day of AIP attack. It was administered 3mg for a day, continued for three days. He was recovered at the 6th day. However, as he continued the behavior which will precipitate the attack of AIP, acute attack had occurred few years later.

Experience of Having Acute Intermittent Porphyria

This video is about a doctor who suffers from Acute Intermittent Porphyria. After recovering from the disorder, she described her experience of having AIP. In the video, she showed her photos to present the huge difference in her appearance before and after treatment. 

Figure 34. The photo of the doctor before and after treatment

In short, people with AIP should receive treatment immediately. As mentioned before, heme treatment is the most effective treatment for AIP and many people who suffer from AIP can lead a normal life after the heme treatment. Although it may not completely cured the disorder, but certainly the symptoms will be reduced. 

The Biopsychosocial Explanation of Acute Intermittent Porphyria

As the video mention, biopsychosocial model is a model to know the cause of mental illness and also the solution to it. The first part which is biologically, it includes heredity, genes, illness, and also mood, and the solution for this is medication, the second part which is psychological, it includes experience and thoughts and feelings, which mostly are negative thoughts and feelings, the solution for it is therapy. The next part is social, which includes family stress, and job stress and transition, the solution for it is to know the boundaries and self-care. 

Figure 30. Biopsychosocial model of health

Biopsychosocial model is a model that says that a disease is result from a combination from the aspect of biology, psychological and social factors, this model is use to improve the previous model which is the biomedical model that says that disease is result from exposure of pathogen (Engel, 1980). Just like Acute Intermittent Porphyria (AIP), this disease is caused by the combination of biology, psychological, and social factors (American Porphyria Foundation, 2010). Just like Acute Intermittent Porphyria (AIP), this disease is caused by the combination of biology, psychological, and social factors (American Porphyria Foundation, 2010). 

Biology factor in AIP says that this disease is passed down from generations to generations through the genes (Sezgin, 2016), in other words, it means that AIP is an inherited disease. Most compelling evidence, previous research indicated that 90% of the individual with AIP who usually W198X mutation in the genes (Andersson, Floderus, Wikberg, & Lithner, 2000; Bylesjö, Wikberg, & Andersson, 2009).

The next factor, which is psychological factor, such as being depress all the time or having too much stress emotionally and physcially or exhaustion, burn-out could also increase the risk of triggering the AIP in the body, provided if the person family generation have the history of AIP (Balwani & Desnick; Ventura, Cappellini, Biolcati, Guida, & Rocchi, 2014). Prior findings highlighted that hypertension was relatively highly associated with Acute Intermittent Porphyria (Bylesjö, Wikberg, & Andersson, 2009).

Figure 33. Alcoholism, smoking and drug abuse

The last factor that could increase the risk of AIP is social factors. Social factors includes smoking, drinking alcohol, and consuming medications or drugs such as barbiturates or  methyldopa could also increase the risk of triggering AIP  (Lopes, Valle, Taguti, Taguti, Betonico, & Medeiros, 2008). Other than that, past study revealed that working environment was the most common factor which lead to severe attack of AIP, especially among men (Bylesjö, Wikberg, & Andersson, 2009).  According to Bylesjö, Wikberg and Andersson (2009), 11 patients had reported that they had shifted work, solvents, stress, physical strain and exhaust fumes.

Treatment for Acute Intermittent Porphyria #2 - Heme Treatment

Heme treatment is one of the latest treatment for AIP currently and it typically utilized when severe attacks of AIP (Meena et al., 2016).  Nowadays, glucose administration has been replaced intravenous heme.  The reason has been replaced is because heme treatment is the most effective treatment for regulate the acute attack in AIP (Anderson et al., 2005; Dosi et al., 2013 & Puy et al., 2010).  According to Dosi et al. (2013), the patient had been improved by the heme treatment in the second day.  Half of a year later, the patient had been recovered from AIP, and can continued to live on.  This study also indicated that heme treatment was to avoid the overproduction in aminolevulinic acid (ALA) and porphobilinogen (PBG) (Dosi et al., 2013). Another case study also using the intravenous heme to regulate the PBG. Elkhatib et al. (2014) revealed that patient administered the heme treatment intravenously to control the PBG.

Figure 28. Intravenous heme

Treatment for Acute Intermittent Porphyria #1 - Glucose Admistration

Regarding to treatment for AIP, there was two types of main and specific treatment to control acute attack from AIP which was including the glucose administration and heme treatment.  Most of the findings recommended the patients administered the glucose intravenously or orally.  Intravenous glucose refer to the injection of the glucose directly into the bloodstream (Lundbaek, 1962).  According to Sezgin (2016), sixty percent of the patients had administered the glucose intravenously in order to control the acute attack of AIP and cure the AIP.  Another notable point for administered the glucose was glucose administration intravenously or orally could not function at all during the fasting period (Sezgin, 2016).

Figure 26. Intravenous glucose 

According to Thomas (2015), patients usually administered intravenous glucose in water solutions in order to prevent excessive in hyponatremia.  On the contrary, one of the prior findings reported the contradictory findings compare with Thomas’s study. This past study emphasized that intravenous glucose in water solution was necessary to be aware and not to be used due to it can increase the risk of hyponatremia (Stein et al., 2012).

Figure 27. Types of hyponatremia

Diagnosis for Acute Intermittent Porphyria

One of the most common and accurate methods to diagnose an individual with acute intermittent porphyria (AIP) is urine test. Typically, the researchers were conducted the urine test in order to examine and measured the level of the urine porphobilinogen (PBG) and urine aminolevulinic acid (ALA) (Larion et al., 2013; Metha et al., 2010).  Past findings found that the level of porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) from the patients with AIP were higher compare with individual who totally do not have AIP at all (Elkhatib et al., 2014; Meena et al., 2016 & Metha et al., 2010).  Forthwith, majority of the patients was utilized the urine test by the researchers and doctors in order to diagnose AIP.  Based on a case study which studied a few of patients with AIP, it showed that 4 out of 5 patients was diagnosed AIP by using the urine test (Sezgin, 2016).  Another studies also supported Sezgin’s diagnosis and reported that the level of PBG and ALA in urine can used to diagnose the AIP due to the level of the urine excretion in porphobilinogen will elevated during acute attack (Stoian et al., 2014; Yuan et al., 2015). Other than that, level of porphobilinogen deaminase (PBGD) enzyme activity in erythrocytes was abnormally lower than normal people (Stoian et al., 2014).

Surprisingly, the color of urine from people with AIP was became totally different compare with normal individual who do not have AIP at all (American Porphyria Foundation, 2015).  Prior findings also supported this view.  However, different case studies had shown minor results in the urine's color.  For example, urine color of the patient were turn into dark color (Yuan et al., 2015).  By the same token, Sezgin (2016) also reported that one of the patient’s urine was became in purple color. Most compelling evidence, Dosi at al. (2013) highlighted and showed that the urine of the patient was became reddish hue. More significantly, the color of urine was changed again after the urine exposure under the sunlight a couple of hours, and it became the darkened which almost became the black color.

Figure 25. Urine of AIP patient before and after exposure to sunlight

Reducing Risks For Acute Intermittent Porphyria #4 - Hormones

For women, occurrence of acute attack is often associated with their menstrual cycle. Hormonal therapy can applied to manage this, that women took the contraceptive pills that control the hormone fluctuation and prevent suffer from AIP attack (Grob, Honcamp, Daume, Frank, Dusterberg, & Doss, 1995). Commonly this type of exogenous therapy will be used if the biopsychosocial model are not sufficient. However, there is the possibility that contraceptive pills will provoke 5% to 14% of acute attack of both latent and manifest AIP. Thus the clinician or physician should evaluated the benefits as well as risks prior this (Andersson, Innala, & Backstrom, 2003; Pischik & Kauppinen, 2015). In addition, parents who are the AIP carriers but would like to have children would go for genetic testing and genetic counselling (Balwani & Desnick). Through these, they are able to know the chances of having a child with AIP, this helps to lower the risks of passing the detective gene to the next generation. All in all, there is not possible to prevent suffer from AIP, but avoid of the precipitating factors and some of the genetic checking may contribute to a later presentation or even no presentation of an acute attack.

Figure 24. Contraceptive pills

Reducing Risks of Acute Intermittent Porphyria #3 - Psychological Factors

Figure 23. Interconnection between behaviour, feeling and thoughts

Besides, people with AIP should try to avoid the condition that caused physical and emotional stress, as well as exhaustion (Bylesjo, Wikberg, & Andersson, 2009). Rather, they would have to find another alternative ways to reduce the stress if the condition is unavoidable, counselling and therapy would be a way for them to express their feelings and emotions. Cognitive behavioral therapy (CBT) is a widely used psychosocial intervention for stress as well as depression which it able to diminish the level of stress (Holdevici & Craciun, 2015).

Another way to reduce the severe attack of AIP from psychological perspective is individual's inner motivation, also known as intrinsic needs.  Inner motivation can reduce the sense of powerlessness to deal with difficulties (Wikberg, Jansson, & Lithner, 2000).

Reducing Risks of Acute Intermittent Porphyria #2 - Smoking/Alcoholism/Dietary Change

Figure 21. Stop smoking and alcoholism

Excessive alcohol assumption and cigarette smoking should be avoided to reduce the risk of triggering AIP (Cappellini, Brancaleoni, Graziadei, Tavazzi, & Pierro, 2010; Doss, 2000). 

Next, the AIP carriers should maintain a healthy diet, including sufficient intake of carbohydrates. Under this circumstances, those who would like to lose weight should be gradually, severe calorie restriction and crash diet, heavy exercise schedule is not recommended (Thadani, Deacon, & Peters, 2000). According to Mehta et al. (2010) study, there are four male suffered from AIP and have differ level of severity. Four of them being managed by high carbohydrates diet for a period of time, and results showed that majority of them have certain level of improvement over time. In short, a balance diet able to reduce the risks of acute attack or deteriorate the condition. 

Reducing Risks of Acute Intermittent Porphyria #1 - Medication

Unfortunately, there is no prevention of suffered from AIP as the detective gene was being passed from the parents to their next generation who are the carries of this inherited disease. However, there are people with inherited AIP seldom develop the symptoms, as they have taken some of the precautions steps which aids in reducing the risks of occurrence and attack of AIP. These steps consists of the biopsychosocial aspects, as well as the behavioral model. The most critical point is to avoid the precipitating factors. 

First and foremost, it is important to pay attention to the drugs or medication prescribed, such as illicit drugs (Stein, Badminton, Barth, Rees, & Stewart, 2013). Commonly newly prescribed medication is triggering. Thus the patients should refer for the expert or professional for advice. They also can refer to list of drugs which considered safe for them to prescribed. 

Figure 20. Example of drugs that to use for acute porphyrias

Risk Factors of Acute Intermittent Porphyria #4 - Hormonal Factor

Figure 18. Number of females is more than males

An acute attack are more commonly occur in women population than men, and it happens rarely before puberty and after menopause as well (Sassa, 2006). It had supported a strong endocrine influence, which it more likely to happen when women experienced premenstrual hormonal changes or pregnancy. Innala et al. (2012) study have supported this point of view. They found that women with AIP showed a relatively lower level of serum concentration in terms of allopregnanoloce when compared to normal women, while the most significant differences was in the luteal phase of menstrual cycle (Innala, Backstrom, Poromaa, Andersson, & Bixo, 2012). These patients break down hormones in an abnormal ways and produce more porphyrins. 

On the other hand, study also showed that pregnancy also potentially exacerbate acute attack (Tollanes , Aarsand, & Sandberg, 2010). It raises an excess risk for the AIP to have a low weight birth, premature delivery, perinatal death, congenital malformations and also other adverse outcomes (Andersson, Innala, & Backstrom, 2003). Rather, women with AIP should be monitored carefully during pregnancy. All in all, usually combination of these factors works in triggering an attack.

Figure 19. Pregnancy

Risk Factors of Acute Intermittent Porphyria #3 - Dietary Style and Psychological Factor

Diet style also have effect on the attack of AIP. Fasting, which one’ who used to lose weight rapidly, or only have little food intake for a prolonged period, may results in exacerbate acute attack (Raigal, Lledo, Raigal, Muriel, Perez, & Monero, 2008). These consequences are the outcome of calorie restriction, especially insufficient carbohydrates intake, as carbohydrate and glucose works in suppress the secretion of ALAS, which possibly in triggering AIP (Handschin et al., 2005). According to Garcia-Diz et al. (2012) study, patients with AlP have relatively lower level of macronutrients and micronutrients intake than the control group. Thus, dieting and lack of carbohydrates intake may provoke AIP. 

Figure 16. Losing weight while staying healthy

Besides of the biological and behavioural factors, psychological factors also play a vital role in affecting occurrence of AIP acute attack. This includes biopsychosocial model aspects, involving physical and emotional stress, exhaustion, intercurrent disease, surgery, infections (Balwani & Desnick, 2013; Ventura, Cappellini, Biolcati, Guida, & Rocchi, 2014).

According to Divecha, Tullu, Gandhi and Deshmukh (2016), one of the main concern and factors of acute attack of AIP is stress.  If an individual often suffer from stress, this stress can cause and increase the rate from acute attack (Divecha, Tullu, Gandhi, & Deshmukh, 2016; Simon & Herkes, 2011).  Prior findings also emphasize that acute attack from AIP typically started from minor changes in psychological ways such as anxiety, impatience, aggresiveness and impulsivity (Demily & Sedel, 2014). Therefore, it would often lead to chronic fatigue and relationship difficulties (Demily & Sedel, 2014).

Figure 17. Picture of stress

Risk Factors of Acute Intermittent Porphyria #2 - Alcohol and Smoking

Alcoholism also will trigger presence of the acute attack, especially excessive alcohol consumption (Doss, 2000). It accelerates the secretion of oxygenate gene which lead to deterioration of AIP (Jadil, Grady, Lee, & Anderson, 2010). According to Sezgin (2016) study, patients suffered from AIP with heavy alcohol assumption obviously reported more severe in the disease, as alcoholism would induce the synthase of aminolevulinic acid synthase (ALAS).

Smoking, includes second smokers, also served as one of the factors that contributed to presence of high AIP attack (Anderson, et al., 2005). Smoking acted as an enzyme inducer, influence the drug metabolic rate as well as steroid hormone metabolism. It had triggered an anti-oestrogenic effects and related to the increase of hepatic mono-oxygenases which bring an effect on triggering the attack (Lip, Mccoll, Goldberg, & Moore, 1991). A conclusion can be drawn that cigarette smoking is associated with the inducing of acute attack. 

Risk Factors of Acute Intermittent Porphyria #1 - Medication

Acute Intermittent Porphyria (AIP) is an inherited disease, which either one or both of the parents who carried the detective gene and passed it to the next generation. However, most of the carriers of AIP never develop symptoms. Basically, certain factors that increase the synthesis of hepatic heme may precipitate symptoms of AIP and caused an acute attack. Exposure to these factors are possibly trigger its earlier occurrence, such as medication (Metha, Rath, Padhy, Marda, Mahajan, & Dash, 2010). 

Figure 11. Medication

There are some of the unsafe and illicit prescribed drugs that proved to be provoke the occurrence of AIP, for example, barbiturates, sulphonamides, progestogens and methyldopa (Lopes, Valle, Taguti, Taguti, Betonico, & Medeiros, 2008).  These drugs will inhibit the secretion of hepatic porphobilinogen deaminase as well as depletion in heme pool enzymes which results in the induction of aminolevulinic acid synthase (ALAS), precipitate the occurrence of acute attack (Hift, Thunell, & Brun, 2011). 

Figure 12. Methyldopa

Commonly, the drugs are applied via topical administration would not caused an acute attack (Hift, Thunell, & Brun, 2011). There are examples of drugs that trigger attack in animals but not in human, and this also works in the opposite way, as the differences in metabolic rate across the species (Kannan & Gowri, 2015). 

In short, drugs served as the most common factors that provoke an acute attack. Usage of medication should be referring to the professional advice.

Figure 13. Use medication under doctors' advice