PAPA Syndrome

PAPA syndrome is inherited in an autosomal dominant fashion, which means that there is a 50% chance that a child will inherit the disease from an affected parent. It usually begins with arthritis at a young age, with the skin changes more prominent from the time of puberty.

What is PAPA syndrome?

  • PAPA syndrome is an acronym for Pyogenic Arthritis, Pyoderma gangrenosum and Acne.

  • It is a rare genetic autoinflammatory disorder characterised by its effects on skin and joints.

  • It is also called PAPGA syndrome (Pyogenic Arthritis, Pyoderma Gangrenosum and Acne).

Causes of PAPA Syndrome

  • Recently the responsible gene, PSTPIP1, has been identified on Chromosome 15q24-q25.1.

  • Two mutations have been found in a protein called CD2 binding protein 1 (CD2BP1).

  • This protein is part of an inflammatory pathway associated with other autoinflammatory syndromes such as familial Mediterranean fever, hyper-IgD (HIDS) and periodic fever syndrome, Muckle-Wells syndrome (MWS), neonatal onset multisystem inflammatory disease and familial cold autoinflammatory syndrome (FCAS).

  • The exact mechanism of how the mutated gene causes the disease is still being investigated.

Symptoms of PAPA Syndrome

  • The arthritis is the predominant feature, noted by its juvenile onset and destructive course.

  • Individuals often recall episodes of arthritis precipitated by a traumatic event.

  • With repeated episodes the joints become damaged with multiple joint replacements required.

  • Hopefully with improved treatment options the damage will be limited in new cases.

  • Pyoderma gangrenosum is variably expressed, which means that it is not always present in all individuals with the disease. It presents as poorly healing ulcers with undermined edges.

  • Pathergy is an important feature (this term refers to the tendency of ulcers to arise at points of injury).

  • There are reports of lesions developing at the site of a joint replacement wound, central venous line and intravenous drip insertion.

  • Acne affects most individuals with PAPA syndrome but to a variable degree.

  • It is usually of a severe nodulocystic type which if untreated results in scarring.

Diagnosis of PAPA Syndrome

  • The clinical features along with the familial tendency may be enough to make a diagnosis, though gene testing may be available at some centres.

  • Prominent inflammation is seen in affected tissues, with a predominance of neutrophil white blood cells within a synovial biopsy (joint tissue) and skin biopsy.

  • Biopsies of pyoderma gangrenosum show superficial ulceration as well as neutrophilic inflammation.

Treatment of PAPA Syndrome

  • Acne treatment may require oral tetracycline antibiotics or isotretinoin.

  • Developments in the treatment of the arthritis and pyoderma gangrenosum are largely in the area of biological response modifiers.

  • These are drugs directed at particular inflammatory proteins (cytokines), and have shown success in the treatment of other inflammatory conditions like rheumatoid arthritis and psoriasis.

  • Treatments directed at tumour necrosis factor (TNF) (infliximab, etanercept, adalimumab) and interleukin 1 (anakinra) have shown a good response in resistant arthritis and pyoderma gangrenosum.

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