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  • 1.
    Croner, Stefan
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Development of atopic disease from birth to adolescence: Relation to family history and cord blood IgE1991Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In a cohort of 1701 consecutively born children, 32.5% developed obvious atopic disease up to 11 yr. The predictive capacity of cord blood IgE and a family history (FH) of atopic disease have been studied. Questionnaire (Q) data at 1.5, 7 and 11 yr showed a prevalence of obvious atopic disease of 4.5, 11.5 and 23.7 % respectively. The prevalence of asthma was 0.5, 2.4 and 3.0 %, a slight increase in comparison with figures from the 50's. A high cord blood IgE (~ 0.9 kUJI), identified most children with early, multiple and continuous symptoms as well as an earlier asthma start. The capacity of cord blood IgE to predict the severity of asthma and the IgE levels at 11 yr was low. The sensitivity of the test to detect atopic disease decreased from 77 % at 1.5 yr to 26 % at 11 yr. The sensitivity for obvious allergy of a FH was 49 % at 1.5 yr and 45 % at 11 yr. The specificity of cord blood IgE was 94 % at 11 yr and of the FH 74 %. Cord blood IgE determination alone can not, without modifications, be recommended as a general screening method for atopy.

    Children with high cord blood IgE, born during peak pollen exposure seem to be at special risk to develop atopic disease. Sensitization to timothy was more common among children born in May as compared to November. The reliability of the Q used at 7 and 11 yr was evaluated by examination of 133 randomly selected children at 11 yr. The Q was found adequate for establishing the prevalence but less so for the cumulative incidence of atopic disease since parents tend to forget symptoms (25%) that their children had some years earlier.

    The natural history of asthma (AB) was studied in all 89 children and adolescents reporting symptoms of asthma. Fifty-nine were available for clinical examination at 11.5-14.5 yr. AB was found more often in children born during August-October. Inadequate medication, undiagnosed chest deformity and wheezing at examination was found in several children emphasizing the need for more regular control of adolescents having AB. Animal danders and pollens were the most common offending allergens. Sensitivity to mites was more common compared to earlier Swedish studies. A "total asthma score" including both days with impact of AB during last year and present medication was found useful for classification of these children with AB.

  • 2.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Croner, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Lahdenne, Pekka
    Hospital for Children and Adolescents, Helsinki University Central Hospital.
    Sillanpää, Heidi
    Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki.
    Seppälä, Ilkka
    Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki.
    Improved Laboratory Diagnostics of Lyme Neuroborreliosis in Children2008In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 27, no 7, p. 605-612Article in journal (Refereed)
    Abstract [en]

    Background: Laboratory diagnostics in Lyme neuroborreliosis need improvement. We hereby investigate 4 new recombinant or peptide Borrelia antigens in cerebrospinal fluid in children with neuroborreliosis to evaluate their performance as diagnostic antigens.

    Methods: An enzyme-linked immunosorbent assay was used to detect IgG antibodies to recombinant decorin binding protein A (DbpA), BBK32, outer surface protein C (OspC), and the invariable region 6 peptide (IR6). The recombinant antigens originated from 3 pathogenic subspecies; Borrelia afzelii, Borrelia garinii, and Borrelia burgdorferi sensu stricto. Cerebrospinal fluid and serum from children with clinical features indicative for neuroborreliosis (n = 57) were analyzed. Classification of patients was based on clinical symptoms and laboratory findings. Controls were children with other neurologic diseases (n = 20) and adult patients with no proven infection (n = 16).

    Results: Sensitivity for DbpA was 82%, for BBK32 70%, for OspC 58% and for IR6 70%. Specificities were 94%, 100%, 97%, and 97%, respectively. No single antigen was superior. When new antigens were combined in a panel, sensitivity was 80% and specificity 100%. The reference flagella antigen showed a sensitivity of 60% and a specificity of 100%. Over all, the B. garinii related antigens dominated.

    Conclusions: Recombinant DbpA and BBK32 as well as the peptide antigen IR6 perform well in laboratory diagnostics of neuroborreliosis in children. New antigens seem to improve diagnostic performance when compared with the routine flagella antigen. If different antigens are combined in a panel to cover the antigenic diversity, sensitivity improves further and a specificity of 100% can be achieve.

  • 3.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Croner, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nordwall, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Eknefelt, Mattias
    Pediatric Clinic, Jönköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Lyme Neuroborreliosis in Children - a Prospective Study of Clinical features, Prognosis, and Outcome2008In: The Pediatric Infectious Disease Journal, ISSN 0891-3668, E-ISSN 1532-0987, Vol. 27, no 12, p. 1089-1094Article in journal (Refereed)
    Abstract [en]

     

    Background: Evaluation of children with clinically suspected neuroborreliosis (NB) is difficult. With a prospective study design we wanted to characterize children with signs and symptoms indicative for NB, investigate clinical outcome and, if possible, identify factors of importance for recovery.

    Material/Methods: Children being evaluated for NB (n = 177) in Southeast Sweden were categorized into 3 groups: "confirmed neuroborreliosis" (41%) with Borrelia antibodies in the cerebrospinal fluid, "possible neuroborreliosis" (26%) with pleocytosis but 110 Borrelia antibodies in the cerebrospinal fluid, and "not determined" (33%) with no pleocytosis and no Borrelia antibodies in the cerebrospinal fluid, Antibiotic treatment was given to 69% of children. Patients were followed during 6 months and compared with a matched control group (n = 174).

    Results: Clinical recovery at the 6-month follow-up (n = 177) was generally good and no patient was found to have recurrent or progressive neurologic symptoms. However, persistent facial nerve palsy caused dysfunctional and cosmetic problems in 11% of patients. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. Influence on daily life was reported to the same extent in patients and controls. Consequently, persistent headache and fatigue at follow-up should not be considered as attributable to NB. No prognostic factors could be identified.

    Conclusions: Clinical recovery was satisfactory in children being evaluated for NB although persistent symptoms from facial nerve palsy occurred. Persistent nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls.

  • 4.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Croner, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ödkvist, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Acute facial palsy in children - a 2-year follow-up study with focus on Lyme neuroborreliosis2003In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, Vol. 67, no 6, p. 597-602Article in journal (Refereed)
    Abstract [en]

    Objective: Acute facial palsy in children is believed to be a rather benign neurological condition. Follow-up-studies are sparse, especially including a thorough otoneurological re-examination. The aim of this study was to examine children with a history of facial palsy in order to register the incidence of complete recovery and the severity and nature of sequelae. We also wanted to investigate whether there was a correlation between sequelae and Lyme Borreliosis, treatment or other health problems.

    Methods: Twenty-seven children with a history of facial palsy were included. A re-examination was performed by an Ear-Nose-Throat (ENT) specialist 1–2.9 years (median 2) after the acute facial palsy. The otoneurological examination included grading the three branches of the facial nerve with the House-Brackman score, otomicroscopy and investigation with Frenzel glasses. A paediatrician interviewed the families. Medical files were analysed.

    Result: The incidence of complete recovery was 78% at the 2-year follow-up. In six out of 27 children (22%), the facial nerve function was mildly or moderately impaired. Four children reported problems with tear secretion and pronunciation. There was no correlation between sequelae after the facial palsy and gender, age, related symptoms, Lyme neuroborreliosis (NB), treatment, other health problems or performance.

    Conclusion: One fifth of children with an acute facial palsy get a permanent dysfunction of the facial nerve. Other neurological symptoms or health problems do not accompany the sequelae of the facial palsy. Lyme NB or treatment seems to have no correlation to clinical outcome. Factors of importance for complete recovery after an acute facial palsy are still not known.

  • 5.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Croner, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Kampanj för TBE vaccination av små barn oetisk och felaktig2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 37, p. 2832-2832Article in journal (Other academic)
  • 6.
    Hedin-Skogman, Barbro
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Nilsson, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Croner, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    TBE-vaccinera barn över 7 år i endemiska områden, men låt de små barnen slippa.2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 43, p. 3367-3367Article in journal (Other (popular science, discussion, etc.))
  • 7. Lundin, B
    et al.
    Croner, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Munchausen syndrome by proxy - a literature review and Swedish case histories2001In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, no 19, p. 2302-+Article in journal (Refereed)
    Abstract [en]

    Munchausen syndrome by proxy (MSbP) is a potentially lethal form of child abuse. Mortality rates around 10 percent have been reported. A knowledge of the characteristics of MSbP is needed in order to reveal the diagnosis and to handle the management correctly. Swedish experience is in accordance with international reports.

  • 8.
    Lundin, Björn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment. Östergötlands Läns Landsting, CPS - Centrum för psykiatri och samhällsmedicin, BUP - Barn- och ungdomspsykiatri.
    Croner, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Barnmisshandel genom förfalskning av symtom.2001In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 98, p. 2302-2311Article in journal (Other academic)
  • 9.
    Widhe, Mona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Hedin Skogman, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Bergström, Sven
    Department of Microbiology, University of Umeå, Sweden.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Eknefelt, Mattias
    Pediatric Clinic, Ryhov County Hospital, Jönköping, Sweden.
    Eneström, Gunilla
    Pediatric Clinic, Västervik Hospital, Västervik, Sweden.
    Nordwall, Maria
    Pediatric Clinic, Vrinnevi Hospital, Norrköping, Sweden.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences.
    Croner, Stefan
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Up-regulation of Borrelia-specific IL-4 and IFN-gamma secreting cells in cerebrospinal fluid from children with Lyme neuroborreliosis2005In: International Immunology, ISSN 0953-8178, Vol. 17, no 10, p. 1283-1291Article in journal (Refereed)
    Abstract [en]

    The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. In adults with neuroborreliosis (NB), a type 1 response with high production of Borrelia-specific IFN-, but no IL-4, has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 responses in children with NB. Cerebrospinal fluid (CSF) and blood were collected from children during the acute stage of ‘confirmed NB’ (n = 34), ‘possible NB’ (n = 30) and ‘non-NB’ (n = 10). The number of Borrelia-specific IL-4- and IFN--secreting cells was measured by enzyme-linked immunospot assay. Borrelia-specific secretion of both IL-4 and IFN- was increased in CSF in confirmed (P < 0.05) and possible (P < 0.01) NB, when compared with non-NB controls. Furthermore, children with NB had significantly higher Borrelia-specific IL-4 secretion in CSF than an adult reference material with NB (P < 0.05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly harmful effects of prolonged IFN- responses, the prominent IL-4 response observed in the central nervous system compartment might contribute to the more benign disease course seen in children with Lyme NB.

  • 10.
    Widhe, Mona
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hedin Skogman, Barbro
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jarefors, Sara
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Eknefelt, Mattias
    Jönköping, Sweden.
    Eneström, Gunilla
    Västervik, Sweden.
    Nordwall, Maria
    Norrköping, Sweden.
    Ekerfelt, Christina
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Croner, Stefan
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    A multicenter study on children with Lyme Neuroborreliosis: Up-regulation of Borrelia-specific IL-4 and IFN-γ secreting cells in cerebrospinal fluid and bloodManuscript (preprint) (Other academic)
    Abstract [en]

    The clinical course and outcome of several infectious diseases are dependent on the type of immune response elicited against the pathogen. As suggested by animal models the interleukin (IL)-4 and interferon (IFN)-γ responses seem to play a role in Lyme borreliosis. In adults with neuroborreliosis (NB), a type 1 like response with high production of Borrelia-specific IFN-γ, but no IL-4, in the cerebrospinal fluid (CSF) and blood has been reported. Since children have a more benign course of NB than adults, we wanted to investigate type 1 and type 2 like responses in children with NB. CSF and blood were collected from children during the acute stage of 'confirmed NB' (n=34), 'possible NB' (n=30) and 'non-NB' (n=10). The number of Borrelia-speciflc IL-4 and IFN-γ producing cells was measured by ELISPOT. Borrelia-specific secretion of both IL-4 and IFN-γ was increased in CSF in confirmed (p<0.05) and possible (p<0,01) NB, compared with non-NB. Furthermore, children with NB had significantly higher Borrelia-speciflc IL-4 secretion in cerebrospinal fluid than an adult reference material with NB (p<0,05). There were no differences in cytokine secretion in relation to onset or recovery of neurological symptoms. Since IL-4 is known to down-regulate the pro-inflammatory and possibly hannful. effects of prolonged IFN-γ responses, the observed prominent IL-4 response in the CNS-compartment might contribute to the more benign disease course seen in children with Lyme NB.

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