Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne Syndrome Maps to Chromosome 15q

Abstract

Pyoderma gangrenosum, cystic acne, and aseptic arthritis are clinically distinct disorders within the broad class of inflammatory diseases. Although this triad of symptoms is rarely observed in a single patient, a three-generation kindred with autosomal-dominant transmission of these three disorders has been reported as "PAPA syndrome" (MIM 604416). We report mapping of a disease locus for familial pyoderma gangrenosum-acne-arthritis to the long arm of chromosome 15 (maximum two-point LOD score, 5.83; recombination fraction [straight theta] 0 at locus D15S206). Under the assumption of complete penetrance, haplotype analysis of recombination events defined a disease interval of 10 cM, between D15S1023 and D15S979. Successful identification of a single disease locus for this syndrome suggests that these clinically distinct disorders may share a genetic etiology. These data further indicate the role of genes outside the major histocompatibility locus in inflammatory disease.

Management of pyoderma gangrenosum

“…Poorer prognosis has been suggested in PG ulcers associated with arthritis, 5 with slower healing and longer treatment duration compared to PG ulcers in general. PAPA syndrome (pyogenic arthritis, PG and acne) is a rare autosomal dominant autoinflammatory syndrome, caused by mutations in the proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene on chromosome 15q, 6 with several mutations identified. Recently, a new syndrome was described in two unrelated patients 7 : PASH syndrome consists …”

Identification of a Homozygous PSTPIP1 Mutation in a Patient With a PAPA-Like Syndrome Responding to Canakinumab Treatment

“…8 So far, 34 affected individuals from 5 families (2 in the United States, 1 in Italy, 1 in the Netherlands, and 1 in New Zealand) have been described worldwide. 5,[8][9][10][11][12] Pyogenic sterile arthritis resulting in joint mutilation is reportedly the most common clinical representation. However, PAPA syndrome manifestations vary among family members carrying the mutation and can lack the clinical characteristics such as PG or a late onset in life.…”

Gene Therapy for Pyoderma Gangrenosum: Optimal Transfection Conditions and Effect of Drugs on Gene Delivery in the HaCaT Cell Line Using Cationic Liposomes

“…PG is one feature of PAPA syndrome (pyogenic arthritis, PG and acne) [1,67,68], an autosomal-dominantly inherited disease. The genetic defect in this syndrome has been mapped to chromosome 15q [69] and is caused by mutations in the PSTPIP1 gene, which encodes CD2 binding protein 1, involved in regulation of the inflammatory response [70,71]. A further syndrome, PG, acne and suppurative hidradenitis (PASH), has also been described in unrelated individuals, and may or may not have an underlying genetic component [72].…”