Extensive pyoderma gangrenosum-like lesions revealing a case of hyperzincemia and hypercalprotectinemia: when to suspect it?

Resende, Ludimila O; Jorge, Marília Formentini Scotton; Schmitt, Juliano Vilaverde

doi:10.1016/j.abd.2018.12.001

Cited by 3 publications

(4 citation statements)

References 7 publications

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“…Hyperzincaemia and hypercalprotectinaemia (also known as PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome) is characterized by severe systemic and cutaneous inflammation, hepatosplenomegaly, arthritis, pancytopenia and failure to thrive owing to the accumulation of zinc 79 . Dermatological symptoms share clinical and histopathological similarities to pyoderma gangrenosum and include vasculitis, furuncle-like ulcers, and eczematous and necrotic lesions that typically affect the lower limbs symmetrically, although eyelids may also be involved 80 . In contrast to PAPA, the hyperzincaemia and hypercalprotectinaemia/PSTPIP1-associated myeloid-related proteinemia inflammatory phenotype has only been associated with a single amino acid change in PSTPIP1, altering the electrostatic potential and enhancing binding to pyrin 79 .…”

Section: Aetiology Of Autoinflammatory Diseasesmentioning

confidence: 99%

IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting

Broderick

Hoffman

2022

Nat Rev Rheumatol

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Over 20 years ago, it was first proposed that autoinflammation underpins a handful of rare monogenic disorders characterized by recurrent fever and systemic inflammation. The subsequent identification of novel, causative genes directly led to a better understanding of how the innate immune system is regulated under normal conditions, as well as its dysregulation associated with pathogenic mutations. Early on, IL-1 emerged as a central mediator for these diseases, based on data derived from patient cells, mutant mouse models and definitive clinical responses to IL-1 targeted therapy. Since that time, our understanding of the mechanisms of autoinflammation has expanded beyond IL-1 to additional innate immune processes. However, the number and complexity of IL-1-mediated autoinflammatory diseases has also multiplied to include additional monogenic syndromes with expanded genotypes and phenotypes, as well as more common polygenic disorders seen frequently by the practising clinician. In order to increase physician awareness and update rheumatologists who are likely to encounter these patients, this review discusses the general pathophysiological concepts of IL-1-mediated autoinflammation, the epidemiological and clinical features of specific diseases, diagnostic challenges and approaches, and current and future perspectives for therapy.

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Section: Aetiology Of Autoinflammatory Diseasesmentioning

confidence: 99%

IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting

Broderick

Hoffman

2022

Nat Rev Rheumatol

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“…Our review identified 252 articles through database searches. After eliminating duplicates and excluding unqualified articles, we included 25 relevant articles that described 43 patients with PAMI syndrome [ 1 , 2 , 3 , 5 , 6 , 7 , 8 , 9 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ].…”

Section: Resultsmentioning

confidence: 99%

“…While primarily affecting these areas, our review highlighted that other organs may also be affected considerably. Several authors have reported gastrointestinal involvement, with 16% of cases experiencing flare-ups of colitis and/or chronic diarrhea [ 3 , 16 , 19 , 20 , 24 , 28 , 29 ]. Notably, 57% of these patients developed the disease within the first few months of life, suggesting that PAMI syndrome should be considered in the differential diagnosis of early onset inflammatory bowel disease (IBD).…”

Section: Discussionmentioning

confidence: 99%

“…While primarily affecting these areas, our review highlighted that other organs may also be affected considerably. Several authors have reported gastrointestinal involvement, with 16% of cases experiencing flare-ups of colitis and/or chronic diarrhea [3,16,19,20,24,28,29]. Notably, 57% of these patients developed the disease within the first few months of life, suggesting that Notably, among the patients who received anti-IL1 therapy, 40% (6/15) showed significant improvement, either when given as monotherapy (4/6), or in combination therapy with cyclosporine (1/6) or tacrolimus and oral steroids (1/6).…”

Section: Discussionmentioning

confidence: 99%

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PSTPIP1-Associated Myeloid-Related Proteinemia Inflammatory (PAMI) Syndrome: A Systematic Review

Mejbri,

Renella,

Candotti

et al. 2023

Genes

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PSTPIP1 (proline-serine-threonine phosphatase-interactive protein 1)-associated myeloid-related proteinemia inflammatory (PAMI) syndrome, previously known as Hyperzincemia/Hypercalprotectinemia (Hz/Hc) syndrome, is a recently described, rare auto-inflammatory disorder caused by specific deleterious variants in the PSTPIP1 gene (p.E250K and p.E257K). The disease is characterized by chronic systemic inflammation, cutaneous and osteoarticular manifestations, hepatosplenomegaly, anemia, and neutropenia. Increased blood levels of MRP 8/14 and zinc distinguish this condition from other PSTPIP1-associated inflammatory diseases (PAID). The aim of this systematic review is to provide a comprehensive overview of the disease phenotype, course, treatment, and outcome based on reported cases. This systematic review adheres to the PRISMA guidelines (2020) for reporting. A literature search was performed in Embase, Medline, and Web of Science on 13 October 2022. The quality of the case reports and case series was assessed using the JBI checklists. Out of the 43 included patients with PAMI syndrome, there were 24 females and 19 males. The median age at onset was 3.9 years. The main clinical manifestations included anemia (100%), neutropenia (98%), cutaneous manifestations (74%), osteoarticular manifestations (72%), splenomegaly (70%), growth failure (57%), fever (51%), hepatomegaly (56%), and lymphadenopathy (39%). Systemic inflammation was described in all patients. Marked elevation of zinc and MRP 8/14 blood levels were observed in all tested patients. Response to treatment varied and no consistently effective therapy was identified. The most common therapeutic options were corticosteroids (N = 30), anakinra (N = 13), cyclosporine A (N = 11), canakinumab (N = 6), and anti-TNF (N = 14). Hematopoietic stem cell transplantation has been recently reported to be successful in five patients. Our review highlights the key characteristics of PAMI syndrome and the importance of considering this disease in the differential diagnosis of patients presenting with early-onset systemic inflammation and cytopenia.

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From bench to bedside: Calprotectin (S100A8/S100A9) as a biomarker in rheumatoid arthritis

2022

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S100A9/S100A8 (calprotectin), a member of the S100 protein family, has been shown to play a pivotal role in innate immunity activation. Calprotectin plays a critical role in the pathogenesis of rheumatoid arthritis (RA), as it triggers chemotaxis, phagocyte migration and modulation of neutrophils and macrophages. Higher calprotectin levels have been found in synovial fluid, plasma, and serum from RA patients. Recent studies have demonstrated better correlations between serum or plasma calprotectin and composite inflammatory disease activity indexes than c-reactive protein (CRP) or the erythrocyte sedimentation rate (ESR). Calprotectin serum levels decreased after treatment, independently of the DMARD type or strategy. Calprotectin has shown the strongest correlations with other sensitive techniques to detect inflammation, such as ultrasound. Calprotectin independently predicts radiographic progression. However, its value as a biomarker of treatment response and flare after tapering is unclear. This update reviews the current understanding of calprotectin in RA and discusses possible applications as a biomarker in clinical practice.

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Extensive pyoderma gangrenosum-like lesions revealing a case of hyperzincemia and hypercalprotectinemia: when to suspect it?

Cited by 3 publications

References 7 publications

IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting

IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting

PSTPIP1-Associated Myeloid-Related Proteinemia Inflammatory (PAMI) Syndrome: A Systematic Review

From bench to bedside: Calprotectin (S100A8/S100A9) as a biomarker in rheumatoid arthritis

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