Auto-inflammatory diseases of unknown cause

Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis (PFAPA)

This condition was first described in 1987 in otherwise healthy American children. Since then it has been diagnosed most frequently in children of European ancestry, and affects boys and girls equally.

The cause is unknown. But up to 1 in 5 of the children who fulfil the criteria for this condition have been found to carry a known fever gene mutation.

Symptoms usually start at around age 2, and include recurrent fever with one of the following:

  • mouth ulcers
  • swollen glands in the neck
  • sore throat

Children are completely well between attacks, and there are no signs of respiratory infection during the attacks.

As in all the inherited fever syndromes there are raised levels of inflammatory markers.

Attacks are often extremely regular, and parents may learn to plan around them in advance, often knowing exactly when an attack will occur.

Doctors must rule out recurrent infections, and problems with white cells levels, which can cause similar symptoms.

The treatment for this condition is corticosteroids, given by mouth. When given at the start of an attack, the effect is dramatic, as the attack is usually completely prevented. There is some evidence that tonsillectomy can cure this syndrome, especially in children with persistently enlarged tonsils. In some cases long term colchicine, given by mouth, can be very helpful in reducing or preventing attacks.  Most children outgrow the symptoms of this condition within a decade.

Schnitzler’s Syndrome

This rare condition was first described in 1974. The cause is unknown.

Symptoms usually start in middle age, but may, rarely, appear in younger adults. It is commoner in men than in women, and most common in Caucasians.

Symptoms include:

  • attacks of fever
  • recurrent urticarial rash
  • joint pain and swelling
  • swollen neck glands

Typical rash in patient with Schnitzler’s syndrome

Blood tests show signs of inflammation and increased quantities of a particular type of antibody produced by immune cells called plasma cells. This is known as a monoclonal gammopathy. Most patients do well over time, but some go on to develop plasma cell malignancy.

Drugs which block the inflammatory protein, IL-1 appear promising for treating this condition, although this is an off license use. These include:

  • Anakinra
  • Canakinumab

Anakinra has to be given at home every day, and Canakinumab is given every month.

The side effects of these drugs include:

  • stinging
  • skin redness at the injection site, in some people
  • increased risk of infection.

In general the infections reported have been mild but all patients should be screened for tuberculosis and asked about a history of other infections before starting such drugs.