PAPA syndrome

Definition

PAPA stands for pyogenic arthritis, pyoderma gangrenosum and acne. It is a rare, autosomal dominantly inherited autoinflammatory disease caused by variants in the PSTPIP1 gene (CD2BP1) on chromosome 15q; it belongs to the PSTPIP1-associated inflammatory diseases.

Aetiopathogenesis

The altered PSTPIP1 proteins are hyperphosphorylated and bind more strongly to pyrin, the familial Mediterranean fever protein; both diseases therefore lie in the same pathway. The result is increased inflammasome activity with overproduction of interleukin-1β; the inflammation is mainly driven by granulocytes. De novo variants also occur.

Clinical features

• Onset in childhood or adolescence.
• Arthritis: the predominant feature, recurrent and destructive; flares are often triggered by trauma.
• Pyoderma gangrenosum: variably expressed; poorly healing ulcers with undermined edges; pathergy (lesions at sites of injury, e.g. catheter insertion sites).
• Acne: in most of those affected, usually a severe nodulocystic form, more prominent from puberty.
• Related conditions: PASH syndrome (pyoderma gangrenosum, acne, hidradenitis suppurativa) and PAPASH syndrome.

Histology

Neutrophil-rich inflammation in synovium and skin; biopsies of pyoderma gangrenosum show superficial ulceration with neutrophilic inflammation.

Diagnosis

• Clinical picture and familial clustering; molecular genetic detection of a PSTPIP1 variant.
• Laboratory: inflammatory markers (CRP, ESR) often markedly raised.
• Joint aspirate: neutrophil-rich; in one case report, repeatedly exceedingly high cell counts – distinguishing it from septic arthritis can be difficult.

Differential diagnoses

• SAPHO syndrome
• Pyoderma gangrenosum
• Hidradenitis suppurativa (acne inversa)
• PAPASH syndrome
• Acne fulminans
• Generalized pustular psoriasis (von Zumbusch)
• Sweet syndrome (acute febrile neutrophilic dermatosis)
• Acne vulgaris

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References (selection)

1. DermNet: PAPA syndrome
2. Clinical, Molecular, and Genetic Characteristics of PAPA Syndrome: A Review
3. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway
4. A de novo heterozygous PSTPIP1 variant associated with PAPA syndrome: a Chinese case report and literature review
5. Pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome: differential diagnosis of septic arthritis by regular detection of exceedingly high synovial cell counts

Cross-references