y to scarring. Tests: Baseline blood gas, serum iron concen- tration, U&E, FBC, glucose. Ir on levels at 4 \200\2236h help determine level of severity. Levels of <350 g/dL ( 60 mol/ L) are associated with minimal symptoms. Lev- els >500 g/dL ( 90 mol/L) are associated wi th serious toxicity. An abdominal radiograph may show tablets within the gut and reveal a b ezoar. \200\207In servere toxicity do not wait for tests: start desferrioxamine. Managemen t: \200 Obtain expert help as this is one of the few instances when gastric lavage/ endoscopy to remove tablets in the stomach may be recommended. \200 Activated charcoal is not given as it has no eff ect on iron absorption. \200 Whole bowel irrigation may help (esp. in slow-release preparations). 606 \200 Supportive care \200\224IV \202 uids and sodium bicarbonate to correct acidosis \200 Chelation with IV desferrioxamine (5 \200\223 15mg/kg/h \200\224start at higher dose then reduce after 4 \200\2236h \200\224max 80mg/kg/2 4h). Therapy should be stopped when the acidosis improves. It is rarely required for >24h. Use of desferrioxamine leads to orangey-red urine which demonstrates that free iron has bee n bound to the desferrioxamine. It is also associated with hypotension, rashes, pulmo- nary oedema and acute respiratory distress syndrome. Haemo \201 ltration has been used in children, in combination with desferriox- amine to ra pidly reduce iron levels. 607 Salicylate poisoning The most common salicylate is acetylsalicylic acid, ie aspirin, which is not rec- ommended in children <16y due to its association with Reye s syndrome (p652). C holine salicylate is found in Bonjela \210\217 for adults. Since 2009, Bonjela teeth- ing g el \210\217 in the UK has used lidocaine as its active ingredient, however Bonjela teething gel \210\217 in other countries (eg Australasia) continues to contain choline salicylate ( 8.7%) and there are reports of toxicity in children. 608 Methyl salicy- late is found in oi l of wintergreen (98%). As little as 3mL can be fatal in chil- dren. 609 Methyl salicylate is also found in muscle rubs such as Bengay \210\217, Deep Heat \210\217, and Tiger Balm \210\217 ( 15 \200\22340%). Presentation: Toxicity occurs at 100mg/kg aspirin. Early signs include tinnitus and hearing loss. Stimulation of respiratory centers leads to tachypnoea and a respiratory alkalosis. Interference with aer- obic metabolism leads to the metabolic (lactic) acidosis which is character- istic of salicylate poisoning. GI irritation (nausea, vomiting, abdominal pain is common). Central eff ects lead to agitation, delirium and seiz ures. Rhabdomy- olysis, pulmonary oedema and electrolyte disturbances may also occur. Tests : Blood gas; FBC; U&E, glucose. Salicylate levels are best obtained at 6 hours (re- \202 ects a peak level) however, do an initial level to con \201 rm diagnosis, and then levels every 2h to con \201 rm levels are decreasing \200\224enteric coated (EC) prepara- tions c an lead to delayed absorption. Large bezoars of EC aspirin may be seen on radiograph. Manag ement: Resuscitate with boluses of 10 \200\22320mL/kg of 0.9% saline. Correct hypoglycaemia . Potassium may be needed as hypokalaemia is common. Serious poisoning is indicated by leve ls >2.5 \200\2233.6mmol/L \200\224consider urinary alkalinization with IV sodium bicarbonat e to enhance elimination (un- der expert guidance in ITU). Activated charcoal is eff ective in adsorbing aspi- rin, but as patients are liable to vomit or experience \200\201GCS con sider intubating \201 rst and using a NGT. Repeat doses can be given. Haemodialysis is th e de \201 nitive treatment: use when evidence of end organ injury 610 (seizures, severe ac idosis, rhabdomyolysis, renal failure, pulmonary oedema). Seek expert help. 192 s c i r t a d e a P i Paracetamol (acetaminophen) poisoning The therapeutic dose is 15mg/kg. Hepatotoxicity can o ccur if \211 150mg/kg/24h ingested. The initial features are nausea and pallor. Hepatic en zymes rise after 24h. Jaundice and an enlarged, tender liver occur after 48h. Hypoglycaemi a, hypotension, encephalopathy, coagulopathy, coma may also occur. Management of single ora l paracetamol overdoses: \200 If you are certain the ingested paracetamol is <150mg/kg in a child with no hepatic risk factors (below), then management may be safely done at home. 611 \200 Admit those presenting within 8h of ingesting >150mg/kg (or an unknown amount or with high risk factors) and do a serum paracetamol concentration at \211 4h post ingestio n. If presenting <1h, and >150mg/kg of tablets ingested, and no contra-indication (eg vomit ing; \200\201GCS), give activated charcoal \200\224not bene \201 cial if elixir has been ingested which is absorbed in 15 mins. 612 \200 Decide if the child has any high-risk fa ctors, eg patients who are on enzyme- inducers (p300) or who are malnourished (eg anorexia, alcoholism, HIV +ve), or have febrile illness \200\224in whom toxicity may occur at doses of >75mg/kg. 613 \200 Consult the nomogram on the opposite page. If the child is high ris k, use the lower treatment line, if not \200\224use the upper line. If plasma paracetamol l evel is above the appropriate line, treat with acetylcysteine (NAC). The initial dose is 15 0mg/kg in up to 200mL (depending weight; see BNF) of 5% dextrose infused over 15min, follow ed by 50mg/kg IVI over the next 4h, and 100mg/kg IVI over next 16h. It is very eff ective i n preventing liver damage if given in <8h. Patients with a delayed presentation (>8h) or in whom a level cannot be ob- tained within 8 h, should have acetylcysteine started immediately if ingested dose is >150mg/kg, or dose is unknown. Check often for hypoglycaemia. Consider the cause: typically teenage girls seeking attention. All need psy- chiatric evalu ation. Causes may be extremely complex and deep-seated: although the patient may claim a se emingly super \201 cial cause this may be hiding deep social or psychiatric pathology. 193 Staggered overdose: Seek expert help: these patients are at potentially great- er risk than those with single point overdoses, and may present with greater delays. 614 Paracetamol le vels alone may not be reliable in staggered overdoses, so LFT and INR are also done. If >8h from 1st dose, treat with NAC; don \200\231t wait for levels as effi cacy is waning fast. If <8h, do levels (see graph). s c i r t a i d e a P Fig 1. Graph for use in deciding who should receive acetylcysteine. Dr Alun Hutchings (University of Wales). \200\207This graph DOES NOT apply to IV paracet amol. If 4h level following IV par- acetamol overdose is >50mg/L (below high-risk treatment line) or if a single IV overdose of >60mg/kg has been given, then treatment should be star ted. 615,616 This is because IV paracetamol plasma concentration peaks at the end of ad- mi nistration. By 4h levels may have dropped considerably. Consult with NPIS. Other countries use diff erent nomograms. Australasian guidelines have a sin- gle treatment line which star ts at 150mg/L \200\224that is midway between the UK high risk and normal treatment lines. 6 17 Acute lymphoblastic leukemia (ALL) ALL is the commonest (80%) childhood leukemia ( 500 case s/yruk); it is a ma- lignant disorder of lymphoid progenitor cells. Other forms: OHCM p346 \200\22353. Peak age is 2 \200\2234years, with a second peak >50y. Incidence is greater in white children than in black children. Causes: Precise cause is unknown. There are genetic associations: ALL is concordant in 25% of monozygotic twins; individuals with trisomy 21 h ave a 4-fold increased risk (also increased risk in Bloom \200\231s syndrome, ataxia-telang ectasia). Chromosomal translocations such as t(12;21) resulting in the TEL-AML fusion gene are associated with 30% of cases (only present in 1% of the general population). t(9;22) \200\224the Philadelphia chromo- som \200\224occurs in 15 \200\22330% (mostly adults) and i s associated with a poor progno- sis. Environmental risk factors which have been implicated include prenatal exposure to x-rays; in utero exposure to infection, delayed postnatal exp osure to infection and environmental radiation. 618 \200\223620 Classi \201 cation The Fre nch-American-British (FAB) criteria of L1, L2, L3 morph- ology is obsolescent and is replac ed by the WHO classi \201 cation of ALL into either B lymphoblastic leukemia or T lymphobl astic leukemia. 614 Prior to 2008 the term pre-B cell ALL was used to distinguish B lymphob lastic leukemia from mature B-cell ALL which is termed Burkitt lymphoma/leukemia. Presentat ion Pancytopenia (pallor, infection, bleeding), fatigue, anorexia, fe- ver, bone pain. Pain less lumps in neck, axilla, groin. The period before diagnosis is often brief (2 \200\2234 weeks). Cranial in \201 ltration may lead to CNS eff ects, eg cranial palsies. Testicular in \201 ltration can lead to orchidomegaly. Tests Bloods: WCC \200\200, \200\201 or \200 \211. Normochromic, normocytic anemia platelets \200\201, urate \200\200, LDH \200\200. Marrow: 50 \200\22398% of nucleated cells will be blasts. CSF: Pleocytosis (with blast form s), protein \200\200, glucose \200\201. Cytogenetic analysis: 80% will have genetic abnor malities at diagnosis. CXR: May show mediastinal mass. Prognosis depends on clinical signs, biologic features of lymphoblasts and response to induction chemotherapy. Based on these f eatures patients can be strati \201 ed into 4 risk categories. Standard risk: Patients are aged 1 \200\2239.9yrs, have WCC of <50 \211\210109/L; lack unfavorable cytogenetic feature s, show a good response to initial chemotherapy and have <5% bone marrow blasts by 14 days and <0.01% blasts by 28 days. Low risk: These patients meet the standard risk criteria and have favorable genetics, such as trisomy 4, 10 or 17. High risk: Pa- tients do not meet sta ndard criteria or have extra-medullary involvement (eg brain/testis). Very high risk: Have unfavorable genetics, such as the Phile- delphia chromosme, hypodiploidy \200\224or poor re sponse to initial chemotherapy. Event-free survival at 5yr is 95% in the low risk group; 30 % in the very high risk. Infant leukemia has the worst outcome: 20%. Overall survival is 80 %. Treatment of ALL typically has 3 phases: Induction therapy: 3-drug induction over 4 week s (eg vincristine, dexamethasone, 621 L-asparaginase) + intrathecal (IT) therapy (methotrex ate cytarabine + hydrocortisone) results in remis- sion of >95%. High-risk patients may get a further agent eg daunorubicin. 614 2% die of infection. Consolidation phase: Cranial irradiation if known CNS disease. Further chemotherapy (eg cyclophosphamide; cytarabine; m ercap- topurine). Continuation phase: For 2 yrs (daily mercaptopurine + weekly methotrexa te vincristine/steroid pulses). 3-monthly intrathecal drugs. Complications Neutropenic s epsis: See BOX. Co-trimoxazole prevents pneu- mocystosis. Revaccinate (1 dose of each type, p151) 6 months after chemothera- py (as vaccine-speci \201 c antibody \200\201). 622 Hype ruricaemia: From massive cell death at induction: pre-treat with \200\200 \202 uid intak e + allopurinol. Poor growth: Monitor carefully. 623 Cancer elsewhere: Risk of CNS tumors o r a 2nd leukemia is 3%. Relapses: Consider FLAG1, clofarabine 624 or marrow transplant; con sider if risk 626 \200\200 \200\200, eg WCC >200 \211\210109/L, MLL gene rearrangement, B- cell ALL with t(8;14). 625 Tyrosine kinase inhibitors (eg imatinib) are used in children wi th t(9 : 22). 194 \200 s c i r t a d e a P i Pitfalls \200\207Ignoring quality of life; eg most cytotoxics may be given at home. \200 Omitting to examine the testes ( \200\207a common site for recurrence). \200 Thio- purin e methyltransferase de \201 ciency may cause fatal myelosuppression (?do pre-treatment pha rmacogenomic analysis).627 \200 Inappropriate transfusion (leu- kostasis, OHCM p346, if W CC >100 \211\210109/L).628 \200 SE of chemotherapy. NB: ondanse- tron is better than othe r anti-emetics. \200 Febrile neutropenic patients who may be septicaemic (eg from an infec ted venous catheter) Suspect infection when untoward events happen in a neutropenic patient (WCC <2 \211\210109/L, or neutrophils <1 \211\210109/L). Do T often; brief rises to \211 38 C may be ignored if lasting for <6h only if the child is well. Emphasize to the pa rents and child the importance of swift routes to hospital. Do blood cultures and MSU; swab all ori \201 ces. Do FBC, CRP & serology. Get help from your senior and a microbiologist; follow local protocols. Likely organisms In one UK study, blood cultures were +ve in 30%. Gram- positive organisms predominated (80%) and most were coagulase-negative staphs. 6% wer e Gram-negative isolates and <1% fungal. 629 Blind treatment Use local protocols, eg Tazoci n 630 gentamicin 631 OR imipenem ( teicoplanin) \200\224the broadest-spectrum \200 - lactam2 antibiotic, which may have advantages over cephalosporins if an anaerobe such as Ba cteroides is suspected (NB: imipenem is not indicated in CNS infections). 632 Tazocin = p iptazobactam = piperacillin + tazobactam IV over 3 \200\2235min or IVI: 1 month \200\22318y rs: 90mg/kg/6h, max 4.5g/6h. (The neonatal dose is 90mg/kg/8h.) Gentamicin Child 1 month \200\22312yrs: 2.5 mg/kg/8h. 12 \200\22318yrs 2mg/kg/8h. Imipenem \200\224Dose in children <40kg: 15mg/kg/6h max 2g/24h. Heavier children have the adult dose: 250 \200\223500mg/6h (l ess sensitive organisms: up to 25mg/kg/6h IVI; max, eg 1g/6h). Do U&E. If creatinine cleara nce <70mL/min, \200\201dose frequency (see Data sheet). NB: do not use IM formulations IV (IM for- mulations are not for use in children). If blood culture does prove +ve, either ch ange imipenem after microbiological advice, or continue it for 5 days, if he has been afebr ile for >24h. If blood cultures are \200\223ve, give for a few days and send home when wel l and afebrile for >24h. SES: (It is usually well-tolerated.) Thrombophlebitis, anuria, pol yuria, seizures (eg in 2%), confusion, psychic disturbance, encephalopathy, vertigo, tinni tus, transient hearing loss, BP \200\201, pruritus, taste perversion, pseudomembranous coli tis; arthralgia; eosinophil- ia; WCC \200\201; Hb \200\201; LFT \200\200. There are few cli nically important drug interactions, eg seizures if co-therapy with ganciclovir. 633 Merope nem is preferred in some units (unlicensed; more active against most Gram \200\223ves than imipenem but is less active against most Gram +ves). 634 Dose: 1 month to 12yrs: 10 \200 \22320mg/kg/8h IVI over 5min. Over 50kg weight: adult dose (eg 1g/8h IVI). SE: D&V (eg anti biotic-associated colitis); abdominal pain; LFT \200\200; platelets \200\201; partial throm boplastin time \200\201; +ve Coombs \200\231 test; eosino- philia; WCC \200\201; headache; paraesthesiae; rash; pruritus; \201 ts (rare). 635 Teicoplanin For blind treatment of the worst infections, consider adding this to imipenem. Dose: 10mg/kg/12h IV for 3 doses, max 400mg, then 6mg/kg/24h (max 400mg); neonates: 16mg/kg on day 1, then 8mg/kg/day). SE: (few) : head- ache; WCC \200\201; platelets \200\201/ \200\200; LFT \200\200; allergy (rare). No major interactions. 636 If fever persists and blood cultures remain \200\223ve ask: Is ac iclovir indicated? Is a fungus possible? For amphotericin see SPC/data sheet & OHCM p168. 195 s c i r t a i d e a P 1 FLAG = Fludarabine, cytarabine (Ara-C), and G-CSF (recombinant human granulocyte-colony s timu- lating factor); clofarabine; it is non-standard.637,638 A novel alternative is myeloa blative chemotherapy and radiation followed by infusion of umbilical cord blood saved after delivery for this kind of eventuality.639 2 Named for the \200 -lactam ring in their stru cture. Examples: penicillins, cephalosporins, etc. Anemia The clinical problem You have the results of a full blood count, showing anae- mia ( Hb <11g/dL, p220, the WHO criterion). How should you proceed? 1 Take a history (include tra vel, diet, ethnic origin); examine the child. 2 MCV <70fL: ?IDA/iron de \201 ciency anemia (poor diet, poverty, bleeding, sto- matitis, koilonychia) or thalassaemia (Mediterranean/S E Asia areas, short stature, muddy complexion, icteric sclerae, distended abdomen \200\223 hepato- splenomegaly, bossed skull, prominent maxillae, from marrow hyperplasia). 3 MCV >1 00fL: suspect \200\201folate (malabsorption; phenytoin), \200\201B12 (breast milk from a vegetarian, \200\201intrinsic factor, malabsorption), or haemolysis. Signs of B12 \200\201 : poor feeding, late milestones; odd movements; microcephaly, failure to thrive. 4 MCV 81 \200\22397fL (normocytic): suspect haemolysis, or marrow failure (transient, after infectio ns, or thyroid, kidney, or liver failure, or malignancy). Causes of aplasia: chloramphenico l; Diamond \200\223Blackfan (p640); Fanconi \200\231s anemia (p644). 5 WCC/diff erential ab normal? Eosinophilia + anemia + tropics \211\210 hookworms. 6 Severe tropical anaemias (eg Hb <5): malaria; bacteraemia (eg nontyphoid salmonella 640); worms; HIV; B12 \200\201; G6D P \200\201; iron de \201 ciency; sickle cell anemia. 196 \200 7 Next look at the ESR and CRP. This may indicate some chronic disease. 8 Movie + reticuloc yte count thick \201 lm for malaria. Hypochromic microcytic RBCs \211\210 IDA; target cells \211\210 liver disease or thalassaemia; ferritin for IDA; sickling tests + Hb elect rophoresis for thalassaemia & sickle-cell anemia; B12; red cell folate. 9 Prevention: no co ws \200\231 milk if <1yr; if formula-fed, use iron-forti \201 ed; wean at s c i r t a d e a P i 4 \200\2236 months. Adequate vitamin c intake; iron supplements if premature. Iron de \201 ciency anemia ( 26% of infants, worldwide; 641 peak age 18 months) this is d espite forti \201 cation of, formula, breakfast cereals and noodles etc. 642 The chief beh avioral eff ect is that iron de \201 cient babies are less happy than others, with \200 \201psychomotor development and poor cognition (?from al- tered myelination). 643 In the UK , dietary causes are common, eg poverty, lack of education, or coeliac disease. In recurren t IDA, suspect bleeding (eg Meckel \200\231s diverticulum, p651, or oesophagitis). \201 \227: Ferrous fumarate syrup (140mg/5mL), 0.25mL/kg/12h PO (if <12yrs old (max20mL), or Syt ron . Warn of the dangers of overdosage, p191. Aim for a rise in Hb of >1g/month (do retic ulocyte count after 2 months). In many places, the 1st step is de-worming. Haemolysis Is ma laria or sickle-cell disease possible? Get help, and try to provide the expert with suffi c ient information to answer these 4 questions: 1 Any evidence of \200\200RBC production? (P olychromasia, reticulocytosis.) 2 Is there decreased RBC survival? (Bilirubin \200\200, ha ptoglobins \200\201.) 3 Is there intravascular haemolysis? (Haemoglobinuria.) 4 Is there a n inborn error of metabolism (eg G6PD de \201 ciency), spherocytosis, or is the defect acquired (usually with +ve Coombs \200\231 test)? Hereditary spherocytosis is the main cause of haemolysis in north European children (mainly autosomal dominant; spontaneous mutations in 25%). It is often mild; parvovirus B19 infect ion can trigger transient severe anemia. Flow cytometric analysis of eosin-5-maleimide (EMA ) binding to red cells, and cryo- haemolysis test have replaced osmotic fragility tests. 64 4 Splenectomy leads to \200\200RBC survival and is sometimes indicated; gallstones may occ ur in the 1st dec- ade, and if symptomatic cholecystectomy splenectomy may be needed. 64 5 Sickle-cell disease: OHCM p334. Hydrate and give O2. Pain relief: Warmth, hydra- tion, ib uprofen 10mg/kg/8h PO,[] morphine sulfate solution, load with 0.4mg/ kg PO, 646 then 0.3 mg/kg/4h + MST 1 \200\2231.5mg/kg/12h[] for background analgesia; this may be preferred t o IVI morphine, eg 0.1mg/kg (+lactulose 2.5 \200\22310mL/12h PO senna). Patient-controll ed analgesia: Morphine 1mg/kg[] in 50mL 5% glucose at 1mL/h with self-delivered extra bolus es of 1mL as needed; do respiration & sed- ation score every h + SAO2 if chest or abdomin al pain. 647,648 Deferasirox (Exjade ) is a good but expensive oral iron chelator; needed if many transfusions are used. 197 Iron de \201 ciency without anemia \200\207Don \200\231t think that if a child is not ane mic he is not iron de \201 cient. CNS iron levels fall before RBC mass. If in doubt, check ferritin. Treating low ferritins may improve: \200 Memory \200 Lassitude \200 Develo pmental delay \200 Mood \200 Cogni- tion \200\224in toddlers and adolescent girls, faci ng demands of puberty and men- struation. NB: pica (eating dirt, p210) is a sign of iron de \201 ciency. Purpura: 2 questions: \200\207is the child ill? \200\207what is the platel et count? \200 If ill & platelets \200\201: Meningococcaemia ( \200 ceftriaxone, p202), leukemia, or disseminated intravascular coagulation (check a visual non-automated blood \201 lm & WCC, discuss with lab). Haemolytic uraemic syndrome (p176). \200 If ill & plate let count \200\211 or \200\200: Viruses (measles; enteroviruses); 649 vasculi- tis (Kawas aki, p646; platelets \200\200); 650 SBE. Meningococcaemia less likely. \200 If well(ish) & platelet count \200\211 and no history of trauma: HSP (below). \200 If well & platelet count \200\201 consider idiopathic thrombocytopenic purpura (rarely, Wiskott \200\223Aldri ch syndrome, p655, or aplastic anemia). NB: vomit- ing or coughing can cause petechiae in s uperior vena cava distribution. s c i r t a i d e a P If in doubt, treat for meningococcaemia. NB: we can \201 nd no case of purpura for >48h b eing caused by meningococcal sepsis in a child who is 100% well. Henoch \200\223Sch nlein purpura (HSP) is an acute immune complex-mediated vasculitis. Most patients have a antecede nt upper respiratory tract infec- tion. Purpura (purple spots/nodules not disappearing on p alpation), arthri- tis/arthralgias (74%) \200\224often knees/ankles \200\224and abdominal p ain (51%) are the classic triad. \200 : \200 \211\2101.3 : 1. 651 Other signs: Renal invo lvement (54%; severe nephropathy in 7%, acute renal insuffi ciency in 2%), scrotal oedema ( 13%), and intussusception (0.6%). Tests: ESR \200\200 (57%), IgA \200\200 (37%), proteinuri a (42%) ASO titres \200\200 (36%). Check U&E & BP. Steroids may help resolve abdo pain, 652 but role in prevention of chronic kidney disease is less clear. 653 Most recover in \200 \2052 months. Recurrences, veri \201 ed in 35%, correlate with \200\200ESR. Complications (worse in adults): massive GI bleeds, ileus, haemoptysis (rare), and acute re nal failure (rare). One option in HSP nephritis (not usually needed) is high-dose steroids + cyclophosphamide; this decreases proteinuria (a risk factor for renal insuffi ciency in H SP). 654 Chronic renal failure occurs in 5%. Idiopathic (immune) thrombocytopenic purpura ( ITP) is most chief ac- quired bleeding disorder in childhood. ITP has acute and chronic for ms. Pres- entation: Acute bruising, purpura, and petechiae. Usually a history of recent URT I or gastroenteritis. May follow CMV, EBV, parvovirus, varicella-zoster, or live virus vacc ine (eg MMR/rubella). If there is signi \201 cant mucosal bleeding, or lymphadenopathy, he patosplenomegaly, or pancytopenia, another diagnosis is likely. Tests: Isolated thrombocyto penia (<20 \211\210109 in 80%); do a \201 lm to en- sure no other abnormalities. Marrow i s unnecessary, unless: 655 \200 Unusual signs are present, eg abnormal cells on a \201 lm, lymphadenopathy. \200 Platelet count is not rising after 2 weeks. \200 Treatment i s contemplated with steroids or immunoglobulin \200\224may de- crease period of profound thrombocytopenia. Intracranial hemorrhage occurs in <1% (mortality is 50%) 656 \200\224do CT if there is head ache or CNS signs. Natural history: Gradual resolution over 3 months for 80% with or witho ut therapy. 20% become chronic (>6 months); the chronic form is compatible with normal long evity, and normal activities, provided contact sports are avoided. \201\227: Admit eg if: \200 Unusual features, eg excessive bleeding. \200 There are rowdy siblings who might e ngage in physical badinage. Life threatening bleeding requires platelet transfusion. Splene c- tomy is considered for chronic ITP and failure of treatment. Rituximab1 and anti-D2 (p9) reduce the need for splenectomy. 1 Rituximab can induce remission in 30%.657 SE: T \201 , pruritus, throat tightness, ser um sickness. 2 Anti-D: a single dose of 50 /kg IV \201 platelet count to \211 20 \211 \210109/L in 70% of children within 3 days.658 The primary antibody de \201 ciencies Synonyms: primary hypogammaglobulinae- mia (not seco ndary to protein-losing enteropa- thy, chronic lymphatic leukemia, or myeloma). Bruton \200 \231s agammaglobulinaemia was the \201 rst immunode \201 ciency syndrome to be described . 659 Essence Antibodies (that are produced by B lymphocytes) can kill pathogens by binding to target antigens and activating complement system or facilitating their uptake by phagoc yte cells. They can also neutralize the toxins secreted by the pathogens. Disorders of B ce lls increase susceptibility to infections by encapsulated bac- teria, but not (usually) vir al or fungal infections. Most are recessive, eg caused by mutations in genes on autosomal o r X chromosomes. 659 The patient When the signs in the MINIBOX are unexplained, refer to an immu- nologist, to assess antibody responses to protein and carbohydrate antigens, measure IgG subclasses, speci \201 c antibodies to the immunized illnesses, and count lymphocytes involved in antibody production (CD4, CD8, CD19, CD23 +ve lym- phocytes). Immunoglobulin l evels are interpreted by age. There is a role for watching responses to test vaccinations. Primary immunode \201 ciency is more likely if there is a positive family history/parental consanguinity. 661 Types of primary immunode \201 ciency See BOX. Management Aim to inclu de the patient and the family in the process. Treat intercurrent infections promptly. This may include postural physiotherapy, and bronchodilators as well as antibiotics. Immunoglobu lin replacement obviates most complications and is best delivered by an immunologist, after detailed assessment. Many patients can join a self-infusion program. Before infu- sions, e xclude active infection (to minimize risk of adverse reactions), and a baseline check of tr ansaminase enzymes, creatinine, and anti-IgA antibody titres should be done. The dose of IV immunoglobulin is determined by the severity and frequency of infections, and the plasma l evel of IgG. Most receive 400mg/kg/month (see data sheet/SPC, usually as 2 doses, 2 weeks apart. [9] 662 Have hydrocortisone and an antihistamine at the ready. SE: headaches, ab- do minal pain, anaphylaxis, transmission of hepatitis. 663 IM immunoglobulins are not favored, but the subcutaneous route is being investigated and ap- pears satisfactory. 664 Complicat ions Chest: Bronchiectasis, granulomas, lymphoma. Gut: Malab- sorption, giardia, cholangiti s, atrophic gastritis, colitis. Liver: Acquired hepati- tis, chronic active hepatitis, bili ary cirrhosis. Blood: Autoimmune haemolysis, ITP (p197), anemia of chronic disease, aplasia . Eyes/CNS : Keratoconjunctivitis, uveitis, granulomas, encephalitis. Others: Septic arthro pathy, arthralgia, sple- nomegaly. Gene therapy Autologous haematopoietic stem cells transd uced with the \200 c gene can restore immune system in boys with severe combined immunode \201 - ciency. A harmless retrovirus carries the replacement gene, and infects the stem ce lls in vitro. When these are replaced in the marrow an immune system develops within a few months1 \200\224obviating the need for intrusive anti-infec- tion isolation measures and IV immunoglobulin. It is an alternative to marrow transplants (eg if no HLA match can be foun d). There is likely to be a limitation to initiation of normal thymopoiesis, so do it promp tly. 198 Typical signs: \200 Frequent infections \200 Bronchiectasis \200 Chronic sinusitis \200 Failure to thrive \200 Nodular lymphoid hyperpla- sia (gut) Absent tonsils \200 Enteropathy \200 Hepatosplenomegaly \200 Anemia \200 Arthropath y \200 Lymphopenia \200 Serum total protein \200\201 (albumin; immunoglobulins are miss ing)660 s c i r t a d e a P i N=40 1 T cells & repertoires of T-cell receptors were normal up to 2yrs post-op; thymopoiesis i s shown by naive T cells. Antibody production is adequate. 199 Types of antibody de \201 ciency IgA de \201 ciency (IgA \200\201 + normal or \200\200 l evels of other immunoglobulins). It is the most common primary antibody de \201 ciency. Ma ny are asymptomatic. It may accompany CVID (below). Patients tend to develop respiratory in fections which may lead to bronchiectasis. Gastrointestinal infection (eg giardia) and diso rders such as malabsorption, coeliac disease, ulcerative colitis are associated with IgA de \201 ciency. Although rare, all blood products/IV im- munoglobulin infusion can lead to s evere, even fatal, anaphylaxis due to the presence of IgA. Ideally blood products if needed should be obtained from a IgA-de \201 cient individual \200\224or washed red cells given. Patients are recom- mended to wear a medical alert bracelet because of this. 665 Prevalenc e: Var- ies with ethnicity: 1 in 143 in Middle East; 1 in 875 in UK; 1 in 18,500 in Japan. 665 Transient hypogammaglobulinaemia of infancy Temporary delay in anti- body production. O nset: 3 \200\2236 months. It is more severe than normal antibody de \201 ciency that happe ns at this age. Immunoglobulin levels become normal by 2 \200\2234 yrs. Prevalence: 1 in 1 0,000. 666 Common variable immunode \201 ciency (CVID) (IgG \200\201, IgA \200\201, IgM va riable). Onset: Second to third decade of life. Enlarged tonsils, splenomegaly, gas- troint estinal disease, liver dysfunction and cancer (esp lymphoma) may be present. Prevalence: 1 in 10,000 \200\22350,000. 667 Bruton X-linked agammaglobulinaemia Tyrosine kinase gene mut ation (Xq21) causes \200\201 immunoglobulins and \200\201mature B cells, 668 hence \200 \200 susceptibil- ity to bacterial (but not viral) infections. Lymphocytes are unable to sy nthe- size immunoglobulin. Onset: 3months \200\2233years. 669 Also: arthropathy + absent Pe yer \200\231s patches, tonsils and appendix. Prevalence: 1 in 250,000 (the com- monest inh erited antibody de \201 ciency). 668 \201\227: Beware septicaemia and CNS in- fections (m ay require interferon- \200 and high-dose IV immunoglobulin). 670 Af- ter marrow transplan tation serum immunoglobin rises to normal levels over 3 months. 671 IgG subclass de \201 ciency There are \200\201 levels of one or more of 4 subclasses of IgG. Total IgG levels m ay be normal. IgG2 \200\201 is the most common and often is associated with IgA \200\201, a nd ataxia \200\223telangiectasia. Severe combined immunode \201 ciency (SCID) T-cell dysfu nction usually causes combined immunode \201 ciency as T cells are necessary for B-cell di ff er- entiation. Onset: 1 \200\2233 months. Patients are susceptible to all types of bacte - rial, viral, fungal, and protozoal infections. Treatment: Stem cell transplant. Prevalenc e: 1 in 50,000 \200\22375,000. 672 s c i r t a i d e a P \200 Rising intracranial pressureAPLS Causes Meningoencephalitis; head injury; subdural/ex tradural bleeds (abused?); hypoxia (eg near-drowning); ketoacidosis; tumors; thrombosis;1 R eye \200\231s (p652). Signs Listless; irritable; drowsy; headache; diplopia; vomiting; tens e fonta- nelle; \200\201level of responsiveness (Children \200\231s Coma Scale if <4yrs, s ee OPPOSITE, or use the Glasgow Coma Scale if >4yrs (p722); If unconscious look for: pu- pi l changes (ipsilateral dilatation); abnormal posturing (decorticate/decere- brate); Cushing s triad (slow pulse, raised BP and breathing pattern abnormali- ties) warns of imminent co ning. Chronic: papilloedema and hydrocephalus. Management Aim to prevent ischaemia. Help ve nous drainage by keeping head in the midline, elevated at 25 . Give O2. Fan/sponge (tepid water) if T >40 C. Treat hypoglycaemia. Control seizures (p208). \200\207Don \200\231t do LP: this risks coning. If severe, take to ITU to monitor ICP & cerebral perfusion press ure (CPP=mean arterial pressure minus ICP; if CPP <40mmHg cerebral ischaemia is likely). \200 Intubate. Hyperventilation is no longer recommended. \200 Give mannitol 20% (check it is crystal-free), eg 2.5mL/kg IVI over 30min 673 or 3% hypertonic saline (5ml/kg bolus) wh ich may have fewer side eff ects. 674 \200 Dexamethasone: if <35kg, 16.7mg IV (20.8mg if > 35kg) then as per BNFc 6.3.2. \200 Fluid restriction & diuresis, avoiding hypovolaemia ( keep Na+ 145 \200\223150mmol/L, 200 \200 s c i r t a d e a P osmolarity to 300 \200\223310, and CVP to 2 \200\2235cmH2O). \200 Pulse & BP continuously. \200 Send to neurosurgical center now. Herpes simplex encephalitis (HSE) is the most treat able encephalitis. \200\207Think of it in any febrile child with focal or general seizures and CNS (esp. temporal lobe) signs \200\201consciousness. Signs are often nonspeci \201 c. 675 Nasolabial herpes is often absent. CNS de \201 cits may be mild or gross (eg h emiparesis). Tests: CT, EEG and CSF often nonspeci \201 c (do PCR). MRI is better than CT. \201\227: \200 Start aci- clovir. If >12yrs old: 10mg/kgIBW/8h by IVI over 1h eg for 3wk s (20mg/kg/8h in neonates). 676 Monitor U&E & urine output; Mortality: 7%. 60% survive int act. CNS sequelae: Kluver \200\223Bucy syndrome (hypersexuality, rage, visual agnosia); aph asia; 677 amnesia; auditory agnosia; autism. 678 Brain tumors \200\207Arrange urgent refer ral if unexplained headache and/or fo- cal symptoms, eg progressive weakness or numbness, u nsteadiness, diffi culty speaking, or vision changes/VI nerve palsy. \205\224 are in the p osterior fossa. Con- sider brain tumors in children with lethargy, behavioral change, visua l dis- turbances, diabetes insipidus (polyuria/polydipsia), growth disturbances (e.g. growt h failure , delayed/arrested/precocious puberty), nausea vomiting. 679 Medulloblastoma: Midline cerebellar embryonal tumor (inferior vermis) causing ICP \200\200, speech diffi cul ty, truncal ataxia falls. \200 : \200 \211\210 4 : 1. Peak age: 4yrs. Seeding is alon g CSF pathways. Rx: surgical resection + radio/chemo-therapy. Brainstem astrocytoma: Most c ommon brain tumor in children. Associated with neuro \201 bromatosis 1) and prior radiatio n. Cranial nerve palsies; pyramidal tract signs (eg hemiparesis); cerebellar ataxia; signs of ICP \200\200 are rare. Midbrain and third ventricle tumors may be astrocytomas, pinealom as or colloid cysts (cause posture-dependent drowsiness). Signs: behavior change (early); p yramidal tract and cerebellar SIGNS; upward gaze defect. Suprasellar gliomas: Visual \201 eld defects; optic atrophy; pituitary disorders (growth arrest, hypothyroidism, delayed pu berty); diabetes insipidus (DI). Cra- nial DI is caused by ADH \200\201, so that there is p olyuria and low urine osmolality (always <800mosmol/L) despite dehydration. Cerebral hemisp heres: Usually gliomas. Meningiomas are rare. Fits are com- mon. Signs depend on the lobe i nvolved (OHCM p503). Tests: MRI/CT EEG. Op- tions: Excision if possible; CSF shunting; r adiotherapy; chemotherapy alone. 680 Other space-occupying lesions Aneurysms; haematomas; g ranulomas; tub- erculomas; cysts (cysticercosis); \200\207abscess: suspect if ICP \200\200 ; T \200\200; WCC \200\200. Get help. 1 Venous sinus thrombosis risk \200\200 if: infecti on; perinatal problems; blood dyscrasias. Signs: \200\201consciousness (50%), papilloedema (18%), cranial nerve palsy (33%), hemiparesis, hypotonia. Thrombolysis may be needed.681 i Children \200\231s coma scale (An objective record of coma level to help quantify prognosis and monitor progress.) Use if <4yrs; if >4, use Glasgow scale, p720. \200 Best motor res ponse (6 grades, quanti \201 ed in the blue numbers below) 6 Carrying out a request ( \200 \230obeying command \200\231): Moves to your request. 5 Localizing response to pain: Put pr essure on the patient \200\231s \201 nger nail bed with a pencil or sternal pressure: pur poseful movements towards chang- ing painful stimuli is a \200\230localizing \200\231 resp onse. 201 4 Withdraws to pain: Pulls limb away from painful stimulus. 3 Flexor response to pain: Pres sure on the nail bed causes abnormal \202 exion of limbs \200\224decorticate posture. 2 Extensor posturing to pain: The stimulus causes limb extension (adduction, internal rotation of shoulder, forearm pronation; decerebrate posture). s c i r t a i d e a P 1 No response to pain. Score best response of any limb. Best verbal response (5 grades) If intubated can the patient grimace? 5 Orientated: Smiles, is orientated to sounds, \201 xes and follows objects. 4 Crying but consolable (or inter action odd/inappropriate) 3 Inconsistently consolable (or moaning) 2 Inconsolable crying (o r irritable) 1 No response Eye opening (4 grades) 4 Spontaneous eye opening. 3 Eye opening in response to speech: Any, not just a request to open eyes. 2 Eye opening to response to pain: Pain to limbs as above. 1 No eye opening. Add the score in the 3 areas. Eg: no response to pain + no verbalization + no eye opening = 3. As a rule of thumb, <8 \211\210intubation needed; 4 \200\2238 \211\210 intermediate p rognosis; 3 \211\210 bad prognosis. Migraine In children we modify migraine criteria to include bilateral or frontal headache l asting 1 \200\22372h with nausea/vomiting + any 2 of: photophobia, phonophobia, dif- \201 culty thinking, lightheadedness, or fatigue 682 (vertigo and abdo pain also occur) sometim es heralded by visual or sensory aura. Most children have to lie down during attacks; sleep resolves the attack. Prevalence: 5% (10% in adolescence). Triggers: School pressure, tantr ums, excitement: upset, hypoglycaemia, sleep lack or excess (weekend migraine), sensory eve nts (noise, light, heat/cold), sympathetic activity (sports). Drugs: (as early as possible in an attack); par- acetamol (p143); ibuprofen 10mg/kg PO (see p143). 683 If this fails and over 6yrs, try sumatriptan, 684 eg if weight >30kg. 683 If vomiting, use rectal (paracetam ol suppositories) or nasal routes (sumatriptan dose: 12 \200\22318 years 10 \200\22320mg st at, repeated once after \211 2h if needed) or IV chlorpromazine (0.15mg/kg if >8y; max 10m g). 685 Non-drug treatments: Relaxation training, biofeedback, self- hypnosis, and guided i magery have a role. 686 Prophylaxis: Encourage regular sleep. Consider propranolol and pizo tifen. Amitriptyline and sodium valproate are used, but note lack of robust evidence of eff i cacy. 687 Nimodipine, timolol, pa- paverine, trazodone, clonidine, metoclopramide, and do mperidone are \200\230ineff ec- tive \200\231. 688 Signs for prompt referral: \200 Heada ches of increasing frequency or severity, or if aged <6yrs. \200 Headache unrelieved by p aracetamol or ibuprofen. \200 Irritable; loss of interest/skills; slowing of physical or cognitive development. \200 Head circumference above the 97th centile, or greatly out of line. Other causes of headache Viruses; meningitis; sinusitis (frontal sinus not de- velope d until >10yrs); hypertension (always do BP), stress, behavioral. (OHCM p462)