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Srdjan Pasic

Publications and source records attributed to Srdjan Pasic.

15 recordsLinked to original sources
PubMed2006

The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the definition of improvement.

OBJECTIVE: To use the Pediatric Rheumatology International Trials Organization (PRINTO) core set of outcome measures to develop a validated definition of improvement for the evaluation of response to therapy in juvenile systemic lupus erythematosus (SLE). METHODS: Thirty-seven experienced pediatric rheumatologists from 27 countries, each of whom had specific experience in the assessment of juvenile SLE patients, achieved consensus on 128 patient profiles as being clinically improved or not improved. Using the physicians' consensus ratings as the gold standard measure, the chi-square, sensitivity, specificity, false-positive and false-negative rates, area under the receiver operating characteristic curve, and kappa level of agreement for 597 candidate definitions of improvement were calculated. Only definitions with a kappa value greater than 0.7 were retained. The top definitions were selected based on the product of the content validity score multiplied by its kappa statistic. RESULTS: The definition of improvement with the highest final score was at least 50% improvement from baseline in any 2 of the 5 core set measures, with no more than 1 of the remaining worsening by more than 30%. CONCLUSION: PRINTO proposes a valid and reproducible definition of improvement that reflects well the consensus rating of experienced clinicians and that incorporates clinically meaningful change in core set measures in a composite end point for the evaluation of global response to therapy in patients with juvenile SLE. The definition is now proposed for use in juvenile SLE clinical trials and may help physicians to decide whether a child with SLE responded adequately to therapy.

Child↗
PubMed2006

Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity.

Tyrosine kinase 2 (Tyk2) is a nonreceptor tyrosine kinase that belongs to the Janus kinase (Jak) family. Here we identified a homozygous Tyk2 mutation in a patient who had been clinically diagnosed with hyper-IgE syndrome. This patient showed unusual susceptibility to various microorganisms including virus, fungi, and mycobacteria and suffered from atopic dermatitis with elevated serum IgE. The patient's cells displayed defects in multiple cytokine signaling pathways including those for type I interferon (IFN), interleukin (IL)-6, IL-10, IL-12, and IL-23. The cytokine signals were successfully restored by transducing the intact Tyk2 gene. Thus, the Tyk2 deficiency is likely to account for the patient's complex clinical manifestations, including the phenotype of impaired T helper 1 (Th1) differentiation and accelerated Th2 differentiation. This study identifies human Tyk2 deficiency and demonstrates that Tyk2 plays obligatory roles in multiple cytokine signals involved in innate and acquired immunity of humans, which differs substantially from Tyk2 function in mice.

Adolescent↗
PubMed2006

Fever of unknown origin in 185 paediatric patients: a single-centre experience.

AIM: We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). METHODS: From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included routine haematological analysis, Epstein-Barr virus (EBV) serology, urine, stool or blood cultures, chest X-ray and tuberculin probe. RESULTS: In 131 (70%) patients diagnosis was established, and 70 (37.8%) had infectious disease. EBV infection was the most common infection followed by visceral leishmaniasis (VL), urinary tract infection (UTI) and tuberculosis. Autoimmune disorders were diagnosed in 24 (12.9%), Kawasaki disease in 12 (6.4%), malignant diseases in 12 (6.4%) and miscellaneous conditions in 15 (8.1%) patients. In the remaining 54 (30%) patients, diagnosis was not established and most of them had self-limited disease. During the investigation, 26 (14%) patients developed serious organ dysfunction and five patients (two with virus-associated haemophagocytic syndrome, one with VL and two unknown) died. CONCLUSION: The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary-care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO.

Adolescent↗
PubMed2006

Burkitt lymphoma-induced ileocolic intussusception in Wiskott-Aldrich syndrome.

A 12-year-old patient with Wiskott-Aldrich syndrome (WAS) was referred because of recurrent abdominal pain and bloody stools. Ileocolic invagination was diagnosed and resection of the terminal ileum was performed. Pathologic examination identified submucosal tumor as the leading point of intussusception. Immunohistochemistry confirmed the diagnosis of Burkitt lymphoma. The use of chemotherapy with anti-CD20 monoclonal antibody led to complete clinical remission of lymphoma. Non-Hodgkin's lymphoma (NHL) accounts for more than 60% of the tumors in children with primary immunodeficiency, and it is the most common type of malignancy observed in WAS. Burkitt lymphoma represents 40% to 50% of all NHL cases in childhood, but in WAS it has rarely been reported. Mutation analysis of the WASP gene in this patient revealed missense mutation (105 C > T) in exon 1. WAS protein (WASP) of normal size was present at a reduced amount in peripheral blood lymphocytes. Complete lack of expression of WASP carries a greater risk for severe infections, bleeding, or malignancy development in WAS. However, rare patients with residual expression of mutated WASP, like this patient, still may develop lymphomas.

Burkitt Lymphoma↗
PubMed2005

Idiopathic CD4+ lymphocytopenia and juvenile laryngeal papillomatosis.

We report on an association of idiopathic CD4+ lymphocytopenia (ICL) and juvenile laryngeal papillomatosis (JLP) in a pediatric-aged patient. Because of a past medical history of recurrent lung infections and severe chickenpox in infancy, immunologic investigations were done at age 6 years. On several occasions, a CD4+lymphocyte count of <300 cells/mm3 was detected, supporting the diagnosis of ICL. During follow-up, both medical (interferon-alpha) and surgical treatments of JLP were only partially efficient. Our patient developed disseminated infection with Mycobacterium avium and died at 10 years of age. Human papillomavirus is an important pathogen in pediatric and adult patients with ICL. In pediatric patients with JLP who develop other unusually severe viral or opportunistic infections, immunological investigations should be considered.

Antibodies, Viral↗
PubMed2004

T-cell lymphoblastic leukemia/lymphoma in Nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS) is a rare autosomal-recessive disorder characterized by microcephaly, immunodeficiency and predisposition to cancer, mainly B-cell lymphomas. Our 10-years-old female patient with NBS developed T-cell lymphoblastic leukemia/lymphoma (TLBL/ALL). The use of standard chemotherapy in our patient, except for cranial irradiation, led to complete and sustained remission of TLBL/ALL. In patients with chromosomal instability syndromes chemotherapy must be modified and radiotherapy must be omitted because of potentially serious toxic complications. Careful prevention of infections, including the use of intravenous immunoglobulin is also essential for successful treatment of lymphoid malignancies in NBS. Immunodeficiency in NBS is profound affecting both humoral and cellular immune system. During long-term follow-up after treatment of malignancy our patient remained free of major infections However, the rise of oligoclonal serum IgM was detected recently. Monitoring of serum IgM concentration may be a useful indicator for early detection of lymphomas in NBS.

Adolescent↗
PubMed2003

Long-term follow-up and prognosis of chronic granulomatous disease in Yugoslavia: is there a role for early bone marrow transplantation?

We report the long-term follow-up of 12 pediatric-aged patients with chronic granulomatous disease (CGD). The mean age at the onset of infections was 5 months with a median delay in diagnosis of 2.5 years. Bacille Calmette-Guérin lymphadenitis was the most common presenting infection (6) followed by suppurative lymphadenitis (4), liver abscess (1), or Salmonella sepsis (1). Prophylaxis with cotrimoxazole was recommended to all patients. During the mean follow-up of 10 years (range, 4-23 years) pneumonitis was the most prevalent infection (91%) followed by lymphadenitis (83%), aphtous stomatitis (58%), and liver abscesses (25%). Seven (58%) patients developed chronic lung disease due to grossly delayed diagnosis (3) or poor compliance with antimicrobial prophylaxis (4). Five (41%) patients died during the second decade of life of aspergillosis (3) or chronic lung disease (2). Probability of survival into the third decade of life was estimated to be only 19%. We argue that HLA-identical bone marrow transplantation (BMT), if possible, should be attempted at early age because of significant morbidity and mortality in adolescence. BMT also should be considered in patients who suffer severe infections despite antimicrobial prophylaxis or patients with evidence of chronic lung disease. Possibility of elective BMT from unrelated donors remains to be carefully evaluated.

Adolescent↗
PubMed2002

Progressive neurodegeneration in patients with primary immunodeficiency disease on IVIG treatment.

We have identified 14 patients with diverse primary immunodeficiencies who have developed progressive neurodegeneration of unknown etiology. All patients had received immunoglobulin replacement therapy for a mean duration of 6.5 years (range of 0.5-13.5 years) at the time of first neurological symptoms. Diagnostic tests of blood and cerebrospinal fluid analyses included chemistry, cultures, PCR for viral genomes, and cytology. In addition, neuroimaging and electrophysiologic studies were performed. Brain tissue histology (n = 5) revealed nonspecific encephalitis with microglial infiltration and neuronal loss. Twelve patients died 6 months to 15 years (median 4.3 years) after onset of neurologic findings. No evidence of any infectious disease that could have explained our patients' progressive encephalopathy was found either during their lifetimes or postmortem. These patients may have had an unusual manifestation of primary immunodeficiency diseases, an autoimmune reaction against neuronal tissue, a yet undefined infectious agent, or a complication of IVIG therapy. To help determine the etiology of this rare complication, an international surveillance system for primary immunodeficiency patients who develop progressive neurodegeneration of unknown cause is recommended.

Adolescent↗
PubMedDate not supplied

Pityriasis lichenoides in a girl with the granulomatous form of common variable immunodeficiency.

Pityriasis lichenoides (PL) is a cutaneous disease of unknown origin. In our 8-year-old female patient with the granulomatous form of common variable immunodeficiency (CVID), PL occurred together with massive splenomegaly and intra-abdominal lymphadenopathy. Prednisone was efficient for treatment of her splenomegaly and autoimmune cytopenias. However, PL was resistant to both topical and systemic steroid treatment. Healing of PL was achieved with the use of a super-potent topical steroid, clobetasol propionate. A defect of T-cell function in CVID may contribute to development of PL. In the granulomatous form of CVID, sarcoid-like granulomas are the most commonly reported cutaneous lesions. PL has not been previously reported.

Administration, Topical↗