Anti-SARS-CoV-2 Vaccination and PIMS-TS-Friends or Foe? Case Reports and Literature Review.

Pediatric inflammatory, multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS), also known as a multisystem inflammatory syndrome in children (MIS-C), is diagnosed in children who develop an inadequate inflammatory response after exposure to the SARS-CoV-2 virus. The pathogenesis of the abnormal response of the immune system to a previous SARS-COV-2 infection has not been explained. Similarly, the safety and effectiveness of COVID-19 vaccinations in this group of patients have become the subject of clinical discussion. Presenting experiences from many centers aims to answer this question. We present 4 cases of patients who suffered from PIMS-TS. Three of them were safely vaccinated against COVID-19 after illness. One patient developed PIMS-TS temporarily associated with COVID-19 vaccination. We also collected and discussed data from other centers.

DOCK8 Mutation in Patient with Juvenile Idiopathic Arthritis and Sjögren's Syndrome.

This study investigated the association between autoimmunity and immunodeficiency in pediatric patients, focusing on the case of a 15-year-old female diagnosed with juvenile idiopathic arthritis (JIA) and secondary Sjögren's syndrome. The patient presented with a variety of symptoms, including joint pain, bronchial asthma, leukopenia, and skin lesions. Genetic testing revealed a de novo mutation in the DOCK8 gene, associated with DOCK8 deficiency, a condition usually associated with immunodeficiencies. The clinical course, diagnostic pathway, and treatment history are detailed, highlighting the importance of molecular diagnostics in understanding the genetic basis of rheumatic diseases. This case highlights the need to consider innate immune errors in patients with multiple diseases or atypical symptoms of rheumatic diseases. Furthermore, the study highlights the importance of targeted treatment, including genetic counseling, to improve patient outcomes. The observed association between autoimmunity and immune deficiency reinforces the importance of molecular testing in elucidating the causes of previously idiopathic rheumatic diseases, contributing to improved patient care and quality of life.

Safety of the COVID-19 vaccination in children with juvenile idiopathic arthritis-A observational study from two pediatric rheumatology centres in Poland.

Introduction: The safety of COVID-19 vaccines in children with juvenile idiopathic arthritis (JIA) is the concern of patients and their parents and doctors in the current pandemic reality. The main objective of the study was to evaluate the safety of COVID-19 vaccine in patients with JIA. Method: A cohort study based on short clinical follow-up of 43 children with JIA was conducted in the years 2021-2022 in two centres of paediatric rheumatology in Poland. All patients received mRNA COVID-19 vaccine. The patients' data were collected using appropriate validated questionnaire. Disease activity was evaluated using Juvenile Arthritis Disease Activity Score 27-joint count (JADAS-27). Results: Ten (22.7%) children had COVID-19 infection before getting COVID-19 vaccine. After first dose of COVID-19 vaccine 25/43 (58.1%) patients presented typical adverse events: arm pain or oedema at the application side or weakness. Also, twenty five (58.1%) children had side effects after second dose of this vaccine, however the spectrum of the symptoms was wider (additionally: headache, fever, lymphadenopathy, arrhythmia). Thirteen out of 43 (30.2%) patients had active disease before and 8/43 (18.6%) after COVID-19 vaccination, while the degree of JADAS-27 activity was higher in the study group before COVID-19 vaccination (p = 0.047). Conclusions: Our study found out that children and adolescents with JIA with remission without treatment or on the long-term treatment-cDMARDs or even bDMARDs, can be safely vaccinated for COVID-19. Moreover, the study found that COVID-19 vaccination does not interfere with the JIA treatment and does not exacerbate symptoms of the disease and that vaccination protected against developing COVID-19 in children with JIA even on treatment.

Programmed Cell Death Protein-1 Upregulation in Response to SARS-CoV-2 in Juvenile Idiopathic Arthritis: A Case-Control Study.

Currently, data regarding the impact of COVID-19 disease (caused by SARS-CoV-2) on patients with childhood rheumatic diseases are significantly limited. To assess the possible connection, we measured levels of IgA and IgG anti-SARS-CoV-2 antibodies in children with juvenile idiopathic arthritis (JIA) and a control group during the pandemic, prior to the introduction of anti-COVID-19 vaccination. We assessed levels of PD-1 suppressive molecule and inflammatory markers in patients and correlated those results with serological response to SARS-CoV-2. In JIA patients, the activity of the disease was assessed using the Juvenile Arthritis Disease Activity Score 71 (JADAS 71) scale. The study consisted of 96 children, 65 diagnosed with JIA, treated with antirheumatic drugs, and 31 healthy volunteers. In patients with JIA, significantly higher levels of SARS-CoV-2 antibodies in the IgA and IgG were demonstrated compared to the control group. We also found significantly higher serum PD-1 levels in JIA patients and control volunteers who were seropositive for SARS-CoV-2 IgA or IgG antibodies compared to those who were seronegative. The humoral immune response to SARS-CoV-2 infection is associated with the persistent upregulation of PD-1 expression in both JIA patients and healthy children. The clinical significance of the detected disorder requires further careful observation.

Is It Inflammatory Bowel Disease Flare or Pediatric Inflammatory Multisystem Syndrome Temporally Associated with COVID-19?

BACKGROUND: Pediatric inflammatory multisystem syndrome temporally associated with COVID-19/multi-system inflammatory syndrome in children (PIMS-TS/MIS-C) is a potentially life-threatening complication of SARS-CoV-2 infection in children. Gastrointestinal manifestations are prominent in children with PIMS-TS/MIS-C. Thus, it is challenging to differentiate this condition from an exacerbation of inflammatory bowel disease (IBD). We aimed to present the clinical characteristics, and diagnostic and therapeutic difficulties in patients with overlapping IBD and PIMS-TS/MIS-C; Methods: We reviewed medical records of children hospitalized due to overlapping IBD and PIMS-TS/MIS-C in a single pediatric hospital from December 2020 to December 2021; Results: There were four children with overlapping IBD flare and PIMS-TS/MIS-C. In three cases, IBD recognition preceded PIMS-TS/MIS-C onset and PIMS-TS/MIS-C occurred during anti-inflammatory therapy of IBD. All children presented with gastrointestinal symptoms at PIMS-TS/MIS-C onset. All patients received IVIG and ASA treatment. In three children there was a need to use steroids to resolve PIMS-TS/MIS-C symptoms. One child was vaccinated against COVID-19; Conclusions: SARS-CoV-2 infection may affect patients with underlying inflammatory conditions such as IBD, inducing systemic symptoms of PIMS-TS/MIS-C, and probably triggering IBD after PIMS-TS/MIS-C. The resemblance of clinical presentations is the main source of diagnostic and therapeutic challenges in PIMS-TS/MIS-C in patients with underlying IBD.

Seroprevalence of Antibodies against SARS-CoV-2 in Children with Juvenile Idiopathic Arthritis a Case-Control Study.

There is limited data on the effect of the novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) on pediatric rheumatology. We examined the prevalence of antibodies against SARS-CoV-2 in children with juvenile idiopathic arthritis (JIA) and a negative history of COVID-19 and the correlation of the presence of these antibodies with disease activity measured by juvenile arthritis disease activity score (JADAS). In total, 62 patients diagnosed with JIA, under treatment with various antirheumatic drugs, and 32 healthy children (control group) were included. Serum samples were analyzed for inflammatory markers and antibodies and their state evaluated with the juvenile arthritis disease activity score (JADAS). JIA patients do not have a higher seroprevalence of anti-SARS-CoV-2 antibodies than healthy subjects. We found anti-SARS-CoV-2 antibodies in JIA patients who did not have a history of COVID-19. The study showed no unequivocal correlation between the presence of SARS-CoV-2 antibodies and JIA activity; therefore, this relationship requires further observation. We also identified a possible link between patients' humoral immune response and disease-modifying antirheumatic treatment, which will be confirmed in follow-up studies.

PIMS-TS, the New Paediatric Systemic Inflammatory Disease Related to Previous Exposure to SARS-CoV-2 Infection-"Rheumatic Fever" of the 21st Century?

Paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) is a new systemic inflammatory disease that mainly affects children. Its course in many features resembles that of acute rheumatic fever (ARF). Therefore, it is interesting that the experiences with ARF can be used in the management of patients with PIMS-TS. The aim of the article is to analyse the current data on PIMS-TS in relation to ARF. PIMS-TS and ARF are associated with an abnormal immune response to specific pathogens (SARS-CoV-2 and group A streptococcus, respectively). The main symptoms of both diseases are fever and cardiac involvement. Current therapy for PIMS-TS is based on anti-inflammatory treatment: intravenous immunoglobulin (first-line), intravenous glucocorticoids (second-line), or biological therapy (third-line; including interleukin [IL]-1 antagonists, IL-6 receptor blockers, and anti-tumour necrosis factor agents). Vaccination might be good prophylaxis, but the efficacy and safety of the vaccines against SARS-CoV-2 have not yet been established in children. Interesting insights may be gained by considering PIMS-TS in light of what is known of ARF due to their similar courses, but there are still many unanswered questions surrounding this disease and its pathogenesis.

The Impact of Epstein-Barr Virus Infection on Juvenile Idiopathic Arthritis Activity and Patient's Response to Treatment.

This study aimed to investigate the relationship between Epstein-Barr virus (EBV) infection and the onset of juvenile idiopathic arthritis (JIA), disease activity, and response to treatment. The study included 44 children with JIA, 23 children with different types of arthritis, and 44 controls. We measured EBV infection markers, including the EBV DNA load and the concentration of antibodies to viral antigens, at disease onset, before treatment. Six months after JIA diagnosis and the initiation of treatment patients with anti-viral capsid antigen IgG had a higher disease activity and worse response to treatment than patients without previous infection. After six months of treatment, the probability of disease inactivity in children without a history of EBV infection was almost 6.5 times greater than in a child with a history of infection. Furthermore, the probability of a better response after six months of treatment in a child with a history of EBV infection was more than five times smaller than in a child without infection. A past EBV infection can have a negative effect on achieving disease remission and may be associated with a worse response to treatment. Our results do not indicate the need for routine assessment of EBV infection markers in patients with JIA.

Could hemophagocytic lymphohistiocytosis be the core issue of severe COVID-19 cases?

BACKGROUND: COVID-19, a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly presents as fever, cough, dyspnea, and myalgia or fatigue. Although the majority of patients with COVID-19 have mild symptoms, some are more prone to serious outcomes, including pneumonia, acute respiratory distress syndrome (ARDS), and even death. Hemophagocytic lymphohistiocytosis (HLH) is a severe, life-threatening inflammatory syndrome associated with intense cytokine release (also known as a "cytokine storm"). Similar to COVID-19, HLH is characterized by aggressive course leading to multi-organ failure. MAIN TEXT: The purpose of this review article is to draw attention to the possibility of the complication of HLH in patients with the severe course of COVID-19. Indeed, some of the clinical characteristics observed in the more severe cases of COVID-19 are reminiscent of secondary HLH (which can be triggered by infections, malignancies, rheumatological diseases, or autoimmune/immunodeficiency conditions). The pathogenesis of SARS-CoV-2 infection also suggests that HLH or a similar hyperinflammatory syndrome is the cause of the severe course of the infection. CONCLUSION: The pathogenesis and clinical symptoms of severe COVID-19 indicate that an increased inflammatory response corresponding to HLH is occurring. Therefore, patients with severe COVID-19 should be screened for hyperinflammation using standard laboratory tests to identify those for whom immunosuppressive therapy may improve outcomes.

The importance of FDG PET/CT in the diagnostic process of the middle aortic syndrome in a 15-year-old boy patient with suspected systemic vasculitis and final diagnosis of Williams-Beuren syndrome.

The differential diagnosis in children with the systemic vasculopathy is still a challenge for clinicians. The progress in vascular imaging and the latest recommendations improve the diagnostic process, but only single reports describe the use of new imaging tests in children. The publication aims to demonstrate the important role of 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography combined with anatomical computed tomography angiography (PET/CTA) imaging in the case of a 15-year-old boy with chest pain, intermittent claudication, hypertension and features of middle aortic syndrome in computed tomography angiography (CTA). The patient was suspected to have Takayasu arteritis, but was finally diagnosed with Williams-Beuren syndrome. The case indicates that the FDG PET/CT imaging might be essential in the diagnostic process of middle aortic syndrome in children. We suggest that this imaging technique should be considered in the diagnostic process of systemic vasculopathy particularly in children.

Interferon alpha as antiviral therapy in chronic active Epstein-Barr virus disease with interstitial pneumonia - case report.

BACKGROUND: Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is defined as a severe, progressive lymphoproliferative disorder associated with active EBV infection persisting longer than 6 months and developing in patients without recognised immunodeficiency. Rarely, interstitial pneumonitis (IP) occurs as a serious complication in CAEBV patients. The standard therapeutic regimen for IP in CAEBV has not yet been defined. Although interferon alpha (IFN-alpha) is known to suppress viral DNA replication by affecting its basal promoter activation process, it is rarely used in CAEBV patients. CASE PRESENTATION: A 22-year-old Caucasian woman, diagnosed with CAEBV 1.5 years earlier, was admitted to the Immunology Clinic due to a 4-week history of productive cough, fever and general weakness. Cultures of blood, urine and sputum were negative, but EBV DNA copies were found in the sputum, whole blood, isolated peripheral blood lymphocytes as well as in the blood plasma. Cytokine assessment in peripheral blood revealed the lack of IFN-alpha synthesis. Disseminated maculate infiltrative areas in both lungs were observed on a computed tomography (CT) chest scan. The patient was not qualified for the allogeneic hematopoietic stem cell transplantation (allo-HSCT) due to the risk of immunosuppression-related complications of infectious IP. Inhaled (1.5 million units 3 times a day) and subcutaneous (6 million units 3 times a week) IFN-alpha was implemented. To the best of our knowledge, this was the first documented use of inhaled IFN-alpha in a patient with CAEBV and concomitant IP. Patient's status has improved, and she was eventually qualified to allo-HSCT with reduced conditioning. Currently, the patient feels well, no EBV was detected and further regression of pulmonary changes was documented. CONCLUSIONS: CAEBV should be considered in patients who present with interstitial lung infiltration and involvement of other organs. Although more promising results have been obtained with allo-HSCT, inhaled IFN-alpha may also be a therapeutic option in patients with CAEBV and a concomitant IP.

Long-term, interventional, open-label extension study evaluating the safety of tocilizumab treatment in patients with polyarticular-course juvenile idiopathic arthritis from Poland and Russia who completed the global, international CHERISH trial.

Efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, were demonstrated in juvenile idiopathic arthritis (JIA) with polyarticular course (pJIA) in the CHERISH trial. This observational, III phase study evaluated long-term treatment of TCZ in pJIA patients was conducted by members of the Pediatric Rheumatology International Trials Organization (PRINTO) from Poland and Russia. Forty-one patients, who had completed the CHERISH core study (104 weeks), were extensionally treated with TCZ (8 mg/kg, intravenous infusion every 4 weeks). Total treatment time was from 131 to 193 weeks. The long-term safety (the primary endpoint) and efficacy were evaluated. All patients achieved ACR70 response in the core study and continued to achieve at least ACR50 response up to week 24 of this study. The safety population comprised 46.41 patient-years (PY). Rates per 100 PY of adverse (AEs) and serious events (SAEs) were 181.0 and 6.46, respectively. Pharyngitis and respiratory tract infections were the most common AEs. Except one AE (severe neutropenia), all others were classified as mild (24.4%) or moderate (29.3%). The incidence of SAEs was low (7.3%). No new safety findings were observed. The safety profile of over 2.5-year treatment with TCZ is consistent with the pre-marketing CHERISH clinical trial. Presented data and continued efficacy response support the use of TCZ in pJIA. EUDRACT No: 2011-001607-12. https://clinicaltrials.gov/ct2/show/study/NCT01575769?term=ML27783.

Problems of patients with cystic fibrosis during transition to adulthood.

The proper care of cystic fibrosis patients extends over their lifetime. More than half of the children with the disease die before adulthood. An important element in the patient's care is a time of transition from a paediatric to the care of an internist and the patient's acceptance of this necessity. Transition from paediatric care to an internist should be adequately prepared. It is not only a question of transfer of medical records, but also careful preparation of patients for such transition. The patients expect not only continuity of care but also the introduction to the management with the disease. The creation of a base for specialist hospital treatment for exacerbation of the disease at the adulthood is an important element in the care of these patients. The problem has been solved in the children group, but is still waiting for solution in adults with cystic fibrosis. It has been proven that care in the centres carried out by a specialized team ensures longer life and better quality of life of these patients. The paper is an overview of these two important elements of care of adults with cystic fibrosis.

Efficacy and safety of tocilizumab in patients with polyarticular-course juvenile idiopathic arthritis: results from a phase 3, randomised, double-blind withdrawal trial.

OBJECTIVE: To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). METHODS: This three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. RESULTS: In part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: -0.21; 95% CI -0.35 to -0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). CONCLUSIONS: Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. TRIAL REGISTRATION NUMBER: NCT00988221.

The clinical profile of Kawasaki disease of children from three Polish centers: a retrospective study.

Kawasaki disease (KD) is one of the most common vasculitides of childhood. The aim of this retrospective study is to determine the incidence of KD and to evaluate its presenting symptoms, clinical course, laboratory tests, and treatment in patients with complete KD and incomplete KD at three pediatric rheumatology centers in Poland from January 2011 to December 2012. A total of 27 Caucasian children (12 boys and 15 girls) with median age of 3 years (range 4 months-12 years) were included in this study. The incidence of complete versus incomplete KD was 17 (63 %) versus 10 (37 %) children, respectively. Patients with incomplete KD significantly less presented cervical lymphadenopathy (20 vs. 88.2 %; p = 0.00075), changes in extremities (30 vs. 76.5 %; p = 0.04), and bilateral nonpurulent conjunctivitis (60 vs. 100 %; p = 0.01). Cardiac assessments show that the majority of patients with KD have not got coronary artery aneurysms (CAA). The median time from the onset of symptoms to intravenous immunoglobulin (IVIG) infusion was 7 days for complete KD and 11 days for incomplete KD. IVIG delay in the incomplete KD had no effect on the incidence of CAA. In conclusion, there were no differences in demographic features, age of onset, and laboratory tests of patients with complete and incomplete KD. Patients with incomplete KD significantly rarely presented cervical lymphadenopathy, changes in extremities, and conjunctival injection. Electrocardiography is a sensitive test to recognize cardiac involvement in the acute phase of KD. Despite the fact that incomplete forms of presentation often delay diagnosis, in most patients treatment with IVIG can avoid complication of CAA.

Mucopolysaccharidosis type VI: a predominantly cardiac phenotype associated with homozygosity for p.R152W mutation in the ARSB gene.

Mucopolysaccharidosis type VI (MPS VI) is a rare lysosomal, autosomal recessive storage disorder caused by deficient activity of N-acetylgalactosamine-4-sulfatase (ARSB). Approximately, 140 ARSB gene mutations have been identified; however, most are private mutations making genotype-phenotype correlation for most MPS VI patients difficult. The aim of this study was to describe the natural clinical course in patients homozygous for the p.R152W mutation from eight unrelated families. From our database of 70 patients with MPS VI, we selected 10 patients homozygous for the p.R152W mutant allele (median age 27.5 years, range 18-38 years). We performed a cross-sectional observational study characterizing the onset and prevalence of clinical manifestations. First signs of the disease, such as cardiac valve disease, slightly decreased joint range of motion and mild growth retardation, were observed in mid-adolescent years (median 15 years). Within the disease course, the most common clinical feature in all the patients was progressive heart disease of predominantly valve origin leading to symptoms of heart failure. Other typical MPS VI features were subtle and not present in all the patients. Delays up to 23 years (median 8.5 years) intervened between symptom onset and disease diagnosis. Patients homozygous for the p.R152W mutation present a cardiac variant of MPS VI characterized by progressive cardiac valve disease leading to serious cardiac complications including abrupt death due to cardiac failure.

Mucopolysaccharidosis type VI: a cardiologist's guide to diagnosis and treatment.

Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome) is an inborn error of metabolism, with incidences at birth ranging from 1 in 1.5 million to 1 in 43,000 live births. This disorder is rarely considered when evaluating patients with common populational cardiovascular diseases. A significant number of MPS VI patients, however, do present cardiovascular disease and MPS VI should be considered as a potential differential diagnosis for other cardiovascular disorders. This article reviews the clinical features, diagnostic tests and treatment options for MPS VI. Although MPS VI affects many organs and systems of the human body this review focuses on MPS VI diseases of the heart and vessels. The most characteristic cardiac presentation of MPS VI is valvular disease, but heart failure, pulmonary hypertension, cardiomyopathy, fibroelastosis and cardiac conduction system disorders may also occur. Cardiovascular disease in MPS VI patients may emerge silently. An early diagnosis is difficult due to joint stiffness, respiratory system involvement or skeletal malformations that limit exercise capacity and mask the underlining heart failure. This article is supposed to serve as a very practical reference for cardiologists who may come across MPS VI in their daily practices. A greater awareness of cardiovascular manifestations of MPS VI among cardiologists can help to reduce misdiagnosis and promote early detection of this inborn disorder and aid the implementation of adequate therapy at the earliest stage possible which is crucial for its efficacy.

Clinical remission in juvenile idiopathic arthritis after termination of etanercept.

Biologicals are very effective for inhibiting disease progression in active juvenile idiopathic arthritis (JIA). To date, there have been no recommendations on how and when to stop therapy with TNF inhibitors. Our objective was to analyze characteristics and the disease course of JIA patients who discontinued etanercept due to achievement of inactive disease. Data of 39 patients with JIA from two clinical pediatric rheumatology centers in Bydgoszcz and Lublin (Poland) were analyzed retrospectively. All patients discontinued etanercept due to a remission on treatment. Etanercept was started after a mean 33.7 ± 36 (range 3-137) months of disease. The mean duration of therapy with etanercept was 34.7 ± 16.7 (range 6-72) months, with a mean duration of remission on medication 21.3 ± 9.6 (range 4-42) months before withdrawal of etanercept. The mean duration of remission after etanercept discontinuation was 14.2 ± 12.1 (range of 1-60) months. Only 12/39 (30.8 %) patients did not develop a disease exacerbation until the end of the study. Early flares, that is less than 6 months after termination of etanercept, were observed in 15/39 (38.5 %) patients. Twelve (30.8 %) patients restarted etanercept after exacerbation-all patients responded satisfactorily. Our data show that etanercept discontinuation in a substantial proportion of JIA patients results in early disease exacerbation. In many cases, reintroduction of etanercept is needed. Patients, in whom etanercept was restarted, responded satisfactorily.

Spinal cord compression in Maroteaux-Lamy syndrome: case report and review of the literature with effects of enzyme replacement therapy.

UNLABELLED: The purpose of this report is to review the literature regarding spinal cord compression in mucopolysaccharidosis type VI (MPS VI), to discuss the possible impact of enzyme replacement therapy (ERT) and to stress the necessity of timely surgical intervention. A 9.5-year-old female patient with severe MPS VI had been receiving ERT since the age of 7. After 2.5 years of treatment, she developed craniovertebral canal stenosis with spinal cord compression and cervical myelopathy. CONCLUSIONS: (1) baseline cervical spine evaluation and regular neurological assessment should be performed in all MPS VI patients, (2) detailed neurological observation should be conducted in patients treated with ERT, especially in the period of improvement in the osteoarticular system, as ERT fails to prevent cervical myelopathy and (3) surgical decompression is required and in order to achieve a satisfying outcome it might be crucial to perform surgery at an early age.

Effect of rapid cessation of enzyme replacement therapy: a report of 5 cases and a review of the literature.

UNLABELLED: Enzyme replacement therapy (ERT) is a treatment modality available for several of the lysosomal storage diseases including mucopolysaccharidosis type II (MPS II). We report a series of patients with MPS II (n = 5, age range at the start of ERT 11-21 years, median 15 years) and the effects of ERT cessation (range 2-8 months, median 3 months) on their clinical status. Additionally, we review previously published cases. In our series, a worsening of the patients' clinical status was observed. Symptoms after ERT discontinuation included recurrent respiratory infections (severe pneumonia) with respiratory insufficiency (80%), difficulty with walking/standing (60%), increased joint stiffness (40%), but also decreased hematological parameters (40%), renal insufficiency (40%) and death (20%). The literature review confirms that the beneficial clinical effects of ERT are soon lost if treatment is discontinued in MPS I and Pompe patients. CONCLUSIONS: 1. Rapid cessation of ERT results not only in the loss of the beneficial effects, but in a significant worsening of the patient's clinical status. 2. Decisions about the introduction of ERT, especially in patients severely affected, should be made carefully. 3. Once started, it is essential to keep an adequate administration schedule of ERT to maintain the clinical benefits of enzyme therapy.