For people with Cyclic Vomiting Syndrome (CVS) – a condition whose symptoms significantly overlap with those of porphyria – a long duration of illness, taking very hot showers/baths to lessen symptoms, and the coexistence of conditions, all are clinical features to prompt genetic testing for acute porphyria, according to a new study.
CVS is characterized by episodes of abdominal pain, nausea, and vomiting, which are similar to symptoms associated with attacks of acute porphyria.
The researchers had sought to identify clinical features of CVS that might suggest whether patients with the vomiting disorder might also have acute porphyria and should undergo genetic testing.
Although none of the cyclic vomiting syndrome patients in this study tested positive for porphyria-related gene mutations, the researchers recommended a one-time urine test for porphyria-related markers for a acute CVS episode to identify those who may have acute porphyria.
The researchers also noted that larger studies are needed to determine the prevalence of acute porphyria in the CVS population.
Disorders with overlapping symptoms
Entitled “Prevalence of undiagnosed acute hepatic porphyria in cyclic vomiting syndrome and overlap of clinical symptoms“, the study was published in the journal Digestive Diseases and Sciences.
The porphyrias are a group of genetic diseases caused by disturbances in the production of heme, a molecule essential for the transport of oxygen in living cells. Such disruptions lead to the toxic accumulation of heme precursors in various tissues. In cutaneous porphyrias, the symptoms mainly affect the skin, whereas in acute porphyrias, they mainly affect the nervous system.
Acute porphyrias are marked by sudden attacks of severe abdominal pain, nausea, and vomiting. Other accompanying symptoms may include anxiety, confusion, insomnia, muscle pain and weakness, and a burning or tingling sensation. Red to brownish urine may occur, along with skin lesions on sun-exposed areas, in some types of acute porphyrias.
CVS is a gut-brain interaction disorder characterized by repeated episodes of nausea and vomiting without apparent cause.
As with acute porphyria, these episodes alternate with longer periods without symptoms. As such, there is considerable symptom overlap between acute porphyria and CVS.
However, it is unknown if there is a subset of CVS patients who have underlying porphyria.
To find out, investigators in the United States asked adults with CVS to fill out a detailed questionnaire about their symptoms.
To be eligible for genetic testing for porphyria, patients had to have experienced recurrent episodes of severe abdominal pain in addition to two or more other symptoms. These typical symptoms of porphyria included red/brownish urine, blistering skin lesions, muscle weakness, numbness, tingling, impaired mental health, high blood pressure (hypertension), irregular heartbeat, or constipation.
The survey was completed by 234 people, with an average age of 38.7 years. Among them, 180 (76.9%) were women. Most participants reported anxiety (68.4%), depression (55.6%), and a history of migraines (53.4%). Irritable bowel syndrome (26.9%), chronic fatigue syndrome (16.2%) and fibromyalgia (10.3%) were also noted as symptoms.
Almost two-thirds (63.7%) of patients said that CVS interfered with their work, and about half (47.4%) took very hot showers or baths to alleviate CVS symptoms.
Although two people reported a family history of porphyria, neither had markers of the disease in their urine, analyzed before study participation. Samples were tested for the heme precursors porphobilinogen (PBG) and aminolevulinic acid (ALA).
During a CVS episode, more than 85% of participants experienced various nervous system symptoms, similar to those of acute porphyrias. Reddish-brown urine was reported in 60.3% of cases. About a quarter (23.5%) of patients reported bullous skin lesions during a CVS episode.
“The reasons for this finding are unclear, and future research to objectively evaluate these findings is warranted,” the team wrote.
Genetic testing yields no positive results
Tests to identify genetic mutations associated with known types of porphyria were completed by 91 of the eligible CVS patients. Among them, only two carried variants of uncertain significance (VUS), which are previously identified genetic variants whose impact in porphyria is unknown.
These variants were found in HMBS gene, which is associated with a form of porphyria called acute intermittent porphyria. Urine tests for ALA and PBG, completed by either of these two individuals, were normal. The remaining 89 participants tested negative for mutations that cause or likely cause acute porphyria.
Individual clinical factors that predicted the need for genetic testing for porphyria in CVS patients included hospitalization due to CVS symptoms within the past year and the presence of coexisting medical conditions.
Eligible participants were also more likely to suffer from irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, depression and migraines.
The researchers also noted that eligible patients were more likely to take hot baths/showers to relieve their symptoms and to have employment problems due to CVS.
In the final adjusted statistical calculations, coexisting conditions, longer duration of CVS symptoms, and hot showers/baths were identified as predictors of acute porphyria test eligibility in CVS patients.
Conversely, gender, age, ethnicity, cigarette smoking, and cannabis use were not predictive.
“Our study did not reveal any positive individuals for [acute porphyria] based on genetic testing,” the researchers wrote. “Although the prevalence of [acute porphyria] is low in the general population, we hypothesized that an enriched sample showing symptoms of [acute porphyria] could yield positive results.
Still, further testing needs to be done in this patient population, the team recommended.
“Rapid and accurate diagnosis and treatment of CVS and AHP will significantly improve patient outcomes and reduce unnecessary investigations and healthcare utilization,” they wrote.
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