Long-term follow-up of acute porphyria in female patients: Update of clinical outcome and life expectancy

Baumann, Katrin; Kauppinen, Raili

doi:10.1016/j.ymgmr.2022.100842

Cited by 14 publications

(16 citation statements)

References 32 publications

(54 reference statements)

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“…The study also reported a normalization of life expectancy during the follow-up time compared with the general population. Additionally, they reported a considerable decrease in the incidence of acute attacks starting between 1960 and 1970 [21]. The results of our study, as well as the findings from the Norwegian and Finnish populations, are in contrast with the high mortality observed in historical cohorts [10][11][12][13][14].…”

Section: Discussioncontrasting

confidence: 79%

Mortality in Pedigrees with Acute Intermittent Porphyria

Neeleman

Musters

Wagenmakers

et al. 2022

Life

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High mortality rates have been reported in historical cohorts of acute intermittent porphyria (AIP) patients. The mortality associated with (hydroxymethylbilane synthase) HMBS variant heterozygosity is unknown. This study estimates all-cause mortality in pedigrees with HMBS gene variants that cause AIP. We collected data on the lifespan of individuals in Dutch AIP pedigrees and performed analyses using the family tree mortality ratio method. This gave us standardized mortality ratios for these pedigrees compared to the Dutch general population as a primary outcome. Between 1810 and 2017, the overall mortality in these pedigrees was identical to that of the general Dutch population: (SMR 1.01, p = 0.441). However, compared with the general population the SMR was significantly higher in women aged 45–64 years (SMR 1.99, p = 0.00003), which was based on excess mortality between 1915 and 1964 (SMR 1.94, p < 0.00002). In men aged 70–74 years, the SMR was 1.55 (p = 0.0021), based on excess mortality that occurred between 1925 and 1964 (SMR 1.92, p = 0000000003). Overall, mortality from HMBS variant heterozygosity was not increased compared with the general population. Severe excess mortality occurred in young women and old men between 1915 and 1964. Heterozygotes reached a normal lifespan during the past half-century, in parallel with disease awareness and the prevention of new attacks through family counselling.

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Section: Discussioncontrasting

confidence: 79%

Mortality in Pedigrees with Acute Intermittent Porphyria

Neeleman

Musters

Wagenmakers

et al. 2022

Life

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“…Patients may also present with seizures, psychological symptoms, chronic pain, and neuropathy 5 . Associations have been found between AHP and long‐term complications (e.g., hypertension, chronic kidney disease, hepatocellular carcinoma) 6 …”

Section: Introductionmentioning

confidence: 99%

“… 5 Associations have been found between AHP and long‐term complications (e.g., hypertension, chronic kidney disease, hepatocellular carcinoma). 6 …”

Section: Introductionmentioning

confidence: 99%

Quantifying the impact of symptomatic acute hepatic porphyria on well‐being via patient‐reported outcomes: Results from the Porphyria Worldwide Patient Experience Research (POWER) study

et al. 2022

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Acute hepatic porphyria (AHP) is a group of rare genetic diseases of heme biosynthesis resulting in severe neurovisceral attacks and chronic complications that negatively impact patients' well‐being. This study evaluated the impacts of AHP on patients' physical and emotional health from a global perspective. Adult patients from the United States, Italy, Spain, Australia, Mexico, and Brazil with AHP with >1 porphyria attack within the past 2 years or receiving intravenous hemin and/or glucose for attack prevention completed an online survey assessing demographics, health characteristics, and patient‐reported outcomes. Results were analyzed collectively and by patient subgroups. Ninety‐two patients with AHP across the six countries completed the survey. More than 70% of patients reported that their physical, emotional, and financial health was fair or poor. Among patients who reported pain, fatigue, and muscle weakness, 94.3%, 95.6%, and 91.4%, respectively, reported that these symptoms limited daily activities. Moderate to severe depression was present in 58.7% of patients, and moderate to severe anxiety in 48.9% of patients. Of the 47% of patients who were employed, 36.8% reported loss in productivity while at work. Among patients, 85.9% reported that they had to change or modify goals that were important to them because of AHP. Aside from differences in healthcare utilization and pain severity, scores did not significantly vary with attack rate or use of hemin or glucose prophylactic treatments. AHP substantially impacts patients' physical and emotional well‐being, regardless of hemin or glucose prophylactic treatment or frequency of attacks. This multinational study demonstrates that there is substantial disease burden for patients with AHP, even among those experiencing sporadic attacks or using prophylactic treatment.

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“…A third to a half of cases reported back pain mainly in the lumbar area ( 8 , 17 ). The back and limb pain were pooled together in most studies with prevalence of 25% in mild sporadic attacks ( 18 ) and 50–70% in severe or mixed attacks suggesting partial association with neuropathy ( 5 ).…”

Section: Clinical Presentation Of Painmentioning

confidence: 99%

“…Although most (82–94.4%) AHP patients do not feel pain outside the attacks ( 9 , 17 ), some groups of patients frequently report mild to moderate chronic pain:…”

Section: Clinical Presentation Of Painmentioning

confidence: 99%

Pain in acute hepatic porphyrias: Updates on pathophysiology and management

2022

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Acute hepatic porphyrias (AHPs) typically present with recurrent acute attacks of severe abdominal pain and acute autonomic dysfunction. While chronic symptoms were historically overlooked in the literature, recent studies have reported increased prevalence of chronic, mainly neuropathic, pain between the attacks. Here we characterize acute and chronic pain as prominent manifestations of the AHPs and discuss their pathophysiology and updated management. In addition to the severe abdominal pain, patients could experience low back pain, limb pain, and headache during acute attacks. Chronic pain between the attacks is typically neuropathic and reported mainly by patients who undergo recurrent attacks. While the acute abdominal pain during attacks is likely mediated by autonomic neuropathy, chronic pain likely represents delayed recovery of the acute neuropathy with ongoing small fiber neuropathy in addition to peripheral and/or central sensitization. δ-aminolaevulinic acid (ALA) plays a major role in acute and chronic pain via its neurotoxic effect, especially where the blood-nerve barrier is less restrictive or absent i.e., the autonomic ganglia, nerve roots, and free nerve endings. For earlier diagnosis, we recommend testing a spot urine porphobilinogen (PBG) analysis in any patient with recurrent severe acute abdominal pain with no obvious explanation, especially if associated with neuropathic pain, hyponatremia, autonomic dysfunction, or encephalopathy. Of note, it is mandatory to exclude AHPs in any acute painful neuropathy. Between the attacks, diagnostic testing for AHPs should be considered for patients with a past medical history of acute/subacute neuropathy, frequent emergency room visits with abdominal pain, and behavioral changes. Pain during the attacks should be treated with opiates combined with hemin infusions. Symptomatic treatment of chronic pain should start with gabapentinoids and certain antidepressants before opiates. Givosiran reduces levels of ALA and PBG and likely has long-term benefits for chronic pain, especially if started early during the course of the disease.

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Long-term follow-up of acute porphyria in female patients: Update of clinical outcome and life expectancy

Cited by 14 publications

References 32 publications

Mortality in Pedigrees with Acute Intermittent Porphyria

Mortality in Pedigrees with Acute Intermittent Porphyria

Quantifying the impact of symptomatic acute hepatic porphyria on well‐being via patient‐reported outcomes: Results from the Porphyria Worldwide Patient Experience Research (POWER) study

Pain in acute hepatic porphyrias: Updates on pathophysiology and management

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