Pyogenic arthritis, pyoderma gangrenosum and acne

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Pyogenic arthritis-pyoderma gangrenosum-acne syndrome is a rare pleiotropic autoinflammatory disorder of childhood, primarily affecting the joints and skin.

To date, only 34 patients with PAPA syndrome have been reported worldwide, from five families (two in the USA, one in Italy, one in the Netherlands, and one in New Zealand).

The first affected family contained ten affected members from three generations and manifested variable expression of a pauciarticular, nonaxial, arthritis that began in childhood; pyoderma gangrenosum; and severe cystic acne in adolescence and beyond. PAPA syndrome is a self-limiting disease, but it can lead to severe joint destruction. Synovial fluid is purulent with neutrophil accumulation, but cultures are invariably negative. Recurrent sterile arthritis usually occurs after minor trauma, but can also occur spontaneously. Other less commonly associated features include adult-onset insulin-dependent diabetes mellitus, proteinuria, and abscess formation at the site of parenteral injections (pathergy).

The gene responsible for the syndrome, the proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) gene (previously known as the CD2 binding protein 1 (CD2BP1) gene), was cloned in 2002. Only two mutations account for the known cases. Recently, the PSTPIP1 protein has been demonstrated to bind pyrin/marenostrin (P/M), the protein encoded by the MEFV gene, mutations in which cause Familial Mediterranean Fever. PAPA-associated PSTPIP1 mutants exhibit increased binding to P/M.

Differential diagnosis for PAPA syndrome should include juvenile idiopathic arthritis and periodic fever.

PAPA syndrome is inherited in an autosomal dominant manner.

Arthritis and skin lesions have sometimes been reported to be responsive to glucocorticoids. However, two alternative therapeutics have been suggested so far. In one report, the disease underwent rapid and sustained clinical remission after treatment withthe tumor necrosis factor inhibitor, etanercept. Another recent paper described the effect of recombinant human interleukin (IL)-1 receptor antagonist (anakinra), which appeared to be an effective therapy to treat disease flares in PAPA syndrome.

Visit the Orphanet disease page for more resources.

Last updated: 10/1/2006

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

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Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

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