Cystic Fibrosis - Diagnosis and treatment of Allergic Bronchopulmonary Aspergillosis (ABPA) in children with cystic fibrosis

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1 Guideline Cystic Fibrsis - Diagnsis and treatment f Allergic rnchpulmnary Aspergillsis (APA) in children with cystic fibrsis Scpe Trust wide Aim The aim f this guideline is t standardize care f infants and children with cystic fibrsis thrughut the trust. 1 Intrductin Aspergillus fumigatus is a fungus that grws at 37 degrees, and prduces a large number f txic and allergenic exprducts. There are a large number f manifestatins in CF including simple clnisatin that des nt warrant any actin. Hwever we are increasingly recgnising Aspergillus brnchitis as a cause f acute deteriratin and treating it accrdingly. Other clinical presentatins include invasive pulmnary aspergillsis, and apsergillma. Children are advised t avid mucking ut stables, and visiting ther places where there is rtting vegetatin, likely t be assciated with a high spre cunt. Hspitals where extensive demlitin and building wrks are in prgress may als pse a risk. Allergic brnchpulmnary aspergillsis (APA) is a serius ptential cause f lung damage and is nt uncmmn in CF (prevalence varies %). Its nset may be insidius r fulminant. Early pick-up depends n screening and a high level f clinical suspicin. Children are screened annually, and with every curse f IV antibitics fr evidence f APA. 2 Diagnsis and recmmendatins Diagnstic criteria - This can be a very difficult diagnsis t make, because in the cntext f CF, mst f the majr and minr criteria can be psitive in the absence f APA. Clinical symptms & signs - Increased wheezing/chestiness particularly if failing t respnd t antibitics and inhaled medicatins. Fever and malaise. Nrflk, Sufflk & Cambridgshire Paediatric CF Netwrk Page 1 f 5 Cystic Fibrsis - Diagnsis and treatment f APA in children with cystic fibrsis

2 3 Investigatins Thick sputum with brwn r black brnchial casts. Majr Criteria CXR pulmnary infiltrates > 1cm diameter and segmental cllapse. High serum IgE - especially an abrupt recent rise t abve 500 iu/ml (nrmal < 150 iu/ml), that falls with prednislne therapy. High specific aspergillus IgE RAST. The nrmal value < 0.35iu/ml may rise x in APA. Psitive IgG aspergillus precipitins using encard standard antigens 1 & 2. Esinphilia (> 0.4 x 10 9 /l). Immediate psitive skin prick test t aspergillus antigen: prick skin wheal f 13mm in diameter with surrunding erythema. The patient shuld nt be n systemic antihistamines. Reversible brnchcnstrictin. Central brnchiectasis. Minr Criteria Aspergillus fumigatus culture frm sputum (N fund in 30% f all CF patients). rwn/black plugs in sputum. Late skin test reactin. The fur minimal diagnstic criteria in rder t make a diagnsis f APA are: Acute r subacute clinical deteriratin (cugh, wheeze, exercise intlerance, exercise induced asthma, decline in pulmnary functin, increased sputum) NOT attributable t anther aetilgy. Immediate cutaneus reactivity t aspergillus OR in vitr presence f A fumigatus specific Ig E antibdies (strngly psitive Aspergillus RAST) Ig E > 500IU/ml Psitive aspergillus precipitans OR new abnrmalities n CXR r CT scan nt respnding t standard therapy. Nrflk, Sufflk & Cambridgshire Paediatric CF Netwrk Page 2 f 5 Cystic Fibrsis - Diagnsis and treatment f APA in children with cystic fibrsis

3 4 Treatment 5 6 Oral crticsterids Prednislne (nn-enteric cated) 2mg/kg/day (t a maximum f 60mg/day) fr 2 weeks, then 1 mg/kg/day fr 2 weeks, then 1 mg/kg/alt day fr tw weeks. Re-evaluate clinical respnse, CXR, and IgE. A reslutin f symptms, return f respiratry functin t previus levels, reslutin f CXR changes and a fall f >35% in ttal IgE is indicative f remissin. Sterid dse is then gradually lwered ver 2-3 mnths guided by clinical respnse, radilgy and Ttal IgE. CXR s shuld be repeated 2 mnthly as sterids are weaned t exclude evidence f relapse. Relapse is cmmn within 2-3 years f 1st episde, and ften high dses f sterids are needed fr a lng time. An equivalent dse f dexamethasne may be used as an alternative if patients find the side effects frm prednislne t difficult t cpe witherrr: Reference surce nt fund. Itracnazle C Suspensin appears t be mre efficacius than capsules. Shuld be taken n an empty stmach. Cmmence with sterids and cntinue fr a minimum f 6 weeks, and pssibly fr the duratin f the sterid curse Dse 5mg/kg/day t a maximum f 400mg/day Given nce daily if dse is < 200mg/day. Once daily dse EXCEEDS 200mg/day a twice daily regimen shuld be fllwed. Duratin 3-6 mnths Liver functin tests (LFT s) shuld be perfrmed regularly, usually at the same time as APA serlgy, as liver dysfunctin has been reprted. Althugh nt cntraindicated in CF patients with established liver disease, cautin shuld be exercised with this grup f patients with LFT s being clsely mnitred. Drug interactins Absrptin is adversely affected by the cncmitant use f antacids, H 2 antagnists and prtn pump inhibitrs, and these shuld be stpped if pssible. It can als cause increased systemic levels f antihistamines, with risks f ventricular arrhythmia. Vricnazle is a newer ral antifungal antibitic, which has better absrptin than itracnazle and is nt affected by gastric ph. Therefre it may be useful as a 2 nd line agent fr patients wh have nt respnded t r cannt tlerate Nrflk, Sufflk & Cambridgshire Paediatric CF Netwrk Page 3 f 5 Cystic Fibrsis - Diagnsis and treatment f APA in children with cystic fibrsis

4 itracnazle. Vricnazle shuld nly be started with cnsultant apprval and fllwing discussin with cnsultant micrbilgist. Dse: Children < 12years 200mg twice daily Children >12 years and <40kg lad with 200mg twice daily fr ne day, and then cntinue with 100mg twice daily Children>12 years and >40kg lad with 400mg twice daily fr ne day and then 200mg twice daily Nebulised amphtericin (nn-lipsmal) May be used in difficult cases at a dse f 5-10 mg twice daily after physitherapy (check fr brnchcnstrictin and use brnchdilatr predse). C Disslve in water t achieve a cncentratin f 2.5mg/ml (20ml water in 50 mg amphteracine). The lipsmal frm wuld be cnsidered nly fr thse in whm brnchcnstrictin is a severe prblem. Indicatins fr intravenus lipsmal amphtericin Prven invasive aspergillsis Severe, chrnic and persistent ther aspergillus lung disease (including APA), with multiple side effects frm cnventinal sterid therapy. This is a cnsultant decisin nly. Iv amphtericin - nn-lipsmal (Amisne) might be cnsidered in a patient wh is significantly unwell, r wh is receiving iv antibitics cncurrently. Dse: 3 mg/kg/day. Start at 1 mg/kg nce daily then gradually increase t 3 mg/kg d. Give test dse f 100 mcg/kg (max 1mg) ver mins. Observe fr 1hr then cntinue treatment. NOTE: Amisme and vricnazle are restricted frmulary drugs and Trust s Drug and Therapeutics Cmmittee has specified that release frm pharmacy requires a request frm the cnsultant clinician and a cnsultant micrbilgist. 7 OTHER MANIFESTATIONS OF ASPERGILLUS LUNG DISEASE Invasive aspergillus disease may ccur, heralded by wrsening f symptms and prgressin f x-ray shadws, smetimes with cavitatin, haemptysis and pleuritic chest pain. Treat aggressively with parenteral lipsmal amphteracin, and discuss with the micrbilgist. Nrflk, Sufflk & Cambridgshire Paediatric CF Netwrk Page 4 f 5 Cystic Fibrsis - Diagnsis and treatment f APA in children with cystic fibrsis

5 Metastatic fungal spread is als pssible in severely debilitated, immunsuppressed (including sterids) r neutrpenic patients. Treat with parenteral lipsmal amphtericin (3 mg/kg/day fr 4 t 6 weeks). Oral/IV flucytsine is smetimes given at the same time (named patient basis nly and fllwing advice frm the micrbilgist). Treatment is ptentially very txic: renal and hepatic damage, hypkalaemia, hypmagnesaemia, and anaemia are amng the pssible prblems. Repeated psitive sputum cultures in a chrnically symptmatic child. Cnsider itracnazle fr ne mnth (cnsultant decisin). Nebulised amphtericin is ccasinally needed. Mycetma is rarely seen in CF but has been described. Suspect if hal sign in a cavity and 6-8 psitive IgG precipitin lines. Cnfirm with CT. Treatment individualised - t rare t ffer guidelines therefre discuss with micrbilgist. Amylidsis is a late, incredibly rare and minus cmplicatin f APA and smetimes CF alne. It shuld be cnsidered if the fllwing ccur: prteinuria with edema (nephrtic), gitre, hepatsplenmegaly nt due t CF liver disease. Mnitring cmpliance and effectiveness Cmpliance with the guideline will be evaluated at clinic visits and annual assessment, by reviewing the medical ntes, and discussed at clinical meetings. Equality and Diversity Statement This dcument cmplies with the Cambridge University Hspitals NHS Fundatin Trust service Equality and Diversity statement. Disclaimer It is yur respnsibility t check against the electrnic library that this printed ut cpy is the mst recent issue f this dcument. Nrflk, Sufflk & Cambridgshire Paediatric CF Netwrk Page 5 f 5 Cystic Fibrsis - Diagnsis and treatment f APA in children with cystic fibrsis