Granulomatosis with polyangiitis

Today, I learned about a new, nasty autoimmune disease called Granulomatosis with polyangiitis (GPA). By analogy, M.S., is an autoimmune disease that causes the immune system to attack the myelin that insulates the nervous system, while GPA causes the immune system to attack the small and medium sized blood vessels that feed key organs like those in the upper respiratory system and the kidneys.

GPA was first identified as a condition by Heinz Klinger, a German medical student, in 1931. Several years later, a German pathologist, Friedrich Wegener, a nasty and unethical Nazi doctor, found additional cases and his name was associated with the disease until the medical community decided that he didn't deserve the recognition.

It had a two year survival rate of under 10% until the 1970s, when immune suppressant drugs and steroid based treatments have brought five year survival rates to 80% or more with some people living as long as twenty years or more after diagnosis. But, 86% of the time, survival comes with serious complications: mainly chronic kidney failure, hearing loss, and deafness. Also, like cancer treatments, GPA treatments often have serious side effects of their own. Remissions following treatment are common (75%), but so are recurrences (they occur in about 50% of people who experience remissions).

GPA afflicts about 1000 people a year in the United States. It affects men and women in roughly equal numbers. It is rare in African-Americans and in Japan. It appears to be most common in Northern Europe with an incidence of up to three and a half times that of the United States. GPA is most common in middle-aged adults, with an average age of onset between 40 and 65 years. It is rare in children, but has been seen in infants as young as 3 months old.

The cause of GPA is unknown, although germs, such as bacteria and viruses, as well as genetics, have been implicated in the biological mechanism by which the disease progresses. According to the Mayo Clinic:

No one knows exactly what causes granulomatosis with polyangiitis. It appears to develop after an infection or other inflammation-causing event triggers an abnormal reaction from your immune system. 

This reaction can lead to inflamed, constricted blood vessels and harmful inflammatory tissue masses (granulomas). Granulomas can destroy normal tissue, and narrowed blood vessels reduce the amount of blood and oxygen that reaches your body's tissues and organs.

It isn't easy to diagnose:

Initial signs are extremely variable, and diagnosis can be severely delayed due to the nonspecific nature of the symptoms. In general, rhinitis is the first sign in most people. Involvement of the upper respiratory tract, such as the nose and sinuses, is seen in nearly all people with GPA.Typical signs and symptoms of nose or sinus involvement include crusting around the nose, stuffiness, nosebleeds, runny nose, and saddle-nose deformity due to a perforated septum. Scleritis and conjunctivitis are the most common ocular signs of GPA; involvement of the eyes is common and occurs in slightly more than half of people with the disease. Other signs and symptoms include: 

• Kidney: rapidly progressive glomerulonephritis (75%), leading to chronic kidney failure

• Upper airway, eye and ear disease:

• Ears: conductive hearing loss due to auditory tube dysfunction, sensorineural hearing loss (unclear mechanism)

• Oral cavity: strawberry gingivitis, underlying bone destruction with loosening of teeth, non-specific ulcerations throughout oral mucosa

• Trachea: subglottal stenosis

• Lungs: pulmonary nodules (referred to as "coin lesions"), infiltrates (often interpreted as pneumonia), cavitary lesions, pulmonary haemorrhage causing haemoptysis, and rarely bronchial stenosis.

• Arthritis: Pain or swelling (60%), often initially diagnosed as rheumatoid arthritis

• Skin: subcutaneous nodules (granulomas) on the elbow, purpura, various others (see cutaneous vasculitis)

• Nervous system: occasionally sensory neuropathy (10%) and rarely mononeuritis multiplex

• Heart, gastrointestinal tract, brain, other organs: rarely affected.

GPA came to my attention because author L.J. Smith (most famous for her "Vampire Diaries" series that was made into a long running television show) was diagnosed with it in 2015 at about age 49.