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Abstract Aims--To evaluate outcome following neonatal bone marrow transplantation (BMT) for severe combined immuno deficiency (SCID) when there is a family history of a previously affected sibling, and to compare [...]

To document pathways of care, management, and interval from onset of symptoms to first pediatric rheumatology multidisciplinary team (PRhMDT) assessment for children with incident juvenile idiopathic arthritis (JIA).We conducted a retrospective observational study of children with incident JIA over a 3‐year period.The study included 152 patients with JIA (87 females). The median interval from symptom onset to first PRhMDT assessment was 20 weeks (range 0–416), with significant variation between JIA subtypes (P = 0.0097); children with extended oligoarticular JIA had the longest interval (median 60 weeks, range 12–320). Prior to pediatric rheumatology assessment, many children had referrals to multiple secondary care specialties and had been subjected to multiple and often invasive procedures including arthroscopy/synovial biopsy (18 [11.8%] of 152), but none were referred for ophthalmologic screening, physical therapy, or nursing input and a diagnosis of JIA was rarely made (98%). At first PRhMDT assessment, most patients had untreated active disease with active joint count ≥1 (135 [89%] of 152), restricted joint count ≥1 (135 [89%] of 152), and functional disability by Child Health Assessment Questionnaire score >0 (53 [68%] of 118); 1 child had undetected uveitis. Following PRhMDT assessment, interventions were invariably indicated, including joint injections (69 [45%] of 152), methotrexate (49 [32%] of 152), and physical therapy programs (all patients).Delay in access to pediatric rheumatology assessment is common with complex pathways of referral. Many children were subjected to inappropriate invasive investigations and many had prolonged untreated active disease at the initial PRhMDT assessment. This delay is likely to affect long‐term outcome and warrants further exploration.

Hereditary angio-oedema is characterised by recurrent swellings in any part of the body and also by recurrent attacks of severe abdominal pain. The disease is inherited in an autosomal dominant manner but up to 25% of cases can occur as a spontaneous mutation. Attacks of swelling can be precipitated by trauma, certain drugs, and emotional stress. Treatment usually involves a combination of prophylaxis, using androgens or antifibrolytic drugs, and replacement with C'1 esterase inhibitor concentrate for acute attacks and before surgery or other traumatic procedures.

Background Pneumocystis carinii is an important pathogen in immunodeficiency but may be an unrecognised cause of respiratory compromise. Objectives To ascertain the incidence of P carinii pneumonia (PCP) at presentation of severe combined immunodeficiency (SCID), whether it had been diagnosed, and the effect of treatment on outcome. Setting The supraregional paediatric bone marrow transplant unit for primary immunodeficiencies at Newcastle General Hospital. Methods Retrospective case note review of infants referred with a diagnosis of SCID from 1992 to 1998. Results Ten of 50 infants had PCP at presentation; only one was diagnosed before transfer. Eight were diagnosed by bronchoalveolar lavage and two by lung biopsy. In only one was P carinii identified in nasopharyngeal secretions. Five required ventilation for respiratory failure but all were successfully treated with co-trimoxazole and methylprednisolone with or without nebulised budesonide. Nine survived to bone marrow transplantation and four are long term survivors after bone marrow transplantation; no deaths were related to PCP. Conclusions PCP is a common presenting feature of SCID but is rarely recognised. Bronchoalveolar lavage or lung biopsy are needed for diagnosis. Treatment with co-trimoxazole is highly successful.

Disseminated Bacillus Calmette‐Guérin infection occurs in few well‐defined immunodeficiencies, such as severe combined immunodeficiency, chronic granulomatous disease and paediatric acquired immunodeficiency syndrome. This severe complication of immunization against tuberculosis has been lethal in the majority of children who had primary immunodeficiency. Our patient, a 9‐y‐old girl with hyperimmunoglobulin E syndrome developed disseminated Bacillus Calmette‐Guerin infection in infancy. Patients with hyperimmunoglobulin E syndrome (HIES) are susceptible to serious staphylococcal and fungal infections. Disseminated Bacillus Calmette‐Guerin infection has not previously been reported in this rare immunodeficiency.

Neurological complications of malignant infantile osteopetrosis are well recognised; successful bone marrow transplantation, when performed early in life, can prevent or halt some of them. In a subgroup of infants osteopetrosis is associated with primary retinal degeneration and/or generalised neurodegeneration. Bone marrow transplantation, in spite of being successful in correcting the osseous and haematological abnormalities, does not influence the progressive course of the neurodegenerative disorder. Thus, the recognition of this subgroup of infants with a very poor prognosis is essential before deciding on bone marrow transplantation.

A case report of an infant with the Wiskott-Aldrich syndrome and clinical and radiological features of infantile cortical hyperostosis (Caffey disease) is presented. This is the third case described of the association of these two rare disorders and gives further support to the role of an immunologic defect in the pathogenesis of infantile cortical hyperostosis.

Background: Severe Primary Immunodeficiencies (PID) have high morbidity and mortality. Umbilical cord blood stem cell transplantation (UCSCT) is curative. Conditioning regimens aid engraftment and long-term thymopoiesis. Modification of cyto-reductive chemotherapy with or without anti-lymphocyte serotherapy may alter immunoreconstitution and outcome.Aims: To examine speed of immunoreconstitution with respect to dose of serotherapy.Methods: A retrospective review of time to neutrophil and platelet engraftment, =200 T cells/µl, thymopoiesis, and lymphocyte subsets at 2,4,6 and 12 months in 33 PID patients who received UCSCT between 1999-2010 in one centre.Results: 12 patients received high dose (>0.6mg/kg), 10 low dose, and 8 no serotherapy. Overall median time to neutrophil and platelet engraftment was 21 and 38 days respectively. There were significant differences in median lymphocyte counts between dosages of serotherapy at specific time periods post UCSCT, with a general trend of low dose resulting in higher counts than high dose or no serotherapy. Exceptions were CD3+ and CD4+ counts at 2 months when no serotherapy led to significantly higher counts. No serotherapy led to a significantly shorter time to =200 CD3 cells/µl (17.5 days, range 10-88, p=0.001) but not to thymopoiesis. 6 evaluable patients achieved viral clearance by a median of 103 days post-UCSCT. Survival was 81%.Conclusions: This study shows that no serotherapy leads to higher lymphocyte counts by 2 months post UCSCT, but that higher lymphocyte counts are achieved with low dose serotherapy in the longer term. Further studies to determine mechanism are needed.

Presentation characteristics were reviewed in 14 children from 12 families with malignant infantile osteopetrosis seen at two large referral centres for bone marrow transplantation. Children from six of these families presented initially with symptoms of hypocalcaemia. These comprised early or late neonatal convulsions in six cases (corrected serum calcium < 1.5 mmol/l), and vomiting and irritability (serum calcium 1.68 mmol/l) in another. One other related child had severe and persistent jittering episodes almost certainly attributable to hypocalcaemia. In seven of eight cases, these symptoms developed during the first 14 days of life. Although occasionally reported previously, malignant infantile osteopetrosis remains essentially unrecognised as a cause of neonatal hypocalcaemia, often resulting in diagnostic confusion and delay. This is important in the context of curative haemopoietic stem cell transplantation where preservation of sight may depend on early intervention.