The case of a man with hereditary angioedema (HAE) who remained undiagnosed for 62 years underscores the importance of carefully evaluating not only the clinical data of suspected patients, but also their family history.
Due to the diagnosis delay the patient was submitted to multiple hospital admissions and ineffective and distressful interventions.
A family history of angioedema symptoms was ignored by consulting physicians and he was only diagnosed after the mother of one of his grandsons suspected of HAE in her child.
Based on information she found on a patient association website, she suggested blood tests (for C4 and C1 esterase inhibitor) that led to the appropriate diagnosis of HAE type 1 in her son and the other affected family members.
The report, “The physician and hereditary angioedema friend or foe: 62-year diagnostic delay and iatrogenic procedures,” was published in the journal Allergy, Asthma & Clinical Immunology.
It describes the case of a 72-year-old man in Bulgaria who started to experience the first symptoms of disease — recurrent and severe abdominal pain — at the age of 8.
The episodes usually began as a colic-like pain that progressively spread to the entire abdomen, accompanied by vomiting, diarrhea, debilitation, and often a temporary loss of consciousness.
During his adolescence and early adulthood, he began to experience episodes of subcutaneous (under the skin) swellings, frequently triggered by minor injuries.
The attacks lasted for two to three days, or more, and did not respond to anti-allergic therapy. A skin rash also occurred sometimes.
The family history suggested the presence of an inherited condition because the patient’s father had similar symptoms; but this evidence was ignored by physicians at the time.
Following his 26th birthday, and for the next 30 years, the patient continued to experience frequent events of abdominal pain, which made him pay numerous visits to the emergency room. He was admitted four to six times a year to the hospital, without receiving a definitive diagnosis.
The multiple diagnosis included cholecystitis (inflammation of the gallbladder), mechanical ileus (bowel obstruction) and acute volvulus (twist in the intestine that causes bowel obstruction).
Several benign colon polyps (small cell overgrowth in the large intestine) were removed through surgery, but seemed unrelated to the patient’s abdominal symptoms.
The patient refused further surgeries given the ineffective and worsening interventions he had experienced.
At age 70, one of his grandsons developed recurrent episodes of face, mouth and throat swellings and abdominal pain, which lasted for one week and were resistant to anti-allergic therapy.
The attacks were unrelated to any obvious trigger (e.g., food, drugs) except that, sometimes, they appeared to be provoked by injuries.
The boy’s mother noticed that similar symptoms had occurred in at least three generations of her husband’s family. She went to search on the internet for possible illnesses associated with such signs and symptoms.
After reading a patient association website, she began suspecting HAE and suggested the boy should be tested for a deficiency in complement C4 and C1 esterase inhibitors (C1-INH) proteins — two biochemical markers of HAE.
The results confirmed the diagnosis of HAE type 1 (reduced blood levels of C1 inhibitor) both in the child and six other family members, including the boy’s grandfather, who had remained undiagnosed almost his entire life.
All patients were treated for bradykinin-mediated angioedema. Adults were given Pharming’s Ruconest (recombinant human CI-INH), and children were treated with CSL Behring’s Berinert (C1-INH), all with a good clinical response.
Researchers now emphasize the importance of looking at the family history of patients suspected of HAE, as the disease may be present in successive generations.
“Therefore, wholesale screening by history and physical, with targeted C1-INH and C4 testing should become the standard of practice for all family members of a patient with HAE,” they stressed.
The study also highlights “the importance of accurate, publicly available information provided by patient associations (http://www.haei.org) and the general paradigm shift towards (…) individualized diagnosis and treatment in rare diseases.”
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