PAPA Syndrome

Pyogenic arthritis, pyoderma gangrenosum and acne

Summary

PAPA is an extremely rare disease that usually presents in childhood. The abbreviation PAPA stands for Pyogenic (involving pus without there being an infection) Arthritis (inflammation of the joints), Pyoderma gangrenosum (abnormality of the skin, causing skin sores) and Acne. It is a hereditary disease. Treatment consists of anti-inflammatory medication.

Symptoms

The most common symptoms of this condition are arthritis (inflammation of the joints), pyoderma gangrenosum (skin ulcers) and acne. Rarely are all three symptoms present in the same patient at the same time. Arthritis occurs usually early in childhood (the first episode occurs between 1 and 10 years of age); it usually involves one joint at a time. The affected joint becomes swollen, painful and red. The clinical appearance resembles septic arthritis (arthritis caused by the presence of bacteria in the joint). Arthritis caused by PAPA syndrome can lead to damage to the cartilage of the joint and the nearby bone. The large ulcerative skin lesions often involve both legs. The cystic acne usually appears during adolescence and may persist into adulthood, involving the face and torso. Symptoms are often precipitated by minor injury to the skin or a joint.

Cause

PAPA syndrome is a genetic disease caused by small changes (mutations) in the genetic material.  The gene that is mutated in patients with PAPA is called PSTPIP1. The mutations change the function of the protein produced by this gene; this protein plays a role in regulating the inflammatory response. PAPA Syndrome is not contagious.

Inheritance

PAPA syndrome is inherited as an autosomal dominant disease. This means that it is not linked to gender. This usually also means that one of the parents has symptoms of the

disease. In many cases, individuals with the disease occur in different generations of a family. A person with PAPA syndrome has a 50% chance that his/her child will also have PAPA syndrome.

Diagnosis

PAPA syndrome will be initially diagnosed based on the clinical picture. If a child has recurrent episodes of painful arthritis that do not respond to antibiotics (in contrast to bacterial arthritis), PAPA syndrome should be considered. Arthritis and skin manifestations may not appear at the same time and may not be present in all patients. It is important that detailed questions are asked to find out if relatives have similar symptoms. Since the syndrome is inherited in an autosomal dominant fashion, there are usually other members of the family with similar symptoms. Blood tests can support the clinical suspicion of PAPA syndrome,

but cannot confirm it with certainty. This requires genetic analysis,

which can detect DNA mutations in the PSTPIP1 gene.

Treatment

Since PAPA syndrome is a genetic disorder, it cannot be cured. With

proper treatment, the inflammatory response in a joint can be reduced, to prevent

damage. This also applies to skin abnormalities, but their response to

medication is slow. Treatment of PAPA syndrome depends on the symptoms that occur. For arthritis, corticosteroids are prescribed, either by mouth or directly into the joint. In some cases, when the medication is not very effective and the inflammation recurs frequently, it is necessary to take corticosteroids for an extended period of time. Pyoderma gangrenosum shows some response to oral corticosteroids and can also be treated with local immunosuppressant and anti-inflammatory drugs. The response to medication is very slow and the lesions may be very painful. Recently, treatment with biologics has been reported to be effective for both the skin lesions and the arthritis. These biologics block IL-1 and TNF, two substances that are involved in triggering an inflammatory response.

Prognosis

The course of the disease is not the same in every child. An individual who carries the mutated gene may have no symptoms at all or may have very mild symptoms (variable penetrance). As the child gets older, the symptoms may change and often get milder as well. Once

permanent joint damage has occurred, this may lead to restriction of movement and premature wear and tear of the joint (= osteoarthritis). Acute episodes of arthritis may temporarily limit the child in his/her daily activities. However, if treated adequately, fast improvement is usually seen. Pyoderma gangrenosum can be very painful and it responds very slowly to treatment. Pyoderma gangrenosum in the face can be of great distress to patients. The patient’s self-image, self-confidence and emotional mood can suffer. In such cases, psychological help is definitely recommended. Children with PAPA syndrome can go to school and participate in sports activities. Later in life, there are also no restrictions with regard to sexuality, contraception and having children. However, on average 50% of these children will have PAPA syndrome.