Henoch-Schönlein purpura in children

Abstract The aim of this work was to describe the clinical features and clinical course of Henoch-Schönlein purpura (HSP) in a prospective setting, to compare the efficacy of cyclosporine A (CyA) and methylprednisolone (MP) pulses for the treatment of severe HSP nephritis (HSN) and to study the effect of prophylactic prednisone treatment given at disease onset on the long-term outcome. A total of 223 children with newly diagnosed HSP were followed up prospectively for 6 months. Patients with severe HSN also had extrarenal symptoms more frequently during this time. Protein loss via the intestine was more common than previously described, occurring in 3% of the patients. HSN developed in the early course of the disease. The results suggest that weekly urine dipstick tests are indicated for 2 months after HSP onset and individually for over 6 months in cases of HSN or HSP recurrences. Prednisone did not affect the frequency or timing of the appearance of HSN. The efficacy of CyA and MP treatments was evaluated in a trial with a mean follow-up time of 6 years involving 24 paediatric patients (11 CyA, 13 MP), 15 of whom were randomized and 9 were treated according to the given protocol without randomization. Oral CyA was not inferior to intravenous MP pulses and proved to be an efficient, safe steroid-sparing treatment for severe HSN. All the CyA-treated patients achieved remission of nephrotic-range proteinuria within 3 months, while remission was achieved more slowly in the MP group and only in 6/13 (46%) with the initial treatment. There was no difference in the renal biopsy findings two years after initiation of the therapy. The 8-year outcome of HSP was assessed by means of a health questionnaire in 160 (94%) of the 171 former patients in the randomized placebo-controlled prednisone trial and in 138 (81%) with urine analysis and measurement of blood pressure. HSP carried a good prognosis, although skin relapses occurred up to a decade after the initial onset and could be accompanied by late-onset nephritis. Hypertension and/or renal abnormalities were recorded in 13% of the patients, being more frequent in those with an initial occurrence of HSN (OR 4.3, p=0.009, 95% CI 1.4–14.0) and warranting long-term follow-up of HSN patients. Early prednisone treatment did not affect the long-term outcome of HSP and should not be routinely used.Tiivistelmä Väitöskirjan tarkoituksena oli kuvata Henoch-Schönleinin purppuran (HSP) oireita ja taudinkulkua, verrata siklosporiini A:n (CyA) ja metyyliprednisolonipulssihoidon (MP-pulssihoidon) tehoa vaikean HSP-nefriitin (HSN) hoidossa ja selvittää taudin alussa annetun prednisonihoidon vaikutusta pitkäaikaisennusteeseen. Taudinkulkua seurattiin prospektiivisesti 6 kuukauden ajan diagnoosista 223 lapsipotilaan aineistossa. Potilailla, joilla oli vaikea HSN, esiintyi myös muita oireita pitempään. Proteiinin menetystä suolistoon esiintyi 3 %:lla, mikä on aiemmin kuvattua yleisempää. HSN ilmaantui taudin alkuvaiheessa. Tutkimustulosten perusteella viikoittainen virtsanäytteiden seuranta riittää 2 kuukauden ajan taudin alusta. Seuranta-aikaa tulee pidentää yksilöllisesti yli 6 kuukauden, jos potilaalla todetaan HSN tai HSP uusiutuu. Prednisonilla ei todettu olevan vaikutusta HSN:n yleisyyteen tai ilmaantumisaikaan. CyA- ja MP-hoitojen tehoa vaikeaan HSN:n seurattiin 24 lapsipotilaan aineistossa (11 CyA, 13 MP) 6 vuoden ajan. Potilaista 15 satunnaistettiin hoitoryhmiin ja 9 hoidettiin tutkimussuunnitelman mukaan ilman satunnaistamista. Suun kautta otettu CyA vaikutti hoidoista tehokkaammalta, sillä kaikilla potilailla nefroottistasoinen valkuaisvirtsaisuus hävisi kolmessa kuukaudessa. MP-hoitoa saaneista vain 6/13 (46 %) pääsi remissioon MP-hoidolla ja hekin CyA-hoidettuja hitaammin. Kaksi vuotta tutkimuksen alusta otettujen munuaisbiopsioiden histologisissa löydöksissä ei ollut eroa ryhmien välillä. Varhaisen kortisonihoidon pitkäaikaisvaikutuksia arvioitiin 8 vuotta lumekontrolloidun prednisonihoitotutkimuksen jälkeen, jolloin aiemman tutkimuksen 171 potilaasta 160 (94 %) vastasi terveyskyselyyn ja 138 (81 %) osallistui virtsa-analyysin ja verenpaineen mittauksen sisältäneeseen seurantatutkimukseen. HSP:n ennuste oli hyvä, vaikka taudin iho-oireet saattoivat uusia jopa 10 vuoden ajan ja taudin uusiutumisen yhteydessä saattoi ilmaantua myöhäinen HSN. Kohonnut verenpaine ja/tai valkuais-/verivirtsaisuus todettiin 13 %:lla. Ne olivat yleisempiä potilailla, joilla oli ollut HSN taudin alkuvaiheessa (OR 4.3, p=0.009, 95 % CI 1.4–14.0). Siten HSN-potilaiden pitkäaikaisseuranta on tarpeen. Varhaisella kortisonihoidolla ei ollut vaikutusta taudin ennusteeseen, minkä vuoksi kortisonia tulee käyttää HSP-potilaiden hoidossa vain harkiten

Optimizing care for children with difficult-to-treat and severe asthma through specialist paediatric asthma centres:expert practical experience and advice

Severe asthma in children carries an unacceptable treatment burden, yet its rarity means clinical experience in treating it is limited, even among specialists. Practical guidance is needed to support clinical decision-making to optimize treatment for children with this condition. This modified Delphi convened 16 paediatric pulmonologists and allergologists from northern Europe, all experienced in treating children with severe asthma. Informed by interviews with stakeholders involved in the care of children with severe asthma (including paediatricians, nurses and carers), and an analysis of European guidelines, the experts built a consensus focused on the gaps in existing guidance. Explored were considerations for optimizing care for patients needing biologic treatment, and for selecting home or hospital delivery of biologics. This consensus is aimed at clinicians in specialist centres, as well as general paediatricians, paediatric allergologists and paediatric pulmonologists who refer children with the most severe asthma to specialist care. Consensus is based on expert opinion and is intended for use alongside published guidelines. Our discussions revealed three key facets to optimizing care. Firstly, early asthma detection in children presenting with wheezing and/or dyspnoea is vital, with a low threshold for referral from primary to specialist care. Secondly, children who may need biologics should be referred to and managed by specialist paediatric asthma centres; we define principles for the specialist team members, tests, and expertise necessary at such centres, as well as guidance on when homecare biologics delivery is and is not appropriate. Thirdly, shared decision-making is essential at all stages of the patient’s journey: clear, concise treatment plans are vital for patient/carer self-management, and structured processes for transition from paediatric to adult services are valuable. The experts identified the potential for specialist paediatric asthma nurses to play a significant role in facilitating multidisciplinary working. Through this project is agreed a framework of practical advice to optimize the care of children with severe asthma. We encourage clinicians and policymakers to implement this practical advice to enhance patient care.</p