SUMMARY
1. Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) Syndrome is a rare autosomal dominant disease characterized by the following clinical symptoms:
Pyogenic arthritis
Pyoderma gangrenosum
Severe cystic acne
2. PAPA syndrome is caused by dominant mutations in the CD2BP1 (PSTPIP1) gene. The CD2BP1 protein is known to bind to pyrin, the protein mutated in familial mediterranean fever. A similar dysregulation of innate immunity likely underlies the inflammation seen in PAPA syndrome.
3. The diagnosis is made based on classic clinical criteria. Sequencing of the CD2BP1 (PSTPIP1) gene can confirm the diagnosis. This test is commercially available.
4. Variable results with anti-inflammatory therapies have been reported. PAPA is only partially responsive to treatment with oral and intra-articular steroids. Successful case reports of anti-TNF alpha and anti-IL-1 therapy have been reported.
OVERVIEW
Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) Syndrome is a rare autosomal dominant disease characterized by the following clinical symptoms:
-Pyogenic arthritis This is the first manifestation to appear (between age 1 and 16 years). It is typically an erosive oligoarticular sterile pyogenic arthritis involving the elbow, knee, or ankle. It may be triggered by mild trauma or occur spontaneously.
-Pyoderma gangrenosum This is characterized by poorly healing ulcerative skin lesions. Sterile abscess formation at injection sites occur in some patients.
-Severe cystic acne This feature develops later in life, often after puberty.
Pancytopenia following administration of sulfa-containing drugs may also occur.
PATHOGENESIS
PAPA syndrome is caused by dominant mutations in the CD2BP1 (PSTPIP1) gene. The CD2BP1 protein is known to bind to pyrin, the protein mutated in familial mediterranean fever. A similar dysregulation of innate immunity likely underlies the inflammation seen in PAPA syndrome.
EVALUATION
The diagnosis should be suspected in patients presenting with pyogenic arthritis and an autosomal dominant inheritance pattern. Severe cystic acne may be present in patients after puberty.
Step 1: Screening Studies
C reactive protein / Erythrocyte sedimentation rate
CRP and ESR may be markedly elevated
Step 2: Genetic Confirmation
CD2BP1 (PSTPIP1) gene sequencing
This is the definitive test for establishing a diagnosis of PAPA syndrome. This test is currently commercially available through Gene Dx.
MANAGEMENT
Variable results with anti-inflammatory therapies have been reported. PAPA is only partially responsive to treatment with oral and intra-articular steroids. Successful case reports of anti-TNF alpha and anti-IL-1 therapy have been reported.
RESOURCES
Diagnostic Resources
1. Gene Dx - PSTPIP1 gene sequencing
Literature Resources
1. Shoham 2003
Pyrin binds protein mutated in PAPA syndrome
2. Dierselhuis 2005
Successful use of Anakinra for pyogenic arthritis in PAPA syndrome
3. Stichweh 2005
Improvement of pyoderma gangrenosum in PAPA syndrome with Infliximab