All recruited patients participated in the interviews. Saturation was achieved in terms of impact and attack symptoms, with the final quintile of interviews generating limited additional information. However, subsequent chronic symptom-focused re-analysis of the data indicated that saturation was achieved for chronic pain but not achieved in terms of non-pain chronic symptoms.
Overall Experience of Acute Intermittent Porphyria
When asked what it is like to have porphyria, patients reported a high burden of disease, experiences of both attack and chronic symptoms, and that AIP impacted a number of different areas of their lives. In total, patients reported 78 unique symptoms attributable to AIP attacks, 35 of which were also experienced chronically. Pain was usually the first symptom cited by patients when they were asked to define porphyria or to describe their symptom experience. Attack or chronic pain (not mutually exclusive) was reported as the most bothersome symptom by 13 patients (68%).
“I’ll feel like hot knives stabbing me.”
Nausea was reported as the next most bothersome by eight patients (42%).
“My nausea is uncontrollable. And I—my body just doesn’t feel right anymore.”
Other bothersome symptoms reported by two or more patients included abdominal pain specifically [n = 6 (32%)], memory loss [n = 4 (21%)], vomiting [n = 3 (16%)], constipation [n = 2 (11%)], and fatigue [n = 2 (11%)].
Attacks were described as extreme incapacitating episodes characterized by progressive and uncontrollable symptoms with widespread dysfunction that preclude usual daily activities (Fig. 1a). Descriptions included:
“Something that is beyond my control.”
“I’ll know from experience I need to be hospitalized.”
Attacks generally lasted 3–5 days, required treatment or hospitalization, and had a long recovery period.
“It will take me a couple of days just to lay in bed and sleep trying to recover.”
The most common attack symptom, reported by all participants, was pain. Patients described attack pain as:
“I’m more than in tears, like I am literally like crying, crying, because the pain is just, it’s so bad, it’s like a stabbing, it’s a burning, it’s a pulling and a twisting, it’s everything you could imagine, it’s the absolute worst pain in the world.”
When asked to describe attack pain severity, patients characterized it as the worst imaginable level of pain, pain worse than the pain of childbirth or broken bones, or pain that is incompatible with life.
“Some days I just feel like I hurt so bad that it’s like I actually will think out loud, like how is porphyria compatible with life, you know? When you get to that point where you’re in that much pain, it’s not compatible with life. You can’t live like that.”
Patients explained that attack pain was “incapacitating,” rendering them unable to function in their work, social, or family roles, or to perform basic daily activities.
“I’ll be in so much pain that I won’t be able to move.”
Patients also explained that they knew they were experiencing an attack when they could no longer control pain at home and needed to seek help at a hospital or clinic, while others stated that attack pain is so severe that it cannot be controlled with pain medication.
“Just so uncontrollable, even with all my medications.”
Attack pain persisted until patients were successfully treated with medication, or until the end of the attack. Attack pain occurred in a variety of body locations, abdominal pain being the most frequent.
“It’s this spearing abdominal pain, like almost like someone is taking a hot butcher knife and tearing it through your stomach.”
Other locations included the entire body, stomach, back and spine, ribs, shoulders, arms, hands, legs, knees, feet, joints, and head. Further patient experiences describing attack pain are presented in Table 2.
The second most common attack symptom was nausea, reported by 16 patients (84%).
“The nausea is what just knocks me out. I mean it just—literally, I cannot do anything. I get up in the morning and if the nausea is that bad, I’ll start eating some toast, trying to at least eat something, because I can’t go without eating because that makes me sicker.”
The next most common attack symptom was vomiting, reported by 15 patients (79%).
“You’re like throwing up to the point where like you want to die, and you’re spitting up bile, and even though your stomach is completely empty and you’re like, ‘where is this coming from? I haven’t eaten in hours. I’ve been throwing up for half a day’. I’m vomiting foam at that point.”
Another common attack symptom was headache, reported by ten patients (53%).
“… headaches so bad that they’ve caused me to lose my sight on numerous occasions.”
The Table in the ESM lists other common attack symptoms reported by seven or more patients, along with descriptions and patient experiences. The symptoms experienced during an attack were described as extending beyond the period of the attack, leaving residual chronic symptoms and included two patients whose attack resulted in a coma.
Patients described the chronic experience of AIP as:
“Something I’m constantly having to manage.”
“I don’t get a whole lot of relief in between attacks.”
Eighteen patients (95%) experienced chronic symptoms (defined as symptoms attributed to AIP experienced between attacks) with the remaining patient only experiencing symptoms during attacks. All the symptoms reported chronically were also reported during an attack, although chronic symptoms were described as less severe. The chronic symptom frequency ranged from occasional experiences with pain, fatigue, or nausea, to daily experiences of a wide range of symptoms (Fig. 1b). Patients also highlighted that the disease is not ‘intermittent’ as the name implies.
“My condition seems to be more chronic than it is intermittent.”
“There’s not a week that goes by that I don’t have [chronic symptoms].”
Chronic pain experienced between attacks was often characterized as sore, dull, aching, throbbing, and/or burning (Table 2) and was the most frequently reported chronic symptom, experienced by 17 patients (78%). Chronic pain was rarely described in the more extreme terms used to characterize attack pain and was not considered as severe.
“When I’m not having an attack I will experience some pain, like some joint pain in my knees and also the neuropathy in my hands. Those are my symptoms that don’t go away.”
However, some patients characterized more severe peak episodes of pain outside of an attack as sharp or stabbing.
“… pain level is probably like at a six out of 10, um, on a daily basis … I would say it feels like you—like I said, you have like little people in there with barbed wires, just like fighting.”
Many rated living with pain in the range of 2–6 out of 10 as a “good day” or “typical day” with porphyria, noting that their perception of pain is different from those who have never dealt with the degree of pain experienced by those with AIP.
“I have pain disassociation so that my level of pain is at a five all the time, which is probably someone else, a normal person’s 10, because I’m so used to the pain.”
Patients reported that chronic pain ranged from manageable with little impact, to having a significant impact on day-to-day activities.
“I don’t really sleep well at night at all from the porphyria because, um, my back hurts and, uh, my feet hurt and my legs, they hurt a lot.”
Twelve patients (63%) reported taking pain medications between attacks. Patients who experienced pain outside of their attacks reported variable frequency and duration of this pain. Some reported that pain was “constant” unless alleviated by medication, while others described pain as a sensation that comes and goes. Chronic pain was reported in a variety of body locations including the entire body, the abdomen, stomach, back (particularly lower back), buttocks, ribs, shoulders, arms, hands, legs, knees, feet, joints, and head. Patients also reported non-specific nerve and bone pain that they associated with AIP.
The second most common chronic symptom, reported by nine patients (47%), was neuropathy. The term was spontaneously generated by patients, and includes tingling, numbness, or loss of sensation.
“Nerve pain and nerve sensations because when you get numbness sometimes there’s nerves that are kind of alive and other parts that are dead. And it feels like something is crawling on you. And it’s like a bug is on your arm or something touches you on the middle of the night. It wakes you up. I get woken up a lot because of nerve sensation.”
The next most common chronic symptom was nausea, reported by seven patients (37%).
“I was nauseated every day and it was like a six to a seven on the scale.”
Other commonly reported chronic symptoms included insomnia by six patients (32%).
“There is a days [sic] I somehow I cannot sleep at all, no matter how, no matter how I am tired.”
Five patients (26%) reported fatigue.
“… it’s so frustrating. You know, you shouldn’t be that tired. You know, you should be able to live a normal life.”
Impact of Acute Intermittent Porphyria on Patients’ Lives
Patients reported AIP as having an impact on a number of different areas of their lives (Table 3). The most frequently reported impact was on sleep [n = 18 (95%)], ability to work [n = 16 (84%)], finances [n = 14 (74%); medical costs or inability to work], difficulty walking [n = 14 (74%)], and decreased socialization [n = 12 (63%)]. Patients frequently reported an impact on sleep from both chronic and attack symptoms.
“I don’t really sleep well at night at all from the porphyria because my back hurts and my feet hurt and my legs, they hurt a lot.”
The unpredictable nature of attacks and symptoms was also noted; patients reported never knowing how they will feel from day to day or when an incapacitating attack will occur, which impedes attendance at work and social activities.
“It’s completely unpredictable. There’s no way I could be a reliable employee to somebody because I could not guarantee that I will be there tomorrow for work.”
Patients highlighted the medical costs of the disease.
“As a matter of fact, I have to make a phone call to my secondary insurance provider finding out why they dropped me because I just received a $650,000 bill.”
The wide-ranging psychological impacts included challenging diagnostic journeys, lack of knowledge of the disease, not being believed by healthcare professionals, and being labeled as drug seeking.
“Very few doctors understand what porphyria is or even how to treat it.”
“I have to take all these stupid medications, and there’s so much stigma in society about prescription pain meds.”