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Rheumatology
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Clarissa Pilkington, Kiran Nistala, Helen Lachman, Paul Brogan
The periodic fever syndromes are disorders of innate immunity, now usually referred to as autoinflammatory diseases. They are characterised by the following: Recurring episodes of fever and constitutional upset, but with normal health between attacks.Systemic inflammatory symptoms affecting: serosal surfacesjointsskineyes.Biochemical markers of inflammation: raised ESR, CRP and leucocytosis.Near normal life expectancy, except for risk of developing AA amyloidosis in later life.Seven major inherited syndromes are well described, but many new monogenic autoinflammatory diseases have recently been discovered (Table 17.1): FMF.TNF receptor-associated period syndrome (TRAPS).mevalonate kinase deficiency (MKD) (also known as hyperimmunoglobulin D and periodic fever syndrome [HIDS]).cryopyrin-associated periodic syndrome (CAPS) (subdivided into familial cold autoinflammatory syndrome [FCAS], Muckle Wells syndrome [MWS] and chronic infantile, neurological, cutaneous and articular syndrome/neonatal onset multi-system inflammatory disease [CINCA/NOMID]).pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome.deficiency of IL-1 receptor antagonist (DIRA).Blau syndrome/early onset sarcoidosis (EOS).
An update on the pathogenesis of hidradenitis suppurativa: implications for therapy
Published in Expert Review of Clinical Immunology, 2018
Deborah Negus, Christine Ahn, William Huang
PAPA syndrome was first defined in 1997 as an autosomal dominant inherited disorder caused by a mutation in the PSTPIP1 gene in most cases, although it may also rarely be sporadic [25]. PSTPIP encodes proline–serine–threonine phosphatase-interacting protein 1, which acts as an adaptor protein of the inflammasome protein complex. Mutations in PSTPIP1-encoded proteins affect the inflammasome or the proteins regulating its function, leading to alterations in the inflammatory signaling pathway. Increased activation of the inflammasome through increased binding affinity to pyrin leads to the activation of caspase-1, which cleaves pro- IL-1β into its active isoform, IL-1β. The end result of this pathway is neutrophil-mediated inflammation and overproduction of IL-1β and IL-17 [26,27]. Mutations in PSTPIP1 have also been identified in PAPASH and PsAPASH syndromes, as well as PAC syndrome, which encompasses PG, acne, and ulcerative colitis, but not HS [28,29]. In contrast, PASH syndrome notably lacks mutations in the PSTPIP1 gene in all but one case reported in the literature, suggested that it is likely a polygenetic entity [25,30].
A developing portrait of hereditary periodic fevers in childhood
Published in Expert Opinion on Orphan Drugs, 2018
Additional diseases characterized by recurrent fevers with an autoinflammatory basis can be gathered in the family of sterile neutrophilic disorders. PAPA (or pyogenic arthritis, pyoderma gangrenosum, acne) syndrome (OMIM 604416) is a rare autosomal-dominant disease caused by mutations in the PSTPIP1 gene, encoding the protein proline-serine-threonine phosphatase-interacting protein 1, a cytoskeleton-associated adaptor protein that interestingly binds pyrin and regulates IL-1β production. PSTPIP1 mutations cause an increased recruitment of caspase-1, inducing excessive IL-1β release [51]. This syndrome is defined by self-limited episodes of oligoarthritides with accumulation of sterile neutrophil-rich material in the synovial fluid and disfiguring purulent skin lesions, which may evolve into necrotic plaques or deep ulcers with undermined violaceous borders, usually healing with atrophic scars [52]. Necessary is differentiating PAPA syndrome from its variants PASH syndrome, consisting of pyoderma gangrenosum, acne and hidradenitis suppurativa, and PAPASH syndrome, consisting of pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa [53]. Clinical management of PAPA syndrome is challenging, due to limited evidence and lack of clinical practice guidelines: treatment should be tailored according to the disease severity and might include corticosteroids, TNF inhibitors, IL-1 antagonists, cyclosporine, thalidomide, or tacrolimus [54].
A case of myeloperoxidase–antineutrophil cytoplasmic antibody and anticardiolipin antibody-positive pyogenic arthritis, pyoderma gangrenosum, acne and hidradenitis suppurativa (PAPASH) syndrome with colitis
Published in Modern Rheumatology Case Reports, 2021
Keishu Kawanishi, Hiroki Nishiwaki, Tsuyoshi Oshiro, Hideto Kajitani, Masahito Amagasa, Natsumi Uehara, Yoshihiko Inoue, Masatsugu Nagahama, Fumihiko Koiwa
PAPA syndrome is a syndrome with a triad of necrotising pyoderma, acne and aseptic pyogenic arthritis. PAC syndrome presents with PG, acne and UC. PAPASH syndrome is a subtype of PAPA spectrum disorder that presents with pyogenic arthritis in addition to PG, acne and hidradenitis suppurativa [2]. This patient’s diagnosis was likely PAPASH syndrome combined with inflammatory bowel disease.