On Thursday, we challenged Well readers to take on the case of a 15-year-old boy with the worst headache of his life. I thought it was a fascinating case and apparently so did many of you. More than 120 readers offered some very thoughtful possibilities and nearly two dozen of you got it right.
The correct diagnosis is:
Hereditary Hemorrhagic Telangiectasias (H.H.T.), or Osler, Weber, Rendu disease.
The first person to identify this unusual inherited disorder was M. Noelle Knight, a veterinarian and Ph.D. candidate at the University of Pennsylvania. Dr. Knight is the second veterinarian to win this contest. Perhaps not coincidentally, she is married to the first vet who won. However, Dr. Knight didn’t need any help making this diagnosis. She has close friends who have this disorder and recognized it immediately. Indeed, hers was the first answer posted, just 10 minutes after the story went online.
The Diagnosis:
H.H.T. is an inherited disorder of abnormal blood vessels in which the usually strong muscular structure of even the smallest vessels instead have thin, delicate walls that have a tendency to dilate and rupture. When these abnormalities occur in the superficial layers of the skin, the bulge caused by the dilated capillary can be seen in the form of tiny red spots that often disappear with pressure only to reappear seconds later. These spots, called telangiectasias, have a tendency to bleed, especially when they form on the more delicate mucus membranes of the lips, mouth, nose and other parts of the gastrointestinal tract.
Indeed, frequent, often daily, nose bleeds – especially those that occur at night – are a hallmark of the disease. The bleeding can be profuse and some with H.H.T. will require transfusions as a result of these frequent episodes of bleeding.
Patients with H.H.T. also have a tendency to form abnormal connections between vessels. Usually arteries (the vessels that carry oxygenated blood from the heart to the rest of the body) are connected to veins (which take deoxygenated blood back to the heart) through a network of capillaries. These are strong but thin-walled vessels where oxygen is delivered to the body and carbon dioxide, along with other waste products, is transferred from the body into the blood stream to be disposed of.
These abnormal connections, known as arteriovenous malformations, or A.V.M.s, can occur anywhere, but are most common in the lungs, liver and brain. At these sites, bacteria and other impurities that have accumulated in the blood stream can bypass the natural filtering organs and pass directly into the body through the arteries. There, this detritus can find new lodging and potentially new trouble. If it lodges in the brain it can cause a stroke or, as in the case of this young man, an infection.
Although H.H.T. is an inherited condition, those who have it may not develop symptoms or signs of these abnormal blood vessels until their teens. Most will have frequent nosebleeds – starting in childhood. The characteristic telangiectasias usually appear on lips, gums, inner cheeks or nasal tissue by young adulthood.
The disease was first recognized as an inherited tendency to bleed in the 19th century. In 1896 Dr. Henri Rendu differentiated the condition from hemophilia when he gave a detailed description of a 52-year-old man with frequent nose bleeds. Dr. Rendu recorded the presence of multiple red spots on the skin of the man’s face and trunk as well as his lips, tongue and palate, and speculated that similar lesions in the nose were probably responsible for the frequent episodes of bleeding there. Dr. Rendu noted that the man’s mother had experienced similar problems.
Until the end of the 20th century the diagnosis of H.H.T. was based exclusively on clinical and radiographic findings. Frequent bleeding from the nose or gastrointestinal tract, plus a family history of the disease, or the presence of telangectasias or A.V.M.s were the diagnostic criteria. Any three of the four was enough to define a case of H.H.T.
In 1994, the first gene linked to the disorder was identified. Since then more than 600 genetic mutations have been linked to H.H.T.
How the Diagnosis Was Made:
Once it was clear that the young man had an abscess in his brain, the team caring for the boy reached out to Dr. Bishara Freij, a pediatric infectious disease specialist, to help identify the source of the infection and choose the best antibiotic. Dr. Freij reviewed the chart and imaging, then headed to the ICU to meet the family and examine his new patient.
The brain is very well protected from most infections externally by the skull and internally by the blood brain barrier, a network of vessels that allows only a few substances (oxygen, some fats, some sugars) to move from the circulatory system into the tissues of the brain. Thus most abscesses are spread directly through brain tissue from existing infections in the ears or sinuses or teeth. However, careful examination of the young man showed no sign of infection anywhere beyond his gauze swathed head.
Nor did the completed blood tests offer any clues to the source of the infection. At the time of the young man’s admission to the hospital, an M.R.I. of the brain and face had been done and confirmed the presence of a large abscess. There were no other abnormalities seen. A chest X-ray was also uninformative on initial read. However, Dr. David Bloom, a pediatric radiologist that Dr. Freij had known and respected for many years, reread the X-ray that morning and he thought there was a subtle abnormality in the lower part of the right lung. After talking with the patient and his family, Dr. Freij headed down to the radiology suite to try to figure out what this abnormality might be and if it could be connected to the boy’s infection.
A Light in the Darkness
Dr. Freij found Dr. Bloom sitting in the darkened radiology suite, illuminated only by the light from the screen before him. The radiologist pulled up the chest X-ray and pointed to a dim but discreet area of lightness where the lung should be mostly dark. What was that?
A favorite teacher once told Dr. Bloom that having a good brain was good, but having old films was even better and so Dr. Bloom had gone back to earlier X-rays. One of the advantages of electronic medical records is that information recorded at different times and often in different places can be immediately available. A quick search had turned up two X-rays done within the past couple of years.
There, he pointed to the same area on each of the images. It was subtle but persistent. Based on the location and appearance, Dr. Bloom thought it probably represented a pulmonary A.V.M. A CT scan confirmed the finding.
A pulmonary A.V.M. made sense. The abnormal communication between the venous system and one of the arteries that took blood to the brain would allow bacteria that should have been filtered out by the lung direct access to the brain. Most of the time the blood brain barrier provides protection from infection. Most of the time, but not always.
Up to 85 percent of patients with pulmonary A.V.M.s will have Hereditary Hemorrhagic Telangiectasia. And Dr. Freij was confident that was what this patient had. On exam he had seen evidence of a bloody nose, though he hadn’t seen any of the characteristic telangiectasias. Still, it was the most likely diagnosis.
The usual treatment for A.V.M.s is to close the vessel off completely using what is known as a coil. These tiny pieces of wire, some no wider than a human hair, are placed into the abnormal vessel. Once there, they take the shape of the vessel and cause clots to form, blocking blood flow.
Home at Last:
After weeks of treatment, the patient was finally able to go home. His most significant souvenir from the ordeal was a loss of vision on his right side. He spent weeks working with an occupational therapist learning how to compensate for this loss. He knew he would never get that sight back, but he learned how to see just as well without it. He was able to go back to school with just two weeks left in the year. He had 21 tests to make up, including both midterms and finals. He managed to finish up on time and in fact ended up with straight A’s. He was a little disappointed, he told me, that one was an A-.
His mother knew he was fully recovered later that summer when he pitched in a championship game. Seeing him on the mound, looking like he always had, brought tears to her eyes. She could hardly watch the game, she was so moved by the sight.
But all that was years ago. These days he’s working on a Ph.D. with an eye on med school once he’s done. His goal: to find a cure for H.H.T.