scholarly journals Clinical and genetic characteristics of PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dan Zhang ◽  
Gaixiu Su ◽  
Yan Liu ◽  
Jianming Lai
Keyword(s):  
Genetic Testing ◽  
Pyoderma Gangrenosum ◽  
White Blood Cells ◽  
Skin Lesions ◽  
Coombs Test ◽  
Genetic Characteristics ◽  
Normal Patient ◽  
Angina Patient ◽  
Reactive Protein ◽  
Pyogenic Arthritis

Abstract Objective To summarise the clinical and genetic characteristics of three children with PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome. Methods This study retrospectively analysed the clinical and genetic data of three children with PAMI syndrome in our hospital between April 2018 and January 2020. Results One male and two female children were 6 years and 5 months, 8 years and 7 months, and 13 years and 3 months of age. All three patients had a recurrent blood trilineage hypoplasia and splenomegaly. Patient 1 had pyoderma gangrenosum, and Ludwig’s 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 mg/L (elevated). Patient 3: Antinuclear antibodies (ANA), 1:100, β2 glycoprotein I, positive; Coombs test, positive; RF, 28.3 U/ml (elevated); C3, 0.77 g/L (decreased). Genetic testing showed that all 3 patients had PSTPIP1 c.748G > A (p.E250K) spontaneous heterozygous mutations, suggesting the diagnosis of PAMI syndrome. Patient 1 was treated with a combination of methylprednisolone and cyclosporine for 8 months. 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 2–3 × 109/L. The haematocrit, platelets, CRP, and AESR were normal. Patient 3 was treated with methylprednisolone, methotrexate, and infliximab 4 times. The patient’s 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. Conclusion 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.

Clinical characteristics and genetic analysis of 3 A20 Haploinsufficiency patients

2021 ◽  
Author(s):  
Dan Zhang ◽  
Zhixuan Zhou ◽  
Jianming Lai ◽  
Gaixiu Su
Keyword(s):  
Genetic Testing ◽  
Age Of Onset ◽  
Immunosuppressive Agents ◽  
Disease Patient ◽  
Gastrointestinal Symptoms ◽  
Coombs Test ◽  
Gradual Improvement ◽  
Genetic Characteristics ◽  
Tnfaip3 Gene ◽  
Oral Ulcers

Abstract Backguound To evaluate the clinical and genetic characteristics of 3 children with HA20. Methods The clinical and genetic testing data of 3 children with HA20 treated at CIP between August 2016 and October 2019 were retrospectively analysed. Results Patient 1 presented with arthritis and inflammatory bowel disease, patient 2 presented with axial spinal arthritis and lupus-like syndrome, and patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses. For laboratory examination, In patient 1, the WBC,CRP and AESR showed high. In patient 2, the WBC was normal, but CRP and AESR showed high. In patient 3, the WBC, CRP, and AESR showed high. Patient 2 was positive for antinuclear antibodies, anti-Sjögren’s syndrome antigen A, dsDNA, rheumatoid factor and Coombs test. Genetic testing showed that the 3 patients were heterozygous for mutations in the TNFAIP3 gene. For treatment, patient 1 used TNFα antagonist and thalidomide, patient 2 used TNFαantagonist and sulfasalazine, and patient 3 used hormones and thalidomide. Patients 1 and 2 were followed up for 4 and 3 months, respectively. There was improvement in joint and gastrointestinal symptoms, inflammatory indices and RF were normal, dsDNA and Coombs test became negative. Patient 3 was treated at an outside hospital and showed gradual improvement in oral ulcers and perianal abscesses. Conclusion HA20 is a single-gene auto-inflammatory disease caused by mutation in the TNFAIP3 gene. It presents clinically as a Behçet-like syndrome and can present as various other autoimmune diseases as well. Hormones and immunosuppressive agents are effective treatments, and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing should be proactively performed for children with an early age of onset or Behçet-like presentation to achieve early diagnosis and accurate treatment.

scholarly journals Analysis of the Clinical and Genetic Characteristics of 3 Cases of A20 Haploinsufficiency

2020 ◽  
Author(s):  
Dan Zhang ◽  
Zhixuan Zhou ◽  
Jianming Lai ◽  
Gaixiu Su
Keyword(s):  
Genetic Testing ◽  
Age Of Onset ◽  
Immunosuppressive Agents ◽  
Disease Patient ◽  
Gastrointestinal Symptoms ◽  
Coombs Test ◽  
Gradual Improvement ◽  
Genetic Characteristics ◽  
Tnfaip3 Gene ◽  
Oral Ulcers

Abstract Background To evaluate the clinical and genetic characteristics of 3 children with HA20. Methods The clinical and genetic testing data of 3 children with HA20 treated at CIP between August 2016 and October 2019 were retrospectively analysed. Results Patient 1 presented with arthritis and inflammatory bowel disease, patient 2 presented with axial spinal arthritis and lupus-like syndrome, and patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses. For laboratory examination, In patient 1, the WBC,CRP and AESR showed high. In patient 2, the WBC was normal, but CRP and AESR showed high. In patient 3, the WBC, CRP, and AESR showed high. Patient 2 was positive for antinuclear antibodies, anti-Sjögren’s syndrome antigen A, dsDNA, rheumatoid factor and Coombs test. Genetic testing showed that the 3 patients were heterozygous for mutations in the TNFAIP3 gene. For treatment, patient 1 used TNFα antagonist and thalidomide, patient 2 used TNFαantagonist and sulfasalazine, and patient 3 used hormones and thalidomide. Patients 1 and 2 were followed up for 4 and 3 months, respectively. There was improvement in joint and gastrointestinal symptoms, inflammatory indices and RF were normal, dsDNA and Coombs test became negative. Patient 3 was treated at an outside hospital and showed gradual improvement in oral ulcers and perianal abscesses. Conclusion HA20 is a single-gene auto-inflammatory disease caused by mutation in the TNFAIP3 gene. It presents clinically as a Behçet-like syndrome and can present as various other autoimmune diseases as well. Hormones and immunosuppressive agents are effective treatments, and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing should be proactively performed for children with an early age of onset or Behçet-like presentation to achieve early diagnosis and accurate treatment.

scholarly journals Chitinase-3-like Protein 1 (YKL-40): A New Biomarker of Inflamma­tion in Pyoderma Gangrenosum

2021 ◽  
Author(s):  
Alina Jankowska-Konsur ◽  
Magdalena Łyko ◽  
Klaudia Rubas ◽  
Danuta Nowicka-Suszko ◽  
Joanna Maj ◽  
...  
Keyword(s):  
Serum Level ◽  
Pyoderma Gangrenosum ◽  
Skin Lesions ◽  
Enzyme Linked Immunosorbent Assay ◽  
C Reactive Protein ◽  
Blood Cell Count ◽  
Inflammatory Biomarker ◽  
Reactive Protein ◽  
Inflammatory Parameters ◽  
Immune Mediated

Pyoderma gangrenosum (PG) is a rare, neutrophil­ic dermatosis with unclear aetiopathology, considered as an autoinflammatory disease, associated with other immune-mediated disorders. Chitinase-3-like protein 1 (YKL-40) is an inflammatory biomarker secreted by a wide variety of cells, including neutrophils. To evaluate YKL-40 serum level in relation to clinicopathological data, 48 patients with PG and 40 healthy controls were enrolled in the study. Skin lesions were measured to calculate the affected area. Inflammatory parameters (C-reactive protein, white blood cell count with neutrophils) were determined from blood samples. YKL-40 and IL-6 levels were measured in serum by enzyme-linked immunosorbent assay. YKL-40 serum level was significantly higher in patients with PG than in controls (58.4 vs 36.4 ng/ml, respectively; p < 0.00001). The positive correlation between YKL-40 level and IL-6 level was observed (r=0.48, p = 0.0006) along with a trend towards significance of relationship between YKL-40 level and C-reactive protein (r=0.28, p = 0.052). YKL-40 can be considered a valuable biomarker of inflammation in PG.

scholarly journals Case Report: Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne: A Single-Center Experience and Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Yumei Wang ◽  
Na Wu ◽  
Keyi Yu ◽  
Min Shen
Keyword(s):  
Literature Review ◽  
Pyoderma Gangrenosum ◽  
Skin Lesions ◽  
Single Center ◽  
Intermittent Fever ◽  
Chinese Han ◽  
Full Spectrum ◽  
Papa Syndrome ◽  
Classical Triad ◽  
Pyogenic Arthritis

ObjectivesThis study aims to describe the characteristics of patients diagnosed with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome at a single center in China and provide an up-to-date literature review.MethodsThe clinical data and genotype of three Chinese Han patients were carefully documented and studied. We also conducted a systematic literature review on PAPA syndrome.ResultsA total of three patients were diagnosed with PAPA syndrome at our center from 2018 to 2020. Arthritis was observed in all three patients, while pyoderma gangrenosum (PG) was found in two patients and acne in one patient. Other manifestations included pathergy reaction, intermittent fever, oral ulcer, keratitis, proteinuria, and hematuria. The PSTPIP1 A230T mutation was identified in two patients, and a novel Y119C variation was revealed in a sporadic patient. A total of 76 patients with PAPA syndrome reported in 29 articles were included in our literature review. The classical triad of arthritis, PG, and acne was visible in only 16 (25.4%) patients, while 24 (38.1%) exhibited only one major symptom. Skin lesions were more commonly seen in patients with adult-onset disease than those with childhood-onset disease (100 vs. 83%), whereas arthritis was less common (50 vs. 98.1%). Steroid and/or biological agents were effective in most patients.ConclusionsThe rarity and phenotypic heterogeneity associated with PAPA syndrome make the diagnosis a huge challenge to physicians, especially in adult patients. A significant portion of patients did not exhibit the full spectrum of the classical triad. Accordingly, gene testing is critically helpful for diagnosis.

scholarly journals Clinical characteristics and genetic analysis of A20 haploinsufficiency

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dan Zhang ◽  
Gaixiu Su ◽  
Zhixuan Zhou ◽  
Jianming Lai
Keyword(s):  
Genetic Testing ◽  
Rheumatoid Factor ◽  
Immunosuppressive Agents ◽  
Disease Patient ◽  
Coombs Test ◽  
Gradual Improvement ◽  
Genetic Characteristics ◽  
Tnfaip3 Gene ◽  
Oral Ulcers ◽  
Tnf Α

Abstract Purpose To evaluate the clinical and genetic characteristics of 3 children with Haploinsufficiency of A20 (HA20). Methods:The clinical and genetic testing data of 3 children with HA20 treated at Capital Institute of Pediatrics (CIP) between August 2016 and October 2019 were retrospectively analysed. Result Patient 1 presented with arthritis and inflammatory bowel disease, patient 2 presented with axial spinal arthritis and lupus-like syndrome, and patient 3 presented with recurrent oral ulcers, gastrointestinal ulcers, and perianal abscesses. Regarding laboratory tests, patients were found to have elevated white blood cell (WBC) count, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The CRP and ESR was reported to be high in all the patients. The WBC was reported to be high in patient 1 and 3. Patient 2 was positive for antinuclear antibodies, anti-Sjögren’s syndrome antigen A, dsDNA, rheumatoid factor and Coombs test. Genetic testing showed that all three patients had heterozygous mutation in TNFAIP3 gene. As for the treatment, patient 1 was treated with TNFα antagonist, patient 2 was treated with TNF α antagonist and sulfasalazine, and patient 3 was treated with corticosteroids and thalidomide. Patients 1 and 2 were followed for four and 3 months, respectively. There was an improvement in joint and gastrointestinal symptoms; inflammatory indices and rheumatoid factor (RF) were normal, and dsDNA and Coombs test became negative. Patient 3 was treated at another hospital and showed gradual improvement in oral ulcers and perianal abscesses. Conclusion HA20 is a single-gene auto-inflammatory disease caused by mutation in tumour necrosis factor (TNF)-α-induced protein 3 (TNFAIP3) gene. It may present as Behçet-like syndrome and resemble various other autoimmune diseases as well. Corticosteroids and immunosuppressive agents are effective treatments, and cytokine antagonists can be used in refractory cases. Whole-exome genetic testing should be proactively performed for children with early-age onset or Behçet-like syndrome to achieve early diagnosis and accurate treatment.

scholarly journals Clinical and Molecular Characteristics and Outcome of Cystic Partially Differentiated Nephroblastoma and Cystic Nephroma: A Narrative Review of the Literature

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 997
Author(s):  
Sophie E. van Peer ◽  
Corine J. H. Pleijte ◽  
Ronald R. de Krijger ◽  
Marjolijn C. J. Jongmans ◽  
Roland P. Kuiper ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Genetic Testing ◽  
Renal Tumor ◽  
Molecular Characteristics ◽  
Extensive Literature ◽  
Cystic Nephroma ◽  
Limited Information ◽  
Review Of The Literature ◽  
Genetic Characteristics ◽  
Excellent Outcome

In children presenting with a predominantly cystic renal tumor, the most likely diagnoses include cystic partially differentiated nephroblastoma (CPDN) and cystic nephroma (CN). Both entities are rare and limited information on the clinical and molecular characteristics, treatment, and outcome is available since large cohort studies are lacking. We performed an extensive literature review, in which we identified 113 CPDN and 167 CN. The median age at presentation for CPDN and CN was 12 months (range: 3 weeks–4 years) and 16 months (prenatal diagnosis–16 years), respectively. No patients presented with metastatic disease. Bilateral disease occurred in both entities. Surgery was the main treatment for both. Two/113 CPDN patients and 26/167 CN patients had previous, concomitant, or subsequent other tumors. Unlike CPDN, CN was strongly associated with somatic (n = 27/29) and germline (n = 12/12) DICER1-mutations. Four CPDN patients and one CN patient relapsed. Death was reported in six/103 patients with CPDN and six/118 CN patients, none directly due to disease. In conclusion, children with CPDN and CN are young, do not present with metastases, and have an excellent outcome. Awareness of concomitant or subsequent tumors and genetic testing is important. International registration of cystic renal tumor cohorts is required to enable a better understanding of clinical and genetic characteristics.

scholarly journals POS0826 SKIN LIMITED IGA VASCULITIS IN ADULTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 666.1-666
Author(s):  
A. Hočevar ◽  
J. Ostrovrsnik ◽  
K. Perdan-Pirkmajer ◽  
M. Tomsic ◽  
Z. Rotar
Keyword(s):  
Clinical Characteristics ◽  
Systemic Disease ◽  
Elevated Serum ◽  
Skin Lesions ◽  
Current Smoker ◽  
P Value ◽  
Symptom Duration ◽  
Iga Vasculitis ◽  
Reactive Protein

Background:IgA vasculitis (IgAV) could be limited to skin or evolve into a systemic disease, affecting characteristically joints, gastrointestinal tract and/or kidneys.Objectives:We aimed to look for differences between adult IgAV patients with disease limited to skin compared to systemic IgAV.Methods:Medical records of histologically proven adult IgAV cases, diagnosed between January 2010 and December 2020 at our secondary/tertiary rheumatology centre were analyzed.Results:During the 132-month observation period we identified 328 new IgAV cases (59.5% males, median (IQR) age 64.3 (45.1; 76.1) years). Ninety-four (40.2%) patients had skin limited disease, and the rest systemic IgAV.Clinical differences between skin limited and systemic adult IgAV are presented in table 1. Adults with IgAV limited to skin were significantly older, had less commonly skin lesions above the waistline and a lower level of C reactive protein compared to patients with a systemic disease. There were no differences in the frequency of skin necroses between the compared IgAV subgroups. The frequency of potential vasculitis triggers (prior infections, new medications, malignancy) was similar between the compared subgroups.Table 1.Clinical characteristics of IgA vasculitis patients with skin limited and systemic diseaseClinical characteristicsSkin limited IgAV (94)Systemic IgAV (234)P valueMale gender (%)54.361.50.263Age (years)*68.0 (55.0-80.5)61.5 (41.7-75.8)0.007Current smoker (%)13.821.80.123Antecedent infection (%)28.733.80.434New medication23.423.51.0History of cancer12.810.70.569Symptom duration (days)*7 (5-21)8 (5-14)0.756Purpura above waistline36.255.60.002Skin necroses (%)52.145.70.329ESR /mm/h) *32 (18-52)34 (17-53)0.873CRP (g/l) *13.5 (1-32)30 (11-68)<0.001Elevated serum IgA (%)50.649.10.892Legend: * median and IQR;Follow up data were available for 250 (76.2%) patients. During the follow up of median (IQR) 12.5 (6.8 – 22.4) months 35 patients relapsed (13/70 (18.6%) with skin limited IgAV and 22/180 (12.2%) with systemic IgAV, p= 0.224).Conclusion:Skin limited IgAV was associated with older age and less extensive skin puprura in adults. However, relapses of purpura were as common as in systemic IgAV.Disclosure of Interests:None declared

scholarly journals Routine blood tests as a potential diagnostic tool for COVID-19

2020 ◽  
Vol 58 (7) ◽  
pp. 1095-1099 ◽  
Author(s):  
Davide Ferrari ◽  
Andrea Motta ◽  
Marta Strollo ◽  
Giuseppe Banfi ◽  
Massimo Locatelli
Keyword(s):  
Blood Test ◽  
Hematological Parameters ◽  
False Negative ◽  
White Blood Cells ◽  
Turnaround Time ◽  
Test Analysis ◽  
Infected People ◽  
Reactive Protein ◽  
Routine Blood ◽  
Glutamyl Transpeptidase

AbstractObjectivesThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to date, the epidemic has gradually spread to 209 countries worldwide with more than 1.5 million infected people and 100,000 deaths. Amplification of viral RNA by rRT-PCR serves as the gold standard for confirmation of infection, yet it needs a long turnaround time (3–4 h to generate results) and shows false-negative rates as large as 15%–20%. In addition, the need of certified laboratories, expensive equipment and trained personnel led many countries to limit the rRT-PCR tests only to individuals with pronounced respiratory syndrome symptoms. Thus, there is a need for alternative, less expensive and more accessible tests.MethodsWe analyzed the plasma levels of white blood cells (WBCs), platelets, C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), alkaline phosphatase and lactate dehydrogenase (LDH) of 207 patients who, after being admitted to the emergency room of the San Raffaele Hospital (Milan, Italy) with COVID-19 symptoms, were rRT-PCR tested. Of them, 105 tested positive, whereas 102 tested negative.ResultsStatistically significant differences were observed for WBC, CRP, AST, ALT and LDH. Empirical thresholds for AST and LDH allowed the identification of 70% of either COVID-19-positive or -negative patients on the basis of routine blood test results.ConclusionsCombining appropriate cutoffs for certain hematological parameters could help in identifying false-positive/negative rRT-PCR tests. Blood test analysis might be used as an alternative to rRT-PCR for identifying COVID-19-positive patients in those countries which suffer from a large shortage of rRT-PCR reagents and/or specialized laboratory.

scholarly journals The Efficacy of Convalescent Plasma Use in Critically Ill COVID-19 Patients

Medicina ◽  
2021 ◽  
Vol 57 (3) ◽  
pp. 257
Author(s):  
Livius Tirnea ◽  
Felix Bratosin ◽  
Iulia Vidican ◽  
Bianca Cerbu ◽  
Mirela Turaiche ◽  
...  
Keyword(s):  
Pilot Study ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Therapeutic Option ◽  
White Blood Cells ◽  
The United States ◽  
Plasma Therapy ◽  
Reactive Protein ◽  
United States Food ◽  
States Food

Background and Objectives: On 24 March 2020, the United States Food and Drug Administration (FDA) announced the approval of convalescent plasma therapy for critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergency investigational new drug. This pilot study from Romania aimed to determine if convalescent plasma transfusion can be beneficial in the treatment of selected critically ill patients diagnosed with a SARS-CoV-2 infection. Materials and Methods: Donor and receiver eligibility for critically ill coronavirus disease 2019 (COVID-19) patients was based on Romanian guidelines issued at the time of the study. Here, we describe the evolution of a total of five eligible patients diagnosed with COVID-19 who received convalescent plasma (CP) in Romania. Results: In spite of our efforts and convalescent plasma administration, three of the five patients did not survive, while the other two recovered completely. Over the course of our five-day laboratory record, the surviving patients had significantly lower values for C-reactive protein, interleukin-6, and white blood cells. Conclusions: This pilot study provides insufficient evidence to determine the efficacy of convalescent plasma use as a therapeutic option for critically ill COVID-19 patients.

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