Mayo Clinic Proceedings
A New Autosomal Dominant Disorder of Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, and Acne: PAPA Syndrome

https://doi.org/10.4065/72.7.611Get rights and content

Objective

To describe a multigenerational family with transmission of an autosomal dominant disorder characterized by pyogenic arthritis, pyoderma gangrenosum, and severe cystic acne.

Material and Methods

We present a detailed case report of a 39-year-old man with arthritic changes in several joints, pyoderma gangrenosum, and cystic acne. Several relatives from three generations of his family underwent clinical and genetic investigations. The findings in this kindred are reported.

Results

Ten affected family members in three generations manifested variable expression of a pauciarticular, nonaxial, destructive, corticosteroid-responsive arthritis that began in childhood; pyoderma gangrenosum; and severe cystic acne in adolescence and beyond. Other less commonly associated features included adult-onset insulin-dependent diabetes mellitus, proteinuria, abscess formation at the site of parenteral injections, and cytopenias attributable to sulfonamide medications. Laboratory evaluation was nondiagnostic. Genetic studies excluded linkage to the major histocompatibility locus.

conclusion

The acronym of PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) is suggested for this newly recognized pleiotropic autosomal dominant disorder. The nature of the genetic alteration in PAPA syndrome is unknown.

Section snippets

REPORT OF CASE

A 39-year-old man had a 20-year history of recurrent leg ulcerations. He described the occurrence of erythematous papules with occasional pustule formation, which broke down spontaneously and rapidly enlarged to form leg ulcers. Initially, these lesions were treated conservatively, and they healed during a period of months. In later years, the leg ulcers became more chronic, and at the time of the current examination, he had an ulcer on the left leg that had been present for 3½ years, waxing

METHODS

Clinical Evaluations.—Family members were assessed by review of medical records or history and physical examination. Family members who were 16 years of age or older were classified as definitely affected if they had two of three major findings: sterile pyogenic arthritis, pyoderma gangrenosum, or severe acne. Adults with one major finding were considered probably affected. Family members younger than 16 years of age were considered affected if sterile pyogenic arthritis was substantiated in

RESULTS

In addition to the proband, eight other family members had childhood onset of relapsing, sterile, intensely inflammatory, destructive, nonaxial arthritides, which occurred after minor joint trauma or without antecedent trauma (Table 1). Radiologic findings included periosteal proliferation of involved joints and, in some cases, ankylosis. Synovial fluid aspirations from various affected family members yielded seropurulent, purulent, cloudy, yellow, or frankly bloody specimens. Microorganisms

DISCUSSION

Herein we report a new autosomal dominant disorder—characterized by pyogenic (but aseptic) arthritis, pyoderma gangrenosum, and severe cystic acne—and suggest the acronym of PAPA syndrome. This syndrome is pleiotropic (affects more than one tissue) and is variably expressed (affected persons may manifest only some of the PAPA features). Typically, joint disease precedes the onset of skin disorders, which seem to develop during puberty. Affected persons may have sulfonamide-induced pancytopenia

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