Fig 1 - uploaded by Radovan Bogdanovic
Content may be subject to copyright.
Source publication
Renal tubular acidosis (RTA) is common in adults with primary Sjogren syndrome (pSS) but to date this condition has only been identified in 12 pediatric cases of pSS. Here we present the case of a 13-year-old, otherwise asymptomatic girl in whom the search for the etiology of incidentally found nephrocalcinosis led to diagnosis of distal RTA and ne...
Context in source publication
Similar publications
Renal tubular acidosis (RTA) has been identified as a well-known cause of osteomalacia. The present study reporting the occurrence of osteomalacia secondary to vitamin D deficiency, underscores the need to evaluate associated RTA in patients who had pain in hip region and lower back.
A young lady with a history of repeated episodes of generalised weakness and fatigue presented to our hospital with similar symptoms and was found to have severe hypokalaemia. She had been previously diagnosed as hypokalaemic periodic paralysis but during this presentation she had also started complaining of the classic sicca-complex of Sjogren's s...
Citations
... It mainly presents as tubular interstitial nephritis (TIN) due to lymphocytic infiltration with tubular dysfunction, resulting in renal tubular acidosis (RTA, usually distal), hypokalaemia, nephrocalcinosis or renal Fanconi syndrome. Glomerulonephritis is rare but has been described [59]. Even though the long-term kidney outcome in cSS is typically favourable, the ongoing need for immunosuppression due to kidney involvement is linked to a poorer prognosis [58,59]. ...
... Glomerulonephritis is rare but has been described [59]. Even though the long-term kidney outcome in cSS is typically favourable, the ongoing need for immunosuppression due to kidney involvement is linked to a poorer prognosis [58,59]. ...
Opinion statement
Paediatric rheumatological diseases are a group of multi-systemic inflammatory diseases affecting children and young people. The kidneys constitute a target organ during the acute presentation and life course of several multi-systemic inflammatory conditions including childhood systemic lupus erythematosus (cSLE), IgA vasculitis and ANCA-associated vasculitis. Unlike adults with rheumatic diseases, who may have prior concomitant kidney disease, children are more likely to have an acute, potentially reversible inflammatory process that typically requires prompt immunosuppressive treatment. Despite broad-spectrum immunosuppression, kidney outcomes remain suboptimal, with children progressing to irreversible chronic kidney disease and ultimately kidney failure, requiring kidney replacement therapy or transplantation. In cSLE, for example, the kidney failure rate is 1–14% depending on the length of follow-up, with the average age of requiring a kidney transplant reported to be 24 years, thus illustrating the importance of follow-up into adulthood. Advances in improving the outcomes for these patients remain slow, and the recruitment of children to drug trials can be challenging. The aim of this review article is to summarise the key paediatric rheumatic diseases that commonly involve the kidney to highlight the epidemiology and current kidney outcomes. Useful information is also provided on suggested screening to detect the presence of active kidney inflammation and improvements in this field for the future.
... Lymphocytes and specific autoantibodies all contribute to the pathogenesis of chronic inflammation, leading to the formation of germinal centers in affected tissue and an increased risk of non-Hodgkin's lymphoma and other malignancies [2][3][4]. Although SS is commonly observed in adults, mainly due to secondary forms, a childhood onset can rarely occur [2,3,[5][6][7][8][9][10]. Indeed, pediatric SS is believed to account for approximately 1% of all SS patients and, 10 years ago, less than 200 cases of pediatric SS had been described [6,[11][12][13][14][15][16]. ...
... Although SS is commonly observed in adults, mainly due to secondary forms, a childhood onset can rarely occur [2,3,[5][6][7][8][9][10]. Indeed, pediatric SS is believed to account for approximately 1% of all SS patients and, 10 years ago, less than 200 cases of pediatric SS had been described [6,[11][12][13][14][15][16]. Typical clinical findings in children with SS include recurrent parotid swelling and, often, significant extraglandular manifestations (EGMs) (Fig. 1) [16,17]. ...
... Kidney involvement is regarded as a relevant feature in pediatric SS, with an estimated prevalence of 5-20.5% (Table 1) [2,3,[7][8][9][10][16][17][18][19][20][21]. However, due to the disease's rarity, epidemiological and clinical data regarding the kidney manifestations of pediatric SS are limited [6,7,17]. The most common kidney injury in affected children is tubulointerstitial nephritis (TIN), which can clinically manifest as renal tubular acidosis (RTA), hematuria, glycosuria, hypokalemia, and impaired urinary concentrating ability [3,6,17,22]. ...
Approximately 1% of all patients with Sjögren's syndrome (SS) are children. Unlike the adult form, in which sicca syndrome is the main presentation, in children, the most common clinical finding is recurrent enlargement of the salivary glands. In pediatric SS, extraglandular manifestations represent a significant feature and, among these, kidney manifestations are relevant. Kidney involvement is observed in 5-20.5% of children with SS, most frequently tubulointerstitial nephritis. This injury can lead to serious phenotypes, including distal kidney tubular acidosis with the development of severe hypokalemia, which can lead to ECG abnormalities, weakness, and hypokalemic periodic paralysis. Kidney implications in pediatric SS also include nephrolithiasis, nephrocalcinosis, and various types of glomerular damage, which often require immunosuppressive therapies. Laboratory findings are usually comparable to adults, including hyperglobulinemia and high rates of antinuclear antibodies (ANA, 63.6-96.2%), and anti-Ro/SSA (36.4-84.6%). The current classification criteria for SS are inaccurate for the pediatric population, and more specific criteria are needed to improve the diagnostic rate. Due to the rarity of the disease, strong recommendations for treatment are lacking, and several therapeutic strategies have been reported, mostly based on glucocorticoids and disease-modifying antirheumatic drugs, with different outcomes. The aim of this paper is to provide an overview of the kidney implications of pediatric SS based on the latest evidence of the medical literature.
... The disease affects children and adolescents. A variety of organ systems may be affected, resulting in neurological, dermatological, musculoskeletal, vascular, gastrointestinal, respiratory, renal, and hematological manifestations (27,28). ...
The combination of imaging of salivary gland tissue and analysis of biopsy samples provides an optimal diagnostic tool for Sjögren’s disease. These techniques enable the treating physician to rule out lymphoma, infection, and other inflammatory or infiltrative processes. The clinician can use various imaging, biopsy, and scoring systems to rate the degree of disease involvement. Obtaining serial measurements can be used to assess the patient’s response to treatment and the degree of disease reversibility. Only a small percentage of patients with Sjögren’s disease undergo these studies, however, and the discussion offered in this chapter provides a rationale for their use.
... Background Distal renal tubular acidosis (dRTA) is a rare disease, due to impaired secretion of hydrogen ions at the distal tubule [1,2], which can be of hereditary [3] or acquired origin [4,5]. The disease is characterised by hyperchloremic metabolic acidosis in the presence of a normal plasma anion gap, and urinary pH > 5.5, resulting in renal calcium, phosphate and potassium wasting and hypocitraturia [6]. ...
Background
Consequences of distal renal tubular acidosis (dRTA) on growth, bone and kidney, sometimes associated with hearing loss, may significantly affect quality of life (QoL). This descriptive qualitative study explores QoL linked to dRTA and gathers the impressions of patients with this rare disease (and caregivers) 5 years after enrolment in a clinical study, during which patients were treated with ADV7103, a prolonged-release granule formulation combining potassium citrate and potassium bicarbonate. Semi-structured, one-hour interviews with 6 adult and 13 paediatric patients with a confirmed diagnosis of dRTA and with parents of paediatric patients were performed using an interview guide. Qualitative analysis of anonymized interview transcripts based on grounded theory was conducted.
Results
The main QoL domains impacted by dRTA and its treatment were education/work, social/family life, and emotional and physical well-being. ADV7103 (administered twice daily) was compared with the standard of care (SoC) taken before study entry (more than twice daily). Patients/parents reported that switching from previous SoC to ADV7103 had changed their lives: Difficulties at school due to burdensome administrative issues and need to explain disease and treatment affecting all families of paediatric patients (n = 13) disappeared, facilitating parents who had stopped working (to deal with their child’s treatment) to return to work,
Family functioning was improved (n = 18), as travel and holidays became easier to organise and patients/parents stopped thinking about managing treatment daily/nightly, reducing tension in the family or couple,
The emotional burden of disease perceived was relieved (n = 12) in the absence of treatment-related invasive questions from others,
Gastro-intestinal adverse events and taste problems improved with ADV7103 (n = 18) and better compliance led to milder physical impacts and less need to be hospitalised.
The mean satisfaction score with ADV7103 compared to SoC was 9 out of 10 (10 = very satisfied). ADV7103 exceeded or met the expectations of 14 out of 17 patients that commented on that.
Conclusions
Qualitative interviews show that dRTA and its treatment have a significant impact on QoL of patients and parents and that ADV7103 helps improve daily-life and reduces treatment burden, resulting in greater overall satisfaction of the patients and their families.
Trial registration EU Clinical Trials Register, EudraCT 2013-003828-36 on the 3rd of September 2013.
... [6][7][8][9][10] The main manifestations of renal involvement in pSS is usually manifested as tubular acidosis and defective urinary concentrating ability and the minor manifestations is Fancon syndrome and glomerular lesions. [11] Approximately 31.4% of renal involvement in pSS patients developed chronic renal failure. The survival rate of renal involvement in pSS patients compared to those without renal involvement was significantly reduced. ...
Objective
To establish and validate a nomogram for individualized prediction of renal involvement in pSS patients.
Methods
A total of 1293 patients with pSS from the First Affiliated Hospital of Wenzhou Medical University between January 2008 to January 2020 were recruited and further analyzed retrospectively. The patients were randomly divided into a development set (70%, n = 910) and a validation set (30%, n = 383). The univariable and multivariate logistic regression were performed to analyze the risk factors of renal involvement in pSS. Based on the regression β coefficients derived from multivariate logistic analysis, an individualized nomogram prediction model was developed. The prediction model of discrimination and calibration was evaluated with the area under the receiver operating characteristic curves and Calibration plot.
Results
Multivariate logistic analysis showed that hypertension, anemia, albumin, uric acid, anti-Ro52, hematuria and Chisholm-Mason grade were independent risk factors of renal involvement in pSS. The area under the receiver operating characteristic curves were 0.797 and 0.750 respectively in development set and validation set, indicating the nomogram had a good discrimination capacity. The Calibration plot showed nomogram had a strong concordance performance between the prediction probability and the actual probability.
Conclusion
The individualized nomogram for pSS patients those who had renal involvement could be used by clinicians to predict the risk of pSS patients developing into renal involvement and improve early screening and intervention.
... Renal manifestations include primarily glomerulonephritis, from immune complex deposition, and interstitial nephritis, from direct infiltration of lymphocytes, which can lead to distal renal tubular acidosis. 11,27,31 Renal tubular acidosis may lead to hypokalemia and even hypokalemic periodic paralysis. 32 Renal involvement is reported in approximately 5% to 10% of pedSD cases. ...
Sjögren disease increasingly is recognized in pediatric patients. Clinical features, primarily parotitis and sicca symptoms, and results of diagnostic tests may be different from those in adult disease. Adult criteria fail to capture most pediatric patients. Pediatric-specific criteria are urgently needed to define the natural history of the disease, identify risk and prognostic factors, and evaluate the impact of therapeutics and other interventions on disease course in young patients.
... recurrent parotitis (26), and parotid swelling and arthralgia in combination with Methotrexate (MTX) (27) (Tables 1,2). A total of 27 children (37.5%) were prescribed oral steroid treatment for JRA (13,17,28), tubulointerstitial nephritis (TIN) (15,(29)(30)(31), systemic lupus erythematosus (SLE) (13), aseptic meningoencephalitis (15), severe isolated pulmonary hypertension (PH)(32), (dRTA) (29), mesangial glomerulonephritis (33), parotitis(11, 28, 34-36), or orbital swelling (37) (Tables 2,3) . ...
... recurrent parotitis (26), and parotid swelling and arthralgia in combination with Methotrexate (MTX) (27) (Tables 1,2). A total of 27 children (37.5%) were prescribed oral steroid treatment for JRA (13,17,28), tubulointerstitial nephritis (TIN) (15,(29)(30)(31), systemic lupus erythematosus (SLE) (13), aseptic meningoencephalitis (15), severe isolated pulmonary hypertension (PH)(32), (dRTA) (29), mesangial glomerulonephritis (33), parotitis(11, 28, 34-36), or orbital swelling (37) (Tables 2,3) . ...
... All 3 patients were female with an average age at SS diagnosis of 15 years (13 -17). The clinical indications were overlapping JIA and SLE with autoimmune hepatitis phenotypes(11, 16) as well as TIN, in which case Azathioprine was used as initial therapy, followed by mycophenolate mofetil (MMF) after loss of efficacy (29). ...
Objectives:
Sjögren's Syndrome (SS) with childhood onset is a rare autoimmune disease characterised by heterogeneous presentation. The lack of validated classification criteria makes it challenging to diagnose. Evidence-based guidelines for treatment of juvenile SS are not available due to the rarity of disease and the paucity of research in this patient population. This systematic review aims to summarise and appraise the current literature focused on pharmacological strategies for management of SS with childhood onset.
Methods:
PubMed and MEDLINE/Scopus databases up to December 2020 have been screened for suitable reports highlighting pharmacological treatment of SS with childhood onset using the PRISMA 2009 reporting checklist. Animal studies have been excluded.
Results:
43 studies (34 case reports, 8 mini case series and one pilot study) were eligible for analysis. The studies retrieved included girls in 88% (120/137) of cases and had very low confidence level.Hydroxychloroquine (HCQ) was prescribed for parotid swelling, as well as in association with methotrexate (MTX) and non-steroidal anti-inflammatory drugs (NSAIDS) in patients with arthritis and arthralgia. Corticosteroids such as long courses of oral prednisone and IV methylprednisolone were commonly prescribed for children with severe disease presentations. Rituximab was mainly indicated for MALT lymphoma, and renal and nervous system complications. Other conventional DMARDs were prescribed in selected cases with extra-glandular manifestations.
Conclusion:
Various therapies are used for the management of juvenile SS and are prescribed based on expert clinician's opinion. There are currently no good quality studies that allow clinical recommendations for treatment in SS with childhood onset.
... Finally, 20 case reports were included in the literature review after extracting and analyzing the data from the articles (Fig. 4). The information that was extracted from the papers were as follows: references and year, age and gender of patient, symptoms at onset, dry eyes or mouth, parotitis,neurologic manifestation, renal damage, elevated ANA, presence of anti-SSA and SSB antibodies, ESR, RF, hyperglobulinemic, schirmer test, CSF, renal and salivary (Table 1) [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. ...
... At present, the treatment of childhood pSS presenting with renal and nerve damage lacks large-scale evidence-based medicine and is mostly based on clinical experience. Although the long-term outcome of renal damage in pediatric pSS is usually good, glucocorticoids were often used in pediatric cases with RTA and TIN, and chronic immunosuppression is needed for the glomerular involvement often associated with a progressive course [5,7,57]. Long term outcomes may be related to the improvement in overall survival rate, renal survival rate, and complete remission rate of renal disease in childhood pSS treated with immunosuppressive therapy. ...
Background:
Sjögren syndrome (SS) is a rare disease in pediatrics, and little attention has been paid to the clinical feature in these patients. To date, there are few cases concern about neurological and nephrological disorders in childhood Sjögren syndrome. We describe a case of Sjögren syndrome in a 12-year-old girl who developed neurological disorders and interstitial nephritis and review the literature currently available on this topic.
Case presentation:
A 12-year-old girl was admitted to our hospital for arthritis and glucosuria. She was required to do labial gland and renal biopsy, because the positive for anti-nuclear antibody and anti-Sjögren syndrome B (anti-SSB) antibody. Then the biopsy was performed revealing the lymphocytic infiltrate in the small area and renal tubular interstitial damage,thus the diagnosis of Sjögren syndrome with tubular interstitial damage was made. Three months later, she presented again with headache, fever, nausea, vomiting and was recovered without drug therapy. Based on the patient's medical history, laboratory and imaging examination, and treatment, we speculate that the disorders of the nervous system were caused by the Sjögren syndrome. The girl has stable renal function and no residual nervous system damage in the next 1.5 years, but she underwent low dose prednisone therapy because of persistent renal glucosuria.
Conclusions:
Nephrological disorders and neurological involvement are rare manifestations of Sjögren syndrome in children, and rarely presented as the initial symptoms. It should be suspected in children presenting with unexplained renal diseases, neurological abnormalities, or unexplained fever. Although there is no guidelines on the diagnosis and treatment of children Sjögren syndrome are currently available, early recognition and the appropriate treatment of renal damage and neurologic involvement would improve prognosis and prevent complications.
... At present, the treatment of childhood pSS presenting with renal and nerve damage lacks large-scale evidence-based medicine and is mostly based on clinical experience. Although the long-term outcome of renal damage in pediatric pSS is usually good, glucocorticoids were often used in pediatric cases with RTA and TIN, and chronic immunosuppression is needed for the glomerular involvement often associated with a progressive course [5,7,57]. Long term outcomes may be related to the improvement in overall survival rate, renal survival rate, and complete remission rate of renal disease in childhood pSS treated with immunosuppressive therapy. ...
... The authors declare that they have no competing interests. Tables 18 Case 1 2 3 4 References/Year Matsui [2] Kornitzer [3] Arabshahi [4] Bogdanovic [5] Age(Gender) 9 References/Year DeGuzman [13] Skalova [14] Yoshida [15] Berman [16] Age(Gender) 14 Case reports ...
Background: Sjögren syndrome(SS) is a rare disease in pediatrics, and little attention has been paid to the clinical feature in these patients. To date, there are few cases concern about neurological and nephrological disorders in childhood Sjögren syndrome. We describe a case of Sjögren syndrome in a 12-year-old girl who developed neurological disorders and interstitial nephritis and review the literature currently available on this topic. Case presentation: A 12-year-old girl was admitted to our hospital for arthritis and glucosuria. She was required to do labial gland and renal biopsy, because the positive for anti-nuclear antibody and anti-Sjögren syndrome B(anti-SSB) antibody. Then the biopsy was performed revealing the lymphocytic infiltrate in the small area and renal tubular interstitial damage,thus the diagnosis of Sjögren syndrome with tubular interstitial damage was made. Three months later, she presented again with headache, fever, nausea, vomiting and was recovered without drug therapy. Based on the patient's medical history, laboratory and imaging examination, and treatment, we speculate that the disorders of the nervous system were caused by the Sjögren syndrome. The girl has stable renal function and no residual nervous system damage in the next 1.5 years, but she underwent low dose prednisone therapy because of persistent renal glucosuria. Conclusion s: Nephrological disorders and neurological involvement are rare manifestations of Sjögren syndrome in children, and rarely presented as the initial symptoms. It should be suspected in children presenting with unexplained renal diseases, neurological abnormalities, or unexplained fever. Although there is no guidelines on the diagnosis and treatment of children Sjögren syndrome are currently available, early recognition and the appropriate treatment of renal damage and neurologic involvement would improve prognosis and prevent complications. Keywords : Neurologic manifestations, Kidney diseases, Sjogren’s syndrome, Children
... A common initial symptom is swelling of the major salivary glands (6,7). Several organ systems may be affected, resulting in neurologic, dermatologic, musculoskeletal, vascular, gastrointestinal, respiratory, renal, and hema-| 79 tologic manifestations (8,9). Extraglandular manifestations occur in approximately 50% of children with juvenile SS (4). ...
Objective
Juvenile Sjögren's syndrome (SS) is a rare, poorly defined, and possibly underdiagnosed condition affecting children and adolescents. The aim of this study was to characterize symptoms and clinical findings of juvenile SS and to explore the clinical application of major salivary gland ultrasonography (SGUS) in patients with juvenile SS.
Methods
A cross‐sectional multicenter study recruited patients with disease onset until age 18 years (n = 67). Disease characteristics were recorded, and unstimulated whole sialometry and SGUS examination of the parotid and submandibular salivary glands were performed.
Results
The female:male ratio was 58:9. The mean age at first symptom was 10.2 years and 12.1 years at diagnosis. Ocular and oral symptoms were noted in 42 of 67 patients (63%) and 53 of 66 patients (80%), respectively. The American‐European Consensus Group or American College of Rheumatology/European League Against Rheumatism classification criteria for primary SS were fulfilled by 42 of 67 patients (63%). Pathologic SGUS findings were observed in 41 of 67 patients (61%); 26 of 41 SGUS+ patients (63%) fulfilled primary SS criteria. Salivary gland enlargements/parotitis were noted in 37 of 58 patients and were nonsignificantly associated with SGUS+ status (P = 0.066). The mean levels of saliva were 5.6 ml/15 minutes in SGUS– patients compared to 3.3 ml/15 minutes in the SGUS+ patients (P = 0.049). A total of 36 of 41 SGUS+ patients (88%) were anti‐Ro/La+ compared to 14 of 26 SGUS– patients (54%) (P = 0.001). In addition, 24 of 39 SGUS+ patients (62%) were positive for rheumatoid factor (RF), whereas only 5 of 25 SGUS– patients (20%) were RF+ (P = 0.001).
Conclusion
Juvenile SS is characterized by a large spectrum of clinical symptoms and findings. Several glandular and extraglandular parameters such as hyposalivation, swollen salivary glands, and autoantibodies are associated with pathologic SGUS findings.
