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Protein-losing enteropathy

MedGen UID:
19522
Concept ID:
C0033680
Disease or Syndrome
Synonyms: Protein-Losing Enteropathies; Protein-losing enteropathy (disease)
SNOMED CT: Protein-losing enteropathy (66972006); PLE - Protein-losing enteropathy (66972006); Exudative enteropathy (22542007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): CD55 (1q32.2)
 
HPO: HP:0002243
Monarch Initiative: MONDO:0009174
OMIM®: 226300
Orphanet: ORPHA566175

Definition

Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy (CHAPLE) is characterized by abdominal pain and diarrhea, primary intestinal lymphangiectasia, hypoproteinemic edema, and malabsorption. Some patients also exhibit bowel inflammation, recurrent infections associated with hypogammaglobulinemia, and/or angiopathic thromboembolic disease. Patient T lymphocytes show increased complement activation, causing surface deposition of complement and generating soluble C5a (Ozen et al., 2017). [from OMIM]

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Clubbing of fingers
MedGen UID:
3129
Concept ID:
C0009080
Finding
Terminal broadening of the fingers (distal phalanges of the fingers).
Clubbing
MedGen UID:
57692
Concept ID:
C0149651
Anatomical Abnormality
Broadening of the soft tissues (non-edematous swelling of soft tissues) of the digital tips in all dimensions associated with an increased longitudinal and lateral curvature of the nails.
Pulmonary embolism
MedGen UID:
11027
Concept ID:
C0034065
Pathologic Function
An embolus (that is, an abnormal particle circulating in the blood) located in the pulmonary artery and thereby blocking blood circulation to the lung. Usually the embolus is a blood clot that has developed in an extremity (for instance, a deep venous thrombosis), detached, and traveled through the circulation before becoming trapped in the pulmonary artery.
Budd-Chiari syndrome
MedGen UID:
163632
Concept ID:
C0856761
Disease or Syndrome
Budd-Chiari syndrome (BCS) is caused by obstruction of hepatic venous outflow at any level from the small hepatic veins to the junction of the inferior vena cava (IVC) with the right atrium, 1 and occurs in 1/100,000 of the general population worldwide. The most common presentation is with ascites, but can range from fulminant hepatic failure (FHF) to asymptomatic forms. Obstruction of hepatic venous outflow is mainly caused by primary intravascular thrombosis, which can occur suddenly or be repeated over time, accompanied by some revascularization, accounting for the variable parenchymal hepatic damage and histologic presentation. Budd-Chiari syndrome is thus a disease, but since it occurs as a manifestation of several other diseases, this term is kept for the present for convenience.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Ascites
MedGen UID:
416
Concept ID:
C0003962
Disease or Syndrome
Accumulation of fluid in the peritoneal cavity.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Intestinal obstruction
MedGen UID:
43933
Concept ID:
C0021843
Disease or Syndrome
Blockage or impairment of the normal flow of the contents of the intestine towards the anal canal.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Malabsorption
MedGen UID:
811453
Concept ID:
C3714745
Finding
Impaired ability to absorb one or more nutrients from the intestine.
Abnormal intestine morphology
MedGen UID:
1388201
Concept ID:
C4316788
Finding
An abnormality of the intestine. The closely related term enteropathy is used to refer to any disease of the intestine.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Hepatic vein thrombosis
MedGen UID:
9217
Concept ID:
C0019154
Disease or Syndrome
An obstruction in the veins of the liver caused by a blood clot (thrombosis).
Iron deficiency anemia
MedGen UID:
57668
Concept ID:
C0162316
Disease or Syndrome
Anemia caused by low iron intake, inefficient iron absorption in the gastrointestinal tract, or chronic blood loss.
Thrombocytosis
MedGen UID:
163397
Concept ID:
C0836924
Disease or Syndrome
Increased numbers of platelets in the peripheral blood.
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Intestinal lymphangiectasia
MedGen UID:
9828
Concept ID:
C0024215
Disease or Syndrome
Angiectasia of lymph vessels (i.e., dilatation of lymphatic vessels) in the intestines.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Decreased circulating antibody concentration
MedGen UID:
892481
Concept ID:
C4048270
Finding
An abnormally decreased level of immunoglobulin in blood.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Hypoalbuminemia
MedGen UID:
68694
Concept ID:
C0239981
Finding
Reduction in the concentration of albumin in the blood.
Hypoproteinemia
MedGen UID:
581229
Concept ID:
C0392692
Finding
A decreased concentration of protein in the blood.
Generalized edema
MedGen UID:
376817
Concept ID:
C1850534
Pathologic Function
Generalized abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.

Term Hierarchy

Conditions with this feature

Cronkhite-Canada syndrome
MedGen UID:
129128
Concept ID:
C0282207
Disease or Syndrome
Cronkhite-Canada syndrome is characterized by gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, skin hyperpigmentation, and diarrhea. It is associated with high morbidity (summary by Sweetser et al., 2012).
Cromer blood group system
MedGen UID:
450551
Concept ID:
C1292305
Body System
Vascular hyalinosis
MedGen UID:
376398
Concept ID:
C1848590
Disease or Syndrome
A rare systemic disease characterized by progressive hyalinosis involving capillaries, arterioles and small veins of the digestive tract, kidneys, and retina, associated with idiopathic cerebral calcifications, manifesting with severe diarrhea (with rectal bleeding and malabsorption), nephropathy (with renal failure and systemic hypertension), chorioretinal scarring, and subarachnoid hemorrhage. Poikiloderma and premature greying of the hair may be additionally observed.
Mullerian derivatives-lymphangiectasia-polydactyly syndrome
MedGen UID:
343489
Concept ID:
C1856159
Disease or Syndrome
A rare genetic disease characterized by the presence of Müllerian duct derivatives (rudimentary uterus, fallopian tubes, and atretic vagina) and other genital anomalies (cryptorchidism, micropenis) in male newborns, intestinal and pulmonary lymphangiectasia, protein-losing enteropathy, hepatomegaly, and renal anomalies. Postaxial polydactyly, facial dysmorphism (including broad nasal bridge, bulbous nasal tip, long and prominent upper lip with smooth philtrum, hypertrophic alveolar ridges, and mild retrognathia, among other features), and short limbs have also been described. The syndrome is fatal in infancy.
MPI-congenital disorder of glycosylation
MedGen UID:
400692
Concept ID:
C1865145
Disease or Syndrome
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006). For a discussion of the classification of CDGs, see CDG1A (212065). CDG Ib is clinically distinct from most other CDGs by the lack of significant central nervous system involvement. The predominant symptoms are chronic diarrhea with failure to thrive and protein-losing enteropathy with coagulopathy. Some patients develop hepatic fibrosis. CDG Ib is also different from other CDGs in that it can be treated effectively with oral mannose supplementation, but can be fatal if untreated (Marquardt and Denecke, 2003). Thus, CDG Ib should be considered in the differential diagnosis of patients with unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy in order to allow early diagnosis and effective therapy (Vuillaumier-Barrot et al., 2002) Freeze and Aebi (1999) reviewed CDG Ib and CDG Ic (603147). Marques-da-Silva et al. (2017) systematically reviewed the literature concerning liver involvement in CDG.
ALG8 congenital disorder of glycosylation
MedGen UID:
419692
Concept ID:
C2931002
Disease or Syndrome
CDGs, previously called carbohydrate-deficient glycoprotein syndromes, grew from hereditary multisystem disorders first recognized by Jaeken et al. (1980). The characteristic biochemical abnormality of CDGs is the hypoglycosylation of glycoproteins, which is routinely determined by isoelectric focusing of serum transferrin. Type I CDG comprises those disorders in which there is a defect in the assembly of lipid-linked oligosaccharides or their transfer onto nascent glycoproteins, whereas type II CDG comprises defects of trimming, elongation, and processing of protein-bound glycans. For a general discussion of CDGs, see CDG1A (212065). CDG1H is a severe form of CDG. The majority of patients have brain involvement, liver pathology, gastrointestinal symptoms, dysmorphism (including brachydactyly), eye involvement (especially cataract), and skin symptoms. Most patients die within the first year of life (summary by Marques-da-Silva et al., 2017).
Agammaglobulinemia 4, autosomal recessive
MedGen UID:
462102
Concept ID:
C3150752
Disease or Syndrome
Any autosomal agammaglobulinemia in which the cause of the disease is a mutation in the BLNK gene.
Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome
MedGen UID:
481620
Concept ID:
C3279990
Disease or Syndrome
IMD31C is a disorder of immunologic dysregulation with highly variable manifestations resulting from autosomal dominant gain-of-function mutations in STAT1 (600555). Most patients present in infancy or early childhood with chronic mucocutaneous candidiasis (CMC). Other highly variable features include recurrent bacterial, viral, fungal, and mycoplasmal infections, disseminated dimorphic fungal infections, enteropathy with villous atrophy, and autoimmune disorders, such as hypothyroidism or diabetes mellitus. A subset of patients show apparently nonimmunologic features, including osteopenia, delayed puberty, and intracranial aneurysms. Laboratory studies show increased activation of gamma-interferon (IFNG; 147570)-mediated inflammation (summary by Uzel et al., 2013 and Sampaio et al., 2013).
Hennekam lymphangiectasia-lymphedema syndrome 1
MedGen UID:
860487
Concept ID:
C4012050
Disease or Syndrome
Hennekam lymphangiectasia-lymphedema syndrome (HKLLS1) is an autosomal recessive disorder characterized by generalized lymphatic dysplasia affecting various organs, including the intestinal tract, pericardium, and limbs. Additional features of the disorder include facial dysmorphism and cognitive impairment (summary by Alders et al., 2014). Genetic Heterogeneity of Hennekam Lymphangiectasia-Lymphedema Syndrome See also HKLLS2 (616006), caused by mutation in the FAT4 gene (612411) on chromosome 4q28, and HKLLS3 (618154), caused by mutation in the ADAMTS3 gene (605011) on chromosome 4q13.
Congenital diarrhea 7 with exudative enteropathy
MedGen UID:
862953
Concept ID:
C4014516
Disease or Syndrome
Diarrhea-7 (DIAR7) is a protein-losing enteropathy characterized by early-onset nonbloody watery diarrhea and unresponsiveness to soy-based or elemental formulas. Patients experience failure to thrive, hypogammaglobulinemia with recurrent infections, and require albumin infusions and parenteral nutrition. Hypertriglyceridemia and digital clubbing have been observed (Stephen et al., 2016). The malabsorption can result in severe deficiency of vitamin D and other nutrients (Gupta et al., 2020). For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700).
Hennekam lymphangiectasia-lymphedema syndrome 3
MedGen UID:
1648368
Concept ID:
C4748408
Disease or Syndrome
Hennekam lymphangiectasia-lymphedema syndrome-3 (HKKLLS3) is characterized by widespread congenital edema that is more severe in more dependent areas of the body. Associated features include facial dysmorphism and protein-losing enteropathy of variable severity (Brouillard et al., 2017). For a discussion of genetic heterogeneity of Hennekam lymphangiectasia-lymphedema syndrome, see HKLLS1 (235510).
Diarrhea 10, protein-losing enteropathy type
MedGen UID:
1648311
Concept ID:
C4748579
Disease or Syndrome
Diarrhea-10 (DIAR10) is a protein-losing enteropathy characterized by intractable secretory diarrhea and massive protein loss due to leaky fenestrated capillaries. Features include early-onset anasarca, severe hypoalbuminemia, hypogammaglobulinemia, and hypertriglyceridemia, as well as electrolyte abnormalities. Some patients exhibit facial dysmorphism and cardiac and renal anomalies. Intrafamilial variability has been observed, and the disease can be severe, with death occurring in infancy in some patients (Broekaert et al., 2018; Kurolap et al., 2018). For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700).
Oculocerebrodental syndrome
MedGen UID:
1674537
Concept ID:
C5193101
Disease or Syndrome
Oculoskeletodental syndrome (OCSKD) is characterized by congenital cataract, short stature and various skeletal anomalies, dysmorphic facial features and dental anomalies, developmental delay, and stroke. Other recurrent features include hearing loss, secondary glaucoma, and nephrocalcinosis (Tiosano et al., 2019).
Mitochondrial complex 4 deficiency, nuclear type 19
MedGen UID:
1729504
Concept ID:
C5436723
Disease or Syndrome
Mitochondrial complex IV deficiency nuclear type 19 (MC4DN19) is an autosomal recessive multisystem metabolic disorder characterized by the onset of symptoms in infancy or early childhood. Affected individuals show global developmental delay and developmental regression with a loss of acquired motor and language skills. Additional features include motor dysfunction, such as hypokinesia and pyramidal signs. More variable features may include recurrent infections with immunodeficiency and possibly protein-losing enteropathy. Serum lactate is increased; T2-weighted lesions in the medulla oblongata have also been reported. Patient tissues show decreased levels and activity of mitochondrial respiratory complex IV (Renkema et al., 2017). For a discussion of genetic heterogeneity of mitochondrial complex IV (cytochrome c oxidase) deficiency, see 220110.
Inflammatory bowel disease 30
MedGen UID:
1737985
Concept ID:
C5436750
Disease or Syndrome
Inflammatory bowel disease-30 (IBD30) is characterized by abdominal pain and watery or bloody diarrhea, with changes in the intestinal tract consistent with Crohn disease (Mao et al., 2018). For a general description and a discussion of genetic heterogeneity of inflammatory bowel disease, including Crohn disease (CD) and ulcerative colitis (UC), see IBD1 (266600).
Liver disease, severe congenital
MedGen UID:
1823968
Concept ID:
C5774195
Disease or Syndrome
Severe congenital liver disease (SCOLIV) is an autosomal recessive disorder characterized by the onset of progressive hepatic dysfunction usually in the first years of life. Affected individuals show feeding difficulties with failure to thrive and features such as jaundice, hepatomegaly, and abdominal distension. Laboratory workup is consistent with hepatic insufficiency and may also show coagulation defects, anemia, or metabolic disturbances. Cirrhosis and hypernodularity are commonly observed on liver biopsy. Many patients die of liver failure in early childhood (Moreno Traspas et al., 2022).

Professional guidelines

PubMed

Jablonski SA, Mazepa ASW, Tolbert MK
J Vet Intern Med 2024 Jan-Feb;38(1):145-151. Epub 2023 Dec 1 doi: 10.1111/jvim.16966. PMID: 38038236Free PMC Article
Otani IM, Lehman HK, Jongco AM, Tsao LR, Azar AE, Tarrant TK, Engel E, Walter JE, Truong TQ, Khan DA, Ballow M, Cunningham-Rundles C, Lu H, Kwan M, Barmettler S
J Allergy Clin Immunol 2022 May;149(5):1525-1560. Epub 2022 Feb 14 doi: 10.1016/j.jaci.2022.01.025. PMID: 35176351
Craven MD, Washabau RJ
J Vet Intern Med 2019 Mar;33(2):383-402. Epub 2019 Feb 14 doi: 10.1111/jvim.15406. PMID: 30762910Free PMC Article

Recent clinical studies

Etiology

Jablonski SA, Mazepa ASW, Tolbert MK
J Vet Intern Med 2024 Jan-Feb;38(1):145-151. Epub 2023 Dec 1 doi: 10.1111/jvim.16966. PMID: 38038236Free PMC Article
Hammer V, Schaeffer T, Staehler H, Heinisch PP, Burri M, Piber N, Lemmer J, Hager A, Ewert P, Hörer J, Ono M
World J Pediatr Congenit Heart Surg 2023 Nov;14(6):691-698. Epub 2023 Aug 7 doi: 10.1177/21501351231185111. PMID: 37551120
Otani IM, Lehman HK, Jongco AM, Tsao LR, Azar AE, Tarrant TK, Engel E, Walter JE, Truong TQ, Khan DA, Ballow M, Cunningham-Rundles C, Lu H, Kwan M, Barmettler S
J Allergy Clin Immunol 2022 May;149(5):1525-1560. Epub 2022 Feb 14 doi: 10.1016/j.jaci.2022.01.025. PMID: 35176351
Al Balushi A, Mackie AS
Can J Cardiol 2019 Dec;35(12):1857-1860. Epub 2019 Jul 26 doi: 10.1016/j.cjca.2019.07.625. PMID: 31711823
Backer CL, Mavroudis C
Methodist Debakey Cardiovasc J 2019 Apr-Jun;15(2):105-110. doi: 10.14797/mdcj-15-2-105. PMID: 31384373Free PMC Article

Diagnosis

Ozen A, Lenardo MJ
N Engl J Med 2023 Aug 24;389(8):733-748. doi: 10.1056/NEJMra2301594. PMID: 37611123
Otani IM, Lehman HK, Jongco AM, Tsao LR, Azar AE, Tarrant TK, Engel E, Walter JE, Truong TQ, Khan DA, Ballow M, Cunningham-Rundles C, Lu H, Kwan M, Barmettler S
J Allergy Clin Immunol 2022 May;149(5):1525-1560. Epub 2022 Feb 14 doi: 10.1016/j.jaci.2022.01.025. PMID: 35176351
Tuano KS, Seth N, Chinen J
Ann Allergy Asthma Immunol 2021 Dec;127(6):617-626. Epub 2021 Sep 3 doi: 10.1016/j.anai.2021.08.413. PMID: 34481993
Brewer BN, Kamen DL
Rheum Dis Clin North Am 2018 Feb;44(1):165-175. doi: 10.1016/j.rdc.2017.09.011. PMID: 29149925Free PMC Article
Braamskamp MJ, Dolman KM, Tabbers MM
Eur J Pediatr 2010 Oct;169(10):1179-85. Epub 2010 Jun 23 doi: 10.1007/s00431-010-1235-2. PMID: 20571826Free PMC Article

Therapy

Jablonski SA, Mazepa ASW, Tolbert MK
J Vet Intern Med 2024 Jan-Feb;38(1):145-151. Epub 2023 Dec 1 doi: 10.1111/jvim.16966. PMID: 38038236Free PMC Article
Hoy SM
Drugs 2023 Nov;83(16):1551-1557. doi: 10.1007/s40265-023-01955-9. PMID: 37856038
Al Balushi A, Mackie AS
Can J Cardiol 2019 Dec;35(12):1857-1860. Epub 2019 Jul 26 doi: 10.1016/j.cjca.2019.07.625. PMID: 31711823
Backer CL, Mavroudis C
Methodist Debakey Cardiovasc J 2019 Apr-Jun;15(2):105-110. doi: 10.14797/mdcj-15-2-105. PMID: 31384373Free PMC Article
Nowak-Węgrzyn A, Katz Y, Mehr SS, Koletzko S
J Allergy Clin Immunol 2015 May;135(5):1114-24. doi: 10.1016/j.jaci.2015.03.025. PMID: 25956013

Prognosis

Chen CB, Hammo B, Barry J, Radhakrishnan K
Curr Gastroenterol Rep 2021 Jul 2;23(8):11. doi: 10.1007/s11894-021-00813-6. PMID: 34213692
Al Balushi A, Mackie AS
Can J Cardiol 2019 Dec;35(12):1857-1860. Epub 2019 Jul 26 doi: 10.1016/j.cjca.2019.07.625. PMID: 31711823
Nowak-Wegrzyn A, Szajewska H, Lack G
Nat Rev Gastroenterol Hepatol 2017 Apr;14(4):241-257. Epub 2016 Dec 21 doi: 10.1038/nrgastro.2016.187. PMID: 27999436
Nowak-Węgrzyn A, Katz Y, Mehr SS, Koletzko S
J Allergy Clin Immunol 2015 May;135(5):1114-24. doi: 10.1016/j.jaci.2015.03.025. PMID: 25956013
Braamskamp MJ, Dolman KM, Tabbers MM
Eur J Pediatr 2010 Oct;169(10):1179-85. Epub 2010 Jun 23 doi: 10.1007/s00431-010-1235-2. PMID: 20571826Free PMC Article

Clinical prediction guides

Hammer V, Schaeffer T, Staehler H, Heinisch PP, Burri M, Piber N, Lemmer J, Hager A, Ewert P, Hörer J, Ono M
World J Pediatr Congenit Heart Surg 2023 Nov;14(6):691-698. Epub 2023 Aug 7 doi: 10.1177/21501351231185111. PMID: 37551120
Ferrua C, Lemoine A, Mosca A, Lopes AA
Nutrients 2023 Jun 22;15(13) doi: 10.3390/nu15132844. PMID: 37447171Free PMC Article
Chen CB, Hammo B, Barry J, Radhakrishnan K
Curr Gastroenterol Rep 2021 Jul 2;23(8):11. doi: 10.1007/s11894-021-00813-6. PMID: 34213692
de Carvalho JF, Lerner A, Gonçalves CM, Shoenfeld Y
Clin Rheumatol 2021 Jun;40(6):2491-2497. Epub 2020 Nov 3 doi: 10.1007/s10067-020-05487-5. PMID: 33145631
Lee M, Hodges WG, Huggins TL, Lee EL
South Med J 1996 Feb;89(2):189-94. doi: 10.1097/00007611-199602000-00006. PMID: 8578348

Recent systematic reviews

Goto M, Tsuchida Y, Terada K, Takahashi H, Sugimori Y, Komai T, Iwasaki Y, Shoda H, Fujio K
Rheumatol Int 2022 Oct;42(10):1863-1872. Epub 2021 Jun 22 doi: 10.1007/s00296-021-04923-2. PMID: 34156527
Kewcharoen J, Mekraksakit P, Limpruttidham N, Kanitsoraphan C, Charoenpoonsiri N, Poonsombudlert K, Pattison RJ, Rattanawong P
World J Pediatr Congenit Heart Surg 2020 Jan;11(1):85-91. doi: 10.1177/2150135119872196. PMID: 31835979
Li Z, Xu D, Wang Z, Wang Y, Zhang S, Li M, Zeng X
Lupus 2017 Oct;26(11):1127-1138. Epub 2017 May 19 doi: 10.1177/0961203317707825. PMID: 28523968
Udink Ten Cate FE, Hannes T, Germund I, Khalil M, Huntgeburth M, Apitz C, Brockmeier K, Sreeram N
Heart 2016 Jul 15;102(14):1115-9. Epub 2016 Mar 31 doi: 10.1136/heartjnl-2015-308823. PMID: 27033590
Al-Mogairen SM
Rheumatol Int 2011 Aug;31(8):995-1001. Epub 2011 Feb 23 doi: 10.1007/s00296-011-1827-9. PMID: 21344315

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