Pyogenic arthritis, pyoderma gangrenosum and acne

Alternate names

PAPA syndrome; Pyogenic arthritis, pyoderma gangrenosum, and severe cystic acne; PAPAS; Familial recurrent arthritis; FRA

Definition

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

Epidemiology

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).

Cause

• 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.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

PAPA syndrome is inherited in an autosomal dominant manner.

Signs and symptoms

• 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).

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Acne
• Arthritis(Joint inflammation)
• Fatigue(Tired)
• Fever
• Limitation of joint mobility(Decreased joint mobility)
• Pustule(Pimple)
• Skin ulcer(Open skin sore)

30%-79% of people have these symptoms

• Arthralgia(Joint pain)
• Increased circulating antibody level
• Lymphadenopathy(Swollen lymph nodes)

5%-29% of people have these symptoms

• Crohn's disease
• Myositis(Muscle inflammation)
• Proteinuria(High urine protein levels)
• Type I diabetes mellitus(Type 1 diabetes)

1%-4% of people have these symptoms Allergy

• Cellulitis(Bacterial infection of skin)
• Colitis
• Cystic acne
• Elbow flexion contracture(Contractures of elbows)
• Elevated C-reactive protein level
• Hepatosplenomegaly(Enlarged liver and spleen)
• Knee flexion contracture
• Microcytic anemia
• Pyoderma gangrenosum
• Sterile arthritis
• Thrombocytosis(Increased number of platelets in blood)

Diagnosis

Clinical features along with the familial tendency may be enough to make a diagnosis. Genetic testing may also be used.

Differential diagnosis

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

Treatment

• 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 with the 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.

NIH genetic and rare disease info

• NIH info on Pyogenic arthritis, pyoderma gangrenosum and acne

Pyogenic arthritis, pyoderma gangrenosum and acne is a rare disease.

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