{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T14:36:23Z","timestamp":1775918183637,"version":"3.50.1"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T00:00:00Z","timestamp":1633564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>To summarise the clinical and genetic characteristics of three children with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study retrospectively analysed the clinical and genetic data of three children with PAMI syndrome in our hospital between April 2018 and January 2020.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>One male and two female children were 6\u2009years and 5\u2009months, 8\u2009years and 7\u2009months, and 13\u2009years and 3\u2009months of age. All three patients had a recurrent blood trilineage hypoplasia and splenomegaly. Patient 1 had pyoderma gangrenosum, and Ludwig\u2019s angina. Patient 2 had pyogenic arthritis, and pyoderma gangrenosum. Patient 3 had hepatomegaly, pyogenic arthritis, and pulmonary hypertension. Laboratory tests revealed that all three children had elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Patient 1: C-antineutrophilic cytoplasmic antibodies(c-ANCA), positive; antiglobulin test (Coombs), positive. Patient 2: blood zinc, 4.38\u2009mg\/L (elevated). Patient 3: Antinuclear antibodies (ANA), 1:100, \u03b22 glycoprotein I, positive; Coombs test, positive; RF, 28.3\u2009U\/ml (elevated); C3, 0.77\u2009g\/L (decreased). Genetic testing showed that all 3 patients had PSTPIP1 c.748G\u2009&gt;\u2009A (p.E250K) spontaneous heterozygous mutations, suggesting the diagnosis of PAMI syndrome. Patient 1 was treated with a combination of methylprednisolone and cyclosporine for 8\u2009months. The patient did not develop new skin lesions. The blood count showed mild neutropenia. The spleen was considerably retracted and the CRP became normal. Patient 2 was treated with etanercept and methylprednisolone. The patient had no further arthralgias and pyoderma gangrenosum showed improvement. The spleen was smaller than before. White blood cells were shown to be approximately 2\u20133\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L. The haematocrit, platelets, CRP, and AESR were normal. Patient 3 was treated with methylprednisolone, methotrexate, and infliximab 4 times. The patient\u2019s joint symptoms disappeared gradually and the liver retracted markedly. The pulmonary artery pressure returned to normal. Moreover, Coombs test result was negative. CRP and AESR were lower than before.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>PAMI syndrome can manifest as pyogenic arthritis, pyoderma gangrenosum, acne, and trilineage hypoplasia, as well as autoimmune diseases. Glucocorticoid and immunosuppressive therapy are partially effective and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing is helpful to confirm diagnosis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12969-021-00636-9","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T12:37:17Z","timestamp":1633610237000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Clinical and genetic characteristics of PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome"],"prefix":"10.1186","volume":"19","author":[{"given":"Dan","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6453-5085","authenticated-orcid":false,"given":"Gaixiu","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianming","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,7]]},"reference":[{"issue":"5","key":"636_CR1","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1007\/s10875-019-00646-z","volume":"39","author":"P Dai","year":"2019","unstructured":"Dai P, Furlong T, Gracie G, Huang ML, Yang T, Wu KHC, et al. Autoinflammation masquerading as autoimmunity in an adult with heterozygous p.E250K PSTPIP1 mutation. J Clin Immunol. 2019;39(5):519\u201322. https:\/\/doi.org\/10.1007\/s10875-019-00646-z.","journal-title":"J Clin Immunol"},{"issue":"6","key":"636_CR2","first-page":"113","volume":"Suppl 108","author":"E Belelli","year":"2017","unstructured":"Belelli E, Passarelli C, Pardeo M, Holzinger D, De Benedetti F, Insalaco A. Haematological involvement associated with a mild autoinflammatory phenotype, in two patients carrying the E250K mutation of PSTPIP1. Clin Exp Rheumatol. 2017;Suppl 108(6):113\u20135.","journal-title":"Clin Exp Rheumatol"},{"issue":"6","key":"636_CR3","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1016\/j.jaci.2018.01.030","volume":"142","author":"J WJM","year":"2018","unstructured":"WJM J, Grobarova V, Leleux J, Jongeneel L, van Gijn M, van Montfrans JM, et al. Proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1) controls immune synapse stability in human T cells. J Allergy Clin Immunol. 2018;142(6):1947\u201355. https:\/\/doi.org\/10.1016\/j.jaci.2018.01.030.","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"636_CR4","first-page":"956","volume":"32","author":"BM Fathalla","year":"2014","unstructured":"Fathalla BM, Al-Wahadneh AM, Al-Mutawa M, Kambouris M, El-Shanti H. A novel de novo PSTPIP1 mutation in a boy with pyogenic arthritis, pyoderma gangrenosum, acne (PAPA) syndrome. Clin Exp Rheumatol. 2014;32(6):956\u20138.","journal-title":"Clin Exp Rheumatol"},{"issue":"1","key":"636_CR5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s00247-018-4246-1","volume":"49","author":"C Martinez-Rios","year":"2019","unstructured":"Martinez-Rios C, Jariwala MP, Highmore K, Duffy KW, Spiegel L, Ronald M. Laxer, Jennifer Stimec, Imaging findings of sterile pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome: differential diagnosis and review of the literature. Pediatr Radiol. 2019;49(1):23\u201336. https:\/\/doi.org\/10.1007\/s00247-018-4246-1.","journal-title":"Pediatr Radiol"},{"issue":"6","key":"636_CR6","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1001\/jamadermatol.2013.2907","volume":"149","author":"AV Marzano","year":"2013","unstructured":"Marzano AV, Trevisan V, Gattorno M, Ceccherini I, De Simone C, Crosti C. Pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PAPASH): a new autoinflammatory syndrome associated with a novel mutation of the PSTPIP1 gene. JAMA Dermatol. 2013;149(6):762\u20134. https:\/\/doi.org\/10.1001\/jamadermatol.2013.2907.","journal-title":"JAMA Dermatol"},{"issue":"2","key":"636_CR7","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1001\/2013","volume":"149","author":"A Geusau","year":"2013","unstructured":"Geusau A, Mothes-Luksch N, Nahavandi H, Pickl WF, Wise CA, Pourpak Z, et al. Identification of a homozygous PSTPIP1 mutation in a patient with a PAPA-like syndrome responding to canakinumab treatment. JAMA Dermatol. 2013;149(2):209\u201315. https:\/\/doi.org\/10.1001\/2013.","journal-title":"JAMA Dermatol"},{"issue":"4","key":"636_CR8","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1111\/ced.12585","volume":"40","author":"T Zeeli","year":"2015","unstructured":"Zeeli T, Padalon-Brauch G, Ellenbogen E, Gat A, Sarig O, Sprecher E. Pyoderma gangrenosum, acne and ulcerative colitis in a patient with a novel mutation in the PSTPIP1 gene. Clin Exp Dermatol. 2015;40(4):367\u201372. https:\/\/doi.org\/10.1111\/ced.12585.","journal-title":"Clin Exp Dermatol"},{"issue":"4","key":"636_CR9","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1111\/bjd.16136","volume":"178","author":"HW Kl\u00f6tgen","year":"2018","unstructured":"Kl\u00f6tgen HW, Beltraminelli H, Yawalkar N, van Gijn ME, Holzinger D, Borradori L. The expanding spectrum of clinical phenotypes associated with PSTPIP1 mutations: from PAPA to PAMI syndrome and beyond. Br J Dermatol. 2018;178(4):982\u20133. https:\/\/doi.org\/10.1111\/bjd.16136.","journal-title":"Br J Dermatol"},{"issue":"1","key":"636_CR10","doi-asserted-by":"publisher","first-page":"e27439","DOI":"10.1002\/pbc.27439","volume":"66","author":"SK Hashmi","year":"2019","unstructured":"Hashmi SK, Bergstrom K, Bertuch AA, Despotovic JM, Muscal E, Xia F, et al. PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome: A rare cause of childhood neutropenia associated with systemic inflammation and hyperzincemia. Pediatr Blood Cancer. 2019;66(1):e27439. https:\/\/doi.org\/10.1002\/pbc.27439.","journal-title":"Pediatr Blood Cancer"},{"issue":"20","key":"636_CR11","doi-asserted-by":"publisher","first-page":"31764","DOI":"10.1016\/j.jaci.2020.11.043","volume":"S0091\u20136749","author":"A Laberko","year":"2020","unstructured":"Laberko A, Burlakov V, Maier S, Abinun M, Skinner R, Kozlova A, et al. HSCT is effective in patients with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome. J Allergy Clin Immunol. 2020;S0091\u20136749(20):31764\u20134. https:\/\/doi.org\/10.1016\/j.jaci.2020.11.043.","journal-title":"J Allergy Clin Immunol"}],"container-title":["Pediatric Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-021-00636-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12969-021-00636-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-021-00636-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T12:41:22Z","timestamp":1633610482000},"score":1,"resource":{"primary":{"URL":"https:\/\/ped-rheum.biomedcentral.com\/articles\/10.1186\/s12969-021-00636-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,7]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["636"],"URL":"https:\/\/doi.org\/10.1186\/s12969-021-00636-9","relation":{},"ISSN":["1546-0096"],"issn-type":[{"value":"1546-0096","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,7]]},"assertion":[{"value":"29 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declares that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"151"}}